An autonomous debating system.

Artificial intelligence (AI) is defined as the ability of machines to perform tasks that are usually associated with intelligent beings. Argument and debate are fundamental capabilities of human intelligence, essential for a wide range of human activities, and common to all human societies. The development of computational argumentation technologies is therefore an important emerging discipline in AI research1. Here we present Project Debater, an autonomous debating system that can engage in a competitive debate with humans. We provide a complete description of the system's architecture, a thorough and systematic evaluation of its operation across a wide range of debate topics, and a detailed account of the system's performance in its public debut against three expert human debaters. We also highlight the fundamental differences between debating with humans as opposed to challenging humans in game competitions, the latter being the focus of classical 'grand challenges' pursued by the AI research community over the past few decades. We suggest that such challenges lie in the 'comfort zone' of AI, whereas debating with humans lies in a different territory, in which humans still prevail, and for which novel paradigms are required to make substantial progress.

A Retrospective Database Analysis of Before and After Social Distancing in Relation to Pediatric Infection Rate and Healthcare Services Usage During the Coronavirus Disease 2019 Pandemic.

BACKGROUND: Social distancing policy was introduced in Israel in 2020 to reduce the spread of coronavirus disease 2019 (COVID-19). The aim of this study was to analyze the effect of social distancing on other infections in children, by comparing disease rate and healthcare utilization before and after social distancing. METHODS: This was a before-and-after study. Within this retrospective database analysis of parallel periods in 2019 (periods 1 and 2) and 2020 (periods 3 [prelockdown period] and 4 [lockdown period]) we included all pediatric population registered in the electronic medical records of the Maccabi Healthcare Services, Israel, looking at the occurrence of non-COVID-19 infections, antibiotic purchasing, physician visits, ambulatory emergency care center visits, emergency department visits, and hospitalizations. RESULTS: A total of 776 828 children were included from 2019, and 777 729 from 2020. We found a lower infection rate in 2020 versus 2019. We did not find a difference in infection rate between periods 1 and 2, while there was a significant difference between periods 3 and 4. We found a significant difference between periods 2 and 4, with a higher RR than for the comparison between periods 1 and 3. There was a modest decrease in ambulatory emergency care center visits in 2020, and lower increases in emergency department visits and hospital admissions. We found decreases in antibiotic purchasing between periods 1 and 3 and between periods 2 and 4, more pronounced in 2020 than in 2019. CONCLUSIONS: Analysis of findings before and after social distancing and masking showed reduced prevalence of non-COVID-19 pediatric infections and reduced consumption of healthcare services and antibiotics related with the lockdown period.

Increased CD11b+ cells and Interleukin-1 (IL-1) alpha levels during cardiomyopathy induced by chronic adrenergic activation.

BACKGROUND: Systemic CD11b+ cells have been associated with several cardiac diseases, such as chronic heart failure. OBJECTIVES: To assess the levels of circulating CD11b+ cells and pro-inflammatory cytokines in cardiomyopathy induced by chronic adrenergic stimulation. METHODS: Male Lewis rats were injected with low doses of isoproterenol (isoprel) for 3 months. Cardiac parameters were tested by echocardiography. The percentage of CD11b+ cells was tested by flow cytometry. The levels of inflammatory cytokines in the sera were determined by an inflammation array, and the expression levels of cardiac interleukin-1 (IL-1) receptors were analyzed by real-time polymerase chain reactions. Cardiac fibrosis and inflammation were determined by histological analysis. RESULTS: Chronic isoprel administration resulted in increased heart rate, cardiac hypertrophy, elevated cardiac peri-vascular fibrosis, reduced fractional shortening, and increased heart weight per body weight ratio compared to control animals. This clinical presentation was associated with accumulation of CD11b+ cells in the spleen with no concomitant cardiac inflammation. Cardiac dysfunction was also associated with elevated sera levels of IL-1 alpha and over expression of cardiac IL-1 receptor type 2. CONCLUSIONS: CD11b+ systemic levels and IL-1 signaling are associated with cardiomyopathy induced by chronic adrenergic stimulation. Further studies are needed to define the role of systemic immunomodulation in this cardiomyopathy.

Differential Effects of Colchicine on Cardiac Cell Viability in an in vitro Model Simulating Myocardial Infarction.

