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The connections between domestic abuse, gun violence, and murder have received substantial media attention in recent months in the aftermath of numerous mass shootings. It seems that in the weeks [...]

Chronic stress has become a predominant factor associated with a variety of psychiatric disorders, such as depression and anxiety, in both human and animal models. Although multiple studies have looked at transcriptional changes after social defeat stress, these studies primarily focus on bulk tissues, which might dilute important molecular signatures of social interaction in activated cells. In this study, we employed the Arc-GFP mouse model in conjunction with chronic social defeat (CSD) to selectively isolate activated nuclei (AN) populations in the ventral hippocampus (vHIP) and prefrontal cortex (PFC) of resilient and susceptible animals. Nuclear RNA-seq of susceptible vs. resilient populations revealed distinct transcriptional profiles linked predominantly with neuronal and synaptic regulation mechanisms. In the vHIP, susceptible AN exhibited increased expression of genes related to the cytoskeleton and synaptic organization. At the same time, resilient AN showed upregulation of cell adhesion genes and differential expression of major glutamatergic subunits. In the PFC, susceptible mice exhibited upregulation of synaptotagmins and immediate early genes (IEGs), suggesting a potentially over-amplified neuronal activity state. Our findings provide a novel view of stress-exposed neuronal activation and the molecular response mechanisms in stress-susceptible vs. resilient animals, which may have important implications for understanding mental resilience.

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The human behaviors are varying depends on the DNA module presents in generation of human life styles. Increasing disease factors in due to DNA from history of family members continuously affects the present’s life. In the sense, the Colon Cancer (CC) is one of the deadliest diseases having the damaged cells to affect the human gene cells to damage cause deaths. The most case limitations uncovered from existing level is non mutual feature selection due to non-impact feature margin decrease the precision and identification accuracy. To resolve this problem, we propose a genetics sequence linear support vector (GSLSV) based feature selection with adaptive ensemble boosting fuzzified deep neural network (AEB-FDNN) to identify the colon cancer. Initially the preprocessing is carried by Box-plot normalization process (Bp-Np) to make noise less transformation. Then synthetic minority oversampling technique (SMOsT) is applied to identify the mutual relational features weight which is support for identifying cancer impact margins. Then colon cancer periodic influence rate (CCPIR) is applied to find the disease affection rate. With the support of marginal weights, the GSLSV based feature selection is applied to select the relation mutual features. Then the selected features is applied using AEB-FDNN to identify the CC based on the risk by class. The proposed system effectively train the dataset by improving the testing and validating accuracy as well higher performance in precision, recall rate, f1-measure and identification accuracy compared to the other system.

This article is concerned with a migration primarily from urban areas of the New York City-Philadelphia corridor to rural north-central Pennsylvania, and especially to the small city of Williamsport. In [...], A 'recovery immigration' of about 300 persons per year from urban Pennsylvania to 'sobriety houses' in a small city, Williams-port, attracted local notice in the late 1980s as African-Americans became more prominent in the 'influx.' While openly racist local reactions have been contained, all local factions now agree on the desirability of limiting further migration.

ABSTRACTIn this paper, we examine the itinerary of the objects and the agencies involved in the construction of the collections of ethnographic artefacts gathered by German ethnographer and priest Martin Gusinde during his fieldtrips to Tierra del Fuego (Argentina and Chile), carried out between 1918 and 1924. In order to study the formation processes of these collections, we will trace the agencies of the Selk´nam, Yagan and Kawésqar Indigenous people in the making, selling, trading or withholding of their material culture, showing the differential impact these had on the collections. We retrace the dispersal of these Fuegian collections into five museums located in Chile, Austria and the Vatican, presenting a reservoir unknown until now. Our exploration of the complex networks of social and material interactions involved in the dynamic biography of these Fuegian ethnographic collections sheds light on the active role of the Indigenous people in their construction.

