Long-Term Follow-Up of Pediatric Patients After Congenital Coronary Artery Fistula Closure.
The surgical closure of congenital coronary artery fistulas (CAF) is associated with excellent immediate outcomes. Few studies have investigated the long-term prognosis in patients who have undergone surgery for the closure of CAF or differentiated among types of CAF or types of surgical procedures. In this study, we performed clinical examinations and computed tomography angiography (CTA) to characterize outcomes after CAF closure in pediatric patients. The medical records of 79 pediatric patients who underwent surgical closure of CAF were retrospectively reviewed. The median age of the patients included in the study at the time of surgery was 3.4 years (range 0.2 to 15.3 years). The patients had been followed up for 11 years (range 1 to 17 years) with electrocardiography, echocardiography, and coronary CTA. There were 67 medium-to-large CAF and 12 small CAF. Twenty-six (32.9%) CAF arose from the branch coronary artery (proximal type); the others arose from the parent coronary artery (distal type). The surgical procedure included endocardial closure in 16 cases, epicardial distal ligation in 51 cases, epicardial proximal and distal ligation in 12 cases. There was no instance of perioperative death among the cases included in the study. Twenty-eight patients were treated with antiplatelet medication postoperatively. No patient required re-operation during the follow-up period. Coronary thrombi were detected in 27 patients (34.2%). There was no instance of myocardial ischemia related to thrombosis. Among the patients with thrombosis, 26 had medium-to-large CAF (96.3%), and 23 had distal-type CAF (85.2%). Average age at surgery was higher among the patients with thrombosis than among the patients without thrombosis (7.4 years vs. 3.3 years, t = 5.509, P = 0.000). Among the patients with distal-type CAF, thrombosis was more common among the patients treated with ligation than treated with endocardial closure (41.5% vs. 16.7%, χ2 = 3.742, P = 0.043). There was no difference in risk for thrombosis between the patients who did vs. did not receive antiplatelet therapy (P = 0.436). The most common complication after CAF closure was thrombosis. Increased risk for thrombosis was associated with large fistulae, distal-type CAF, and older age at presentation. Antiplatelet treatment did not appear to decrease the risk of thrombosis. Among patients with distal-type CAF, risk for thrombosis was lower among patients treated with endocardial closure, compared with patients treated with epicardial ligation.


Insulin therapies: Current and future trends at dawn.
Insulin is a key player in the control of hyperglycemia for type 1 diabetes patients and selective individuals in patients of type 2 diabetes. Insulin delivery systems that are currently available for the administration of insulin include insulin syringes, insulin infusion pumps, jet injectors and pens. The traditional and most predictable method for the administration of insulin is by subcutaneous injections. The major drawback of current forms of insulin therapy is their invasive nature. To decrease the suffering, the use of supersonic injectors, infusion pumps, sharp needles and pens has been adopted. Such invasive and intensive techniques have spurred the search for alternative, more acceptable methods for administering insulin. Several non-invasive approaches for insulin delivery are being pursued. The newer methods explored include the artificial pancreas with closed-loop system, transdermal insulin, and buccal, oral and pulmonary routes. This review focuses on the new concepts that are being explored for use in future.


Emergency Department Use by Terminally Ill Patients: A Systematic Review.
Terminally ill patients (TIP) frequently visit the emergency department (ED), but the prevalence of these visits is unclear. To determine the prevalence of TIP visiting the ED. Systematic review of observational studies published between 1998 and 2018 reporting adults TIP who used the hospital ED, searching in PubMed, CINAHL, SciELO, LILACS, and Cochrane. Three evaluators selected and extracted data (kappa concordance 0.63). The quality of the studies was evaluated with the Newcastle-Ottawa scale and global estimates were made, calculating combined prevalence (95% confidence interval [CI]) and heterogeneity of the studies (I2). We identified 2429 publications, ultimately including 31 studies in 14 countries; 79% were from high-income countries, 21% from medium-income countries, and none from low-income countries. Most were from 2015. We found that 45% of patients with cancer visited the ED in the last month of life [95% CI 37-54%] and 75% in the last six months of life [95% CI 62-83%]; I2 = 100%. Overall, 17% of patients who visited the ED had a terminal illness [95% CI 12-23%]; I2 = 98%. Few studies reported terminal nononcologic illness, specific age groups or diseases, hospital admission rates, use of palliative care or nonresuscitation, or other criteria that could be used for grouping. Patients with terminal cancer frequently use the ED at the end of life, although use varies among patients and few studies have examined low-income countries or patients with nononcologic terminal illness. The global prevalence of TIP in the ED cannot be calculated from limited reports.


