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INTRODUCTION: Surgical creation of a radiocephalic fistula is the gold standard of vascular access for hemodialysis. Recently, an endovascular approach for upper arm fistula creation (endoAVF) has been developed, which may be an alternative to open surgery. We describe a case series of eight cases showing feasibility, early complications and outcome of this novel treatment option. MATERIALS AND METHODS: Between July 2015 and February 2016, we created an endoAVF in eight patients. Indications for endoAVF were confirmed by a multidisciplinary vascular board upon the exclusion for Cimino fistula candidates. Patients were suitable for the procedure after a pre-therapeutic ultrasound showed adequate brachial and ulnar vessels and no ipsilateral central venous stenosis. Patient characteristics, technical success, total patient radiation dose, complication rates, time to maturation of endoAVF and clinical effectiveness at six months were assessed retrospectively. RESULTS: Creation of endoAVF using the everlinQ endoAVF system (TVA Medical Inc., Austin, TX, USA) was successful in all eight cases. There were one minor intraprocedural complication and no postoperative complications. Median time to endoAVF maturation was 63 days (range 26-137 days). One patient was lost to follow-up after the first monitoring visit. In the remaining seven patients, hemodialysis was started without problems. Patency after 6 months was 100%. DISCUSSION: The endoAVF demonstrated to be feasible and safe for the creation of arteriovenous fistula suitable for hemodialysis access. Further studies with more patients and longer follow-up periods are needed to assess long-term outcomes and comparability to surgical dialysis access creation.
To evaluate the dynamic changes of pulmonary arterial pressure (PAP) and cardiac function in neonates with pulmonary or extra-pulmonary acute respiratory distress syndrome (ARDSp/ARDSexp).</AbstractText>An observational study was conducted. A total of 128 neonates with ARDS admitted to neonatology department of the Affiliated Yancheng Hospital of Southeast University Medical College from January 2016 to December 2020 were enrolled, with 67 neonates in ARDSp group and 61 neonates in ARDSexp group. After starting mechanical ventilation, oxygenation index [OI, OI = mean airway pressure (Pmean)&#xd7;fraction of inspired oxygen (FiO2</sub>)/arterial partial pressure of oxygen (PaO2</sub>)&#xd7;100], PAP, cardiac function parameters [cardiac index (CI), left ventricular ejection fraction (LVEF), right ventricular Tei (RV-Tei)], and plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) were compared between the two groups; the incidence of pulmonary arterial hypertension [PAH, pulmonary artery systolic pressure (PASP) was more than 35 mmHg (1 mmHg = 0.133 kPa) or more than 2/3 of the systolic blood pressure of the body circulation] of neonates was recorded. The correlation between PAP and NT-proBNP was analyzed by Pearson correlation method. The dynamically changes in PAP and RV-Tei before and after using Milrinone in neonates with ARDSp and ARDSexp combined with moderate-severe PAH (PASP 50-69 mmHg was moderate, and PASP &#x2265; 70 mmHg was severe) were observed. The duration of mechanical ventilation, total length of hospital stay and prognosis were recorded; Kaplan-Meier survival curve was drawn to analyze the 28-day survival of the two groups.</AbstractText>The occurrence rate of PAH in ARDSp group was significantly higher than that in ARDSexp group (97.01% vs. 70.49%, P &lt; 0.01). OI, PAP, NT-proBNP and RV-Tei were also higher [OI: 17.61&#xb1;6.12 vs. 11.04&#xb1;5.35, PAP (mmHg): 64.27&#xb1;9.54 vs. 53.61&#xb1;6.47, NT-proBNP (ng/L): 23 126.32&#xb1;1 485.14 vs. 18 624.24&#xb1;1 647.15, RV-Tei: 0.61&#xb1;0.22 vs. 0.52&#xb1;0.19, all P &lt; 0.05], but there was no significant difference in CI or LVEF between the two groups. Pearson correlation analysis showed that PAP was significantly positively correlated with NT-proBNP (r = 0.918, P &lt; 0.01). There were 97 ARDS neonates with moderate-severe PAH with 63 in ARDSp group and 34 in ARDSexp group. Both PAP and RV-Tei in the two group showed a decreasing trend with the prolongation of Milrinone treatment, the decrease was more significant in the ARDSexp group compared with ARDSp group, the difference was statistically significant at 72 hours of treatment [PAP (mmHg): 38.42&#xb1;8.95 vs. 45.67&#xb1;13.32, RV-Tei: 0.58&#xb1;0.19 vs. 0.61&#xb1;0.13, both P &lt; 0.05]; there was no significant difference in PAP or RV-Tei before extubation between the two groups. The duration of mechanical ventilation and the total length of hospital stay in ARDSp group were significantly longer than those in ARDSexp group [duration of mechanical ventilation (days): 10.12&#xb1;1.36 vs. 6.31&#xb1;1.31, total length of hospital stay (days): 16.52&#xb1;3.25 vs. 13.12&#xb1;3.57, both P &lt; 0.01]. Kaplan-Meier survival curve showed that neonate in ARDSp group had a significantly lower 28-day cumulative survival rate as compared with ARDSexp group (82.09% vs. 95.01%; Log-Rank test: &#x3c7;2</sup> = 5.062, P = 0.025).</AbstractText>Both PAP and RV-Tei were significantly increased in neonates with ARDS, PAP in neonates with ARDSp were significantly higher than that in neonates with ARDSexp. Dynamic monitoring of PAP and RV-Tei can reflect the severity of ARDS in neonates, and targeted intervention of pulmonary surfactant combined with Milinone for improving oxygenation and reducing PAP is one of the effective methods for the treatment of PAH.</AbstractText>
Marfan syndrome (MFS) is a connective tissue disorder caused by mutations in the Fibrillin-1 gene (FBN1). Here, we undertook the first epigenome-wide association study (EWAS) in patients with MFS aiming at identifying DNA methylation loci associated with MFS phenotypes that may shed light on the disease process.</AbstractText>The Illumina 450&#xa0;k DNA-methylation array was used on stored peripheral whole-blood samples of 190 patients with MFS originally included in the COMPARE trial. An unbiased genome-wide approach was used, and methylation of CpG-sites across the entire genome was evaluated. Additionally, we investigated CpG-sites across the FBN1-locus (15q21.1) more closely, since this is the gene defective in MFS. Differentially Methylated Positions (DMPs) and Differentially Methylated Regions (DMRs) were identified through regression analysis. Associations between methylation levels and aortic diameters and presence or absence of 21 clinical features of MFS at baseline were analyzed. Moreover, associations between aortic diameter change, and the occurrence of clinical events (death any cause, type-A or -B dissection/rupture, or aortic surgery) and methylation levels were analyzed.</AbstractText>We identified 28 DMPs that are significantly associated with aortic diameters in patients with MFS. Seven of these DMPs (25%) could be allocated to a gene that was previously associated with cardiovascular diseases (HDAC4, IGF2BP3, CASZ1, SDK1, PCDHGA1, DIO3, PTPRN2). Moreover, we identified seven DMPs that were significantly associated with aortic diameter change and five DMP's that associated with clinical events. No significant associations at p&#x2009;&lt;&#x2009;10-8</sup> or p&#x2009;&lt;&#x2009;10-6</sup> were found with any of the non-cardiovascular phenotypic MFS features. Investigating DMRs, clusters were seen mostly on X- and Y, and chromosome 18-22. The remaining DMRs indicated involvement of a large family of protocadherins on chromosome 5, which were not reported in MFS before.</AbstractText>This EWAS in patients with MFS has identified a number of methylation loci significantly associated with aortic diameters, aortic dilatation rate and aortic events. Our findings add to the slowly growing literature on the regulation of gene expression in MFS patients.</AbstractText>&#xa9; 2021. The Author(s).</CopyrightInformation>
Fenofibrate is a peroxisome proliferator-activated receptor alpha agonist widely used in clinical practice, but its mechanism of action is incompletely understood.</AbstractText>The aim of the study was to assess whether improvement in subclinical inflammation or glucose metabolism contributes to its antiatherogenic effects in insulin-resistant subjects with the metabolic syndrome (MetS).</AbstractText>We conducted a randomized, double-blind, placebo-controlled study in the research unit at an academic center.</AbstractText>We studied 25 nondiabetic insulin-resistant MetS subjects.</AbstractText><AbstractText Label="INTERVENTION(S)" NlmCategory="METHODS">We administered fenofibrate (200 mg/d) and placebo for 12 wk.</AbstractText>Before and after treatment, we measured plasma lipids/apolipoproteins, inflammatory markers (high-sensitivity C-reactive protein, IL-6, intercellular adhesion molecule/vascular cell adhesion molecule), adipocytokines (adiponectin, TNFalpha, leptin), and insulin secretion (oral glucose tolerance test). We also assessed adipose tissue, hepatic and peripheral (muscle) insulin resistance fasting and during a euglycemic insulin clamp with (3)H glucose and (14)C palmitate infusion combined with indirect calorimetry.</AbstractText>Subjects displayed severe insulin resistance and systemic inflammation. Fenofibrate significantly reduced plasma triglyceride, apolipoprotein (apo) CII, apo CIII, and apo E (all P &lt; 0.01), with a modest increase in high-density lipoprotein-cholesterol (+12%; P = 0.06). Fenofibrate markedly decreased plasma high-sensitivity C-reactive protein by 49.5 +/- 8% (P = 0.005) and IL-6 by 29.8 +/- 7% (P = 0.03) vs. placebo. However, neither insulin secretion nor adipose tissue, hepatic or muscle insulin sensitivity or glucose/lipid oxidation improved with treatment. Adiponectin and TNF-alpha levels were also unchanged. Improvement in plasma markers of vascular/systemic inflammation was dissociated from changes in triglyceride/high-density lipoprotein-cholesterol, apo CII/CIII, or free fatty acid concentrations or insulin secretion/insulin sensitivity.</AbstractText>In subjects with the MetS, fenofibrate reduces systemic inflammation independent of improvements in lipoprotein metabolism and without changing insulin sensitivity. This suggests a direct peroxisome proliferator-activated receptor alpha-mediated effect of fenofibrate on inflammatory pathways, which may be important for the prevention of CVD in high-risk patients.</AbstractText>
Pace mapping has been used to identify the site of origin of focal ventricular arrhythmias. The spatial resolution of pace mapping has not been adequately quantified using currently available three-dimensional mapping systems.</AbstractText>The purpose of this study was to determine the spatial resolution of pace mapping in patients with idiopathic ventricular tachycardia or premature ventricular contractions originating in the right ventricular outflow tract.</AbstractText>In 16 patients with idiopathic ventricular tachycardia/ectopy from the right ventricular outflow tract, comparisons and classifications of pace maps were performed by two observers (good pace map: match &gt;10/12 leads; inadequate pace map: match &lt; or =10/12 leads) and a customized MATLAB 6.0 program (assessing correlation coefficient and normalized root mean square of the difference (nRMSd) between test and template signals). With an electroanatomic mapping system, the correlation coefficient of each pace map was correlated with the distance between the pacing site and the effective ablation site. The endocardial area within the 10-ms activation isochrone was measured.</AbstractText>The ablation procedure was effective in all patients. Sites with good pace maps had a higher correlation coefficient and lower nRMSd than sites with inadequate pace maps (correlation coefficient: 0.96 +/- 0.03 vs 0.76 +/- 0.18, P &lt;.0001; nRMSd: 0.41 +/- 0.16 vs 0.89 +/- 0.39, P &lt;.0001). Using receiver operating characteristic curves, appropriate cutoff values were &gt;0.94 for correlation coefficient (sensitivity 81%, specificity 89%) and &lt; or =0.54 for nRMSd (sensitivity 76%, specificity 80%). Good pace maps were located a mean of 7.3 +/- 5.0 mm from the effective ablation site and had a mean activation time of -24 +/- 7 ms. However, in 3 (18%) of 16 patients, the best pace map was inadequate at the effective ablation site, with an endocardial activation time at these sites of -25 +/- 12 ms. Pace maps with correlation coefficient &gt; or =0.94 were confined to an area of 1.8 +/- 0.6 cm2. The 10-ms isochrone measured 1.2 +/- 0.7 cm2.</AbstractText>The spatial resolution of a good pace map for targeting ventricular tachycardia/ectopy is 1.8 cm2 in the right ventricular outflow tract and therefore is inferior to the spatial resolution of activation mapping as assessed by isochronal activation. In approximately 20% of patients, pace mapping is unreliable in identifying the site of origin, possibly due a deeper site of origin and preferential conduction via fibers connecting the focus to the endocardial surface.</AbstractText>
Pleuropericardial effusion is an extremely rare complication of gemcitabine chemotherapy. The patient was a 56-year-old woman administered systemic chemotherapy with gemcitabine for local recurrence of pancreatic cancer and lymph node metastasis developing 4 years after pancreaticoduodenectomy. Four months after the start of the chemotherapy, she presented with exertional dyspnea and edema in both her legs and face. Echocardiography and computed tomography revealed pericardial and bilateral pleural effusion. A pericardiocentesis was immediately performed to prevent the development of cardiac tamponade as well as to examine the cause of the pericardial effusion. As a result, the patient's exertional dyspnea and edema resolved. No metastases to the thorax or mediastinum were noted. A cytological study of the pericardial and pleural effusions revealed no malignant cells. Cultures for bacteria, mycobacteria and fungi were negative. Tests for autoantibodies indicating autoimmune disease were also negative, and hormonal assays for the detection of endocrine disease were normal. She was followed up after discontinuation of the gemcitabine treatment, and no further episodes of pericardial or pleural effusion occurred. Thus, it is speculated that the pericardial effusion and bilateral pleural effusion may have been caused by gemcitabine.
We have developed a novel method for estimating subject-specific hemodynamics during hemorrhage. First, a mathematical model representing a closed-loop circulation and baroreceptor feedback system was parameterized to match the baseline physiology of individual experimental subjects by fitting model results to 1 min of pre-injury data. This automated parameterization process matched pre-injury measurements within 1.4 +/- 1.3% SD. Tuned parameters were then used in similar open-loop models to simulate dynamics post-injury. Cardiac output (CO) estimates were obtained continuously using post-injury measurements of arterial blood pressure (ABP) and heart rate (HR) as inputs to the first open-loop model. Secondarily, total blood volume (TBV) estimates were obtained by summing the blood volumes in all the circulatory segments of a second open-loop model that used measured CO as an additional input. We validated the estimation method by comparing model CO results to flowprobe measurements in 14 pigs. Overall, CO estimates had a Bland-Altman bias of -0.30 l/min with upper and lower limits of agreement 0.80 and -1.40 l/min. The negative bias is likely due to overestimation of the peripheral resistance response to hemorrhage. There was no reference measurement of TBV; however, the estimates appeared reasonable and clearly predicted survival versus death during the post-hemorrhage period. Both open-loop models ran in real time on a computer with a 2.4 GHz processor, and their clinical applicability in emergency care scenarios is discussed.
The purpose of this pre-approval access program is to give talquetamab monotherapy (treatment with single drug) to participants with relapsed or refractory multiple myeloma (a type of cancer that begins in plasma cells [white blood cells that produce antibodies] which has returned or difficult to treat) who have relapsed on or are refractory to all locally available and clinically appropriate treatment and who are not eligible for a clinical trial.Talquetamab (JNJ-64407564) is a humanized immunoglobulin G4 proline, alanine, alanine (IgG4PAA) bispecific antibody designed to target G-Protein Coupled Receptor (5DGPRC5D) and cluster of differentiation 3 (CD3). Redirecting T-cells to a tumor surface antigen using bispecific antibody approaches may be an effective means to harness the immune system to destroy cancer cells expressing GPRC5D and create meaningful and long-lasting clinical responses. Talquetamab is supplied as single-dose Investigational Product (IP) vials for subcutaneous administration. Safety assessments will include adverse events, serious adverse events, adverse drug reactions, and special situations which will be reported during the duration of the pre-approval access program.