The effect of nonporous (NP-PCL) and porous (P-PCL) fibrous polycaprolactone (PCL) meshes, used as templates, on in vitroCaCO3crystallization via a gas diffusion (GD) method at 20 °C for 24 h was studied. The nonporous random (NPR-PCL) and porous random (PR-PCL) and the nonporous-aligned (NPA-PCL) and porous-aligned (PA-PCL) fibrous PCL meshes were directly spun on flat or rotary collectors from 18% PCL solutions using ethyl acetate/acetone or ethyl acetate/dimethyl sulfoxide, respectively. The morphology and type of CaCO3crystal grown on PCL fiber scaffolds were analyzed by Fourier transform infrared spectroscopy (FTIR), contact angle measurements, scanning electron microscopy coupled with energy dispersive X-ray spectroscopy (SEM-EDS), focused ion beam combined with scanning electron microscopy (FIB-SEM), and X-ray diffraction (XRD) techniques. The PCL fibers distributions affected the nucleation and stabilized calcite and vaterite polymorphs of CaCO3with different crystal population densities. The crystal density of vaterite was higher than calcite (2:1) when the NPA-PCL and PA-PCL fibers were used as a template, but calcite predominated (2:1) on P-PCL fiber mesh with respect to the NP-PCL fiber mesh. We found that CaCO3crystals covered the surface of PCL fibers, and some of them grown from inside of the PCL fibers showed that PCL fibers were occluded inside the CaCO3crystals during the GD crystallization. The nano- and microscale topological features of PCL scaffolds control the diffusion of carbon dioxide (CO2) gas through PCL fiber meshes in the soaking of PCL meshes into a calcium chloride (CaCl2) solution during the GD crystallization affecting subsequently the nucleation and growth of CaCO3crystals. Indeed, pore size feature of the micrometric A-PCL and nanometric R-PCL fiber meshes affected the intensities of the crystallographic faces of calcite and vaterite as observed by XRD. Contact angle measurements of the aqueous and crystallization liquid droplet on NPR-PCL, PR-PCL and A-PCL fibrous showed different hydrophobic character of the PCL meshes. This study shows the role of the nano- and microscale topological features and the presence of pores on PCL fiber scaffolds on the mineralization behavior of CaCO3deposited on R-PCL and A-PCL fiber scaffolds, and by this approach various aspects of controlled CaCO3crystallization such as nucleation and crystal growth of biomaterials based on CaCO3can be studied with potential biotech applications.

Children with single ventricle cardiac disease (SVCD) have poor growth in early life. Tube‐assisted feeding (TF) is used to improve weight gain, but its impact on long‐term growth remains unknown. We sought to compare the longitudinal growth of SVCD patients receiving TF after initial cardiac surgery with those fed entirely by mouth. We conducted a retrospective cohort study of SVCD patients who underwent initial surgical palliation between 1999 and 2009. We defined TF as the use of nasogastric, gastrostomy, or jejunostomy TF. We compared maximal attained growth z‐scores for each year of life between TF and non‐TF patients. A secondary analysis compared surgical and clinical factors between groups. A total of 134 patients were included; 64% were male and 68% underwent the Norwood operation. One third of patients (44) received TF. Adjusting for age, TF patients had an average of 0.56 lower weight‐for‐age z‐score (WAZ) than non‐TF patients (P= 0.007) through the age of 6 years. Longitudinal height was not affected by TF status (P= 0.15). In a subanalysis of Norwood patients, TF patients had lower WAZ at initial hospital discharge despite longer LOS. TF patients had diminished WAZ after adjusting for complications, interstage hospitalizations, and timing of subsequent operations. In this single‐center study, patients with SVCD requiring TF at discharge from initial surgical palliation had diminished WAZ at discharge and on long‐term follow‐up, despite controlling for other identifiable risk factors. Further investigation is needed to understand the mechanisms underlying this phenomenon and to risk stratify infants who go home on TF.

AbstractCell migration, a fundamental process in development, wound healing, and immune function, is a common topic in undergraduate cell biology courses. We developed laboratory exercises with an inquiry-based learning (IBL) approach in which cell migration could be examined with the scratch assay, adapted from the primary literature. A narrow scratch was created in a confluent monolayer of cells growing on the bottom of a cell culture dish. Migration into the resultant cell-free zone from both sides of the scratch was measured after one day using the scale bar function of a digital camera. The Chinese hamster ovary cell line was used, but any adherent cell type could be examined. Students used the scratch assay to formulate hypotheses and design experiments in which variables affecting cell migration could be investigated. For example, the effect of cytoskeletal disruption was evaluated by adding the microtubule- and microfilament-disrupting drugs, colcemid and phallacidin, respectively, to the growth medium when the scratch was made. Optimal drug concentration parameters were determined for students to reference. Low drug concentrations inhibited cell migration, while higher concentrations killed the cells. This study demonstrated that the scratch assay is an accessible IBL method for studying cell migration.

