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Iron is often accumulated in the liver during pathological conditions such as cirrhosis and cancer. Elevated expression of glucose transporters GLUT1 and GLUT3 is associated with reduced overall survival in patients with hepatocellular carcinoma. However, it is not known whether iron can regulate glucose transporters and contribute to tumor proliferation. In the present study, we found that treatment of human liver cell line HepG2 with ferric ammonium citrate (FAC) resulted in a significant upregulation of GLUT3 mRNA and protein in a dose-dependent manner. Similarly, iron accumulation in mice fed with high dietary iron as well as in mice injected intraperitoneally with iron dextran enhanced the GLUT3 expression drastically in the liver. We demonstrated that iron-induced hepatic GLUT3 upregulation is mediated by the LKB1/AMPK/CREB1 pathway, and this activation was reversed when treated with iron chelator deferiprone. In addition, inhibition of GLUT3 using siRNA prevented iron-mediated increase in the expression of cell cycle markers and cellular hyperproliferation. Furthermore, exogenous sodium beta-hydroxybutyrate treatment prevented iron-mediated hepatic GLUT3 activation both in vitro and in vivo. Together, these results underscore the importance of iron, AMPK, CREB1 and GLUT3 pathways in cell proliferation and highlight the therapeutic potential of sodium beta-hydroxybutyrate in hepatocellular carcinoma with high GLUT3 expression.

Purpose: We investigated the aqueous humor proteome and associated plasma proteome in patients with infectious or noninfectious uveitis., Methods: AH and plasma were obtained from 28 patients with infectious uveitis (IU), 29 patients with noninfectious uveitis (NIU) and 35 healthy controls undergoing cataract surgery. The proteins profile was analyzed by SomaScan technology., Results: We found 1844 and 2484 proteins up-regulated and 124 and 161 proteins down-regulated in the AH from IU and NIU groups, respectively. In the plasma, three proteins were up-regulated in NIU patients, and one and five proteins were down-regulated in the IU and NIU patients, respectively. The results of pathway enrichment analysis for both IU and NIU groups were related mostly to inflammatory and regulatory processes., Conclusion: SomaScan was able to detect novel AH and plasma protein biomarkers in IU and NIU patients. Also, the unique proteins found in both AH and plasma suggest a protein signature that could distinguish between infectious and noninfectious uveitis.

The high seroprevalence of Toxoplasma gondii infection in Blood Banks could be a potential risk for contamination of blood recipients. The discovery of new biomarkers may help to distinguish between seropositive and seronegative donors. This study determined the seroprevalence and profile of systemic immune biomarkers associated with Toxoplasma gondii infection among blood donors from Southern Brazil. Peripheral blood was collected from 510 blood donors (52.2 % male; mean age: 36.61), 310, and 200 from Erechim, and Chapecó municipalities, respectively. Specific Toxoplasma gondii IgG and IgM antibodies were detected by Eletrochemioluminescence. Nested PCR and qPCR were performed to detectToxoplasma gondii DNA. Twenty-seven inflammatory factors were analyzed using a high-performance Luminex assay. Among 310 blood donors from Erechim, 44.5 % (138/310) were IgM(-)/IgG(+), and 1.3 % (4/310) were IgM(+)/IgG(+), while out of 200 blood donors from Chapeco, 42.5 % (85/200) were IgM(-)/IgG(+), and 2 % (4/200) were IgM(+)/ IgG(+). We did not find Toxoplasma gondii DNA in the samples analyzed by Nested PCR and qPCR.Additionally, IgM(-)/IgG(+) donors presented higher levels ofdistinct systemic mediators, and were indicated to be high producers of several systemic mediators (CCL11, CCL2, CCL3, CCL4, CXCL10, IL-1β, IL-17, IFN-γ, IL-4, IL-9, IL-13, IL-10, IL-1Ra, vascular endothelial growth factor/VEGF, platelet-derived growth factor/PDGF, granulocyte-macrophage colony-stimulating factor/GM-CSF, and IL-7). However, IgM(+)/IgG(+) donors were found as high producers of CXCL8, CXCL10, CCL4, IL-1β, IL-1Ra, IL-9, IL-13, and PDGF, while IgM(-)/IgG(-) donors showed unaltered levels for the most soluble mediators evaluated. These distinct biomarker signatures might help identify potential factors to distinguish between IgM(-) and IgM(+) donors., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Competing Interests: Conflict of interest: The authors report no conflict of interest.

