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Abstract Microbubble contrast agents in ultrasound/echocardiography are used to increase the echogenicity of the target tissues, thereby raising the contrast resolution of the resultant image. Recently, the trend has shifted toward the development of phase-convertible nanodroplets as ultrasound contrast agents due to their promising theragnostic potential by switching capability at the active site. Herein, we fabricated pre-PGS- perfluoropentane phase convertible nanodroplets and checked their in vitro and in vivo enhancement and safety profile. For this, we performed experiments on 20 male Wistar rats and 2 dogs. Biochemical assays of both rats and dogs included complete blood profiles, liver function tests, and renal function tests. For rat vitals, monitoring and histopathological analysis were also performed. Converted nanodroplets showed excellent contrast enhancement, better than Sonovue upon in vitro testing, with an enhancement time of up to 14 min. In vivo, experiments showed comparable opacification of the ventricles of both rats and dogs. All biochemical assays remained within the normal range during the study period. The histopathological analysis did not show any signs of drug-induced toxicity, showing the safety of these nanodroplets. Pre-PGS-PFP nanodroplets hold great potential for use in echocardiography and abdominal imaging in both human and veterinary applications after clinical trials.

Summary: Background: Liver disease is a major cause of mortality and morbidity worldwide and its epidemiology depends on the genetic background, exposure to risk factors, access to healthcare and other sociodemographic characteristics. Brazil is a large country with diverse multicultural and ethnic heritages and important socioeconomic inequalities. The burden of liver disease in Brazil, its regions and population is unknown. Methods: We retrieved data from the Unified Health System regarding liver diseases and analyzed the mortality and morbidity from 1996 to 2022 by gender, race/ethnicity, age, region and overall. We calculated the age-specific risk of deaths by liver disease, age-standardization of the data, mean hospitalization and liver transplant-associated costs. Findings: Malignant neoplasm of the liver and intrahepatic bile ducts, alcohol-associated liver disease, fibrosis, and cirrhosis of the liver, other diseases of the liver, hepatic failure, chronic viral hepatitis were identified as the major causes of death and morbidity in Brazil in the period analyzed. The epidemiology of these diseases was diverse, with variations according to geographic regions, gender and race/ethnicity. The major economic burden of liver disease is related to liver transplants, a common outcome of the progression of these diseases. Interpretation: Liver disease in Brazil is a serious issue for the public health system due to the high number of deaths and increasing mortality rate. Our study contributes as a necessary prerequisite for the development of tailored public health policies aimed at mitigating the increasing burden of liver diseases in specific populations and regions. Funding: CNPq, INCT, CAPES, FAPEMIG.

Current food safety techniques and equipment are struggling to meet the evolving demands of the food industry [...]

Liver test abnormalities are frequently observed in patients with coronavirus disease 2019 (COVID‐19) and are associated with worse prognosis. However, information is limited about pathological changes in the liver in this infection, so the mechanism of liver injury is unclear. Here we describe liver histopathology and clinical correlates of 27 patients who died of COVID‐19 in Manaus, Brazil. There was a high prevalence of liver injury (elevated alanine aminotransferase and aspartate aminotransferase in 44% and 48% of patients, respectively) in these patients. Histological analysis showed sinusoidal congestion and ischemic necrosis in more than 85% of the cases, but these appeared to be secondary to systemic rather than intrahepatic thrombotic events, as only 14% and 22% of samples were positive for CD61 (marker of platelet activation) and C4d (activated complement factor), respectively. Furthermore, the extent of these vascular findings did not correlate with the extent of transaminase elevations. Steatosis was present in 63% of patients, and portal inflammation was present in 52%. In most cases, hepatocytes expressed angiotensin‐converting enzyme 2 (ACE2), which is responsible for binding and entry of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), even though this ectoenzyme was minimally expressed on hepatocytes in normal controls. However, SARS‐CoV‐2 staining was not observed. Most hepatocytes also expressed inositol 1,4,5‐triphosphate receptor 3 (ITPR3), a calcium channel that becomes expressed in acute liver injury. Conclusion: The hepatocellular injury that commonly occurs in patients with severe COVID‐19 is not due to the vascular events that contribute to pulmonary or cardiac damage. However, new expression of ACE2 and ITPR3 with concomitant inflammation and steatosis suggests that liver injury may result from inflammation, metabolic abnormalities, and perhaps direct viral injury.