Objective: We aimed at summarizing current evidence about mechanisms for potentially harmful effects of Proton Pump Inhibitors (PPIs). Methods: A Pubmed search was performed, and 207 studies concerning the relationship between use of PPIs and cardiovascular diseases, kidney impairment, nutritional disorders, fractures, infections, functional decline, and mortality were selected and reviewed. Results: PPIs may cause potentially harmful effects by several mechanisms, including endothelial dysfunction, hypomagnesemia, drug interactions, reduced absorption of selected nutrients, increased gastric microbiota and small intestine bacterial overgrowth, reduced immune response, tubular-interstitial inflammation, increased bone turnover, accumulation of amyloid in the brain. Clinical and epidemiologic evidence is not consistent in regard to some negative outcomes during PPI treatment. Data from randomized clinical trials seem to deny most of them, but they are usually designed to investigate efficacy of drugs in ideal conditions and are not powered enough to detect adverse events. Besides being at special risk of experiencing negative outcomes during long-term treatment with PPIs, older and complex patients treated with polypharmacy regimens are persistently excluded from randomized clinical trials. Thus, large observational studies involving real-world patients should be considered as an important informative source about potential risks related to PPIs. Conclusions: Current evidence suggests that use of PPIs may be associated with negative outcomes by eliciting several different pathophysiologic mechanisms. While short-term PPIs could be considered effective and safe in adult patients with acid-related disorders, their long-term and often inappropriate use in patients carrying vulnerability to adverse events and/or high risk of drug-interactions should be avoided.

'WHAT IS YISRAEL Beitenu going to do about the idiotic decision on the part of the liberal Israeli High Court in allowing disloyal Arab parties to abuse our democracy and [...]

Subtalar joint arthrodesis is a procedure used in posttraumatic arthritis, osteoarthritis, tarsal coalition management, posterior tibial tendon dysfunction, and inflammatory arthropathies, and can be used in deformity correction. The goals of the procedure are to eliminate pain, improve function, restore stability, and realign the hind foot. The procedure has high patient satisfaction with low complications while preserving motion in adjacent tarsal joints. Joint preparation is important and time should be spent preparing the joint for successful arthrodesis and the fixation construct needs to be done well and effectively to provide a solid Arbeitsgemeinschaft für Osteosynthesefragen (AO) construct for good results.

Sinus venosus defects (SVD) of the inferior vena cava (IVC) type, or inferior SVDs, are an uncommon form of atrial communication located outside the confines of the fossa ovalis and involve override of the IVC. Despite numerous studies describing the anatomical and echocardiographic features of the inferior SVD, distinguishing this defect from a large secundum atrial septal defect (ASD) by echocardiography is often challenging. Accurate diagnosis of an inferior SVD and correct differentiation from a secundum ASD is essential for appropriate presurgical planning. Absence of the posterior rim in the parasternal short-axis views may serve as a useful clue in diagnosing inferior SVDs. We sought to determine the utility of using the presence or absence of a posterior atrial rim in the parasternal short-axis view to help distinguish an inferior SVD from a secundum ASD. This sign may help clinch the diagnosis when subcostal imaging is suboptimal.

Introduction:Children in need of heart transplant (Tx) have a high risk of death on the Tx waitlist due to scarcity of donor organs. Studies of previous eras have shown that ventricular assist devices (VADs) reduce waitlist mortality. We sought to determine whether a survival benefit for VAD patients persists in the current Tx allocation system.Methods:Using the Scientific Registry of Transplant Recipients database, we identified patients listed for primary Tx between 3/22/2016-9/1/2020. Characteristics at time of Tx listing were compared between VAD and non-VAD groups. Cox proportional hazards models were used to identify risk factors for one-year Tx waitlist mortality.Results:Among 5,054 total patients, 764 (15%) had a VAD at time of Tx listing. The VAD group was older, heavier, and had higher prevalence of cardiomyopathy, mechanical ventilation (MV), and impaired renal function. Unadjusted waitlist mortality was similar between the VAD and non-VAD groups (p=0.55, Figure), with the curves crossing ~90 days after listing. A multivariable Cox model showed infant age (HR 2.94, 95% CI 2.26-3.81), Black race (HR 1.59, 95% CI 1.33-1.90), congenital heart disease (HR 1.37, 95% CI 1.56-1.62), renal impairment (HR 2.62 95% CI 2.15-3.19), IV inotropes (HR 1.19, 95% CI 1.01-1.40) and MV (HR 2.58, 95% CI 2.13-3.13), were associated with one-year waitlist mortality. VAD use was not associated with mortality in the first 90 days after Tx listing (HR 0.87, 95% CI 0.65-1.18) but was protective for those waiting ≥90 days (HR 0.40, 95% CI 0.24-0.66).Conclusions:VADs reduce waitlist mortality in the current era, but only for those waiting ≥90 days after Tx listing. Potentially modifiable risk factors, including MV and renal impairment, are associated with mortality. These findings suggest that Tx listing without VAD may be a reasonable option if a short waitlist time is anticipated. However, VAD use may confer benefits, particularly for those expected to wait more than 90 days.