OBJECTIVES: We aimed to examine the effects of colchicine, currently in clinical trials for acute myocardial infarction (AMI), on the viability of cardiac cells using a cell line model of AMI. METHODS: HL-1, a murine cardiomyocyte cell line, and H9C2, a rat cardiomyoblast cell line, were incubated with TNFα or sera derived from rats that underwent AMI or sham operation followed by addition of colchicine. In another experiment, HL-1/H9C2 cells were exposed to anoxia with or without subsequent addition of colchicine. Cell morphology and viability were assessed by light microscopy, flow cytometry and Western blot analyses for apoptotic markers. RESULTS: Cellular viability was similar in both sera; however, exposing both cell lines to anoxia reduced their viability. Adding colchicine to anoxic H9C2, but not to anoxic HL-1, further increased their mortality, at least in part via enhanced apoptosis. Under any condition, colchicine induced detachment of H9C2 cells from their culture plates. This phenomenon did not apply to HL-1 cells. CONCLUSIONS: Colchicine enhanced cardiomyoblast mortality under in vitro conditions mimicking AMI and reduced their adherence capability. HL-1 was not affected by colchicine; nevertheless, no salvage effect was observed. We thus conclude that colchicine may not inhibit myocardial apoptosis following AMI.

Down-Regulation of Cardiac Erythropoietin Receptor and its Downstream Activated Signal Transducer Phospho-STAT-5 in a Rat Model of Chronic Kidney Disease.

BACKGROUND: Chronic kidney disease (CKD) is often accompanied by impairment of cardiac function that may lead to major cardiac events. Erythropoietin (EPO), a kidney-produced protein, was shown to be beneficial to heart function. It was suggested that reduced EPO secretion in CKD may play a role in the initiation of heart damage. OBJECTIVES: To investigate molecular changes in the EPO/ erythropoietin receptor (EPO-R) axis in rat cardiomyocytes using a rat model for CKD. METHODS: We established a rat model for CKD by kidney resection. Cardiac tissue sections were stained with Masson's trichrome to assess interstitial fibrosis indicating cardiac damage. To evaluate changes in the EPO/EPO-R signaling cascade in the myocardium we measured cardiac EPO and EPO-R as well as the phosphorylation levels of STAT-5, a downstream element in this cascade. RESULTS: At 11 weeks after resection, animals presented severe renal failure reflected by reduced creatinine clearance, elevated blood urea nitrogen and presence of anemia. Histological analysis revealed enhanced fibrosis in cardiac sections of CKD animals compared to the sham controls. Parallel to these changes, we found that although cardiac EPO levels were similar in both groups, the expression of EPO-R and the activated form of its downstream protein STAT-5 were significantly lower in CKD animals. CONCLUSIONS: CKD results in molecular changes in the EPO/EPO-R axis. These changes may play a role in early cardiac damage observed in the cardiorenal syndrome.

Power-Assisted Liposuction Versus Tissue Resection for the Isolation of Adipose Tissue-Derived Mesenchymal Stem Cells: Phenotype, Senescence, and Multipotency at Advanced Passages.

BACKGROUND: Adipose tissue-derived mesenchymal stem cells (ASCs) can be isolated from subcutaneous fat harvested by tissue resection or liposuction. OBJECTIVES: The authors compared ASCs isolated by tissue resection or power-assisted liposuction (PAL) to determine whether either surgical procedure yielded ASCs with improved purity and competence that was preserved for several passages. METHODS: For this experimental study, ASCs were isolated from fat harvested by tissue resection or PAL from six patients who underwent abdominoplasty. ASCs were counted to determine cell yields, and viabilities were assessed with an amine-reactive dye and by fluorescence-activated cell sorting (FACS). Cell phenotypes were determined by immunostaining and FACS, and doubling times were calculated. Senescence ratios of the cells were detected by gene profiling and by assaying ß-galactosidase activity. Multipotency was evaluated by induced differentiation analyses. RESULTS: No significant differences were observed in cell numbers or viabilities of ASCs isolated following either surgical method of fat harvesting. Both populations of cultured ASCs expressed markers of mesenchymal stem cells and preserved this expression pattern through the third passage. PAL and tissue resection yielded ASCs with similar division rates, similar senescence ratios into the fourth passage, and similar capacities to differentiate into osteocytes or adipocytes. CONCLUSIONS: Fat harvested by PAL or tissue resection yielded uniform cultures of ASCs with high division rates, low senescence ratios, and multipotency preserved into passages 3 and 4. Because PAL is less invasive, it may be preferable for the isolation of ASCs.