Introduction Medical-education is associated with high overall stress and it is important to identify relevant factors. Objectives The study was aimed to discern the differences in perceived stress among the students of public and private medical colleges of Pakistan and to identify factors subservient to any hypothesized difference. Methods This cross-sectional study was conducted at different private and public medical colleges of Pakistan using validated tools: PSS-14 (Perceived Stress Scale) to find out the levels of stress faced by each sector and MSSQ (Medical Student Stressor Questionnaire) to determine the factors associated with increased stress. Results Total of 424 medical students from various public and private medical colleges of Pakistan (212 each) filled the questionnaires. The mean score +/- SD of PSS-14 was 36.17 ± 6.096 for the public sector and 36.29 ±5.732 for the private sector. Hence, there was no difference between the two comparative means of PSS score, t(422)=-0.213,p=0.831.The results for both sectors were classified as high perceived stress (27-40 score is high perceived stress). Out of 40 individual stress-causing factors in MSSQ, the students from private-sector scored higher as compared to public-sector: Quota System in examination t(422)=-3.951,p=0.000, stress caused by lack of time for friends and family t(422)=-3.225,p=0.001, stress caused by Tests/Examination t(422)=-2.131,p=0.034, stress caused by the parental wish for them to study medicine t(422)=-2.346,p=0.019 and stress caused by fear of getting poor marks t(422)=-2.183,p=0.030. Conclusions There exists no overall difference in the perceived-stress among the medical students of public and private medical colleges despite private-sectors having significantly more operational financial resources. Disclosure No significant relationships.

Yellow fever (YF) is a viral hemorrhagic fever that typically involves the liver. Brazil recently experienced its largest recorded YF outbreak, and the disease was fatal in more than a third of affected individuals, mostly because of acute liver failure. Affected individuals are generally treated only supportively, but during the recent Brazilian outbreak, selected patients were treated with liver transplant. We took advantage of this clinical experience to better characterize the clinical and pathological features of YF‐induced liver failure and to examine the mechanism of hepatocellular injury in YF, to identify targets that would be amenable to therapeutic intervention in preventing progression to liver failure and death. Patients with YF liver failure rapidly developed massive transaminase elevations, with jaundice, coagulopathy, thrombocytopenia, and usually hepatic encephalopathy, along with pathological findings that included microvesicular steatosis and lytic necrosis. Hepatocytes began to express the type 3 isoform of the inositol trisphosphate receptor (ITPR3), an intracellular calcium (Ca2+) channel that is not normally expressed in hepatocytes. Experiments in an animal model, isolated hepatocytes, and liver‐derived cell lines showed that this new expression of ITPR3 was associated with increased nuclear Ca2+ signaling and hepatocyte proliferation, and reduced steatosis and cell death induced by the YF virus. Conclusion: Yellow fever often induces liver failure characterized by massive hepatocellular damage plus steatosis. New expression of ITPR3 also occurs in YF‐infected hepatocytes, which may represent an endogenous protective mechanism that could suggest approaches to treat affected individuals before they progress to liver failure, thereby decreasing the mortality of this disease in a way that does not rely on the costly and limited resource of liver transplantation.

Green synthesis gaining a significant importance for the preparation of nanoparticles (NPs) and NPs-based biocomposites gained much attention in biological applications. In the current study, gold (Au) nanoparticles were prepared via green approach using cinnamon extract. The Au nanocomposite (NC) was prepared with MnO2 nanofiber mesh structure. The NC was characterized by XRD, SEM, FT-IR, EDX, UV–visible and DLS techniques. The MnO2 nanofibers diameter was in 10–25 nm range, which was arranged in a mesh form and Au NPs was combined with nanofibers randomly. The MnO2-Au NC antimicrobial activity was measured against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus strains. The antimicrobial activity of MnO2-Au NC was highly promising against tested microorganisms in comparison to control (ciprofloxacin, a standard drug). The antimicrobial activity of MnO2-Au NC was found in following order; > S. aureus > E. coli > P. aeruginosa with the zones inhibition of 22, 18 and 15 (mn), respectively. The MIC (minimum inhibitory concentration) values were 316, 342 and 231 (µg/mL) for E. coli, P. aeruginosa and S. aureus, respectively. In view of promising antimicrobial activity, the MnO2-Au NC prepared via green approach could have potential applications in medical field and future study can be engrossed on the biocompatibility evaluation of MnO2-Au NC using bioassays.