Purpose: We analyzed the frequency, viability, and genetic characteristics of T. gondii in pork heart samples., Methods: Thirty-five fresh pork samples were purchased in a slaughterhouse in Erechim city. The DNA was extracted and qPCR was performed. T. gondii genotyping was performed using PCR-RFLP analysis. Positive samples were digested and inoculated in mice for viability analysis., Results: Our results showed that T. gondii DNA was detected in 25.7% of the pork heart samples and genotyping revealed one new atypical strain. The viability analyses demonstrated that 40% of mice presented clinical signs of T. gondii infection. qPCR was positive in the lung, liver, and brain of mice that presented clinical signs of T. gondii infection. Also, the histopathology analysis showed retinal disorganization, retinal detachment, inflammatory cell infiltration, and fibrosis in the eyes analyzed., Conclusion: Our findings have shown that pork eat from southern Brazil may contain live T. gondii that could be associated with toxoplasmosis.

Purpose: We investigated the prevalence of ocular abnormalities in infants vertically exposed to Toxoplasma gondii infection during an outbreak in Santa Maria City, Brazil., Design: Consecutive case series., Participants: A total of 187 infants were included., Methods: The infants were recruited from January 2018 to November 2019. All mothers were screened for syphilis and human immunodeficiency virus before delivery. Toxoplasmosis infection was confirmed in all mothers and infants based on the presence of serum anti-T. gondii immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies. All infants underwent an ophthalmologic examination; ocular abnormalities were documented using a wide-field digital imaging system. Neonatal cranial sonography or head computed tomography was performed in 181 infants, and the cerebrospinal fluid (CSF) was screened for anti-T. gondii IgG and IgM antibodies in 159 infants. Peripheral blood samples from 9 infants and their mothers were analyzed for the presence of T. gondii DNA by real-time polymerase chain reaction., Main Outcome Measures: Ocular abnormalities associated with congenital toxoplasmosis., Results: A total of 187 infants were examined. Twenty-nine infants (15.5%) had congenital toxoplasmosis, of whom 19 (10.2%) had ocular abnormalities, including retinochoroiditis in 29 of 38 eyes (76.3%), optic nerve abnormalities in 5 eyes (13.2%), microphthalmia in 1 eye (2.6%), and cataract in 2 eyes (5.3%). Bilateral retinal choroidal lesions were found in 10 of 19 infants (52.6%). Nine eyes of 6 infants had active lesions, with retinal choroidal cellular infiltrates at the first examination. Thirteen (7.2%) of 181 infants screened presented with cerebral calcifications. Eighty-three percent of the screened infants were positive for anti-T. gondii IgG and negative for IgM antibodies in the CSF. Congenital toxoplasmosis was higher in mothers infected during the third pregnancy trimester, and maternal treatment during pregnancy was not associated with a lower rate of congenital toxoplasmosis., Conclusions: High prevalence rates of clinical manifestations were observed in infants with congenital toxoplasmosis after a waterborne toxoplasmosis outbreak, the largest yet described. Cerebral calcifications were higher in infants with ocular abnormalities, and maternal infection during the third pregnancy trimester was associated with a higher rate of congenital toxoplasmosis independent of maternal treatment., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

This study established a protocol to purify Toxoplasma gondii tachyzoite microvesicles and exosomes, called as extracellular vesicles (EVs). In addition, the investigations were conducted to determine the kinetic of EV release by tachyzoites and whether EV proteins are able to modulate the host immune response. The particle size and concentration released by tachyzoites in culture medium at different incubation-period were characterized by nanoparticle tracking analysis. Tachyzoites (1 × 10 6 ) released around 4.37 ± 0.81 × 10 8 EVs/mL/h, with size varying between 138.2 and 171.9 nm. EVs released into the medium were purified by gel-exclusion chromatography and screened by ELISA, using a pool of human positive sera for toxoplasmosis. EV-fractions contained high concentration of proteins, and EVs were analyzed by scanning and transmission electron microscopies. Tachyzoites released EVs into the culture medium throughout all membrane surface, and these vesicles contain small RNAs/miRNA. Pooled sera from chronically infected human or mice (infected with 2 different T. gondii strains) recognized distinct EV electrophoretic patterns in immunoblotting. T. gondii EVs significantly induced IL-10, TNF-α and iNOS in murine macrophages. In conclusion, this study shows that T. gondii secrete/excrete EVs (microvesicles and exosomes) contain miRNA and they were immunologically recognized by host immune response., (© 2018 John Wiley & Sons Ltd.)