Accelerated renal fibrosis in cardiorenal syndrome is associated with long-term increase in urine neutrophil gelatinase-associated lipocalin levels.

BACKGROUND: Cardiac events are the main cause of death among patients with end-stage renal failure. Even a mild renal disease is currently considered a major risk factor for cardiovascular complications following myocardial infarction (MI). The aim of the present study was to detect histological, sera and urine characteristics of kidney injury in cardiorenal syndrome (CRS) compared to chronic kidney disease (CKD) with an intact cardiac function. METHODS: We employed a rat model for CRS, in which an acute MI (AMI) was induced 4 weeks after establishment of subtotal nephrectomy. Four weeks later, left ventricular function was assessed by echocardiography and changes in renal performance were examined using histological and biochemical parameters. RESULTS: Increased interstitial fibrosis as well as renal inflammation were observed in renal sections derived from CRS rats, compared to subtotal nephrectomy (CKD)-only animals. Moreover, we found that even though AMI on the background of CKD was not associated with a further decrease in creatinine clearance or a further increase in sera BUN levels compared to CKD only, a significant long-term elevation in urine neutrophil gelatinase-associated lipocalin (Ngal) levels was detectable post-MI induction. CONCLUSIONS: AMI in the CKD setting is associated with accelerated renal fibrosis and long-term elevated urine Ngal values, suggesting that cardiac dysfunction contributes to accelerated intrinsic kidney injury in CKD. The data indicate that elevated urine Ngal may potentially serve as an early non-invasive laboratory parameter for a left ventricular dysfunction-related renal injury.

Continuous Remote Patient Monitoring Shows Early Cardiovascular Changes in COVID-19 Patients.

COVID-19 exerts deleterious cardiopulmonary effects, leading to a worse prognosis in the most affected. This retrospective multi-center observational cohort study aimed to analyze the trajectories of key vitals amongst hospitalized COVID-19 patients using a chest-patch wearable providing continuous remote patient monitoring of numerous vital signs. The study was conducted in five COVID-19 isolation units. A total of 492 COVID-19 patients were included in the final analysis. Physiological parameters were measured every 15 min. More than 3 million measurements were collected including heart rate, systolic and diastolic blood pressure, cardiac output, cardiac index, systemic vascular resistance, respiratory rate, blood oxygen saturation, and body temperature. Cardiovascular deterioration appeared early after admission and in parallel with changes in the respiratory parameters, showing a significant difference in trajectories within sub-populations at high risk. Early detection of cardiovascular deterioration of COVID-19 patients is achievable when using frequent remote patient monitoring.

Meconium ileus in patients with cystic fibrosis is not a risk factor for clinical deterioration and survival: the Israeli Multicenter Study.

OBJECTIVES: Patients with cystic fibrosis (CF) presenting with meconium ileus (MI) tend to have worse outcomes than those without MI. We evaluated the clinical characteristics and survival rates among Israeli patients with CF with and without MI after a prolonged follow-up (15-30 years). PATIENTS AND METHODS: A multicenter retrospective study. Forty-nine patients with CF, representing 13.8% of all patients with CF in Israel, presented with MI (current age 17.4 +/- 7.9 years) between 1975 and 2006. They were compared with 38 patients with CF (current age 19.3 +/- 6.5 years) without MI matched by sex and CF transmembrane conductance regulator mutation. RESULTS: A total of 66.2% of patients with MI and 73.6% without MI were followed for a prolonged period (24.9 +/- 2.7 years). Of the patients with MI, 31 were managed operatively, whereas 18 were treated successfully with gastrograffin enema, with similar clinical outcomes. Five patients in the MI group and 3 in the control group died during the study period. Bacterial colonization, z score of body mass index, and pulmonary function tests were similar in patients with and without MI in the long term. In younger patients, many clinical parameters were more prevalent in patients with MI (P = 0.004). However, these differences disappeared after the long-term follow-up (up to 31-years). CONCLUSIONS: Patients with CF presenting with MI had similar pulmonary function and nutritional status, as well as survival rates as did the control patients without MI. The distinct genetic mutation found in our population may explain in part the favorable results compared with other studies. In addition, it seems that early diagnosis and treatment of MI in patients with CF may be beneficial, subsequently lowering morbidity, and increasing survival.

Galectin-3 regulates RasGRP4-mediated activation of N-Ras and H-Ras.