The main pathologenesis of vein graft restenosis is neointimal hyperplasia associated with vascular smooth muscle cell migration and proliferation. Gene therapy offers a novel treatment method for reducing or delaying early thrombosis, intimal hyperplasia, and late atherosclerosis. In this review, we will (1) describe sequential pathologies of vein graft disease; (2) summarize the applications of gene therapy in vein graft restenosis; and (3) discuss novel gene therapy for vein graft failure.
Despite advances in myocardial reperfusion therapies, acute myocardial ischaemia/reperfusion injury and consequent ischaemic heart failure represent the number one cause of morbidity and mortality in industrialized societies. Although different therapeutic interventions have been shown beneficial in preclinical settings, an effective cardioprotective or regenerative therapy has yet to be successfully introduced in the clinical arena. Given the complex pathophysiology of the ischaemic heart, large scale, unbiased, global approaches capable of identifying multiple branches of the signalling networks activated in the ischaemic/reperfused heart might be more successful in the search for novel diagnostic or therapeutic targets. High-throughput techniques allow high-resolution, genome-wide investigation of genetic variants, epigenetic modifications, and associated gene expression profiles. Platforms such as proteomics and metabolomics (not described here in detail) also offer simultaneous readouts of hundreds of proteins and metabolites. Isolated omics analyses usually provide Big Data requiring large data storage, advanced computational resources and complex bioinformatics tools. The possibility of integrating different omics approaches gives new hope to better understand the molecular circuitry activated by myocardial ischaemia, putting it in the context of the human 'diseasome'. Since modifications of cardiac gene expression have been consistently linked to pathophysiology of the ischaemic heart, the integration of epigenomic and transcriptomic data seems a promising approach to identify crucial disease networks. Thus, the scope of this Position Paper will be to highlight potentials and limitations of these approaches, and to provide recommendations to optimize the search for novel diagnostic or therapeutic targets for acute ischaemia/reperfusion injury and ischaemic heart failure in the post-genomic era.
This study aims to determine temperature effect on nerve conduction block induced by high-frequency (kHz) biphasic stimulation (HFBS).</AbstractText>Frog sciatic nerve-muscle preparation was immersed in Ringer's solution at a temperature of 15 or 20&#xa0;&#xb0;C. To induce muscle contractions, a bipolar cuff electrode delivered low-frequency (0.25 Hz) stimulation to the nerve. To induce nerve block, a tripolar cuff electrode was placed distal to the bipolar cuff electrode to deliver HFBS (2 or 10 kHz). A bipolar hook electrode distal to the blocking electrode was used to confirm that the nerve block occurred locally at the site of HFBS. A&#xa0;thread tied onto the foot was attached to a force transducer to measure the muscle contraction force.</AbstractText>At 15 &#xb0;C, both 2- and 10-kHz HFBSs elicited an initial transient muscle contraction and then produced nerve block during the stimulation (ie, acute block), with the 10 kHz having a significantly (p&#xa0;&lt; 0.001) higher acute block threshold (5.9&#xa0;&#xb1; 0.8 mA peak amplitude) than the 2 kHz (1.9&#xa0;&#xb1; 0.3 mA). When the temperature was increased to 20 &#xb0;C, the acute block threshold for the 10-kHz HFBS was significantly (p&#xa0;&lt; 0.0001) decreased from 5.2&#xa0;&#xb1; 0.3 to 4.4&#xa0;&#xb1; 0.2 mA, whereas the 2-kHz HFBS induced a tonic muscle contraction during the stimulation but elicited nerve block after terminating the 2-kHz HFBS (ie, poststimulation block) with an increased block duration at a higher stimulation intensity.</AbstractText>Temperature has an important influence on HFBS-induced nerve block. The blocking mechanisms underlying acute and poststimulation nerve blocks are likely to be very different.</AbstractText>Copyright &#xa9; 2021 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.</CopyrightInformation>
Bortezomib/Liposomal doxorubicin (V-DD) is preferred to bortezomib single agent in salvage therapy for Multiple Myeloma (MM). The present study is designed to assessment the efficacy and safety study of Bortezomib in combination with Liposomal Doxorubicin and Dexamethasone in treatment of Plasma Cell Leukemia (PCL). Primary study endpoint is the overall response rate (sCR+CR+VGPR+PR). Secondary endpoints is the rate of complete response (sCR+CR), partial remission rate (VGPR + PR), duration of response (DOR), overall survival (OS).Patient with Plasma Cell Leukemia(PCL ) and multiple myeloma (MM); KPS ≥ 60scores
To determine normal blood pressure (BP) in apparently healthy, asymptomatic school children in the age group of 6-16&#x2009;years and to determine the correlation of BP values with different sex, weight, height, and body mass index (BMI) and also to find out prevalence of hypertension in school going population.</AbstractText>This prospective, observational study enrolled 3,302 urban children (1,658 boys and 1,644 girls) in the age group of 6-16&#x2009;years. These were analyzed to study the distribution pattern of systolic blood pressure (SBP) and diastolic blood pressure (DBP) at different ages, sex, weight, height, and BMI. The SBP and DBP were noted as per age and sex. The association was seen between mean SBP and mean DBP with weight, height, and BMI. Information was collected about the family history of hypertension and was correlated with the obtained SBP and DBP readings.</AbstractText>The mean SBP in males at 6&#x2009;years was 99.69&#x2009;&#xb1;&#x2009;3.62&#x2009;mm of Hg, at 10&#x2009;years was 102.20&#x2009;&#xb1;&#x2009;2.16&#x2009;mm of Hg, and at 16&#x2009;years was 115.33&#x2009;&#xb1;&#x2009;1.26&#x2009;mm of Hg. The mean SBP in females at 6&#x2009;years was 96.55&#x2009;&#xb1;&#x2009;2.86&#x2009;mm of Hg, at 10&#x2009;years was 101.16&#x2009;&#xb1; 2.12&#x2009;mm of Hg, and at 16&#x2009;years was 112.41&#x2009;&#xb1;&#x2009;1.06&#x2009;mm of Hg. The correlation coefficient for relationship between age and SBP in males and females was 0.89 and 0.91, respectively, and for DBP was 0.92 and 0.90, respectively. The correlation coefficient for relationship between height and SBP in males and females was 0.91 and 0.93, respectively, and for DBP was 0.92 and 0.88, respectively. The correlation coefficient for relationship between weight and SBP in males and females was 0.92 and 0.92, respectively, and for DBP was 0.94 and 0.91, respectively. In the nomogram obtained in the study, 95% of study population fall between mean +2SD and -2SD.</AbstractText>The blood pressure (BP) (SBP and DBP) tends to increase with age, weight, height, and BMI. The BP values (SBP and DBP) increases grossly after 11&#x2009;years of age. The students with positive family history of hypertension had higher valve when compared to other student. The BP of children and adolescents can be evaluated using the reference table according to age. The table provided helps to classify as "normal" or "hypertension" (&gt;+2SD).</AbstractText>
To investigate the genetic causes of idiopathic sporadic prenatal generalized edema.</AbstractText>In a series of 12 patients, in whom in utero generalized skin edema or hydrops fetalis had been diagnosed, we screened 3 lymphangiogenic genes, VEGFR3, FOXC2, and SOX18.</AbstractText>In 3 of the patients, we identified a mutation: 2 in VEGFR3 and 1 in FOXC2. Two of the mutations were de novo and one was either de novo or nonpenetrant inherited. In these patients, the generalized edema resorbed spontaneously, either in utero or after birth. In the 2 individuals with a VEGFR3 mutation, edema remained limited to lower limbs.</AbstractText>Mutations in the VEGFR3 and FOXC2 genes account for a subset of patients with unexplained in utero generalized subcutaneous edema and hydrops fetalis without family history of lymphedema. Lymphangiogenic genes should be screened for mutations in sporadic patients diagnosed with fetal edema.</AbstractText>
sinus rhythm.. poor r wave progression - probable normal variant. borderline ecg.
sinus rhythm. atrial premature complex. borderline prolonged pr interval. rbbb and lpfb.
Thrombosis of vascular anastomosis in the field of reconstructive microsurgery is a clinical problem of extraordinary importance for the devastating consequences for affected patients. Sildenafil has been shown to be relaxing vascular action on the peripheral vascular system in vivo and have an ability to reduce platelet aggregation. There is no study up to date on the effect of sildenafil on microvascular anastomosis, neither experimental studies nor clinical settings.</AbstractText>A purposeful thrombotic back-wall stitch was performed in the groin flap pedicle to obtain an anastomosis with thrombotic potential where the drug effect was studied.</AbstractText>Data in the experimental group treated with papaverine or sildenafil indicate a considerable decrease in the percentage of necrotic flaps (20% necrotic flaps in papaverine group versus 30% necrotic flaps in sildenafil group) in comparison with control group (60% necrotic flaps). In papaverine group, in 100% cases, flap necrosis was established in the first 24 h, but in sildenafil group, 66% flap necrosis was established between the second and the seventh postoperative days.</AbstractText>The study did not demonstrate significant differences between the groups, but it does suggest a benefit in applying papaverine and sildenafil in the anastomosis with already thrombogenetic disease, compared to the nonapplication of antithrombotic drugs. The establishment of thrombosis in the necrotic flaps in the group treated with sildenafil was later than in the group treated with papaverine, with a statistical trend but without becoming significant.</AbstractText>
The production of odiferous metabolites, such as 2-methlyisoborneol (MIB), is a major concern for water utilities worldwide. Although MIB has no known biological function, the presence of the earthy/musty taste and odor attributed to this compound result in the reporting of numerous complaints by consumers, which undermines water utility performance and the safe and adequate provision of potable waters. Cyanobacteria are the major producers of MIB in natural waters, by mechanisms that have heretofore remained largely unstudied. To investigate the fundamental biological mechanism of MIB biosynthesis in cyanobacteria, the genome of a MIB-producing Pseudanabaena limnetica was sequenced using Next Generation Sequencing, and the recombinant proteins derived from the putative MIB biosynthetic genes were biochemically characterized. We demonstrate that the biosynthesis of MIB in cyanobacteria is a result of 2 key reactions: 1) a S-adenosylmethionine-dependent methylation of the monoterpene precursor geranyl diphosphate (GPP) to 2-methyl-GPP catalyzed by geranyl diphosphate 2-methyltransferase (GPPMT) and 2) further cyclization of 2-methyl-GPP to MIB catalyzed by MIB synthase (MIBS) as part of a MIB operon. Based on a comparison of the component MIB biosynthetic genes in actinomycetes and cyanobacterial organisms, we hypothesize that there have been multiple rearrangements of the genes in this operon.
BACKGROUND: Previous studies have shown that viable but stunned myocardium displays contractile reserve and exhibits cardiac cycle-dependent variations of integrated backscatter (CVIB), whereas infarcted myocardium does not. HYPOTHESIS: This study was designed to clarify whether assessment of the acoustic properties of the myocardium can predict contractile reserve in patients with chronic coronary artery disease (CAD). METHODS: In all, 21 patients with chronic CAD and 19 normal control subjects were studied. The magnitude of CVIB of the myocardium was measured in the basal and mid segment of the anterior septum and posterior wall of the left ventricle, using a real-time, two-dimensional integrated backscatter imaging system. The results were compared with the percent systolic wall thickening and the wall motion before and after revascularization. The wall motion was graded as normal, hypokinetic, or akinetic, and contractile reserve was considered present when an akinetic or hypokinetic segment improved after revascularization. RESULTS: The average magnitude of CVIB was lower among dysfunctional segments of CAD than among normal segments of controls (3.73 +/- 1.71 vs. 6.35 +/- 0.69, p < 0.001). Of the 77 segments examined, 38 showed reversible dysfunction. Before revascularization, percent systolic wall thickening was similar among segments showing contractile reserve compared with those with persistent dysfunction myocardium (17.97 +/- 8.41 vs. 16.83 +/- 6.37%, p = 0.19), and the mean CVIB was significantly greater in segments with than in those without contractile reserve (4.73 +/- 1.47 vs. 2.75 +/- 1.31, p < 0.001). The CVIB above 3 dB before percutaneous transluminal coronary angioplasty predicted segments with contractile reserve with a sensitivity and specificity of 84.2 and 79.5%, respectively. CONCLUSIONS: Cardiac cycle-dependent variations of integrated backscatter reflected myocardial contractility and functional capacity of the myocardium. They predicted segmental contractile reserve in patients with CAD.
We report a rare finding of a pair of coronary artery anomalies noted on computed tomography coronary angiography in an asymptomatic 75-year-old woman. This patient had a single coronary artery that bifurcated into a left main coronary artery (with an unfavorable interarterial course) and a right coronary artery. This gave rise to a vascular ring around the atrioventricular groove. We propose that the presence of this vascular ring may have been protective against the potentially ischemic course of the single-origin coronary artery passing between the aorta and pulmonary trunk.
<AbstractText Label="BACKGROUND/PURPOSE" NlmCategory="OBJECTIVE">Human parvovirus B-19 (PB-19) is a cause of hemolysis, red blood cell aplasia, and severe conditions in patients with sickle cell anemia, but the molecular mechanisms of the infection are still insufficiently understood. This study aimed to detect PB-19 DNA together with its antibodies in the sera of Egyptian children with sickle cell disease and to assess the contribution of this infection, which causes transient cessation of erythropoiesis, in precipitating severe anemia in some cases.</AbstractText>One hundred children with sickle cell disease seeking medical advice in the pediatric-hematology clinic were recruited. Sera of the patients were compared with those of 60 healthy children regarding the presence of PB-19 immunoglobulin (Ig)G and IgM as well as detection of its DNA by nested-polymerase chain reaction technique.</AbstractText>There were statistically significant differences in the prevalence of PB-19 IgM, IgG, and DNA among patients when compared with controls (p&#xa0;&lt; 0.001, p&#xa0;=&#xa0;0.001, and p&#xa0;&lt;&#xa0;0.001 respectively). Acute PB-19 infection detected by positive IgM and DNA was found in 30% of the patients, while chronic PB-19 infection detected by positive IgG and DNA was detected in 24% of the patients. Anemia was worse in children with acute PB-19 infection than in those with chronic infection, while anemia was mild in children with old infection.</AbstractText>PB-19 infection is detected at high rates among Egyptian children with sickle cell disease and it may result in severe anemia. So, PB-19 must be suspected and screened for in such group of patients.</AbstractText>Copyright &#xa9; 2015. Published by Elsevier B.V.</CopyrightInformation>
Beta-blockers (BBs) and angiotensin-converting enzyme inhibitors (ACEIs) have been associated with an increased risk and severity of anaphylaxis. However, the evidence supporting these findings is contradictory.</AbstractText>We carried out a systematic review and meta-analysis of studies that assess the influence of BBs and ACEIs on anaphylaxis.</AbstractText>We searched PubMed/MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews, and the Web of Science for relevant observational studies. We searched for studies where the presence and severity of anaphylaxis were compared between patients taking BBs, ACEIs, both types of drug, or neither type of drug. We performed a meta-analysis using a random-effects model.</AbstractText>A total of 21 studies met the study criteria. Of these, 15 assessed the severity and 9 the incidence of anaphylaxis. The studies brought together 22,313 anaphylaxis episodes for the severity studies and 18,101 anaphylaxis episodes for the studies of new cases of anaphylaxis. BBs and ACEIs increased the severity of anaphylaxis (BBs, odds ratio [OR] 2.19, 95% confidence interval [CI] 1.25-3.84; ACEIs, OR 1.56, 95% CI 1.12-2.16), but not the presence of new cases of anaphylaxis (BBs, OR 1.40, 95% CI 0.91-2.14; ACEIs, OR 1.38, 95% CI 0.39-4.86). It was not possible to perform an analysis adjusted for cardiovascular diseases, because only 1 study each for BBs and ACEIs, respectively, had adjusted data.</AbstractText>The quality of evidence showing that the use of BBs and ACEI increases the severity of anaphylaxis is low owing to differences in the control of confounders arising from the concomitant presence of cardiovascular diseases.</AbstractText>Copyright &#xa9; 2018 American Academy of Allergy, Asthma &amp; Immunology. Published by Elsevier Inc. All rights reserved.</CopyrightInformation>
Although A1C is now recommended to diagnose diabetes, its test performance for diagnosis and prognosis is uncertain. Our objective was to assess the test performance of A1C against single and repeat glucose measurements for diagnosis of prevalent diabetes and for prediction of incident diabetes.</AbstractText>We conducted population-based analyses of 12,485 participants in the Atherosclerosis Risk in Communities (ARIC) study and a subpopulation of 691 participants in the Third National Health and Nutrition Examination Survey (NHANES III) with repeat test results.</AbstractText>Against a single fasting glucose &#x2265;126 mg/dl, the sensitivity and specificity of A1C &#x2265;6.5% for detection of prevalent diabetes were 47 and 98%, respectively (area under the curve 0.892). Against repeated fasting glucose (3 years apart) &#x2265;126 mg/dl, sensitivity improved to 67% and specificity remained high (97%) (AUC 0.936). Similar results were obtained in NHANES III against repeated fasting glucose 2 weeks apart. The accuracy of A1C was consistent across age, BMI, and race groups. For individuals with fasting glucose &#x2265;126 mg/dl and A1C &#x2265;6.5% at baseline, the 10-year risk of diagnosed diabetes was 88% compared with 55% among those individuals with fasting glucose &#x2265;126 mg/dl and A1C 5.7-&lt;6.5%.</AbstractText>A1C performs well as a diagnostic tool when diabetes definitions that most closely resemble those used in clinical practice are used as the "gold standard." The high risk of diabetes among individuals with both elevated fasting glucose and A1C suggests a dual role for fasting glucose and A1C for prediction of diabetes.</AbstractText>
The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). RESONATE ¼ Twice-daily Oral Direct Thrombin Inhibitor Dabigatran Etexilate in the Long Term Prevention of Recurrent Symptomatic VTE. See Table 1 and 4 legends for expansion of other abbreviations and GRADE Working Group grades of evidence. a Patients with VTE who had completed at least 3 initial mo of therapy. b Dabigatran 150 mg twice daily. c Placebo-control study outcomes used from Schulman et al47 (RESONATE).