Abstract The present study aimed to determine the effect of different levels of protein on the growth, body composition, amino acid profile and serology of Channa marulius fingerlings. The experiment was conducted in ten happas installed in earthen ponds, each stocked with 10 fishes for 90 days. Four commercial fish feeds having 25%, 30%, 32% and 40% crude protein (CP) levels were fed to fish at 3% of their wet body weight three times a day. The results of the study revealed that highest weight gain, feed conversion ratio and survival rate were observed in 30% protein feed. Meanwhile, moisture content was higher in fish fed with 30% CP feed while highest crude protein was recorded in 40% CP fed fish. Lowest fat content was observed in 32% CP feed. Amino acid profile of fish revealed better results in 30% CP feed. Total protein, glucose and globulin were also highest in fish feeding 30% CP feed, while albumin was highest in 40% CP feed. It is concluded that 30% CP feed showed better results in terms of growth, amino acid profile and serological parameters without effecting fish body composition.

Abstract Ninety days study was conducted in hapas installed in earthen ponds. Fish of an average initial weight (220g) were evenly distributed in triplicate groups within fifteen hapas. Five experimental diets labeled as T1 (25% CP and NRC recommended amino acid level) as control diet, T2 (with 2% low protein and 5% amino acid supplementation), T3 (with 2% low protein and 10% amino acid supplementation), T4 (with 4% low protein and 10% amino acid supplementation) and T5 (with 4% low protein and 20% amino acid supplementation) were prepared. Fish were fed with @3% of their body weight twice a day at 10.00 & 16:00 hour. Significantly higher percent weight gain (420.18 ± 66.84a) and specific growth rate (13499.33±1273.54a) along with improved feed conversion ratio (1.29 ± 0.09b) and hundred percent survivals were recorded during the trial. Furthermore proximate analysis of meat showed significant improvement in the crude protein level (81.77 ± 0.19a) served with diet containing 20% limiting amino acids mixture. Therefore, limiting amino acids can be a source of cost effective feed and use safely in L. rohita diet.

The lysosome has a key role in the presentation of lipid antigens by CD1 molecules. While defects in lipid antigen presentation and in invariant Natural Killer T (iNKT) cell response were detected in several mouse models of lysosomal storage diseases (LSD), the impact of lysosomal engorgement in human lipid antigen presentation is poorly characterized. Here, we analyzed the capacity of monocyte-derived dendritic cells (Mo-DCs) from Fabry, Gaucher, Niemann Pick type C and Mucopolysaccharidosis type VI disease patients to present exogenous antigens to lipid-specific T cells. The CD1b- and CD1d-restricted presentation of lipid antigens by Mo-DCs revealed an ability of LSD patients to induce CD1-restricted T cell responses within the control range. Similarly, freshly isolated monocytes from Fabry and Gaucher disease patients had a normal ability to present α-Galactosylceramide (α-GalCer) antigen by CD1d. Gaucher disease patients' monocytes had an increased capacity to present α-Gal-(1-2)-αGalCer, an antigen that needs internalization and processing to become antigenic. In summary, our results show that Fabry, Gaucher, Niemann Pick type C, and Mucopolysaccharidosis type VI disease patients do not present a decreased capacity to present CD1d-restricted lipid antigens. These observations are in contrast to what was observed in mouse models of LSD. The percentage of total iNKT cells in the peripheral blood of these patients is also similar to control individuals. In addition, we show that the presentation of exogenous lipids that directly bind CD1b, the human CD1 isoform with an intracellular trafficking to the lysosome, is normal in these patients.