Galectin-3 (Gal-3) is a pleiotropic beta-galactoside-binding protein expressed at relatively high levels in human neoplasms. Its carbohydrate recognition domain (CRD) contains a hydrophobic pocket that can accommodate the farnesyl moiety of K-Ras. Binding of K-Ras to Gal-3 stabilizes K-Ras in its active (GTP-bound) state. Gal-3, which does not interact with N-Ras, was nevertheless shown to reduce N-Ras-GTP in BT-549 cells by an unknown mechanism that we explored here. First, comparative analysis of various cancer cell lines (glioblastomas, breast cancer cells and ovarian carcinomas) showed a positive correlation between low N-Ras-GTP/high K-Ras-GTP phenotype and Gal-3 expression levels. Next we found that epidermal growth factor-stimulated GTP loading of N-Ras, but not of K-Ras, is blocked in cells expressing high levels of Gal-3. Activation of Ras guanine nucleotide releasing proteins (RasGRPs) by phorbol 12-myristate 13-acetate (PMA) or downregulation of Gal-3 by Gal-3 shRNA increased the levels of N-Ras-GTP in Gal-3 expressing cells. We further show that the N-terminal domain of Gal-3 interacts with and inhibits RasGRP4-mediated GTP loading on N-Ras and H-Ras proteins. Growth of BT-549 cells stably expressing the Gal-3 N-terminal domain was strongly attenuated. Overall, these experiments demonstrate a new control mechanism of Ras activation in cancer cells whereby the Gal-3 N-terminal domain inhibits activation of N-Ras and H-Ras proteins.

Molecular evaluation of circulating endothelial progenitor cells in children undergoing hemodialysis and after kidney transplantation.

Increased risk of cardiovascular disease in end-stage renal disease (ESRD) has been explained by accelerated atherosclerosis and impaired angiogenesis, in which endothelial progenitor cells (EPC) may play key roles. Circulating cells with endothelial progenitor phenotype have not been evaluated in children with ESRD. Using a quantitative reverse transcriptase polymerase chain reaction (RT-PCR) approach, we measured endothelial-specific and progenitor-associated genes VE-cadherin (VE-C), CD146, CD31, tyrosine-protein kinase receptor (Tie-2), Flk1, CD133, and growth factors promoting EPC function, vascular endothelial growth factor (VEGF), erythropoietin (EPO), and stromal cell-derived factor-1 (SDF-1) in the blood of pediatric patients undergoing hemodialysis and after transplantation. Patients' metabolic parameters were correlated with EPC marker gene levels. Compared with controls, circulating VE-cadherin, CD146, Flk1, VEGF, and EPO RNA levels were decreased in ESRD and normalized in transplanted patients. Levels of VE-cadherin, which were the most significantly reduced in ESRD (p = 0.001) inversely correlated in all of the patient population with serum urea and creatinine concentration, whereas among the ESRD group showed an inverse correlation with diastolic blood pressure (BP), interventricular septum thickness (IVST), and left ventricular mass index. Pediatric ESRD patients may have lower angiogenic potential and increased cardiovascular morbidity, because of decreased expression of circulating endothelial cell specific transcripts. Prospective studies are required to link this expression pattern and its restoration in transplanted patients to cardiovascular outcome.

Perceptual-motor coordination in persons with mild intellectual disability.

BACKGROUND: There is limited experimental evidence to support the view that individuals with intellectual disabilities (ID) have a deficit in motor control. This work is a first attempt to evaluate their motor coordination. PURPOSE: The study assessed the relationship between cognitive ability and sensorimotor integration. The clinical hypothesis is that adults with ID fall below non-ID adults in motor skills that involve hand-eye coordination. METHOD: A group of 42 adults with ID (ID group) was compared to 48 age-matched typical adults (TA) using a mixed experimental design ('Task' as the within-subjects factor and 'Group' as the between-subjects factor). Participants performed the following tests twice: Box-and-Blocks, 25-Grooved-Pegboard, Stick Catching and overhead Beanbag-Throw. Pearson correlations and ANOVAs were used to test the hypothesis (p < or = 0.05). RESULTS: As expected, TA outperformed the ID group in all tests regardless of the hand used during for the assessment. However, TA individuals scored significantly better with one hand (i.e., the preferred and dominant hand) as opposed to persons with ID, who exhibited no hand preference. Test-retest correlations among the first and second assessment scores yielded moderate-strong coefficients, depending on the type of test (Box-and-Blocks = 0.92 and 0.96, 25-Grooved-Pegboard = 0.69 and 0.83, Stick-Catching = 0.88 and 0.94, Beanbag-Throw = 0.58 and 0.91 for ID and TA, respectively). DISCUSSION: Difficulties in the integration of perceptual information into motor action may result in inadequate solutions to daily motor problems. As it stems from our results, intellectual disability relates to inability to integrate visual inputs and hand movements. In people with mild ID such inability is observed using both hands (i.e., they show no hand preferences). Poor perceptual-motor coordination might have a functional significance in that it may lead to exclusion from vocational and recreational activities, and a decreasing competence of ADL. Assessing coordination in adults with ID may contribute to understanding the nature of the ID condition and may encourage an early rehabilitation.