Trypanosoma cruzi , the aetiologic agent of Chagas disease, releases vesicles containing a wide range of surface molecules known to affect the host immunological responses and the cellular infectivity. Here, we compared the secretome of two distinct strains (Y and YuYu) of T. cruzi , which were previously shown to differentially modulate host innate and acquired immune responses. Tissue culture-derived trypomastigotes of both strains secreted extracellular vesicles (EVs), as demonstrated by electron scanning microscopy. EVs were purified by exclusion chromatography or ultracentrifugation and quantitated using nanoparticle tracking analysis. Trypomastigotes from YuYu strain released higher number of EVs than those from Y strain, enriched with virulence factors trans -sialidase (TS) and cruzipain. Proteomic analysis confirmed the increased abundance of proteins coded by the TS gene family, mucin-like glycoproteins, and some typical exosomal proteins in the YuYu strain, which also showed considerable differences between purified EVs and vesicle-free fraction as compared to the Y strain. To evaluate whether such differences were related to parasite infectivity, J774 macrophages and LLC-MK2 kidney cells were preincubated with purified EVs from both strains and then infected with Y strain trypomastigotes. EVs released by YuYu strain caused a lower infection but higher intracellular proliferation in J774 macrophages than EVs from Y strain. In contrast, YuYu strain-derived EVs caused higher infection of LLC-MK2 cells than Y strain-derived EVs. In conclusion, quantitative and qualitative differences in EVs and secreted proteins from different T. cruzi strains may correlate with infectivity/virulence during the host-parasite interaction.

Introduction: Sensory blockade of the brachial plexus with local anaesthetics for perioperative analgesia leads to stable haemodynamics intraoperatively, smoother emergence from general anaesthesia and decreased need for supplemental analgesics or suppositories in the Post-operative period. However, increasing the duration of local anaesthetic action is often desirable because it prolongs surgical anaesthesia and analgesia. Various studies in adults prove that steroids increase the duration of action of local anaesthetics when used as adjuncts., Aim: The study aimed at determining the efficacy of dexame-thasone as an adjuvant to bupivacaine for Post-operative analgesia following sensory blockade of the brachial plexus in paediatrics., Materials and Methods: The study was divided into two groups of 15 each, group BD receiving dexamethasone (0.1mg/kg) as an adjunct to bupivacaine 0.125% and group B receiving bupivacaine alone. The duration of analgesia was taken as time from completion of the block to the patient receiving rescue analgesia, the haemodynamics were measured until 180 minutes after surgery, the incidence of Post-operative Nausea and Vomiting (PONV) was measured., Results: The duration of analgesia in the group BD was 27.1±13.4 hours and was significantly higher as compared to the group B, in which it was 13.9±11.3 hours (p<0.05). The pulse rate measured Post-operatively between both groups at 20 minutes (p-value 0.634), 60 minutes (p-value 0.888), 120 minutes (p-value 0.904) and 180 minutes (p-value 0.528) showed no statistical significance. Likewise the mean blood pressure measured between the two groups at 20 minutes, 60 minutes, 120 minutes and 180 minutes Post-operatively showed no significance. There was no significant difference in incidence of PONV in both groups with p-value of 0.624., Conclusion: Dexamethasone as an adjuvant to local anaesthetic in brachial plexus blocks significantly, prolongs duration of analgesia in children undergoing upper limb surgeries.

Introduction: Anaesthesia and upper abdominal surgeries alter lung compliance and functional residual capacity resulting from atelectasis. Upper abdominal surgeries also cause a decrease in peak expiratory flow rates, cough reflex due to pain limited inspiration., Aim: This study aimed to study the effect of thoracic epidural analgesia (TEA) on the peak expiratory flow rates in patients undergoing upper abdominal surgeries., Materials and Methods: A total of 44 patients posted for elective surgery were enrolled. Group 1 patients received GA + 0.125% bupivacaine infusion TEA and Group 2 received GA + Inj. Diclofenac sodium 50 mg slow i.v. TID for Postoperative analgesia. Haemodynamics, VAS pain score, PEFR measurements were done at 60 minutes, 24 hours, 48 hours and 4 days after surgery in both groups. ABG analysis was taken pre operatively and 24 hours after surgery., Results: The SBP and DBP values obtained at 60 minutes (p<0.016) 24 and 48 hours (p<0.001) and day 4 (p<0.02) postoperative showed highly significant difference between the two groups which indicate better haemodynamic parameters in patients receiving epidural analgesia. Postoperatively the difference in PEFR values at 60 minutes, 24 hour, 48 hour and day 4 were very highly significant. (p<0.001). Group1 had a 10.739% deficit on day 4 from its pre operative baseline value while group 2 showed a 34.825 % deficit which was very highly significant (p<0.001). The difference in VAS scores recorded at 60 minutes, 24 hours, 48 hours and day 4 post op were very highly statistically significant (p < 0.001). The ABG taken at 24 hours shows statistically significant difference with patients in group 2 showing decreased values in pCO2 and pO2 reflecting poorer ventilation and oxygenation., Conclusion: Thoracic epidural analgesia provides superior analgesia, better cough reflex as seen by better PEFR values, were haemodynamically more stable and their ABG values were better than the NSAID group.