Residual cardiovascular risk in patients with hypertriglyceridemia, despite optimal low-density lipoprotein cholesterol levels being achieved with intensive statin treatment, is a global health issue. The purpose of this study was to investigate the efficacy and tolerability of treatment with a combination of high-dose atorvastatin/&#x3a9;-3 fatty acid compared to atorvastatin&#xa0;+&#xa0;placebo in patients with hypertriglyceridemia who did not respond to statin treatment.</AbstractText>In this multicenter, randomized, double-blind, placebo-controlled study, patients who had residual hypertriglyceridemia after a 4-week run-in period of atorvastatin treatment were randomly assigned to receive UI-018 (fixed-dose combination atorvastatin/&#x3a9;-3 fatty acid 40 mg/4 g) or atorvastatin 40 mg&#xa0;+&#xa0;placebo (control). The primary efficacy end points were the percentage change from baseline in non-high density lipoprotein cholesterol (non-HDL-C) level at the end of treatment and the adverse events recorded during treatment. A secondary end point was the percentage change from baseline in triglyceride level.</AbstractText>After 8 weeks of treatment, the percentage changes from baseline in non-HDL-C (-4.4% vs +0.6%; p&#xa0;=&#xa0;0.02) and triglycerides (-18.5% vs +0.9%; p &lt; 0.01) were significantly greater in the UI-018 group (n&#xa0;=&#xa0;101) than in the control group (n&#xa0;=&#xa0;99). These changes were present in subgroups of advanced age (&#x2265;65 years), status (body mass index &#x2265;25 kg/m2</sup>), or without diabetes. The prevalences of adverse events did not differ between the 2 treatment groups.</AbstractText>In patients with residual hypertriglyceridemia despite receiving statin treatment, a combination of high-dose atorvastatin/&#x3a9;-3 fatty acid was associated with a greater reduction of triglyceride and non-HDL-C compared with atorvastatin&#xa0;+&#xa0;placebo, without significant adverse events.</AbstractText>Copyright &#xa9; 2021 The Author(s). Published by Elsevier Inc. All rights reserved.</CopyrightInformation>
Type 2 diabetes is preceded by years of insulin resistance and is characterized by reduced bioavailability of the antiatherosclerotic signaling molecule nitric oxide (NO) and premature atherosclerosis. The relationship between resistance to the glucoregulatory actions of insulin and its effects on the vasculature (in particular NO-dependent responses) is poorly characterized. We studied this relationship in mice heterozygous for knockout of the insulin receptor (IRKO), which have a mild perturbation of insulin signaling. Male heterozygous IRKO mice aged 8-12 weeks were compared with age- and sex-matched littermates. IRKO mice had fasting blood glucose, insulin, free fatty acid, and triglyceride levels similar to those of wild-type mice. Intraperitoneal glucose and insulin tolerance tests were also similar in the two groups. Insulin levels in response to a glucose load were approximately twofold higher in IRKO compared with wild-type mice (1.08 +/- 0.11 vs. 0.62 +/- 0.13 ng/ml; P = 0.004). Despite this mild metabolic phenotype, IRKO mice had increased systolic blood pressure (124 +/- 4 vs. 110 +/- 3 mmHg; P = 0.01). Basal NO bioactivity, assessed from the increase in tension of phenylephrine preconstricted aortic rings in response to the NO synthase inhibitor N(G)-monomethyl-l-arginine, was reduced in IRKO (61 +/- 14 vs. 152 +/- 30%; P = 0.005). Insulin-mediated NO release in aorta, assessed as the reduction in phenylephrine constrictor response after insulin preincubation, was lost in IRKO mice (5 +/- 8% change vs. 66 +/- 9% reduction in wild-type; P = 0.03). Insulin-stimulated aortic endothelial NO synthase phosphorylation was also significantly blunted in IRKO mice (P &lt; 0.05). These data demonstrate that insulin-stimulated NO responses in the vasculature are exquisitely sensitive to changes in insulin-signaling pathways in contrast to the glucoregulatory actions of insulin. These findings underscore the importance of early intervention in insulin-resistant states, where glucose homeostasis may be normal but substantial abnormalities of the vascular effects of insulin may already be present.
Patients with inflammatory rheumatism very often have residual pain that is not easily relieved by conventional treatments. They can then use non-drug methods, such as physiotherapy, hypnosis or even cannabis. The aim of this study is to assess the percentage of patients who use cannabis to better relieve their pain or anxiety in chronic inflammatory rheumatism.Thanks to a better understanding of the pathophysiological mechanisms of inflammatory rheumatism, rheumatology has known for several decades a growth in its therapeutic arsenal (csDMARDs, bDMARDs, tDMARDs). rheumatism control has thus been optimized. however, patients very often keep pain, anxiety, residual fatigue, poorly controlled by our conventional therapies. patients then turn to non-drug therapies, among which the use of cannabis. endocannabinoids have an analgesic and anti-inflammatory action recognized in pre-clinical trials. however, investigators currently lack the data to authorize its use in clinical rheumatology. the aim of this study is to determine the prevalence of cannabis users in patients with rheumatoid arthritis, ankylosing spondyloarthritis or psoriatic arthritis in our unit. as a second intention, investigators will refine the consumption characteristics. Investigators will also look for possible risk factors for consumption (sensitivity to pain, catastrophism, standard of living, anxiety, depression, rheumatic activity and quality of life).
We describe an elderly woman with paroxysmal atrial fibrillation who was evaluated by electrocardiogram-gated multidetector-row computed tomography (MDCT) prior to left atrial radiofrequency ablation therapy to rule out coronary artery disease and to obtain a 3-dimensional anatomical map of the left atrium and pulmonary veins. MDCT documented the dynamic bidirectional motion of an interatrial septal aneurysm associated with a patent foramen ovale. MDCT findings correlated well with transesophageal and intracardiac echocardiograms.
To determine the prevalence of Campylobacter-contaminated transport crates and to determine whether contaminated crates represent a risk for contamination of chickens during transport to slaughter.</AbstractText>Samples were collected from cleaned transport crates before they were dispatched to the farms. Chicken groups were sampled within 24 h before transport to slaughter and at the slaughterhouse. Campylobacter spp. were isolated from 69 of 122 (57%) sampled batches of transport crates. Twenty-six slaughter groups, negative at farm level, were transported in batches of crates from which Campylobacter spp. had been isolated. In 11 (42%) of these 26 slaughter groups, Campylobacter spp. were found in samples taken at slaughter. The corresponding figure for at-farm-negative slaughter groups transported in negative crates was four (15%) testing positive at slaughterhouse of 27 slaughter groups [relative risk (RR) = 2.9, 95% CI 1.1-7.3]. In four of 11 slaughter groups, genetic subtyping by pulsed-field gel electrophoresis was able to support the hypothesis of contamination from crates to chickens during transport to slaughter.</AbstractText>Despite washing and disinfection, crates were frequently contaminated with Campylobacter and it could have contaminated chickens during transport to slaughter.</AbstractText>Campylobacter-positive crates are a risk factor for chickens testing campylobacter-positive at slaughter.</AbstractText>
In-hospital hyperglycemia (HH) is frequent and related to higher morbidity and mortality. Despite the benefits of HH treatment, glycemic control is often poor and neglected. The use of health applications to support diagnosis and therapy is now incorporated into medical practice. Medical applications for inpatient glycemic management have potential to standardize this handling by the nonspecialist physician. However, related studies are scarce. We aim to evaluate the efficacy in inpatient glycemic control parameters of medical software applications in non-critical care settings.</AbstractText>This systematic review on in-hospital insulin applications was performed according to PRISMA guidelines. Data were extracted in triplicate and methodological quality was verified. Specific outcomes of interest were glycemic control efficacy, hypoglycemia risk, length of in-hospital stay, integration with the electronic medical record and healthcare staff acceptance.</AbstractText>Among the 573 articles initially identified and subsequent revision of the references of each one, seven studies involving six applications were eligible for the review. A better glycemic control was reported with the use of most in-hospital insulin applications in the studies evaluated, but there was no mention of the time to reach the glycemic goal. The risk of hypoglycemia was low. Different reasons influenced the varied acceptance of the use of applications among health professionals.</AbstractText>The six applications of inpatient insulin therapy in a non-critical care environment proved to be useful and safe compared to the usual management. Medical apps are tools that can help improve the quality of patient care.</AbstractText>&#xa9; The Author(s) 2020.</CopyrightInformation>
This is a phase-2 safety trial to demonstrate the ability of frameless stereotactic aspiration and thrombolysis of ICH to safely remove blood.</AbstractText>Patients with ICH in the deep basal ganglia and internal capsule of &gt; 5 cc volume were consented to undergo computed tomographic imaging for frameless stereotactic guidance registration. Using the frameless stereotactic (CT) guidance, a 4-mm diameter catheter was inserted into the body of the hematoma using a frontal burr hole approach. The catheter was aspirated and then flushed with saline and aspirated to remove unclotted blood. After a confirmatory CT scan to localize the catheter, 1 mg of recombinant tissue plasminogen activator (t-PA) was infused into the clot, permitted to bathe the clot for 30 minutes, and then drained into a closed circuit collection system. t-PA was infused every 8 hours for 48 hours. A follow up CT scan was obtained at 48 hours.</AbstractText>28 patients with ICH (mean age 67.1) were admitted and underwent the procedure. Mean initial ICH volume was 54.6 cc +/-6 37.8. Mean time from onset to aspiration was 44 hours (range 7-180). Mean initial NIH Stroke scale (NIHSS) score was 24 (range 15-33). Compared with initial CT scan, there was a mean reduction of ICH volume by 77 +/-6 13% on final CT scan (p &lt; 0.0002). Compared with initial NIHSS, the discharge mean NIHSS (16 +/- 6) was significantly improved (p &lt; 0.001). There were no infectious, hemodynamic or neurologic complications. There were no episodes of symptomatic hemorrhagic enlargement and one case of asymptomatic bleeding along the catheter tract.</AbstractText>Frameless stereotactic aspiration and thrombolysis (FAST) of deep spontaneous intracerebral hemorrhage is a safe therapy that is associated with reduction in ICH volume, early improvement in NIHSS and potentially could be used to improve outcome.</AbstractText>
BACKGROUND/AIMS: The purpose of this study is to analyze the expression and biological function of lncRNA ANRIL, microRNA-199a, TLR4, and nuclear factor-kappa B (NF-κB) in acute renal injury (AKI) induced by lipopolysaccharide (LPS). METHODS: The levels of ANRIL and microRNA-199a in mouse cells and kidneys were detected by quantitative-polymerase chain reaction. Western blot analysis was used for the NF-κB pathway protein. MTT assay was used for cell viability. Enzyme-linked immunosorbent assay was used for the secretion of inflammatory factors in mouse kidney tissue. Apoptosis was measured by flow cytometry and Western blotting. The potential binding region between ANRIL and miR-199a was verified by luciferase reporter assay. RESULTS: The upregulation of ANRIL can reduce the expression of microRNA-199a and increases the number of apoptotic cells. The expression levels of ANRIL in LPS-induced AKI mice and LPS-treated HK2 cells were upregulated compared with the control group. Overexpression of ANRIL increased apoptosis and promoted TLR4 (Toll-like receptor 4), NF-κB phosphorylation, and downstream transcription factor production. CONCLUSION: ANRIL/NF-κB pathway in LPS-induced apoptosis provided theoretical guidance for ANRIL in the treatment of AKI.
The risks and benefits of a concomitant Maze procedure for patients with LV dysfunction undergoing major cardiac surgery have not yet been elucidated. This study aimed to evaluate the clinical impacts of the Maze procedure in patients with atrial fibrillation and left ventricular (LV) dysfunction.</AbstractText>Between January 1999 and March 2011, a total of 139 patients (mean age 52.7&#xb1;12.3 years, 54 females) with valvular atrial fibrillation (AF) and an LV ejection fraction (EF) of 40% or less underwent open heart surgery with (n=77) or without (n=62) a concomitant Maze procedure. We compared adverse outcomes (death and composite of death, thromboembolic events and congestive heart failure [CHF]) during a median follow-up period of 66.0 months (inter-quartile range, 27.5-106.9 months).</AbstractText>Adverse events occurred in 41 patients, including 36 deaths, seven thromboembolic events and eight hospitalizations due to CHF. After adjustment for baseline profiles with the use of propensity scores and inverse probability weighting, patients who had the Maze procedure were at lower risks of death (hazard ratio, 0.39; 95% confidence interval, 0.16-0.93; P=0.033) and composite adverse outcomes (hazard ratio, 0.28; 95% confidence interval, 0.14-0.57; P=0.017) than those not undergoing the Maze procedure. Furthermore, the Maze procedure resulted in superior functional status (P&lt;0.001) and reduced the need for long-term anticoagulation therapy (67.1% vs. 91.2%, P=0.001).</AbstractText>Performing the Maze procedure on patients with valvular AF and LV dysfunction reduced serious adverse outcomes and the need for long-term anticoagulation therapy when compared to cardiac surgery alone without the Maze procedure.</AbstractText>Crown Copyright &#xa9; 2013. Published by Elsevier Ireland Ltd. All rights reserved.</CopyrightInformation>
sinus rhythm. normal ecg.