Pathological presentation of cardiac mitochondria in a rat model for chronic kidney disease.

BACKGROUND: Mitochondria hold crucial importance in organs with high energy demand especially the heart. We investigated whether chronic kidney disease (CKD), which eventually culminates in cardiorenal syndrome, could affect cardiac mitochondria and assessed the potential involvement of angiotensin II (AngII) in the process. METHODS: Male Lewis rats underwent 5/6 nephrectomy allowing CKD development for eight months or for eleven weeks. Short-term CKD rats were administered with AngII receptor blocker (ARB). Cardiac function was assessed by echocardiography and cardiac sections were evaluated for interstitial fibrosis and cardiomyocytes' hypertrophy. Electron microscopy was used to explore the spatial organization of the cardiomyocytes. Expression levels of mitochondrial content and activity markers were tested in order to delineate the underlying mechanisms for mitochondrial pathology in the CKD setting with or without ARB administration. RESULTS: CKD per-se resulted in induced cardiac interstitial fibrosis and cardiomyocytes' hypertrophy combined with a marked disruption of the mitochondrial structure. Moreover, CKD led to enhanced cytochrome C leakage to the cytosol and to enhanced PARP-1 cleavage which are associated with cellular apoptosis. ARB treatment did not improve kidney function but markedly reduced left ventricular mass, cardiomyocytes' hypertrophy and interstitial fibrosis. Interestingly, ARB administration improved the spatial organization of cardiac mitochondria and reduced their increased volume compared to untreated CKD animals. Nevertheless, ARB did not improve mitochondrial content, mitochondrial biogenesis or the respiratory enzyme activity. ARB mildly upregulated protein levels of mitochondrial fusion-related proteins. CONCLUSIONS: CKD results in cardiac pathological changes combined with mitochondrial damage and elevated apoptotic markers. We anticipate that the increased mitochondrial volume mainly represents mitochondrial swelling that occurs during the pathological process of cardiac hypertrophy. Chronic administration of ARB may improve the pathological appearance of the heart. Further recognition of the molecular pathways leading to mitochondrial insult and appropriate intervention is of crucial importance.

The Pam18/Tim14-Pam16/Tim16 complex of the mitochondrial translocation motor: the formation of a stable complex from marginally stable proteins.

The vast majority of mitochondrial proteins are imported from the cytosol. For matrix-localized proteins, the final step of translocation across the inner membrane is mediated by the mitochondrial translocation motor, of which mhsp70 is a key component. The ATP-dependent function of mhsp70 is regulated by a complex, composed of a J-protein (called Pam18 or Tim14) and a J-like protein (called Pam16 or Tim16), and the nucleotide exchange factor Mge1. In this study, we investigated the structural properties of a recombinant purified Pam18/Tim14-Pam16/Tim16 complex using cross-linking with the bifunctional reagent DSS and CD-spectroscopy. The results of the study show that both Pam18/Tim14 and Pam16/Tim16 are thermally unstable proteins that unfold at very low temperatures (T(m) values of 16.5 degrees C and 29 degrees C, respectively). Upon mixing the proteins in vitro, or when both proteins are co-overexpressed in bacteria, Pam18/Tim14 and Pam16/Tim16 form a heterodimer that is thermally more stable than the individual proteins (T(m) = 41 degrees C). Analysis of the properties of the complex in GdnHCl shows that dissociation of the heterodimer is the limiting step in achieving full denaturation.

TRPV2 knockout mice demonstrate an improved cardiac performance following myocardial infarction due to attenuated activity of peri-infarct macrophages.