Mobility-disability is a common condition in older individuals. Many factors, including the age-related hormonal dysregulation, may concur to the development of disability in the elderly. In fact, during the aging process it is observed an imbalance between anabolic hormones that decrease (testosterone, dehydroepiandrosterone sulphate (DHEAS), estradiol, insulin like growth factor-1 (IGF-1) and Vitamin D) and catabolic hormones (cortisol, thyroid hormones) that increase. We start this review focusing on the mechanisms by which anabolic and catabolic hormones may affect physical performance and mobility. To address the role of the hormonal dysregulation to mobility-disability, we start to discuss the contribution of the single hormonal derangement. The studies used in this review were selected according to the period of time of publication, ranging from 2002 to 2013, and the age of the participants (≥65 years). We devoted particular attention to the effects of anabolic hormones (DHEAS, testosterone, estradiol, Vitamin D and IGF-1) on both skeletal muscle mass and strength, as well as other objective indicators of physical performance. We also analyzed the reasons beyond the inconclusive data coming from RCTs using sex hormones, thyroid hormones, and vitamin D (dosage, duration of treatment, baseline hormonal values and reached hormonal levels). We finally hypothesized that the parallel decline of anabolic hormones has a higher impact than a single hormonal derangement on adverse mobility outcomes in older population. Given the multifactorial origin of low mobility, we underlined the need of future synergistic optional treatments (micronutrients and exercise) to improve the effectiveness of hormonal treatment and to safely ameliorate the anabolic hormonal status and mobility in older individuals.

The effect of low sample frame rate on interpretability is often confused with the impact it has on encoding processes. In this study, the confusion was avoided by ensuring that none of the low-frame rate clips had coding artifacts. Under these conditions, the lowered frame rate was not associated with a statistically significant change in interpretability. Airborne, high definition 720P, 60 FPS video clips were used as source material to produce test clips with varying sample frame rates, playback rates, and degrees of target motion. Frame rates ranged from 7.5 FPS to 60 FPS. Playback rates ranged up to 8X normal speed. Target motion ranged from near zero MPH up to 300 MPH.

Introduction:Children with dilated cardiomyopathy (DCM) are increasingly bridged to heart transplant (Tx) with intracorporeal continuous flow ventricular assist devices (VADs), but there continues to be variability in hospital discharge. We sought to assess the impact of a quality improvement (QI) project promoting hospital discharge in pediatric VAD patients with DCM.Methods:Patients enrolled at sites participating in the Discharge and De-Escalation QI project of the Advanced Cardiac Therapies Improving Outcomes Network (ACTION) registry were eligible. Patients with a HeartWare (HVAD) or HeartMate3 (HM3) VAD, implanted between April 2018 and February 2021, were included. Patient characteristics and outcomes were compared before and after the QI initiative, which targeted team and family expectations, was implemented in November 2019.Results:There were 85 patients (75%) with DCM and/or myocarditis who were included in this study (median age 14 years; median weight 57.1 kg; 67% male). Among 57 patients in the baseline group, 56% (n=32) were discharged with a mean post-implant hospital length of stay (LOS) of 36 days and 44% (n=25) underwent Tx during index VAD admission, with a mean of 52 days on device. There were 28 patients in the intervention group; 64% (n=18) were discharged with a mean LOS of 45 days, while 29% (n=8) patients underwent Tx during index VAD admission, with a mean of 44 hospital days on device. There was no significant difference in the frequency of hospital discharge or in hospital LOS between groups.Conclusions:Pediatric centers discharged just over half of DCM patients supported on an HVAD or HM3, with nearly one third of patients undergoing transplant during the index VAD admission. The QI intervention did not significantly alter the discharge rate. Further work is required to understand practice variation between centers with respect to Tx listing and organ acceptance for children on intracorporeal continuous flow VADs.