Background: Optimizing cardiovascular function to ensure adequate tissue oxygen delivery is a key objective in the care of critically ill patients with burns. Hemodynamic monitoring may be necessary to optimize resuscitation in serious burn patients with reasonable safety. Invasive central venous pressure (CVP) monitoring has become the corner stone of hemodynamic monitoring in patients with burns but is associated with inherent risks and technical difficulties. Previous studies on perioperative patients have shown that measurement of peripheral venous pressure (PVP) is a less invasive and cost-effective procedure and can reliably predict CVP., Objective: The aim of the present prospective clinical study was to determine whether a reliable association exists between changes in CVP and PVP over a long period in patients admitted to the Burns Intensive Care Unit (BICU)., Subjects and Methods: The CVP and PVP were measured simultaneously hourly in 30 burns patients in the BICU up to 10 consecutive hours. The predictability of CVP by monitoring PVP was tested by applying the linear regression formula and also using the Bland-Altman plots of repeated measures to evaluate the agreement between CVP and PVP., Results: The regression formula revealed a reliable and significant association between CVP and PVP. The overall mean difference between CVP and PVP was 1.628 ± 0.84 mmHg (P < 0.001). The Bland-Altman diagram also showed a perfect agreement between the two pressures throughout the 10 h period., Conclusion: Peripheral venous pressure measured from a peripheral intravenous catheter in burns patients is a reliable estimation of CVP, and its changes have good concordance with CVP over a long period of time.

This study seeks to identify the formation of social support networks of people with physical disabilities, and how these networks can help facilitate access to health services and promote social inclusion. It is a cross-sectional study, with data collected via a form applied to physically disabled persons over eighteen years of age registered with the Family Health Teams of the municipal district of João Pessoa in the state of Paraíba. It was observed that the support networks of these individuals predominantly consist of family members (parents, siblings, children, spouses) and people outside the family (friends and neighbors). However, 50% of the interviewees declared that they could not count on any support from outside the family. It was observed that the support network contributes to access to the services and participation in social groups. However, reduced social inclusion was detected, due to locomotion difficulties, this being the main barrier to social interaction. Among those individuals who began to interact in society, the part played by social support was fundamental.

This study evaluated the in vivo potential antihypertensive effect of hydroalcoholic extract of Syzygium cumini leaves (HESC) in normotensive Wistar rats and in spontaneously hypertensive rats (SHR), as well as its in vitro effect on the vascular reactivity of resistance arteries. The hypotensive effect caused by intravenous infusion of HESC (0.01-4.0 mg/kg) in anesthetized Wistar rats was dose-dependent and was partially inhibited by pretreatment with atropine sulfate. SHR received HESC (0.5 g/kg/day), orally, for 8 weeks and mean arterial pressure, heart rate, and vascular reactivity were evaluated. Daily oral administration of HESC resulted in a time-dependent blood pressure reduction in SHR, with a maximum reduction of 62%. In the endothelium-deprived superior mesenteric arteries rings the treatment with HESC reduced by 40% the maximum effect (E max⁡) of contraction induced by NE. The contractile response to calcium and NE of endothelium-deprived mesenteric rings isolated from untreated SHR was reduced in a concentration-dependent manner by HESC (0.1, 0.25, and 0.5 mg/mL). This study demonstrated that Syzygium cumini reduces the blood pressure and heart rate of SHR and that this antihypertensive effect is probably due to the inhibition of arterial tone and extracellular calcium influx.

The scope of this study was to monitor the access of persons with disabilities and permanent mobility restrictions to the Unified Health System in João Pessoa, State of Pernambuco. This is a descriptive field study, consisting of a random sample of 523 people with disabilities or permanent mobility restrictions. Data collection occurred between August 2007 and December 2008 and consisted of home interviews. The neuromusculoskeletal functions and those related to movement (52%) were among the most affected body functions, with a higher incidence among body structures related to movement (44.2%) and those of the nervous system (39.2%), with special emphasis on the high number of cases (14%) due to the sequelae from strokes. Among the respondents, 63.9% stated that there had not been sufficient and appropriate means to lessen the physical obstacles between their homes and the places where they received healthcare, and 41.7% claimed that there were no special facilities for the handicapped in the healthcare offices. Brazilian law ensures rights for people with disabilities, which were not broadly respected. Action is necessary to prevent the development of disabilities, especially those resulting from the sequelae from strokes.

The extension project of Physiotherapy in the Community is developed in the neighborhood of Grotão linked to the family health units, in the city of João Pessoa. The aim of this work is to value popular knowledge and practices. The domiciliary physiotherapeutical assistance to the light of the popular education, at the same time that it promotes assistance to the unassisted population, extends our vision of health as an educational process. In each domiciliary visit we observed the social reality of the popular layers and the problems these people face, reflecting in its state of health, being evident for us the partner-economic conditionants of the process health-illness. This is observed that when carrying out domiciliary consultation on the basis of the principles of the popular education, it extents the perspective of the performance of the physiotherapist. This is so, because it is an education based on the dialogue, that proposes the exchange between scientific and popular knowledge, motivating the perspective of a commitment to the health together with the community.