Researchers will compare the effects of lidocaine versus air, as a way to fill the breathing tube cuff which is gently inflated to hold in place the trachea (airway) during surgery. Air is the traditional method used to inflate the breathing tube cuff. Researchers wish to find if lidocaine works better than air to facilitate tolerance to the breathing tube (decreased coughing, sore throat, hoarseness). They also want to learn more about its effectiveness for this particular surgical intervention.At the induction of anesthesia, Participants will be breathing 100% oxygen via a face mask and then, become anesthetized according to a standard protocol and at the discretion of the attending anesthesiologist. Participants will be receive fentanyl, lidocaine and either succinylcholine or vecuronium to facilitate tracheal intubation. Laryngoscopy will then be performed and the trachea intubated with a standard cuffed ETT. Inflation of the ETT cuff will be performed in accordance with the randomization of either air or 1.8% lidocaine/0.76% solution until such time as there is no air leak around the tube when administering positive pressure to 20 cm H2O. Anesthesia will be maintained with volatile anesthetic with or without a Propofol infusion. Vecuronium will be used to maintain the ulnar nerve train-of-four at 0-3 of four twitches. Lungs will be mechanically ventilated with tidal volumes of 6-8 mL/kg to maintain end-tidalCO2 concentration at 30-35 mm Hg. Anesthesia maintenance will occur until the near end of the surgical procedure. The volatile anesthetic will be discontinued and Propofol will be initiated via a continuous infusion to facilitate transportation to the intensive care unit (ICU). After arrival to the ICU, Neuromuscular blockade will then be antagonized with neostigmine and glycopyrrolate, and the pharynx being gently suctioned under direct vision. Mechanical ventilation to be maintained until swallowing or spontaneous respiration begins, and then, converted to assisted manual ventilation. Extubation will be performed when all of the following criteria are met: 1) full reversal of neuromuscular block (ulnar nerve T4/T1 ratio 1:1, with sustained tetanus at 50 Hz for 5 s and no fade); 2) spontaneous ventilation; and 3) the ability to follow verbal commands (eye opening or hand grip) or demonstrate purposeful unilateral movement (attempting self-extubation); 4) demonstration of hemodynamic stability; 5) adequate hemostasis with combined chest tube output < 100 ml/hour. The Participant then will be closely monitored as a 1:1 by the room nurse, and by other staff (respiratory therapist, and ICU fellows and consultants) for toleration of the ventilator (coughing, double triggering, "bucking," etc.). on the cardiac surgical intensive care unit. Sedation amount will be recorded electronically once the patient lands in the ICU, until the time of extubation. A member from the study team will physically record "yes," or "no," on the form provided regarding the patient coughing, complaining of a sore throat or difficulty swallowing, having hoarseness or difficulty speaking.
Many centres appear to perform carotid endarterectomy solely based on the findings of duplex scanning. There are two fundamental methods aimed at assessing the stenosis degree during an altrasonographic study, i. e., planimetric examination and Doppler altrasonography. Doppler ultrasonographic criteria have an independentsignificance when the assessment of the stenosis degree in the ultruasonographic B-mode is complicated. However, the currently available guidelines on haemodynamic assessment of the stenosis degree are solely based on the parameters of local blood flow without taking into consideration the state of central haemodynamics. The present study has shown that blood flow in the region ofstenosis of the internal carotid arteries (ICAs) depends not only on the stenosis degree but on the value of systemic arterial pressure (AP) at examination. Based on the obtained findings, we worked out Doppler ultrasonographic criteria for ICA stenosis degree "by the area" corrected for the value of systemic AP. It was determined that using pulse AP increases their prognostic eficiency.
<AbstractText Label="PURPOSE/AIM">Intravitreal bevacizumab (Avastin) is an irreversible vascular endothelial growth factor (VEGF) inhibitor used to treat severe retinopathy of prematurity (ROP) in extremely low gestational age neonates (ELGANs). ELGANs who are at the highest risk for developing severe ROP often experience brief intermittent hypoxia (IH) episodes which may cause oxidative damage. We tested the hypothesis that intravitreal Avastin leaks into the systemic circulation during exposure to IH and has adverse effects on biomarkers of pulmonary microvascular maturation, thus leading to pulmonary hemorrhage and long-term pulmonary sequelae.</AbstractText>Neonatal rats at postnatal day (PN) 0 (birth) were exposed to either: 1) hyperoxia (50% O2</sub>) or 2) neonatal IH (50% O2</sub> with brief episodes of 12% O2</sub>) from PN0 to PN14. Room air (RA) littermates served as controls. At PN14, the time of eye opening in rats, a single dose of Avastin (0.125&#x2009;mg in 5&#x2009;&#xb5;L) was injected into the vitreous cavity of the left eyes. A control group received equivalent volume saline. At PN23 and PN45, blood gases, lung-to-body weight ratios, histology, immunofluorescence, and lung biomarkers of angiogenesis were examined.</AbstractText>At PN23, Avastin increased lung VEGF, nitric oxide derivatives (NOx), and hypoxia-inducible factor (HIF)1a</sub> in the hyperoxia-exposed groups, but decreased soluble VEGFR-1 (sVEGFR-1). At PN45, lungs from animals exposed to neonatal IH and treated with Avastin were severely hemorrhagic with morphologic changes in lung architecture consistent with chronic lung disease. This was associated with higher VEGF and NOx levels, and lower insulin-like growth factor (IGF)-I and sVEGFR-1.</AbstractText>These findings prove our hypothesis that intravitreal Avastin penetrates the blood-ocular barrier in IH and alters lung biomarkers of angiogenesis. Avastin targeting of VEGF could affect normal lung development which may be exaggerated under pathologic conditions such as IH, ultimately leading to vascular permeability, vessel rupture, and pulmonary hemorrhage.</AbstractText>
sinus bradycardia.. prolonged qt interval. borderline ecg.
The performances of implantable cardioverter defibrillators and leads are important issues for healthcare providers and patients. In 2007 Sprint Fidelis leads were found to be associated with an increased failure rate and so the purpose of the study was to evaluate long-term mortality and clinical outcomes in patients implanted with Sprint Fidelis leads compared with Sprint Quattro leads.</AbstractText><AbstractText Label="DESIGN, SETTING, PATIENTS" NlmCategory="METHODS">508 patients with Sprint Fidelis leads and 468 with Sprint Quattro leads were prospectively followed in 12 Italian cardiology centres.</AbstractText>Information on hospitalisations and other clinical events were collected during scheduled and unscheduled hospital visits. Deaths were identified from medical records or via phone contacts with patients' family members or through the National Office of Vital Statistics.</AbstractText>Over a mean follow-up of 27&#xb1;18 months 141 deaths occurred in the overall population. No death was observed in patients with diagnosed failing lead. Kaplan-Meier patient survival differed between the two lead groups (80&#xb1;2% in Fidelis leads vs 70&#xb1;4% in the Sprint Quattro leads at 4 years, p=0.002). Multivariate analyses showed that mortality was neither associated with lead type nor with diagnosed failed lead. The annual rate of lead failure was 1.8% patient-year for Fidelis leads and 0.2% for the Sprint Quattro leads.</AbstractText>In our multicentre research, the clinical outcomes of patients with Fidelis leads differed from those of patients with Sprint Quattro leads. Nevertheless, neither mortality nor the combined endpoint of mortality and heart failure hospitalisations was associated with the lead type. http://clinicaltrials.gov/ct2/show/NCT01007474.</AbstractText>
Diabetic retinopathy is the leading cause of blindness in those of working age in the world. However, it is a preventable vision loss. According to current animal studies, it could be hypothesized that using angiotensin-converting enzyme inhibitors could play a crucial role as a protective factor in the progression of retinopathy in human. Because little known is about this effect in humans, we designed a case-control study to explore whether captopril could be a protective factor for prevention of retinopathy in patients with diabetes.</AbstractText>A case-control study was conducted on 164 patients with type 2 diabetes. Thirty-three patients with retinopathy were considered as cases, and 41 patients, without retinopathy, were designated as controls. All biochemical data were collected from results of laboratory tests at the last clinical visit. Dilated eye examination was performed by a trained ophthalmologist using direct and indirect ophthalmoscopy on dilated pupils.</AbstractText>Retinopathy was determined to be 35.4% and occurred more in men. Older age, male sex, longer duration of diabetes, higher systolic blood pressure, uncontrolled diabetes, and lower body mass index were associated with retinopathy. In our model only age (odds ratio [OR] = 3.2, 95% confidence interval [CI] = 1.3-7.9) and hemoglobin A1c (HbA1c) (OR = 3.6, 95% CI = 1.3-9.9) were found to be associated with the risk of retinopathy. Forty-five percent had hypertension. Age (OR = 2.9, 95% CI = 1.8-4.7), duration of diabetes (OR = 2.4, 95% CI = 1.5-3.87), and HbA1c (OR = 3.73, 95% CI = 1.82-7.64) were associated with developing retinopathy in patients with diabetes and hypertension. However, captopril was shown to be a protective factor after adjusting other variables in our model. This effect was not statistically significant (OR = 1.5, 95% CI = 0.37-6.2).</AbstractText>The benefit of using captopril to slow or prevent the progression of retinopathy has been demonstrated in this study. However, statistically it is very difficult to be confident in interpreting the results, and therefore more trials are needed.</AbstractText>
Interaction between the complement system and carbon nanotubes (CNTs) can modify their intended biomedical applications. Pristine and derivatised CNTs can activate complement primarily via the classical pathway which enhances uptake of CNTs and suppresses pro-inflammatory response by immune cells. Here, we report that the interaction of C1q, the classical pathway recognition molecule, with CNTs involves charge pattern and classical pathway activation that is partly inhibited by factor H, a complement regulator. C1q and its globular modules, but not factor H, enhanced uptake of CNTs by macrophages and modulated the pro-inflammatory immune response. Thus, soluble complement factors can interact differentially with CNTs and alter the immune response even without complement activation. Coating CNTs with recombinant C1q globular heads offers a novel way of controlling classical pathway activation in nanotherapeutics. Surprisingly, the globular heads also enhance clearance by phagocytes and down-regulate inflammation, suggesting unexpected complexity in receptor interaction.</AbstractText>Carbon nanotubes (CNTs) maybe useful in the clinical setting as targeting drug carriers. However, it is also well known that they can interact and activate the complement system, which may have a negative impact on the applicability of CNTs. In this study, the authors functionalized multi-walled CNT (MWNT), and investigated the interaction with the complement pathway. These studies are important so as to gain further understanding of the underlying mechanism in preparation for future use of CNTs in the clinical setting.</AbstractText>Copyright &#xa9; 2015 The Authors. Published by Elsevier Inc. All rights reserved.</CopyrightInformation>
Abdominal aortic aneurysm (AAA) is a common disease caused by segmental weakening of the aortic walls and progressive aortic dilation leading to the eventual rupture of the aorta. Currently no biomarkers have been established to indicate the disease status of AAA. Tenascin-C (TN-C) is a matricellular protein that is synthesized under pathological conditions. In the current study, we related TN-C expression to the clinical course and the histopathology of AAA to investigate whether the pattern of TN-C expression could indicate the status of AAA. We found that TN-C and matrix metalloproteinase (MMP)-9 were highly expressed in human AAA. In individual human AAA TN-C deposition associated with the tissue destruction, overlapped mainly with the smooth muscle actin-positive cells, and showed a pattern distinct from macrophages and MMP-9. In the mouse model of AAA high TN-C expression was associated with rapid expansion of the AAA diameter. Histological analysis revealed that TN-C was produced mainly by vascular smooth muscle cells and was deposited in the medial layer of the aorta during tissue inflammation and excessive destructive activities. Our findings suggest that TN-C may be a useful biomarker for indicating the pathological status of smooth muscle cells and interstitial cells in AAA.
Proteomics is the measurement of one or more protein populations or proteomes, preferably in a quantitative manner. A protein population may be the set of proteins found in an organism, in a tissue or biofluid, in a cell, or in a subcellular compartment. A population also may be the set of proteins with a common characteristic, for example, those that interact with each other in molecular complexes, those involved in the same process such as signal transduction or cell cycle control, or those that share a common posttranslational modification such as phosphorylation or glycosylation. Proteomics experiments that involve mass spectrometry are divided into five categories: (1) protein identification, (2) protein quantitation or differential analysis, (3) protein-protein interactions, (4) post-translational modifications, and (5) structural proteomics. Each of these proteomics categories is reviewed. Examples are given for quantitative experiments involving two-dimensional gel electrophoresis, and for gel-free analysis using isotope-coded affinity tags. The impact of proteomics on biological research and on drug development is discussed. Challenges for further development in proteomics are presented, including sample preparation, sensitivity, dynamic range, and automation.
BACKGROUND: Intraoperative and in-hospital mortality after surgery for acute type A dissection depends largely on preoperative conditions, specifically the presence of localized or generalized ischemia. Recently, the Penn classification of patients with acute type A aortic dissection has been described. The primary aim was to validate the Penn classification and to investigate preoperative variables related to mortality. METHODS: All consecutive patients operated for acute type A aortic dissection, 1990 to 2009 (n = 360), were included in a retrospective observational study. Univariate and multivariable analyses were used to identify variables related to intraoperative and in-hospital mortality. Propensity scoring was used to adjust for treatment selection bias. RESULTS: Overall intraoperative mortality was 7% (24 of 360) and in-hospital mortality was 19% (69 of 360). Two hundred nineteen patients (61%) were Penn class Aa (14% in-hospital mortality), 51 (14%) class Ab (24% mortality), 63 (18%) class Ac (24% mortality), and 27 (8%) class Abc (44% mortality), p =0.007. In multivariable analysis, Penn class Ac and Abc were independently related to intraoperative death (odds ratio 5.0 and 5.4, respectively), and Penn class Abc and non-Aa were independently related to in-hospital mortality (odds ratio 3.4 and 2.3, respectively). Concomitant coronary artery bypass grafting, older age, DeBakey type I dissection, and prolonged periods of cardiopulmonary bypass and hypothermic circulatory arrest were also independently associated with mortality. CONCLUSIONS: The Penn classification of acute type A aortic dissection is purposeful and its continued usage encouraged. Penn class indicating localized or generalized ischemia is independently related to intraoperative and in-hospital mortality.
A field survey was conducted to investigate the presence of Borrelia burgdorferi sensu lato (s.l.) in six counties of Taiwan. Spirochetes were successfully isolated from one rodent ear sample out of 485 rodent ears and 53 live, fed tick (Ixodes granulatus) samples. The spirochetes were confirmed to be B. burgdorferi s.l. by real-time PCR. In addition, 23 of 113 tick samples were tested positive for Borrelia DNA according to real-time PCR. The Borrelia isolate from the rodent and the 23 Borrelia DNA samples from the ticks were identified as B. valaisiana-related genospecies by phylogenetic analysis based on flagellin gene sequences. These findings suggest that the Borrelia valaisiana-related strains are maintained in a zoonotic cycle between tick vectors and reservoir hosts in Taiwan.
sinus rhythm. borderline prolonged pr interval. st elevation suggests acute pericarditis.