Background:Ventricular assist devices (VAD) are increasingly used in children with end-stage heart failure. Bleeding is a major complication of VAD, but most reports have focused on central nervous system (CNS) bleeding. Our objective was to determine the incidence & consequences of non-CNS bleeding in pediatric VADs.Methods:We examined adverse events (AE) & outcomes of all patients implanted with a VAD at Advanced Cardiac Therapies Improving Outcomes Network (ACTION) centers between 9/2018-5/2021. Major bleeding event (MBE) was defined as an episode of suspected bleeding resulting in death, reoperation, hospitalization or blood transfusion (>7days after implant). Variables were analyzed using chi square & Mann Whitney test and outcomes were assessed by Kaplan Meier (KM) survival curves.Results:A total of 407 patients were prospectively enrolled in the ACTION registry, of which 82 (20.1%) had a MBE. The median duration of support was 72 days (range 6-1101). MBE was most common in paracorporeal continuous flow devices (42/82 devices, 51%). MBE was gastrointestinal in 30.3% & thoracic in 38.5%. Patients with MBE were more likely to have congenital heart disease (CHD) or previous cardiac operation & were less likely to have had VAD as a bridge to transplant (Table). Within 14 days post MBE, 31 subjects had another major AE (14 major infection, 13 another MBE, 2 stroke and 1 device malfunction). Unadjusted survival in patients with MBE was significantly worse than those without (p<0.001) (Figure).Conclusion:MBE after VAD implant was seen in 20% of pediatric VAD patients, a higher proportion of whom had CHD. MBE was associated with other major AEs post-VAD and also with worse survival.

BACKGROUND: Cardiogenic shock (CS) is a dreadful complication of acute myocardial infarction (AMI) associated with a poor prognosis. Percutaneous coronary intervention (PCI) is widely recommended by current treatment guidelines. AIM: To evaluate the in-hospital and 30-day mortality rate and to determine independent predictors of mortality in a cohort of unselected consecutive patients with CS. METHODS AND RESULTS: Rabin Medical Center cardiac catheterization laboratory database was analyzed between 1/2000 and 8/2003. Fifty of the 472 patients (10.6%) treated using emergent PCI for AMI had cardiogenic shock on presentation. Patients with cardiogenic shock were older, more likely to be female and with higher frequency of co-morbidities. The time from symptom onset until seeking medical treatment was longer in cardiogenic shock patients. In-hospital mortality rate was 48.0% in the cardiogenic shock group as compared to 3.3% in the non-cardiogenic shock group (P<0.0001). In patients with shock, total mortality after 30 days was 52% (26/50). Most of these patients (25/26) died within 48hours following admission because of refractory cardiogenic shock. A multivariate analysis adjusted for baseline differences showed that age ≥75 years (odds ratio [OR]: 11; 95% confidence interval [CI]: 1.0–1.24, P = 0.05), and the use of GP 2b/3a antagonist (OR: 0.97; 95% CI: 0.95–1.0, P = 0.05), were independent predictors of all cause mortality at 30 days. CONCLUSION: Cardiogenic shock remains an important cause of mortality in AMI. Younger age and the use of GP 2b/3a antagonists during primary PCI for cardiogenic shock patients seems to be associated with better clinical outcomes.