BACKGROUND: We have recently shown that the expression of the transient receptor potential vanilloid 2 channel, TRPV2, is upregulated in the peri-infarct zone 3-5 days following an acute myocardial infarction (AMI). Further analysis has demonstrated that invading monocytes maturing to macrophages merely harbor the documented elevated expression of this channel. PURPOSE: Assess cardiac function in TRPV2-KO mice compared to TRPV2-WT following AMI and analyze the potential involvement of TRPV2-expressing macrophages in the recovery process. METHODS: TRPV2-KO or WT mice were induced with AMI by ligation of the left anterior descending artery (LAD). In another set of experiments, TRPV2-KO mice induced with AMI, were intravenously (IV) injected with WT or TRPV2-KO peritoneal macrophages in order to directly assess the potential contribution of TRPV2-expressing macrophages to cardiac healing. Cardiac parameters were obtained by echocardiography 1 day and 30 days post infarction. The relative changes in the ejection fraction (EF) and additional cardiac parameters between baseline (day 1) and day 30 were calculated and statistical significance was determined (SPSS). RESULTS: The in vivo study showed that while EF was significantly decreased in the WT animals between baseline and day 30, EF was only slightly and insignificantly reduced in the KO animals. Likewise LVESD and LVESA were significantly modified exclusively in the WT animals. Moreover, intravenous administration of peritoneal WT macrophages, but not KO macrophages, significantly reduced survival of post-MI TRPV2-KO mice. CONCLUSION: The data suggest that knockout of the TRPV2 channel may attenuate macrophage-dependent pro-inflammatory processes and result in better cardiac recovery. TRPV2 may thus represent a novel therapeutic target for treatment of patients undergoing an acute MI.

Sustained Elevation of Vascular Endothelial Growth Factor and Angiopoietin-2 Levels After Transcatheter Aortic Valve Replacement.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) exposes the systemic vasculature to increased mechanical forces. Endothelial adaptation to mechanical stimuli is associated with angiogenic activation through various growth factors. We studied the potential angiogenic shift evoked by TAVR. METHODS: From a cohort of 69 consecutive patients undergoing TAVR, we excluded patients with conditions known to affect angiogenic factors, and serum vascular endothelial growth factor (VEGF) and angiopoietin (Ang)-1 and Ang-2 were assessed by ELISA. We assessed in vitro the properties of endothelial cells after exposure to serum collected from patients undergoing TAVR using adhesion, migration, and Matrigel angiogenesis assays. The correlation between changes in angiogenic factors and cardiac functions was evaluated on 30- day echocardiograms. RESULTS: The study population consisted of 46 patients (82 ± 5 years). Two days after TAVR the post/pre TAVR ratio of VEGF, Ang-1, and Ang-2 was 5.38 ± 4 (P < 0.001), 1.05 ± 0.49 (P = 0.27), and 4.65 ± 2.01 (P < 0.001), respectively. The increase in VEGF and Ang-2 showed a significant correlation (r = 0.609; P < 0.001), but no correlation was found with hemolysis or tissue injury markers. Patients with relatively low levels of VEGF or an Ang-2 rise had more severe aortic stenosis and coronary disease at baseline. Exposure of endothelial cells to post-TAVR serum induced adhesion, migration, and tube formation compared with pre-TAVR serum. An increase in VEGF levels correlated with improvement in pulmonary systolic pressure and a right ventricular fractional area change at 30 days, (r = 0.54 and r = 0.48, respectively; P < 0.01). CONCLUSIONS: Sustained elevation of VEGF and Ang-2 levels occur after TAVR, reflecting a systemic angiogenic shift. A rise in VEGF levels is associated with a decrease in pulmonary blood pressure in patients undergoing TAVR.

Serum ischemia modified albumin and vascular endothelial growth factor levels following intravitreal bevacizumab injections.