The investigators propose to test the hypothesis that the incidence of major complications related to infection or inadequate healing is reduced in morbidly obese patients given 80% inspired oxygen during, and for 12-18 hours after, surgery compared with patients given 80% oxygen only during surgery. The primary outcome will be a composite of major complications plausibly related to infection or healing.Wound infection is a common and serious consequence of anesthesia and surgery. Infection is associated with major complications including intra-abdominal abscess, peritonitis without leakage, and sepsis. The average wound infection thus prolongs hospitalization by a week, doubles the need for ICU care, and doubles mortality. The first few hours following bacterial contamination constitute a decisive period during which infection is established. Techniques aimed at improving resistance to surgical wound infections are thus most effective when implemented during the decisive period - even though infections are not detected clinically until five-to-ten days after surgery. The primary defense against surgical pathogens is oxidative killing by neutrophils. This reaction critically depends on tissue oxygen tension. It is therefore unsurprising that subcutaneous tissue oxygen tension (PsqO2) is inversely correlated with the risk of surgical wound infection. As might be expected, supplemental perioperative oxygen administration increases tissue oxygen partial pressure (compared with an FIO2 of 30%) and decreases wound infection risk. While 100% oxygen is associated with atelectasis and pulmonary inflammation, we and others have shown that 80% oxygen is not. Inadequate healing is also common. Scar formation starts with transcription of pro-collagen, which undergoes post-translational hydroxylation of the abundant proline and lysine residues. This promotes the cross-linking within and between collagen strands that provides tensile strength which begins the healing process. The prolyl and lysyl hydroxylases that catalyze this reaction depend on the substrate oxygen. The Km (substrate concentration at which the velocity of the reaction is half-maximal) for O2 of prolyl hydroxylase has been variously estimated at 20, 25, and 100 mmHg. Even using the most conservative estimate, these data suggest that proline hydroxylation of collagen (e.g., scar formation) will be PO2 dependent through the range of 0 to ≈200 mmHg, with 90% of the effect occurring by 90 mmHg. In vitro and in vivo animal evidence supports this theory. Inadequate healing is associated with anastomotic leakage, wound dehiscence, and bleeding. In morbidly obese patients, the incidence of infection and major complications related to either infection or inadequate healing is 15-20% after gastric bypass based on our preliminary data and a review of records at Washington University. Roughly 30% of the American population is now obese with a body mass index (BMI) > 30 kg/m2; about 5% of the population is morbidly obese, with a BMI exceeding 40 kg/m2. These patients are at extraordinarily high risk of wound infection, and infections in these patients are especially severe. Cardiac output, circulating blood volume, and resting oxygen consumption are all increased in the obese; however, total blood flow is sub-normal in relation to body weight. Obesity augments the size of individual fat cells without increasing blood flow. Specifically, fat tissue is hypoperfused and poorly oxygenated. Intraoperative tissue oxygenation is abnormally low in obese patients and postoperative tissue oxygenation is especially low - although it can be improved by oxygen administration. It thus seems likely that inadequate tissue oxygenation contributes to the observed extraordinary high wound infection risk in obese patients. Although supplemental oxygen during surgery and for the first two-to-six hours after surgery halves the risk of surgical wound infection, it remains unknown whether prolonged supplemental postoperative oxygen significantly augments the benefits of intraoperative oxygen. There is some evidence suggesting that prolonged postoperative oxygen administration may be helpful. For example, experimental infections in guinea pigs are reduced by administration of supplemental oxygen for 45 h. In contrast, restricting oxygen for only 45 minutes after contamination reduces tensile wound strength in rabbits no more than restricting oxygen for 5 full days. No study in humans has evaluated the effects of supplemental postoperative oxygen on surgical wound infection or associated complications. To the extent that supplemental oxygen after surgery is likely to reduce the incidence of major complications related to wound infection and healing, benefit is especially likely in morbidly obese patients because their baseline tissue oxygenation is usually sub-optimal and their risk is high. We thus propose to test the hypothesis that the incidence of major complications related to infection or inadequate healing are reduced in morbidly obese patients given 80% inspired oxygen during and for 12-18 hours after surgery compared with patients given 80% oxygen only during surgery. Patients will be enrolled at two OUTCOMES RESEARCH Group sites: the University of Louisville and the Cleveland Clinic. Patients undergoing gastric bypass will all be given 80% intraoperative oxygen and then randomly assigned to 30% or 80% oxygen until the first postoperative morning. The primary outcome will be a composite of major complications plausibly related to infection or healing. A maximum of 1,276 patients will provide a 90% power to detect a 25% reduction in the proportion of patients with at least one major complication. Supplemental oxygen is safe and inexpensive, costing only a few dollars per patient. Confirming our hypothesis would indicate that clinicians can reduce the risk of serious complications by making an essentially trivial modification in postoperative patient care.
To evaluate the clinical effectiveness and safety of acupoint catgut embedding and acupuncture on simple obesity by Meta-analysis.</AbstractText>Studies on clinical randomized controlled trials of acupoint catgut embedding for simple obesity which were published from January 2015 to November 2020 were searched in Cochrane Central Register of Control Trials (Central), PubMed, China Science and Technology Journal Database, China National Knowledge Infrastructure Database and Wanfang data-bases. And those that met the inclusion criteria were screened. RevMan5.3 was used for Meta-analysis. The "Risk of Bias" tool was used to evaluate the quality of included studies. R studio software was used for the measurement of publication bias.</AbstractText>A total of 33 studies were included for Meta-analysis, including 2685 patients with simple obesity. Meta-analysis results showed the comparison of effectiveness rate was relative risk () = 1.12, 95%(1.08, 1.16), body mass index (BMI) was mean difference () = -1.12, 95% (-2.09, -0.14), waist circumference was = -2.14, 95% (-4.22, -0.06), and body mass was = -2.36, 95% (-3.99, -0.73). On the basis of diet and exercise intervention, the effectiveness rate [ = 1.12, 95% (1.05, 1.19)], BMI [ = -0.88, 95% (-1.35, -0.40)], waist circumference [ = -1.10, 95%(-4.27, 2.07)], and body mass [ = -0.68, 95%(-2.90, 1.54)]. The risk of bias of included literatures was low.</AbstractText>Acupoint catgut embedding therapy was slightly better than acupuncture therapy in most of the outcomes. Moreover, the treatment frequency of acupoint catgut embedding is less with larger stimulation intensity, which is more conducive to clinical promotion.</AbstractText>
sinus rhythm. low qrs voltages in precordial leads. borderline ecg.
Danon disease is a rare disease caused by glycogen storage lysosomal disorder. It is related to the pathogenic mutation of the LAMP2 gene. In this case report, we present a patient with a novel pathogenic mutation (c.764_765insGA) with cardiac-only symptoms. Her family members do not carry the same mutation she does, suggesting this is a de novo mutation. Further tests revealed vacuoles and glycogen disposition in the patient's heart tissue and a significant decrease in LAMP2 protein expression. Protein structure remodeling of LAMP2 predicted that the mutant protein has conformational change lacking an important transmembrane domain, subsequently causing protein destabilization.
The periodic paralysis (PP) and myotonic syndromes have been recognized as muscle ion channelopathies (MIC) consequent to the discovery of genetic abnormalities of muscle ion channels. Genetic studies are therefore indispensable in the diagnosis of MIC. However, it is not practical to examine all muscle ion channels immediately upon identification of clinical symptoms. Clinical symptoms of MIC occur due to the abnormal excitability of the muscle membrane which is in turn related to abnormal ion channel genes. Therefore, a series of electrophysiologic tests is useful in examining the characteristics of abnormal excitability and predicting the abnormal ion channel Needle EMG studies can detect myotonic discharges while the prolonged exercise test can distinguish between primary and secondary PP. For myotonia, pattern I which includes the repeated short exercise test at room temperature or at cold skin temperature is specific for paramyotonia congenita, pattern II is characteristic for myotonia congenita, and pattern III is useful for Na channel myotonia. The decrement of CMAP with 10 Hz repetitive stimulation is related to mutation type in myotonia congenita. Thus, these electrophysiological tests may be of use in screening for MIC to narrow down the diagnosis and the selection of candidates for gene analysis.
Myocardial infarction is a major cause of mortality and heart failure worldwide. One of the most effective methods of this injury is direct delivery of cardioprotective drugs to ischemia-reperfusion (IR) myocardium. The aim of the present study was to fabricate an adenosine (Ade) prodrug-based, atrial natriuretic peptide (ANP)-modified nanosystem for the treatment of myocardial infarction.</AbstractText>Oleate adenosine prodrug (Ade-OA) and ANP-distearoylphosphatidylethanolamine-polyethylene glycol were synthesized. ANP-modified Ade-loaded lipid nanocarriers (ANP Ade/LNCs) were then self-assembled by using solvent evaporation method. In vitro drug release in the presence of plasma was evaluated. In vivo inhibition effect on infarct size, tissue distribution, and pharmacokinetics were investigated in rats with ischemic myocardium after intravenous injection.</AbstractText>In vivo inhibition effect on infarct size, tissue distribution, and pharmacokinetics studies in acute myocardial infarction (AMI) rats showed that ANP Ade/LNCs exhibited better efficiency than non-modified Ade/LNCs and free Ade in all respects.</AbstractText>These results indicated that the ANP Ade/LNCs can be used as a promising system for the treatment of cardiovascular diseases.</AbstractText>
sinus rhythm. left ventricular hypertrophy.
BACKGROUND: Management of atrial fibrillation (AF), besides prevention of stroke, mainly stresses symptom control and improvement of quality of life (QOL). In patients with permanent AF, exercising may improve QOL, rhythm, and symptoms. The purpose of this study was to determine the impact of aerobic physical rehabilitation on the QOL of patients suffering from AF and admitted to a coronary care unit (CCU). METHODS: This randomized controlled clinical trial study was conducted on 50 patients who were hospitalized with chronic AF in the CCU of Montazeri Hospital, Najafabad, Iran, and had the inclusion criteria. The participants were selected using convenience sampling method, and were randomly divided into experimental (n = 25) and control (n = 25) groups. The experimental group received a rehabilitation program in the form of an educational package and scheduled physical activity of aerobics for 8 weeks, and the control group received CCU routine care. The researcher measured the patients' QOL before and after the intervention using the 36-Item Short Form Health Survey (SF-36). RESULTS: There was no significant difference in the mean score of total QOL between the control and experimental groups before the intervention (P > 0.050). However, the comparison of the mean score of total QOL after the intervention showed a significant increase in the experimental group (P < 0.050). CONCLUSION: Aerobic rehabilitation activities are effective on the QOL of patients with chronic AF.
Tachycardia and tachyarrhythmias are associated with increased morbidity and mortality in adult patients in the ICU. This study examines the effects of nebulized bronchodilator therapy (albuterol and ipratropium) on heart rate and arrhythmias in this population and tests the proposition that levalbuterol is safer than albuterol in that regard.</AbstractText>The design was a randomized, single-blind, crossover, prospective study in 70 critically ill adult patients treated with nebulized bronchodilators. Patients were randomized to nebulized albuterol alternating with levalbuterol every 4 to 6 h. Group A received albuterol 2.5 mg alternating with levalbuterol 0.63 mg. Group B received albuterol 2.5 mg alternating with levalbuterol 1.25 mg. All patients received nebulized ipratropium bromide with each treatment. Heart rate was recorded before and after each treatment. Cardiac rhythm was continuously monitored using electronic telemetry units.</AbstractText>In group A, mean &#xb1; SD change in heart rate after albuterol 2.5 mg (n = 303) was 0.89 &#xb1; 4.5 beats/min compared with 0.85 &#xb1; 5.3 beats/min after levalbuterol 0.63 mg (n = 301) (P = .89). In group B (n = 114), heart rate decreased 0.16 &#xb1; 5.1 beats/min after albuterol 2.5 mg compared with an increase of 1.4 &#xb1; 5.4 beats/min after levalbuterol 1.25 mg (n = 118) (P = .03). Five events of arrhythmias (0.6%) occurred during the course of 836 treatments. Four consisted of occasional premature ventricular contractions. Only one patient stopped treatment because of a 5-beat run of ventricular tachycardia (one in 70 patients [1.4%]).</AbstractText>In critically ill adult patients, nebulized albuterol and ipratropium does not cause significant tachycardia or tachyarrhythmias. Substitution of levalbuterol for albuterol to avoid tachycardia and tachyarrhythmias is unwarranted.</AbstractText>ClinicalTrials.gov; No.: NCT01151579; URL: www.clinicaltrials.gov.</AbstractText>
The aim of this study was to evaluate the functional effects of bridging a gap in the sciatic nerve of the rat with either a biodegradable copolymer of DL-lactide and epsilon-caprolactone [p(DLLA-epsilon-CL)] nerve guide or an autologous nerve graft. Electromyograms (EMGs) of the gastrocnemius (GC) and tibialis anterior (TA) muscles were recorded 3.5 and 5 months after bridging the nerve gaps. Furthermore, the rats' gait was recorded on video and the quality of the gait was analyzed. EMG patterns of the contralateral nonoperated side were essentially normal. The EMG patterns on the operated side were irregular in all animals, but the quality of gait was better in the nerve guide group. We conclude that the surgical technique (nerve guide or nerve graft) does not influence the occurrence of abnormal EMG patterns, but gait improves to a greater extent when the nerve gap is bridged by a nerve guide.
Patients with existing internal cardioverter defibrillators (ICDs) often require upgrading to a biventricular ICD for treatment of congestive heart failure (CHF). Placement of a left ventricular (LV) lead can be technically challenging in the best of circumstances. A subclavian vein stenosis or occlusion related to previously placed leads adds a major obstacle to a successful implant. We report a technique of implanting an LV lead from the same side as the existing ICD system despite complete occlusion of the subclavian vein.
Patients with chronic kidney disease (CKD) experience poor outcomes after acute myocardial infarction. This study investigated how CKD affects clinical outcomes in patients with non-ST segment elevation myocardial infarction (NSTEMI) receiving PCI.</AbstractText>This retrospective study analyzed record-linked data for 314 patients who had received PCI for NSTEMI between January 2008 and September 2010. The 141 patients with advanced CKD were compared with 173 patients who had mild or no CKD. The primary endpoint was long-term mortality. The secondary endpoint was long-term major adverse cardiac events.</AbstractText>Compared to the control group, the advanced CKD group had older patients, more females, and more patients with diabetes mellitus and hypertension. The advanced CKD group also had a lower left ventricular ejection fraction and more patients with advanced HF and pulmonary edema. The advanced CKD group and the control group did not significantly differ in total in-hospital mortality, cardiac death or temporary hemodialysis post-PCI. The advanced CKD group had a significantly higher rate of long-term events. Finally, multiple stepwise Cox regression analysis showed that old age, advanced CKD and advanced HF were independent predictors of primary endpoint. The best predictors of secondary endpoint were post-PCI Thrombolysis in Myocardial Infarction-3 flow, multiple vessel disease, advanced HF and advanced CKD.</AbstractText>In NSTEMI patients undergoing PCI, in-hospital mortality does not significantly differ between patients with and without advanced CKD. However, long-term follow up of CKD patients consistently reveals poor outcomes.</AbstractText>Copyright &#xa9; 2016 Elsevier Ireland Ltd. All rights reserved.</CopyrightInformation>
Islets of myocytes within fibrofatty scars represent the substrate for reentrant ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy (ARVC). Electroanatomic mapping can reliably identify such areas.</AbstractText>To prospectively test the association between late and fragmented electrograms within scar and arrhythmic events in patients with ARVC.</AbstractText>High-density right ventricle electroanatomic mapping was performed in 32 patients with ARVC without history of cardiac arrest or sustained ventricular arrhythmias. Standard definitions of electroanatomic scars and fragmented, isolated, and very late potentials were used. All patients received an implantable cardioverter-defibrillator for the primary prevention of sudden death.</AbstractText>After a mean follow-up of 25 &#xb1; 7 months, 12 (38%) patients received appropriate implantable cardioverter-defibrillator shock for sustained ventricular arrhythmias. With the exception of a higher rate of previous syncope (P = .053), patients with arrhythmic events at follow-up did not differ from those who remained free from arrhythmic events in terms of other clinical variables, including cardiac magnetic resonance findings. Electroanatomic scars were present in all patients. The distribution and extent of electroanatomic scars were similar in the 2 groups (38 &#xb1; 25 cm(2) vs 33 &#xb1; 20 cm(2); P = .51). However, patients with implantable cardioverter-defibrillator shock had a higher prevalence of fragmented electrograms (92% vs 20%; P &lt;.001), of isolated late potentials (75% vs 20%; P = .004), and of very late potentials (67% vs 25%; P = .030). Fragmented electrograms were the only variable independently associated with arrhythmic events at follow-up (hazard ratio 21; P = .015).</AbstractText>The presence of fragmented and delayed electrograms within the scar predicts arrhythmic events in ARVC.</AbstractText>Copyright &#xa9; 2012 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.</CopyrightInformation>
Meta-analysis on immunohistological (IHC) concepts for the detection of inflammatory cardiomyopathy (InfCM) in endomyocardial biopsies (EMB). We included 61 publications, with 10,491 patients (mean age 47.1 years; men 66%) who underwent EMB and IHC evaluation. The 460 control patients were devoid of IHC proof of InfCM. The mean IHC detection rate of InfCM was 50.8% (95% CI 47.7-53.8%; range 18.4-91.7%). A publication bias was excluded (Funnel Plot p = 0.4264). This IHC detection rate was significantly (p < 0.0001) higher compared to the histological detection of myocarditis according to the Dallas criteria (mean 8.04%; 95% CI 5.08-12.5%; subset of 3274 patients in 30 publications). However, 13 different diagnostic IHC criteria were described in the publications, with various thresholds of diverse phenotypes of quantified infiltrates, and endothelial expression of diverse cell adhesion molecules (CAM), quantified either visually or by digital image analysis (DIA). The comparison of IHC with cardiac magnetic resonance (CMR) data available in a subset of 13 publications with 1185 patients revealed a sensitivity for CMR of 69% (95% CI 58-79%), a specificity of 73% (95% CI 59-84%), and a ROC-AUC of 0.77 (95% CI 0.73-0.81). This meta-analysis encompassing 10,491 patients confirms a mean detection rate of InfCM in 50.8% of EMB, being significantly more sensitive compared to the histological Dallas criteria. IHC cannot be fully substituted by CMR. However, standardization of the diverse IHC markers and protocols seems pertinent, especially considering the published adverse prognostic impact of IHC-confirmed InfCM and its published suitability for the selection of candidates responding favorably to immunosuppression.
sinus rhythm. left axis deviation. rbbb with left anterior fascicular block. left ventricular hypertrophy. abnormal ecg.