BACKGROUND: Cardiogenic shock (CS) is a dreadful complication of acute myocardial infarction (AMI) associated with a poor prognosis. Percutaneous coronary intervention (PCI) is widely recommended by current treatment guidelines. AIM: To evaluate the in‐hospital and 30‐day mortality rate and to determine independent predictors of mortality in a cohort of unselected consecutive patients with CS. METHODS AND RESULTS: Rabin Medical Center cardiac catheterization laboratory database was analyzed between 1/2000 and 8/2003. Fifty of the 472 patients (10.6%) treated using emergent PCI for AMI had cardiogenic shock on presentation. Patients with cardiogenic shock were older, more likely to be female and with higher frequency of co‐morbidities. The time from symptom onset until seeking medical treatment was longer in cardiogenic shock patients. In‐hospital mortality rate was 48.0% in the cardiogenic shock group as compared to 3.3% in the non‐cardiogenic shock group (P<0.0001). In patients with shock, total mortality after 30 days was 52% (26/50). Most of these patients (25/26) died within 48 hours following admission because of refractory cardiogenic shock. A multivariate analysis adjusted for baseline differences showed that age ⩾75 years (odds ratio [OR]: 11; 95% confidence interval [CI]: 1.0–1.24, P= 0.05), and the use of GP 2b/3a antagonist (OR: 0.97; 95% CI: 0.95–1.0, P= 0.05), were independent predictors of all cause mortality at 30 days. CONCLUSION: Cardiogenic shock remains an important cause of mortality in AMI. Younger age and the use of GP 2b/3a antagonists during primary PCI for cardiogenic shock patients seems to be associated with better clinical outcomes.

The increased concentration of adenosine triphosphate (ATP) in erythrocytes from patients with chronic renal failure (CRF) has been observed in many studies but the mechanism leading to these abnormalities still is controversial. It is believed that hyperphosphatemia and metabolic acidosis triggering enhanced reutilization of purine bases are the factors responsible for changes in erythrocyte nucleotide concentration. During the past decade we have performed several studies. A summary of the obtained results is presented. A high-performance liquid chromatography technique was used for the determination of plasma and intraerythrocyte nucleotide concentrations. Labeled adenine and adenosine were used for measuring adenine incorporation. In CRF patients treated conservatively increased concentrations of ATP levels and other nucleotides such as adenosine diphosphate were found. Adenosine monophosphate and hypoxanthine levels were lower than in controls. In hemodialyzed patients both ATP and adenosine monophosphate intraerythrocyte concentrations were higher than in controls. At the same time, adenosine monophosphate and hypoxantine level were comparable with levels in healthy people. The main pattern of nucleotides during hemodialysis remained unchanged, independent from the mode of therapy. The only exception was a decreased level of hypoxantine. Results of a consecutive study have suggested that the increased rate of adenine incorporation into the adenine nucleotide pool could be partially responsible for the increased ATP concentration in uremic erythrocytes. Last but not least, trying to elucidate the pathomechanism of adenine nucleotide disturbances in uremia, we have found that the concentration of N-methyl-2-pyridone-5-carboxamide (2PY), one of the end products of nicotinamide-adenine dinucleotide degradation, were enhanced in CRF patients to values that are potentially toxic. Our findings suggest that 2PY could be a novel uremic toxin. Disturbances of nucleotide metabolism are one of the important components of uremic syndrome.

ABSTRACTAccurate laboratory tests for the diagnosis of active human herpesvirus 8 (HHV-8) infection are becoming essential to study the pathogenesis of HHV-8-associated tumors and for the clinical management of HHV-8-infected individuals. We have developed a highly sensitive, calibrated quantitative real-time PCR assay for the measurement of cell-free HHV-8 DNA in body fluids, based on the addition of a synthetic DNA calibrator prior to DNA extraction. The calibrator controls each sample for the presence of PCR inhibitors, determines a cutoff value of sensitivity for negative samples, and normalizes positive samples for the efficiency of DNA recovery. The assay shows a wide dynamic range of detection (between 1 and 106viral genome equivalents/reaction) and a high degree of accuracy even in the presence of high amounts (up to 1 µg) of human genomic DNA. Moreover, the assay has a very high sensitivity (lower detection limit, 10 genome equivalents/ml) and a high degree of reproducibility and repeatability with a coefficient of variation (CV) of <15 and 23%, respectively. Furthermore, the use of the calibrator improves the accuracy of quantitation and decreases the intersample variability (CV, 9 and 6%, respectively). The sensitivity and specificity of the assay were tested with a series of clinical specimens obtained from patients affected by various HHV-8-related diseases, as well as from a wide number of controls. In conclusion, our calibrated real-time PCR assay provides a reliable high-throughput method for quantitation of HHV-8 DNA in clinical and laboratory specimens.