PURPOSE: Previous reports have demonstrated that the serum levels of vascular endothelial growth factor (VEGF) are reduced after intravitreal injections of bevacizumab. This study aimed to determine the serum levels of ischemia-modified albumin (IMA), a marker of ischemia, and VEGF following intravitreal injections of bevacizumab. METHODS: This was a prospective study. Blood samples were drawn prior to injection and at 1, 7, and 30 days after injection. RESULTS: A total of 11 patients participated in this study. Mean serum IMA levels were lower than baseline during follow-up, with statistically significant differences compared to baseline levels at day 1 and day 30 (preinjection: 49.82 ± 15.28 ng/mL; 44.57 ± 12.01 ng/mL, p = 0.007, and 43.71 ± 13.82 ng/mL, p = 0.001, respectively). Mean serum VEGF levels were lower than baseline throughout the follow-up period (from 307.45 ± 273.45 pg/mL at baseline to 159.55 ± 120.68 pg/mL at day 30). Mean serum VEGF levels were significantly lower compared to baseline levels at day 1 and day 7 (147.09 ± 106.08 pg/mL, p = 0.014; 72.91 ± 50 pg/mL, p = 0.011, respectively). CONCLUSIONS: In this study, mean serum IMA and VEGF levels were lower following intravitreal bevacizumab injections.

Leptin, ghrelin, and adiponectin in the metabolic adjustment to burn injury in children.

OBJECTIVE: Leptin, adiponectin, and ghrelin have diverse roles in the control of inflammation and metabolism in a normal state as well as in a chronic disease state. The aim of this study was to evaluate their role in the extreme metabolic and proinflammatory state after burn injury and during the initial weeks of recovery. METHODS: A prospective descriptive study in a tertiary care center was undertaken. Patients were comprised of 5 children aged 20-108 months with severe burn injury; burn size ranged from 15%-36% of total body surface area. Early enteral feeding, according to estimated energy expenditure, was initiated as 150% of the recommended dietary allowance and in accordance with the patients' nitrogen balance. Seven blood samples were collected sequentially, approximately 5 days apart, during the first 65 days after the burn injury. Samples were tested for leptin, ghrelin, and adiponectin. RESULTS: Leptin, ghrelin, and adiponectin had a similar trajectory of concentration over time: low levels at the beginning, increasing until 2-3 weeks post-burn, where they reached a plateau at 5 weeks post-injury. The typical inverse correlations of ghrelin and adiponectin with leptin were absent. Interleukin-6 was negatively associated with ghrelin and adiponectin and was not associated with leptin. Insulin-like growth factor-1 (IGF-1) had a positive association with the 3 hormones; however, their profiles differ in their relationship to the expected concentration based on a literature review. Ghrelin and adiponectin were higher, leptin and IGF-1 were lower than expected. CONCLUSIONS: In the early weeks after burn injury, the hypermetabolic state and inflammation have a major effect on leptin, ghrelin, and adiponectin. The concurrent and similar change of the 3 hormones serves the parallel anabolic and catabolic processes during the recovery from burn injury. .

The transient receptor potential vanilloid 2 cation channel is abundant in macrophages accumulating at the peri-infarct zone and may enhance their migration capacity towards injured cardiomyocytes following myocardial infarction.

PURPOSE: A novel family of transient receptor potential (TRP) channels, that may hold a role in calcium homeostasis, has recently been described. By employing a GeneChip array analysis we have demonstrated a clear and specific upregulation of the TRP vanilloid 2 (TRPV2) mRNA in the left ventricles (LV) 3-5 days post-acute myocardial infarction (MI) compared to sham-operated controls, both in rats and in mice. We sought to characterize the cardiac cellular subpopulations in which TRPV2 is overexpressed upon acute MI. METHODS: Lewis rats underwent an acute MI by ligation of the left anterior descending artery or chest opening only (sham). The animals were terminated at various time points and an immunohistochemical (IHC) and immunofluorescent (IFC) staining of the LV sections as well as a flow cytometry analysis of LV-derived cells were carried out, using anti-TRPV2 and anti-monocyte/macrophage antibodies. Rat alveolar macrophage cells, NR8383, transiently transfected with TRPV2 siRNA were allowed to migrate towards hypoxic conditioned media of the rat cardiac myoblast line H9C2 using a trans-well migration assay. The macrophage cells migrating to the bottom side of the inserts were counted. RESULTS: The IHC and IFC staining as well as the flow cytometry data demonstrated a substantial expression of TRPV2 in infiltrating macrophages in the peri-infarct region 3-5 days post-acute MI. The in vitro migration assay data demonstrated that following inhibition of the TRPV2 channel, the number of migrating macrophages towards conditioned medium of hypoxic cardiomyocytes was significantly reduced. CONCLUSIONS: TRPV2 is highly expressed on the peri-infarct infiltrating macrophages and may play an important role in post-MI phagocytosis. Better characterization of this channel may pave the way for identifying a new target for modulating the dramatic post-MI immune reactions.