BACKGROUND: While there are convergent data suggesting that overall cardiovascular mortality is increased in patients with rheumatoid arthritis, the relative contributions of myocardial infarction and stroke remain unclear. AIMS: We sought to clarify this issue by conducting a meta-analysis of cohort studies on myocardial infarction and stroke in patients with rheumatoid arthritis. METHODS: A MEDLINE search from January 1960 to September 2009 and abstracts from international conferences from 2007 to 2009 were searched for relevant literature. All cohort studies reporting on standardized mortality ratio or incidence rate ratio of myocardial or stroke associated with rheumatoid arthritis, with available crude numbers, were included. STATA meta-analysis software was used to calculate pooled risk estimates. RESULTS: Seventeen papers fulfilled the inclusion criteria, corresponding to a total of 124,894 patients. Ten studies reported on standardized mortality ratio for fatal myocardial infarction, which ranged from 0.99 to 3.82. The overall pooled estimate was 1.77 (95% confidence interval [CI] 1.65-1.89). Incidence rate ratio for myocardial infarction was reported in five studies; the pooled estimate was 2.10 (95% CI 1.52-2.89). Nine studies reported on fatal stroke, with standardized mortality ratio ranging from 1.08 to 2.00; the pooled estimate was 1.46 (95% CI 1.31-1.63). The pooled incidence rate ratio for stroke (three studies) was 1.91 (95% CI 1.73-2.12). CONCLUSION: Our results show that risks of myocardial infarction and stroke are increased in patients with rheumatoid arthritis. In addition, both account for the observed increased mortality in individuals with rheumatoid arthritis.
Our goal was to report the transcatheter closure of a paravalvular leak after transcatheter aortic valve replacement (TAVR) using 3-dimensional (3D) printing.</AbstractText>A 66-year-old man who had undergone transapical and TAVR 2&#x2009;years ago due to aortic regurgitation, presented with palpitations and shortness of breath owing to exacerbation of paravalvular regurgitation. Echocardiography suggested that the stented aortic valve was fixed securely in place and the valve leaflets moved normally after TAVR, but there was severe paravalvular regurgitation (3 bundles, volume 11.0&#x2009;mL). Due to the high surgical risk, we closed the transcatheter paravalvular leak using preprocedural guidance with 3D printing and intraprocedural guidance with digital subtraction angiography. Postoperative echocardiography showed that the paravalvular leak was significantly reduced. 3D construction showed that the occluders and the stent valve were well placed.</AbstractText>Transcatheter closure of a paravalvular leak of the aortic valve may be feasible with appropriate pre- and intraoperative 3D printing guidance.</AbstractText>3D printing technology may help surgeons to make accurate preoperative strategy before occlusion procedures.</AbstractText>
sinus rhythm. normal ecg.
This study examined the effects of shiftwork on the cardiovascular system. The blood pressure (BP) and heart rate variability (HRV) of 134 male workers, who worked 8-hour shifts with rapid rotation of shifts at 3-day intervals, were examined for all the three shifts. In addition, the job stress was measured by Karasek's JCQ 49-item questionnaire and the circadian type was assessed by the morningness-eveningness questionnaire. The smoking and alcohol drinking habits, marital status and past medical history were also obtained. The method of analyzing the measured data based on a mixed model was used to illustrate the association between the shiftwork duration and the BP or HRV. The average age of workers was 29 years (between 25-44). Among them, 77.9% were current smokers, 50% showed the passive type of job strain in Karasek's model. The mean shiftwork duration was 5.21 years (range 5.4 months--10 years). In the circadian type, none of them belonged to a definitely morning type or a definitely evening type. In the multivariate analysis adjusted by age, job strain, shift, circadian rhythm and smoking, the blood pressure showed significantly increasing trends according to shiftwork duration in both the systolic and diastolic BP. The heart rate variability also showed a significantly decreasing trend according to the shiftwork duration in both the parasympathetic and sympathetic functions (p &lt; 0.05). These results suggests that there are negative health effects arising from shiftwork on the cardiovascular system.
Tongxinluo Capsule(TXLC) is a well-known traditional Chinese medicine prescription with effects of tonifying Qi and activating blood based on the Chinese herbal medicine theory that has been recommended as routine adjuvant treatment in patients with coronary heart disease (CHD) in China.</AbstractText>This meta-analysis aimed to evaluate the efficacy and safety of TXLC as supplementation in the prevention of adverse cardiovascular events in patients with CHD.</AbstractText>We performed a literature search in Pubmed, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), Wan Fang Database, and Chinese Biomedical Database (CBM) from their inceptions to March 2020. Only randomized controlled trials (RCTs) that assessed supplementation with TXLC or placebo and with adverse cardiovascular outcomes, were included in this meta-analysis. Primary end points were myocardial infarction (MI), target vessel revascularization (TVR) or in-stent restenosis (ISR), and cardiovascular death. Secondary end points included cerebrovascular accidents, heart failure (HF), and unscheduled readmission for cardiovascular diseases (CVDs). Adverse drug events were also evaluated. Trial sequential analysis (TSA) was conducted to reduce random errors introduced by possible insufficient sample size.</AbstractText>Eleven RCTs involving 1505 patients were analyzed. The mean(SD) age of included patients were 59.03(9.7) years. Treatment duration varied from 2 months to 12 months. Compared with placebo, TXLC supplementation showed significant effects on reducing the risk of MI (RR&#xa0;=&#xa0;0.44, [95% CI, 0.24-0.80]), TVR or ISR (RR&#xa0;=&#xa0;0.43, [95% CI, 0.31-0.58]), cerebrovascular accidents(RR&#xa0;=&#xa0;0.17, [95% CI, 0.06-0.46]), HF (RR&#xa0;=&#xa0;0.41, [95% CI, 0.21-0.79]), and unscheduled readmission for CVDs (RR&#xa0;=&#xa0;0.72, [95% CI], P&#xa0;=&#xa0;0.04), but did not have associations with incidence of cardiovascular death (RR&#xa0;=&#xa0;0.53, [95% CI, 0.15-1.91]). Subgroups of trials with 2-month (MI: RR&#xa0;=&#xa0;0.44, [95% CI, 0.13-1.53]; cardiovascular death: RR&#xa0;=&#xa0;0.30, [95% CI, 0.01-7.67]; cerebrovascular accidents: RR&#xa0;=&#xa0;0.04, [95% CI, 0.01-0.26]; unscheduled readmission for CVDs: RR&#xa0;=&#xa0;0.43, [95% CI, 0.20-0.94]) and 12-month (MI: RR&#xa0;=&#xa0;0.42, [95% CI, 0.20-0.89]; TVR or ISR: RR&#xa0;=&#xa0;0.42, [95% CI, 0.31-0.58]; HF: RR&#xa0;=&#xa0;0.34, [95% CI, 0.14-0.78]; unscheduled readmission for CVDs: RR&#xa0;=&#xa0;0.85, [95% CI, 0.59-1.22]) intervention period were analyzed. The adverse drug reactions were mild with no significant difference between TXLC and placebo.</AbstractText>This meta-analysis indicated that TXLC supplementation had beneficial effects on the prevention of cardiovascular adverse events, especially in TVR or ISR after coronary revascularization and may possibly lower the incidence of first or recurrent MI and HF within 12 months in patients with CHD, while insufficient sample size implied that these results lacked certain stability. And the effects of TXLC on cardiovascular mortality, cerebrovascular events, and unscheduled readmission for CVDs could not be confirmed due to insufficient cases. Clinical trials with large-sample sizes and extended follow-up time are of interest in the future researches.</AbstractText>Copyright &#xa9; 2022 Elsevier B.V. All rights reserved.</CopyrightInformation>
This report describes a 47-year-old woman with human immunodeficiency virus (HIV) and end-stage renal disease on hemodialysis, treated with combination antiretroviral drug therapy, who developed an acute, severe type B lactic acidosis 24 hours after homograft root replacement for endocarditis. She fully recovered after HIV medication was discontinued, along with administration of riboflavin and supportive measures including hemodialysis. The timing of this complication and previous reports suggest that open heart surgery may be a risk factor for nonischemic (type B) lactic acidosis in patients taking nucleoside analogue reverse transcriptase inhibitors.
sinus rhythm with borderline 1st degree a-v block. leftward axis. rsr'(v1) - probable normal variant. inferior infarct - age undetermined. septal t wave changes are nonspecific. abnormal ecg.
A full-term, female neonate developed acute hypoxemic respiratory failure complicated by persistent pulmonary hypertension of the newborn (PPHN), and responded to high-frequency oscillatory ventilation (HFOV) and inhaled nitric oxide (iNO). Discontinuation of iNO was attempted three times and was followed by severe desaturation due to right-to-left shunt through the patent ductus arteriosus and patent foramen ovale. As a result of iNO dependency state and rebound pulmonary hypertension, the neonate was maintained on iNO therapy for dipyridamole alone was unsuccessful. However, successful discontinuation of iNO therapy was achieved by combination of L-Arginine and dipyridamole. Exogeous NO may lead to down regulation of endogenous NO production, and further lead to rapid hydrolization of cyclic guanosine 3', 5' monophosphate (cGMP), the smooth muscle relaxant, by the enzyme phosphodiesterase. Moreover L-Arginine, the precursor for the formation of endogenous NO, has been found to be deficient in neonates with PPHN, so we speculated that by inhibiting phosphodiesterase and administrating L-Arginine smooth muscle relaxation occurred, and consequent weaning from iNO was achieved.
Patients with Turner syndrome (TS) are at an increased risk of morbidity and mortality from cardiovascular disease. This study was undertaken to establish the prevalence of hypertension in patients with TS and to establish to what extent cardiovascular or renal abnormalities contribute to the measured blood pressure.</AbstractText>62 patients with TS, age 5.4-22.4 years, had 24 h-ABPM (ambulatory blood pressure monitoring), echocardiography, renal imaging and measurement of recumbent plasma renin activity (PRA). Blood pressure was compared with population standards.</AbstractText>21% of the TS study population had mean systolic and 17% mean diastolic 24 h-ABPM measurements above the 95th percentile for age and sex (i.e. mild hypertension). Borderline blood pressure (i.e. 90th to 95th percentile) was found in another 17% of the patients. 57% of the patients had a blunted (i.e. less than 10%) fall in the night-time blood pressure. 24% of the patients had a detectable cardiac abnormality, 42% a detectable renal abnormality and 52% were found to have raised plasma renin activity. The presence of a cardiac or renal abnormality had no significant effect on blood pressure. Blood pressure of patients on growth and/or pubertal therapy was not different from those patients on no such treatment.</AbstractText>Over 30% of patients with Turner syndrome were found to be mildly hypertensive and over 50% had an abnormal diurnal blood pressure profile. In this study we were unable to demonstrate that the presence of renal or cardiac abnormalities had an effect on recorded blood pressure. The use of growth hormone and oestrogen to manage growth failure and pubertal delay did not seem to affect blood pressure. This study suggests that there is a high prevalence of raised blood pressure in Turner syndrome patients. The 24 h-ambulatory blood pressure monitoring profile suggests that this may be secondary in origin, but we were unable to demonstrate an underlying mechanism with the renal and cardiac investigations performed.</AbstractText>
<b>Purpose:</b> Left ventricle (LV)-only pacing is non-inferior to biventricular pacing but permanent fusion pacing is needed to ensure cardiac resynchronization therapy (CRT) responsiveness. The role of systematic exercise testing (ET) in these patients has not been established. This study was designed to assess clinical and therapeutic implications (device programming/drugs) of systematic ET in patients requiring fusion-pacing CRT without an&#xa0;right ventricle (RV) lead. <b>Methods:</b> Consecutive patients with a right atrium/LV-only dual-chamber (DDD) pacing system were included. Prospective data were obtained: device interrogation, ET, and echocardiography at every 6-month follow-up visit. CRT assessment during ET included maximal heart rate, beat-to-beat echocardiography analysis of LV fusion pacing, LV loss of capture, and improvement in exercise capacity. If LV loss of capture or unsatisfactory LV fusion pacing occurred, reprogramming was individualized for each patient and ET redone. <b>Results:</b> A total of 55 patients (29 male) aged 62&#xb1;11 years were included. During follow-up (39&#xb1;18 months), a total of 235 ETs were performed, with mean exercise load 6.4&#xb1;1.3 metabolic equivalents of task (118&#xb1;35 W, maximal heart rate 119&#xb1;17 beats/min). Twenty patients (36%) had inadequate pacing or loss of LV capture during ET, due to exceeding the maximum tracking rate (11%), chronotropic incompetence (7%), and LV pacing outside the fusion-pacing band (18%), caused by physiological shortening of the PR interval or exagerated LV preexcitation during maximum exercise. Post-ET CRT-device optimization included reprogramming of rate-adaptive atrioventricular interval (total decrease 23&#xb1;8 ms), individualized programming of maximum tracking rate, or rate-response function. Drug optimization was performed in 32% of patients, and ET redone in 36%. <b>Conclusion:</b> In one of three ETs, an intervention in device and medication optimization was done to ensure a better outcome. Routine ET should be a standard approach to maximize fusion-pacing CRT response during follow-up.
atrial fibrillation. abnormal ecg.
An emerging body of evidence from in vitro studies and in vivo animal models supports a pathogenic role of antibodies in the development of peripheral neuropathy associated with monoclonal gammopathy of undetermined significance (MGUS). Although the assessment of motor and sensory nerve fiber function is of clinical importance, it is seldom applied experimentally. We describe the application of an electrophysiologic method for the evaluation of motor and sensory nerve fiber function using an experimental model of MGUS neuropathy. Supramaximal stimulation of the tibial nerve elicited an early motor response (M-wave, 1.7 +/- 0.1 ms, n = 10) and a late sensory (H-reflex, 7.8 +/- 0.1 ms, n = 10) response that was recorded from the hind foot of anesthetized rats. Intraneural injection of serum antibodies from a MGUS patient with sensorimotor polyneuropathy, but not from an age-matched control subject, produced a marked attenuation of the H-reflex (P &lt; 0.01, n = 10) without affecting the M-wave. Light and electron microscopy of affected nerve showed myelinoaxonal degeneration with sparing of the smaller unmyelinated nerve fibers. The combined electrophysiologic and morphologic findings presented in this study are consistent with a selective sensory conduction deficit in MGUS neuropathy. Selective injury of afferent nerve fibers by this patient's serum antibodies may result from reactivity to neural antigens uniquely expressed by sensory neurons.