Patients with Kaposi’s sarcoma (KS) have a human herpesvirus-8 (HHV-8) load higher than patients without KS and present a CD8+ T-cell activation with production of Th1-type cytokines both in tissues and peripheral blood mononuclear cells (PBMC). Because in tissues of KS patients detection of inflammatory cytokines (IC) can precede detection of HHV-8 DNA and because signs of immunoactivation and/or dysregulation can precede KS development, we investigated the effect of IC on HHV-8 infection. To achieve this goal, PBMC and purified cell populations from 45 patients with KS and 45 patients at risk of KS were analyzed for HHV-8 DNA and/or gene expression and for cell survival, growth, and phenotype before or after culture with or without the IC increased in KS. The results indicate that PBMC that are polymerase chain reaction (PCR)-positive at day 0 generally loose the virus upon culture. However, the presence of IC maintains HHV-8 DNA load in cultured cells. In addition, IC increase viral load to detectable levels in PBMC from serologically positive patients that were PCR-negative before culture. ? Interferon is sufficient for these effects, whereas tumor necrosis factor and interleukin-6 have little or no activity. The increase of HHV-8 DNA by IC is observed after short-term (7 days) or long-term (28 days) culture of the cells and occurs in one or both of the two circulating cell types that are infected in vivo: B cells and monocytes. In both cases it is associated with lytic gene expression, suggesting that virus reactivation is one of the most likely mechanisms for the effect of IC on virus load. However, IC have also effects on the cells target of HHV-8 infection, because they increase B-cell survival and induce the growth and differentiation of monocytes into KS-like spindle cells with markers of endothelial macrophages. Because cells with markers of endothelial macrophages are present in blood and lesions from KS patients and are infected by HHV-8, these data may explain the high HHV-8 load associated with KS development and suggest that infected monocytes may carry the virus to tissues, transmit the infection, or differentiate in loco in spindle cells with endothelial macrophage markers.

ABSTRACTInfection by human herpesvirus 8 (HHV-8) is associated with the development of Kaposi’s sarcoma (KS). Since regression of KS can be achieved by treatment of the patients with alpha interferon (IFN-a), we analyzed the effects of IFN-a or anti-IFN-a antibodies (Ab) on HHV-8 latently infected primary effusion lymphoma-derived cell lines (BCBL-1 and BC-1) and on peripheral blood mononuclear cells (PBMC) from patients with all forms of KS and from at-risk subjects. IFN-a inhibited in a dose-dependent manner the amplification of HHV-8 DNA in BCBL-1 cells induced to lytic infection with tetradecanoyl phorbol acetate (TPA). This effect was associated with the inhibition of the expression of HHV-8 nut-1and kaposin genes that are induced early and several hours, respectively, after TPA treatment. In addition, IFN-a inhibited virus production and/or release from BCBL-1 cells. Inhibition of nut-1and kaposin genes by IFN-a was also observed in BC-1 cells induced with n-butyrate. Conversely, the addition of anti-IFN-a Ab to TPA-induced BCBL-1 cells resulted in a larger number of mature enveloped particles and in a more extensive cytopathic effect due to the neutralization of the endogenous IFN produced by these cells. IFN was also produced by cultured PBMC from HHV-8-infected individuals, and this was associated with a loss of viral DNA during culture. However, the addition of anti-IFN-a Ab or anti-type I IFN receptor Ab promoted the maintenance of HHV-8 DNA in these cells that was associated with the detection of the latency-associated kaposin RNA. Finally, the addition of IFN-a reduced the HHV-8 load in PBMC. Thus, IFN-a appears to have inhibitory effects on HHV-8 persistent infection of PBMC. These results suggest that, in addition to inhibiting the expression of angiogenic factors that are key to KS development, IFN-a may induce KS regression by reducing the HHV-8 load and/or inhibiting virus reactivation.

Nous avons étudié par diffraction et microscopie électroniques la croissance de dépôts de bismuth préparés par vaporisation thermique sur des supports amorphes et sur des faces de clivage d'halogénures alcalins maintenus à la température ambiante.