The current research aims at knowing the "following a snowball strategy in the collection of history for students first grade average and Dafiethn to learn the art." To achieve this, the researcher adopted on an experimental design with a partial adjustment has chosen a random sample choice and numbered (62) student And abide by the experimental groups; one of (30) students studied in accordance with the snowball strategy officer and the other includes (32) students studied in the traditional manner. The researcher rewarded students between the two sets of search variables) months old, the previous school year degrees in history and the level of achievement of the parents). For research tools researcher prepared a test of the collection and the measure of motivation where it was drafting (30) paragraph objective risk trial of multiple choice,, and the measure of motivation to learn about history, consisting of (35) items. It was sure to extract Alsekoumtrah characteristics and extract reliability coefficients. After the end of the experiment, it was tested two groups of research testing and grades measure of motivation. Upon analysis of the data shows superiority of students in the experimental group that studied the material in accordance with the strategy of a snowball in the collection and Aldafieh.aly control group which studied the same material in the traditional way. In light of these results was a set of recommendations and proposals and use them in other educational institutions Kalmaahid developed and proposed for subsequent studies to complement the current research

Lipid-specific T cells comprise a group of T cells that recognize lipids bound to the MHC class I-like CD1 molecules. There are four isoforms of CD1 that are expressed at the surface of antigen presenting cells and therefore capable of presenting lipid antigens: CD1a, CD1b, CD1c, and CD1d. Each one of these isoforms has distinct structural features and cellular localizations, which promotes binding to a broad range of different types of lipids. Lipid antigens originate from either self-tissues or foreign sources, such as bacteria, fungus, or plants and their recognition by CD1-restricted T cells has important implications in infection but also in cancer and autoimmunity. In this review, we describe the characteristics of CD1 molecules and CD1-restricted lipid-specific T cells, highlighting the innate-like and adaptive-like features of different CD1-restricted T cell subtypes.

Neutrophil infiltration occurs in a variety of liver diseases, but it is unclear how neutrophils and hepatocytes interact. Neutrophils generally use granule proteases to digest phagocytosed bacteria and foreign substances or neutralize them in neutrophil extracellular traps. In certain pathological states, granule proteases play a destructive role against the host as well. More recently, nondestructive actions of neutrophil granule proteins have been reported, such as modulation of tissue remodeling and metabolism. Here, we report a completely different mechanism by which neutrophils act nondestructively, by inserting granules directly into hepatocytes. Specifically, elastase-containing granules were transferred to hepatocytes where elastase selectively degraded intracellular calcium channels to reduce cell proliferation without cytotoxicity. In response, hepatocytes increased expression of Serpin E2 and A3, which inhibited elastase activity. Elastase insertion was seen in patient specimens of alcohol-associated hepatitis, and the relationship between elastase-mediated ITPR2 degradation and reduced cell proliferation was confirmed in mouse models. Moreover, neutrophils from patients with alcohol-associated hepatitis were more prone to degranulation and more potent in reducing calcium channel expression than neutrophils from healthy individuals. This nondestructive and reversible action on hepatocytes defines a previously unrecognized role for neutrophils in the transient regulation of epithelial calcium signaling mechanisms., Introduction Neutrophils are the most abundant type of polymorphonucleated leukocytes in circulation, typically accounting for around 60% of the total in humans. When organs such as the liver, lungs, and [...]

Universities are encouraging the implementation of innovative methodologies and teaching strategies to develop an interactive and appealing educational environment where students are the focus of the learning process. In such a personalised learning environment, an increase of the students' engagement and the improvement of the outcomes arise. MathE has been developed to help achieve this goal. Based on collaborative procedures, internet resources -- both pre-existing and freely available as well as resources specifically conceived by the project team -- and communities of practices, MathE intends to be a tool to nurture and stimulate the learning of Mathematics in higher education. This study introduces and describes the MathE platform, which is divided into three sections: Student's Assessment, Library and Community of Practice. An in-depth description of the Student's Assessment section is presented and an analysis of the results obtained from students, when using this feature of the platform, is also provided. After this, and based on the answers to an online survey, the impact of the MathE platform among students and teachers of eight countries is shown. Although the number of collected results is still scarce, it allows the recognition of a trend regarding the use of the material of the Student's Assessment section for autonomous study. The results indicate the platform is well organized, with a satisfactory amount and diversity of questions and good interconnection between the various parts. Nevertheless, both teachers and students indicate that more questions should be introduced. The overall opinion about the MathE platform is very favourable.