To study prevalence of androgen deficiency and its relations with clinicopsychological disorders in males with ischemic heart disease (IHD).</AbstractText>A total of 87 males aged 31-60 years (58 with stable angina of effort FCII-III, 29 with progressive angina of effort) participated in the study. Clinical symptoms of androgen deficiency, severity of anxiety and depression, quality of life were characterized with scales AMS, HADS, D. M. Aronov and V.P. Zaitsev method (2002), respectively. Left ventricular myocardial mass (L VMM) was calculated according to R. Devereux and N. Reichek formula.</AbstractText>Symptoms of male sexual hormones deficiency were seen in 67.8% examinees. In the age groups 31-40, 41-50, 51-60 years androgenic deficiency was diagnosed in 50, 85.7 and 82.9% patients, respectively. A direct correlation was found between androgenic deficiency and total cholesterol (R=0.38), prothrombin index (R=0.39), LVMM index (R=0.48), severity of depression (R=0.71), anxiety (R=0.5) and inverse correlation--between androgenic deficiency and quality of life (R = -0.69).</AbstractText>Young and middle-aged patients with ischemic heart disease have symptoms of androgenic deficiency in 67.8% cases. This fact necessitates screening testing of such patients with AMS questionnaire. Male sex hormones deficiency is associated with high anxiety and depression, while quality of life is subnormal.</AbstractText>
BACKGROUND AND PURPOSE: Evolution of intracranial aneurysmal disease is known to be related to hemodynamic forces acting on the vessel wall. Low wall shear stress (WSS) has been reported to have a negative effect on endothelial cells normal physiology and may be an important contributor to local remodeling of the arterial wall and to aneurysm growth and rupture. METHODS: Seven patient-specific models of intracranial aneurysms were constructed using MR angiography data acquired at two different time points (mean 16.4+/-7.4 months between the two time points). Numeric simulations of the flow in the baseline geometries were performed to compute WSS distributions. The lumenal geometries constructed from the two time points were manually coregistered, and the radial displacement of the wall was calculated on a pixel-by-pixel basis. This displacement, corresponding to the local growth of the aneurysm, was compared to the time-averaged wall shear stress (WSS TA) through the cardiac cycle at that location. For statistical analysis, radial displacement was considered to be significant if it was larger than half of the MR pixel resolution (0.3 mm). RESULTS: Mean WSS TA values obtained for the areas with a displacement smaller and greater than 0.3 mm were 2.55+/-3.6 and 0.76+/-1.5 Pa, respectively (P<0.001). A linear correlation analysis demonstrated a significant relationship between WSS TA and surface displacement (P<0.001). CONCLUSIONS: These results indicate that aneurysm growth is likely to occur in regions where the endothelial layer lining the vessel wall is exposed to abnormally low wall shear stress.
We have previously reported that the developing rat cerebellum is affected by hypergravity exposure. The effect is observed during a period of both granule and glial cell proliferation and neuronal migration in the cerebellum and coincides with changes in thyroid hormone levels. The present study begins to address the molecular mechanisms involved in the cerebellar response to hypergravity. Specifically, the study focuses on the expression of cerebellar proteins that are known to be directly involved in cell-cell interactions [protein expressing 3-fucosyl-N-acetyl-lactosamine antigen (CD15), neuronal cell adhesion molecule (NCAM-L1)] and those that affect cell-cell interactions indirectly [glial fibrillary acidic protein (GFAP)] in rat neonates exposed to centrifuge-produced hypergravity. Cerebellar mass and protein expression in rat neonates exposed to hypergravity (1.5 G) from gestational day (G) 11 to postnatal day (P) 30 were compared at one of six time points between P6 and P30 against rat neonates developing under normal gravity. Proteins were analyzed by quantitative western blots of cerebellar homogenates prepared from male or female neonates. Cerebellar size was most clearly reduced in male neonates on P6 and in female neonates on P9, with a significant gender difference; differences in cerebellar mass remained significant even when change in total body mass was factored in. Densitometric analysis of western blots revealed both quantitative and temporal changes in the expression of selected cerebellar proteins that coincided with changes in cerebellar mass and were gender-specific. In fact, our data indicated certain significant differences even between male and female control animals. A maximal decrease in expression of CD15 was observed in HG females on P9, coinciding with maximal change in their cerebellar mass. A shift in the time-course of NCAM-L1 expression resulted in a significant increase in NCAM-L1 in HG males on P18, an isolated time at which cerebellar mass does not significantly differ between HG and SC neonates. A maximal decrease in expression of GFAP was observed in HG males on P6, coinciding with maximal change in their cerebellar mass. Altered expression of cerebellar proteins is likely to affect a number of developmental processes and contribute to the structural and functional alterations seen in the CNS developing under altered gravity. Our data suggest that both cerebellar development and its response to gravitational manipulations differ in males and females.
The coronavirus disease (COVID-19) pandemic has caused 2.69 million deaths and 122 million infections. Great efforts have been made worldwide to promptly develop effective vaccines and reduce morbidity and mortality rates from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Available vaccines have proven highly effective at preventing symptomatic disease in clinical trials and real-world reports and are playing an essential role in flattening the epidemiology curve and, mostly, in reducing COVID-19 hospitalizations. Some concerns have been raised after very rare cases of myocarditis and pericarditis recently reported by the Centers for Disease Control and Prevention (CDC) as potentially associated with COVID-19 mRNA vaccinations, namely the Pfizer-BioNTech mRNA vaccine (BNT162b2) and the Moderna mRNA vaccine (mRNA-1273). Therefore, the aim of this document is to explore the possible link between COVID-19 mRNA vaccination and the development of myocarditis and/or pericarditis by performing a critical analysis of available data and to provide indications for specific subgroups of individuals.
Evidence suggests that caregivers of people with heart failure (HF) often experience caregiver burden and emotional distress. However, these studies measured the caregiving experience using generic tools since a disease-specific tool was not available. Recently, the Dutch Objective Burden Inventory (DOBI) was developed as a disease-specific tool measuring objective caregiver burden in a Dutch HF population of caregivers. Using a cross-sectional design, caregivers of HF patients attending an outpatient HF clinic completed the DOBI, the Hosptial Anxiety and Depression Scale (HADS) and the Caregiver Reaction Assessment (CRA). Caregivers (n=47) were mainly female (72%) and spouses (72%) of the HF patients with a mean age of 63.1 (±10.4) years. Patients were older (mean age 72.7; ±10.6), 64% male and had advanced HF. Feasibility for the objective portion of the DOBI was excellent with <10% missing values. The subjective component of the DOBI was incomplete and could not be used in the analyses. Seven items had minimal variability. Significant relationships emerged between the DOBI, CRA and HADS revealing construct validity for all subscales of the DOBI. Cronbach's alpha was >.80 for all DOBI subscales. The DOBI is the only disease-specific tool that measures burden for caregivers of HF patients. The objective portion of the DOBI showed evidence of adequate internal consistency and construct validity in a Canadian population of caregivers of HF patients attending a HF Clinic. Further testing is needed to determine floor and ceiling effects for DOBI items and responsiveness of this tool.
Here we present an open-source solution, comprising several 3D-printable mechanical pieces and software tools, for frameless stereotaxic targeting in young and adult pigs of varying weights.</AbstractText>Localization was achieved using an IR camera and CT imaging. The positions of the tools were followed, after registration of the pig stereotaxic space, with a CT scan and open-source brain atlas. The system was used to target the lateral ventricle and the subthalamic nucleus (STN) in one piglet and two adult Yucatan miniature pigs, which were either normal weight or obese.</AbstractText>Positive targeting was confirmed in the first trial for all subjects, either by radiopaque CT enhancement of the ventricle or actual recording of the STN electrophysiological signature. We conclude that open-source freely available models, easily built with low-end 3D printers, and their associated software can be effectively used for brain surgery in pigs, at a minimal cost, irrespective of the weight of the animal.</AbstractText>Copyright &#xa9; 2021 Elsevier B.V. All rights reserved.</CopyrightInformation>
South Asian refugees experience a high risk of obesity and diabetes yet are often underrepresented in studies on chronic diseases and their risk factors. The gut microbiota and gut permeability, as assessed through circulating lipopolysaccharide binding protein (LBP), may underlie the link between chronic inflammation and type 2 diabetes (T2D). The composition of the gut microbiota varies according to multiple factors including demographics, migration, and dietary patterns, particularly fiber intake. However, there is no evidence on the composition of the gut microbiota and its relationship with metabolic health in refugee populations, including those migrating to the United States from Bhutan. The objective of this study was to examine glycemic status in relation to LBP, systemic inflammation fiber intake, and gut microbiota composition in Bhutanese refugee adults residing in New Hampshire (n</i> = 50).</AbstractText>This cross-sectional study included a convenience sample of Bhutanese refugee adults (N</i> = 50) in NH. Established bioinformatics pipelines for metagenomic analysis were used to determine relative genus abundance, species richness, and alpha diversity measures from shallow shotgun sequences. The relationships between inflammatory markers, gut microbiota composition, dietary fiber, and glycemic status were analyzed.</AbstractText>We identified a substantial chronic disease burden in this study population, and observed a correlation between glycemic status, LBP, and inflammation, and a correlation between glycemic status and gut microbiome alpha diversity. Further, we identified a significant correlation between proinflammatory taxa and inflammatory cytokines. SCFA-producing taxa were found to be inversely correlated with age.</AbstractText>To date, this is the most comprehensive examination of metabolic health and the gut microbiome in a Bhutanese refugee population in NH. The findings highlight areas for future investigations of inflammation and glycemic impairment, in addition to informing potential interventions targeting this vulnerable population.</AbstractText>Copyright &#xa9; 2023 Moser, Moore, Khadka, Lyons, Foxall, Andam, Parker, Ochin, Garelnabi, Sevigny, Thomas, Bigornia and Dao.</CopyrightInformation>
Multifactorial diseases refer to diseases having a genesis known to be influenced both by the genome and the environment. Examples include cardiovascular diseases, asthma, autoimmune diseases and various neurological and psychiatric diseases. Technical development has made possible a considerably more accurate measurement of genetic variation, having already led to the identification of hundreds of predisposing genes. We do not, however, still understand enough about the mechanisms of action of genes. The increasing progress in DNA sequencing techniques is currently changing the prospects of research more quickly than ever before.
Data suggest that renal denervation (RDN) in treatment-resistant hypertension (TRHT) is safe in terms of renal function. However, most studies report kidney function as creatinine-based estimated glomerular filtration rate (eGFR), which may be biased by non-renal factors. Damage markers other than albuminuria have never been evaluated after RDN. In this non-randomized RDN trial, we studied changes in kidney function, assessed as measured GFR (mGFR) and various GFR estimates, six months and two years after RDN. We also examined changes in albuminuria and a biomarker of tubular dysfunction. Adult non-diabetic patients with TRHT and eGFR ≥45 ml/min/1.73 m2 were recruited from hypertension clinics. Before bilateral RDN, mGFR was measured by iohexol clearance. We estimated eGFR from serum creatinine and cystatin C (eGFRcrea , eGFRcys, and eGFRcreacys ), and albumin-creatinine ratio (ACR) and N-acetyl-β-D-glucosaminidase (NAG)-creatinine ratio (NAG-CR) were measured in spot urines. All measurements were repeated after six and twenty-four months. Twenty patients, mean age 54 (±9) years and baseline mGFR 83 (±20) ml/min/1.73 m2  underwent RDN. After six months, mGFR fell, eGFRcrea remained unchanged, whereas eGFRcys and eGFRcreacys increased. At 2 years' follow-up, eGFRcreacys was significantly lower than at baseline. mGFR was 78 (±28) ml/min/1.73 m2 . Change in ambulatory systolic BP predicted change in eGFRcrea . Urinary NAG-CR, but not ACR, increased during follow-up. Different GFR assessments gave diverging results after RDN. Therefore, care should be taken to method when evaluating kidney function after RDN. Increases in a tubular dysfunction biomarker suggest that kidney damage may occur. Long-term renal follow-up is needed after RDN.
Bulk and magnetic core-shell Molecularly Imprinted Polymers (MMIPs) have been introduced and compared to extract and determine amiodarone from a complex matrix, i.e., plasma, due to the importance of Therapeutic Drug Monitoring (TDM). Polymer synthesis was confirmed by FTIR, AFM, TGA, DLS, VSM, TEM, and the adsorption studies such as capacity, isothermal models, selectivity, and regeneration were performed to evaluate and compare polymer efficiency in extraction and separation of amiodarone from sample solutions and human plasma. Both nano-sized and bulk polymers successfully extracted the target molecule at the low therapeutic ranges and the overdose concentrations (recoveries of 98.38%-102.70%). The maximum adsorption capacity of the MMIPs was 42.5&#xa0;&#x3bc;g/mg compared with 2.6&#xa0;&#x3bc;g/mg for bulk polymers. The imprinting factors of the polymers were 15.12 and 6.84 for MMIPs and bulk, respectively. MMIPs and bulk polymers presented 4.68 and 1.66 selectivity factors, respectively, towards amiodarone compared with lidocaine. LOD, LOQ, and enrichment factor in human plasma were 0.09, 0.28&#xa0;&#x3bc;g&#xa0;mL<sup>-1</sup>, and 10 respectively. Recoveries of therapeutic concentration from plasma were 91.38 and 97.33% for bulk and MMIPs, respectively. MMIPs as an adsorbent in amiodarone extraction from plasma offered reduced necessary sample amount, less adsorbent consumption, reduced pretreatment time, and reduced elution solvent waste while yielding higher extraction recovery and more specificity for the target compared with the bulk polymer. Bulk polymers have a more straightforward synthesis procedure due to fewer synthesis steps and fewer variables, and Molecularly Imprinted Polymer Solid-phase Extraction (MIP-SPE) has already been introduced commercially. MMIPs prevail on a small scale, and in the context of a simple extraction, separation, or concentration in large-scale bioanalysis, efforts towards optimization and development of MMIPs can unearth tremendous opportunities for green chemistry principles.
The aim of the study was to describe our experience using a modified nasal cannula to deliver nasal continuous positive airway pressure and/or nasal intermittent positive pressure ventilation during primary neonatal resuscitation of preterm and term newborns.</AbstractText>Data were collected retrospectively for all neonates resuscitated with nasal cannula in the delivery room. The primary outcome was the number of newborns intubated in the delivery room. Secondary outcomes included need for chest compressions, intubations in the first 24 hours, air-leaks, and surfactant administration.</AbstractText>A total of 102 infants were resuscitated using nasal cannula. Eight (7.8%) were intubated in the delivery room, five (4.9%) required chest compressions, and five (4.9%) had pneumothorax noted on chest X-ray. No deaths occurred in the delivery room. Twenty-eight patients (27.5%) received early rescue surfactant after admission to the neonatal intensive care unit.</AbstractText>Neonatal resuscitation can be effectively performed in preterm and term newborns using a modified nasal cannula in the delivery room.</AbstractText>Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.</CopyrightInformation>
RATIONALE: Photodynamic therapy uses light and drugs that make cancer cells more sensitive to light to kill tumor cells. This may be an effective treatment for esophageal cancer. PURPOSE: Phase II trial to study the effectiveness of photodynamic therapy in treating patients with Barrett's esophagus who have in situ esophageal cancer.OBJECTIVES: I. Evaluate the efficacy of photodynamic therapy (PDT) using porfimer sodium (Photofrin) and controlled uniform laser light in patients with carcinoma in situ in Barrett's esophagus or severe dysplasia in Barrett's esophagus. II. Evaluate the safety of the treatment on this patient. OUTLINE: This is a noncomparative study. PDT consists of IV porfimer sodium followed 40-50 hours later by laser red light delivered by optic fibers passed through the biopsy channel of an endoscope. Retreatment, if necessary, consists of up to 3 injections at least 30 days apart and up to 6 laser light treatments, with a maximum of 2 following each injection. Patients are followed monthly for 4 months, and then periodically for at least 5 years. PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.
sinus tachycardia. probable left atrial enlargement.
This is a report on a new clinical symptom manifested in the form of an asymmetrical pattern of pulsation in the cervical vessels in healthy people. A study included 820 healthy people of different sex and age, including 40 children. The physiological asymmetry of the jugular veins was demonstrated.
OBJECTIVE: Waiting time is inevitable during cardiovascular (CV) care. This study examines whether waiting room-based CV education could complement CV care. METHODS: A 2:1 randomised clinical trial of patients in waiting rooms of hospital cardiology clinics. Intervention participants received a series of tablet-delivered CV educational videos and were randomised 1:1 to receive another video on cardiopulmonary resuscitation (CPR) or no extra video. Control received usual care. The primary outcome was the proportion of participants reporting high motivation to improve CV risk-modifying behaviours (physical activity, diet and blood pressure monitoring) post-clinic. SECONDARY OUTCOMES: clinic satisfaction, CV lifestyle risk factors (RFs) and confidence to perform CPR. Assessors were blinded to treatment allocation. RESULTS: Among 514 screened, 330 were randomised (n=220 intervention, n=110 control) between December 2018 and March 2020, mean age 53.8 (SD 15.2), 55.2% male. Post-clinic, more intervention participants reported high motivation to improve CV risk-modifying behaviours: 29.6% (64/216) versus 18.7% (20/107), relative risk (RR) 1.63 (95% CI 1.04 to 2.55). Intervention participants reported higher clinic satisfaction RR: 2.19 (95% CI 1.45 to 3.33). Participants that received the CPR video (n=110) reported greater confidence to perform CPR, RR 1.61 (95% CI 1.20 to 2.16). Overall, the proportion of participants reporting optimal CV RFs increased between baseline and 30-day follow-up (16.1% vs 24.8%, OR=2.44 (95% CI 1.38 to 4.49)), but there was no significant between-group difference at 30 days. CONCLUSION: CV education delivery in the waiting room is a scalable concept and may be beneficial to CV care. Larger studies could explore its impact on clinical outcomes. TRIAL REGISTRATION NUMBER: ANZCTR12618001725257.