Summary: Fifty-four specimens of heart with persistent truncus arteriosus (PTA) were reviewed anatomically. According to the Collett-Edwards classification [11] there were 28 examples of type I and 26 type II. The sex distribution was equal. The number of the truncal cusps ranged from one to four (42% tricuspid, 30% bicuspid, 24% quadricuspid, and 4% unicommissural). A unicommissural truncal valve has not been previously reported. In 72% of cases, the truncal valve leaflets were thickened or dysplastic. Two valves were stenotic. The truncus arteriosus originated from both ventricles equally in 42% of the cases, predominantly from the right ventricle in 42%, and predominantly from the left ventricle in 16% of the cases. In unoperated cases of PTA originating predominantly from the right ventricle, it appeared to us that usual operative correction might result in left ventricular outflow obstruction. Variations in coronary arterial origins and patterns were present in nearly half of the cases. A single coronary artery was observed in ten cases (18.5%). Stenosis of the ostium of one coronary artery was seen in each of four cases (7%). High posterior origin of the left coronary artery was observed in ten cases (18.5%). Among the associated cardiovascular anomalies, the most common were right aortic arch (36%) and interruption of the aortic arch (11%). Three cases with the latter condition exhibited crossed pulmonary arteries. Isolated cases with tricuspid atresia, vascular sling (left pulmonary artery arising from right pulmonary artery), and persistent common atrioventricular canal were encountered.

Using high-performance liquid chromatography, concentrations of erythrocyte adenine nucleotides and hypoxanthine were evaluated in patients undergoing regular acetate hemodialysis before dialysis, immediately following dialysis, and 24 hr after. It was shown that adenosine triphosphate concentration was maintained consistently high, not only just after hemodialysis but also 24 hr later. There was also no difference in concentration of mono- and diphosphates of adenosine. Hypoxanthine concentration decreased twofold after hemodialysis. However, it was still markedly higher than normal values. The level of hypoxanthine was maintained at the postdialysis level, 24 hr later. This suggests that hypoxanthine production could be stimulated during acetate dialysis.

Simultaneous inflation of two balloons may be necessary for balloon dilation valvuloplasty in patients with a large annulus. We examined the cardiovascular effects of dilating the pulmonary annulus with two balloons in 18 normal dogs using pulsed Doppler ultrasound and gross and microscopic examination. When the ratio of the cross-sectional area (CSA) during dilation to the CSA of the pulmonary annulus was between 1.04 and 1.28, there was valvar regurgitation in only one dog, in which catheter manipulation was complicated by heartworms, and damage was confined to intimal changes. (The dog was killed 24 hours after dilation.) With ratios between 1.67 and 1.76 (equal to the CSA of a single balloon with a diameter 33 greater than the annulus), there was trivial or mild tricuspid or pulmonary regurgitation, and anatomic changes were more prominent but still superficial. Two animals killed after nine days had resolution of valvar regurgitation and healing damage. With CSA ratios greater than 2.00 or with balloon rupture, myocardial damage and laceration of the pulmonary arteries resulted. Simultaneous inflation of two balloons within the right ventricular outflow tract with CSA ratios of up to 1.76 results in minimal cardiovascular trauma.

Five cases are described in which noninflammatory pulmonary arterial aneurysmal disease existed. In each case, severe pulmonary hypertension had been present. In one (woman, age 50 years), the pulmonary hypertension was of the primary type, while in each of the others, congenital heart disease was an underlying condition (atrial septal defect in three cases; each woman, age range 35 to 56 years) and complete transposition in the remaining case (boy, age ten). In one case with atrial septal defect, saccular aneurysm involving each major pulmonary arterial branch was considered to have resulted from atherosclerotic disease. In each of the remaining cases, cystic medial necrosis was present, and the aneurysmal disease was the result of laceration of a major pulmonary arterial segment. In one of the cases with atrial septal defect, the laceration was recent and extended through the full thickness of the pulmonary trunk in a circumferential manner. In the remaining three cases, lacerations were usually old and had not extended through the full thickness of the involved arterial segments. Saccular aneurysm formation (usually multiple) had resulted from weakness of the wall as a result of laceration and retraction of tissue.

Several letters to the editor are presented in response to the article "How to Make $100,000 Per Year," by Meagan Holub in the November 2010 and December 2010 issues.

Several letters to the editor is presented in response to article published in previous issues including "Preserve Thai Massage" in February 2008, "The Truth About Massage Franchises" in the February 2008 issue, and "Medical Model is Not Desirable" in March 2008.

Supplemental Digital Content is available in the text.

A unique case of aortic atresia and tricuspid atresia associated with transposition of the great vessels is described in a newborn infant. The clinical, echocardiographic, and heart catheterization data are presented. The embryological and surgical implications are discussed.