It has been reported that chronic inflammation of the vessel wall is a hallmark of atherosclerosis. Interleukin-6 (IL-6) is regarded as an important modulator of inflammatory events occurring during all stages of atherogenesis. Although many factors that induce IL-6 expression have been identified, the effect of homocysteine (Hcy) on the expression of IL-6 in atherogenesis and the underlying mechanisms are not entirely clear. The objective of the present study was to investigate the role of Hcy in IL-6 expression in rat aorta vascular smooth muscle cells (VSMCs). After VSMCs were incubated with Hcy for various time periods, enzyme-linked immunosorbent assay (ELISA) and semi-quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) were performed to measure the expression of IL-6. Electrophoretic mobility shift assay (EMSA) was used to examine nuclear factor kappaB (NF-kappaB) activity. Hcy (0.01-0.25 mmol/l) significantly increased the expression of IL-6 mRNA and protein in rat VSMCs. The increase in IL-6 expression was associated with the activation of NF-kappaB. Pyrrolidine dithiocarbamate (PDTC) suppressed Hcy-induced IL-6 release, a finding compatible with involvement of reactive oxygen species as second messengers in cytokine production mediated by Hcy. The present study has clearly demonstrated the ability of Hcy to elicit an inflammatory response in rat VSMCs by stimulation of IL-6 production and activation of NF-kappaB. Inflammation activation on vessel walls by elevation of Hcy may contribute to the pathogenesis of atherosclerosis.
To investigate the effects of acute caffeine (CAFF) intake on physical performance in elite women handball players.</AbstractText>A total of 15 elite women handball players participated in a randomized, double-blind study. In 2 different trials, participants ingested either a placebo (cellulose) or 3&#xa0;mg of CAFF per kilogram of body mass (mg/kg bm) before undergoing a battery of neuromuscular tests consisting of handball throws, an isometric handgrip strength test, a countermovement jump, a 30-m sprint test (SV) and a modified version of the agility T test. Then, participants performed a simulated handball game (2 &#xd7; 20&#xa0;min), and movement patterns were recorded with a local positioning system.</AbstractText>Compared with the placebo, CAFF increased ball velocity in all ball throws (P = .021-.044; effect size [ES] = 0.39-0.49), strength in isometric handgrip strength test (350.8 [41.2] vs 361.6 [46.1]&#xa0;N, P = .034; ES = 0.35), and countermovement-jump height (28.5 [5.5] vs 29.8 [5.5]&#xa0;cm; P = .006; ES = 0.22). In addition, CAFF decreased running time in the SV (4.9 [0.2] vs 4.8 [0.3]&#xa0;s; P = .042; ES = -0.34). In the simulated game, CAFF increased the frequency of accelerations (18.1 [1.2] vs 18.8 [1.0] number/min; P = .044; ES = 0.54), decelerations (18.0 [1.2] vs 18.7 [1.0] number/min; P = .032; ES = 0.56), and body impacts (20 [8] vs 22 [10] impacts/min; P = .032; ES = 0.30). However, postexercise surveys about self-reported feelings of performance indicate that players did not feel increased performance with CAFF.</AbstractText>Preexercise ingestion of 3&#xa0;mg/kg bm of CAFF improved ball-throwing velocity, jump, and sprint performance and the frequency of in-game accelerations and decelerations in elite women handball players.</AbstractText>
The multibranched off-the-shelf stent graft is a promising treatment option for thoracoabdominal aortic aneurysm (TAAA). A commercially available, multibranched, off-the-shelf endograft called the t-Branch stent graft has demonstrated favourable midterm outcomes. Another two investigational off-the-shelf endografts, the GORE EXCLUDER Thoracoabdominal Branch Endoprosthesis and E-nside multibranch stent graft system, are still being developed. However, these three endografts have an unsatisfactory anatomic feasibility rate in patients with TAAA. Based on the concept of Guo's renovisceral artery reconstruction-1, a novel, multibranched, off-the-shelf endograft with different configurations has been developed.</AbstractText>This prospective, multicentre, single-arm, cohort study will enrol 73 patients with TAAA. Preoperative and postoperative clinical data, as well as CT angiography images at each follow-up timepoint, will be analysed to evaluate the safety and efficacy of this novel, multibranched, off-the-shelf endograft for the treatment of TAAA. The primary safety end point is the major adverse event rate within 30 days after index endovascular aortic repair, including all-cause death, hepatic failure, bowel necrosis, renal failure, stroke, permanent paraplegia, cardiac infarction and respiratory failure. The primary efficacy end point is the successful treatment rate within 12 months after procedure, which is a composite of immediate technical success and no secondary surgical intervention related to TAAA within 12 months after the procedure.</AbstractText>The protocol has been reviewed and approved by the ethics committee of Chinese PLA General Hospital (reference number: 2021-NO.-007) and each participating hospital. The findings of this study will be disseminated through conference presentations, peer-reviewed journal publications and social media.</AbstractText>NCT05054985.</AbstractText>&#xa9; Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.</CopyrightInformation>
Giant, partially-thrombosed basilar artery (BA) aneurysms are extraordinarily difficult to treat. Due to the high risk of rupture exclusion of these aneurysms from the circulation is imperative. In certain instances, direct clipping is unsuitable, and high-flow bypass and proximal parent vessel clip occlusion is required. We report a case of a recurrent partially-thrombosed giant BA apex aneurysm treated with endovascular stent-coiling through a previous radial artery bypass graft. Following the initial bypass and aneurysm trapping six years prior, the patient was neurologically stable until three months prior to admission when he developed new diplopia and left third nerve palsy. Imaging studies demonstrated interval enlargement of the thrombosed portion of the aneurysm and increased size in the filling portion of the aneurysm. In the present case, the existing radial artery bypass graft between left VA and left PCA permitted successful stent-assisted embolization of the recurrent BA aneurysm. To our knowledge, this is the first published case of endovascular stent-coiling of a BA aneurysm through a radial artery bypass graft. This novel technique can be a useful alternative for endovascular aneurysm treatment in these challenging lesions.
Hypertrophic cardiomyopathy (HCM) is a disease of the myocardium caused by mutations in sarcomeric proteins with mechanical roles, such as the molecular motor myosin. Around half of the HCM-causing genetic variants target contraction modulator cardiac myosin-binding protein C (cMyBP-C), although the underlying pathogenic mechanisms remain unclear since many of these mutations cause no alterations in protein structure and stability. As an alternative pathomechanism, here we have examined whether pathogenic mutations perturb the nanomechanics of cMyBP-C, which would compromise its modulatory mechanical tethers across sliding actomyosin filaments. Using single-molecule atomic force spectroscopy, we have quantified mechanical folding and unfolding transitions in cMyBP-C domains targeted by HCM mutations that do not induce RNA splicing alterations or protein thermodynamic destabilization. Our results show that domains containing mutation R495W are mechanically weaker than wild-type at forces below 40 pN and that R502Q mutant domains fold faster than wild-type. None of these alterations are found in control, nonpathogenic variants, suggesting that nanomechanical phenotypes induced by pathogenic cMyBP-C mutations contribute to HCM development. We propose that mutation-induced nanomechanical alterations may be common in mechanical proteins involved in human pathologies.
Extending Ba&#x15f;ar's theory of event-related EEG oscillations, here we hypothesize that even in quiet wakefulness, transient increases in delta rhythms may enhance global cortical arousal as revealed by the desynchronization of alpha rhythms in normal (Nold) seniors with some derangement in Alzheimer's disease dementia (ADD). Clinical and EEG datasets in 100 ADD and 100 Nold individuals matched as demography, education, and gender were taken from an international archive. Standard delta (&lt; 4&#xa0;Hz) and alpha1 (8-10.5&#xa0;Hz) bands were used for the main analysis, while alpha2 (10.5-13&#xa0;Hz), theta (4-8&#xa0;Hz), beta1 (13-20&#xa0;Hz), beta2 (20-35&#xa0;Hz), and gamma (35-40&#xa0;Hz) served as controls. In the interpretation, the higher the alpha1 power (density), the lower that arousal. As expected, when compared to the Nold group, the ADD group showed higher global (scalp) power density at the delta-theta band and lower global power density at the alpha-beta bands. As novel findings, we observed that: (1) in the Nold group, the global delta and alpha1-2 power were negatively and linearly correlated; (2) in the ADD group, this correlation was just marginal; and (3) in both Nold and AD groups, the EEG epochs with the highest delta power (median value for stratification) were associated with the lowest global alpha1 power. This effect was related to eLORETA freeware solutions showing maximum alpha1 source activations in posterior cortical regions. These results suggest that even in quiet wakefulness, delta and alpha rhythms are related to each other, and ADD partially affects this cross-band neurophysiological mechanism.
HMG-CoA reductase inhibitors (statins) have antiatherogenic effects beyond their cholesterol-lowing effect. Whether atorvastatin has a stronger antioxidant effect than other statins is uncertain.</AbstractText>To determine the effects of simvastatin and atorvastatin on markers of oxidative stress in patients with coronary heart disease (CHD).</AbstractText>This study was comprised of 164 patients with CHD and a control population of 122 healthy subjects. The patients with CHD were divided into 2 groups and treated with either simvastatin 20 mg/day or atorvastatin 10 mg/day. The markers of oxidative stress were measured before and after 12 weeks of treatment.</AbstractText>The effects of atorvastatin on reducing oxidative stress were significantly greater compared with those of simvastatin (P &lt; 0.05). The changes in the markers of oxidative stress did not correlate with the changes in the plasma lipid profile (P &gt; 0.05).</AbstractText>This study suggests that atorvastatin reduces oxidative stress more effectively than simvastatin.</AbstractText>Copyright 2010 Wiley Periodicals, Inc.</CopyrightInformation>
The diagnostic and therapeutic strategy for acute pulmonary thromboembolism (APTE) was published by the Japanese Circulation Society. But in Japan, there has been no report on how to improve the pre-test probability in APTE-suspected cases, to determine a practically available diagnostic strategy, nor has been a report that compares diagnostic methods and therapies for APTE by decision analysis.</AbstractText>APTE was found in 66.7% before using diagnostic imaging techniques. Compared with the absence of APTE, prolonged immobilization, cancer, tachycardia, unilateral leg swelling and inverted T-wave in V(1-3) were found more often in the presence of APTE. The rate of obtaining the result on the day of ordering the examination test was 100% with arterial blood gas analysis, trans-thoracic echocardiography and computed tomography (CT), 78.2% in D-dimer, 85.5% in pulmonary angiography, and 54.5% in perfusion lung scan. Decision analysis showed that the highest expected utility was anticoagulant over 0.51 in pre-test probability, with CT between 0.13 and 0.51.</AbstractText>The pre-test probability of APTE has already been high before using specific diagnostic imaging techniques in Japan. Our results showed that the diagnostic strategy for APTE made by the Japanese Circulation Society was available in most hospitals in Japan.</AbstractText>
To report the use of a branched, balloon-deployable stent-graft to treat abdominal aortic aneurysm (AAA) in the setting of a solitary kidney.</AbstractText>A 72-year-old man with a solitary intrapelvic kidney and multiple comorbid conditions was diagnosed with an asymptomatic 5.3-cm abdominal aortic aneurysm (AAA); the renal artery emerged from the aneurysm sac. A customized branched, balloon-deployable, aortomonoiliac stent-graft was utilized to exclude the AAA and preserve perfusion to the single renal artery. A synthetic bypass was then implanted to restore perfusion to the contralateral limb. The diameter of the aneurysm decreased from 5.3 to 2.7 cm at 18 months. The renal artery was patent without evidence of stenosis; renal function was normal.</AbstractText>The deployment of a novel branched stent-graft represents an interesting alternative approach to the treatment of a juxtarenal aneurysm.</AbstractText>
Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors reduce low-density lipoprotein (LDL) cholesterol and cardiovascular event rates, yet due to their high price remain underutilized and difficult to prescribe in clinical practice. In March 2018, their price was significantly reduced. We evaluated whether the price reduction would improve prescribing patterns of PCSK9 inhibitors in eligible patients with atherosclerotic cardiovascular disease (ASCVD).</AbstractText>We identified the number of eligible ASCVD patients and those prescribed a PCSK9 inhibitor for each year between July 2015 and December 2019. Patient demographics and clinical characteristics for those prescribed a PCSK9 inhibitor were extracted from their electronic health record.</AbstractText>In total 1059 patients of eligible patients received a new prescription for a PCSK9 inhibitor. From 2015 to 2019, the rate of new prescriptions among eligible patients increased from 0.5 to 3.3% (p</i> &lt; 0.001) and continuation rates increased from 18 to 60% (p</i> &lt; 0.001). Following the price reduction, patients who were prescribed a PCSK9 inhibitor were younger and more likely to be female, but less likely to have Medicare insurance.</AbstractText>Despite the reduction in the cost of PCSK9 inhibitors, most eligible patients are not prescribed one. The reduction in cost has improved adherence, primarily in patients with commercial insurance. Older patients and those on Medicare still face significant barriers in accessing a PCSK9 inhibitor. Further reductions in the price of the PCSK9 inhibitors are needed as is further study of the barriers that exist in prescribing one.</AbstractText>
Maladaptive neuroplasticity-related learned response in substance use disorder (SUD) can be ameliorated using noninvasive brain stimulation (NIBS); however, inter-individual variability needs to be addressed for clinical translation.</AbstractText>Our first objective was to develop a hypothesis for NIBS for learned response in SUD based on a competing neurobehavioral decision systems model. The next objective was to develop the theory by conducting a computational simulation of NIBS of the cortico-cerebello-thalamo-cortical (CCTC) loop in cannabis use disorder (CUD)-related dysfunctional "cue-reactivity"-a construct closely related to "craving"-that is a core symptom. Our third objective was to test the feasibility of a neuroimaging-guided rational NIBS approach in healthy humans.</AbstractText>"Cue-reactivity" can be measured using behavioral paradigms and portable neuroimaging, including functional near-infrared spectroscopy (fNIRS) and electroencephalogram (EEG) metrics of sensorimotor gating. Therefore, we conducted a computational simulation of NIBS, including transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS) of the cerebellar cortex and deep cerebellar nuclei (DCN) of the CCTC loop for its postulated effects on fNIRS and EEG metrics. We also developed a rational neuroimaging-guided NIBS approach for the cerebellar lobule (VII) and prefrontal cortex based on a healthy human study.</AbstractText>Simulation of cerebellar tDCS induced gamma oscillations in the cerebral cortex, while transcranial temporal interference stimulation induced a gamma-to-beta frequency shift. A preliminary healthy human study (N = 10) found that 2 mA cerebellar tDCS evoked similar oxyhemoglobin (HbO) response in the range of 5 &#xd7; 10-6</sup> M across the cerebellum and PFC brain regions (&#x3b1; = 0.01); however, infra-slow (0.01-0.10 Hz) prefrontal cortex HbO-driven phase-amplitude-coupled (PAC; 4 Hz, &#xb1;2 mA (max)) cerebellar tACS evoked HbO levels in the range of 10-7</sup> M that were statistically different (&#x3b1; = 0.01) across these brain regions.</AbstractText>Our healthy human study showed the feasibility of fNIRS of cerebellum and PFC and closed-loop fNIRS-driven ctACS at 4 Hz, which may facilitate cerebellar cognitive function via the frontoparietal network. Future work needs to combine fNIRS with EEG for multi-modal imaging for closed-loop NIBS during operant conditioning.</AbstractText>