The Use of Environmental Enrichments Affects Performance and Behavior of Growing Rabbits Housed in Collective Pens.
This study assessed the effects of an elevated plastic-slatted platform and/or a plastic hiding tube in collective pens with large group sizes (27 or 36 rabbits/pen; 16 rabbits/m2) on the performance and welfare of rabbits kept from weaning (at 33 days of age) to slaughter (at 68 or 75 days of age). Growth performance, injuries, and behavior (video recorded for 24 h) of rabbits (n = 504) were recorded. The platform allowed rabbits to adopt the rearing position more frequently (+0.14 events during 2 min every 30 min across 24 h) and to rest with stretched body for longer (+3.8% of observed time) (p ≤ 0.001). Production parameters and reactivity at the open field test were not modified, but the occurrence of injured rabbits at the trial end was higher in pens with platforms (+8.9%; p ≤ 0.01). This result was possibly related to the higher group size in pens with platforms (36 rabbits) compared to those without platforms (27 rabbits). The inclusion of the tube decreased growth (-2.2 g/d; p ≤ 0.05), whereas it was scarcely used by rabbits and it did not substantially change their behavior or the occurrence of injuries. In conclusion, under the experimental conditions of this study, elevated platforms worked as a useful structural enrichment in view of animal behavior but negatively impacted on the rate of injuries, whereas the usefulness of the tube was not confirmed.


Electrocoating of stainless steel coronary stents for extended release of paclitaxel.
Nonbiodegradable polymer coating based on N-(2-carboxyethyl)pyrrole (PPA) and butyl ester of PPA (BuOPy) were successfully electrodeposited on a stainless steel stent surface using cyclic voltammetry. Chemical composition of the coating was examined by X-ray photoelectron spectroscopy. Polymer stability was examined by immersing the coated stent into 1:1 solution of fetal calf serum:seline solution up to 1 year and implantation subcutaneously in mouse for 1 week. Morphology changes were then recorded by scanning electron microscopy. Paclitaxel loading was carried out by immersion into drug solution and its release was detected by HPLC. The results show that thin (single micrometers), uniform coating with various morphology and hydrophobicity can be created by electrochemical deposition. The polymer did not show significant histopathological or morphological changes in vitro and in vivo. The surface properties allow loading appropriate amounts of paclitaxel and release it slowly up to a month.


Inhibition of pyruvate dehydrogenase complex by moniliformin.
The mechanism for the inhibition of pyruvate dehydrogenase complex from bovine heart by moniliformin was investigated. Thiamin pyrophosphate proved to be necessary for the inhibitory action of moniliformin. The inhibition reaction was shown to be time-dependent and to follow first-order and saturation kinetics. Pyruvate protected the pyruvate dehydrogenase complex against moniliformin inactivation. Extensive dialysis of the moniliformin-inactivated complex only partially reversed inactivation. Moniliformin seems to act by inhibition of the pyruvate dehydrogenase component of the enzyme complex and not by acting on the dihydrolipoamide transacetylase or dehydrogenase components, as shown by monitoring the effect of moniliformin on each component individually. On the basis of these results, a suicide inactivator mechanism for moniliformin on pyruvate dehydrogenase is proposed.


Nursery pigs fed with feed contaminated by aflatoxin B1 (Aspergillus flavus) and anti-mycotoxin blend: Pathogenesis and negative impact on animal health and weight gain.
The present study aimed to evaluate whether a moderate dose of aflatoxin B1 in pigs' diet interferes with pigs' growth and health in the nursery phase and whether an anti-mycotoxin mixture minimizes the adverse effects of the toxin. One blend with Saccharomyces cerevisiae lysate, zeolite, silicon dioxide, propylene glycol, Carduus marianus extract, soy lecithin, and carbonate was used as an anti-mycotoxin. Four treatments, with six repetitions per treatment and three pigs/pen: Afla0-AntiMyc0 - negative control (without aflatoxin); Afla500-AntiMyc0 - positive control (500 ppb of aflatoxin); Afla0-AntiMyc1000 - 1000 mg/kg of anti-mycotoxin blend; Afla500-AntiMyc1000 - 500 ppb aflatoxin +1000 mg/kg of anti-mycotoxin blend. It was observed that pigs in the positive control (Afla500-AntiMyc0) had lower body weight and weight gain when compared to the other treatments during the experimental period. Also, pigs from Afla500-AntiMyc0 had lower feed intake between days 1-20 and 1 to 30 than Afla0-AntiMyc0. The pigs from Afla500-AntiMyc0 had higher levels of liver enzymes aspartate aminotransferase and alanine aminotransferase compared to other treatments. The pigs from Afla500-AntiMyc0 had higher villus height than the other treatments, while the folded size was smaller in this treatment. Crypts were deeper in the intestines of pigs in both treatments that consumed aflatoxin. In general, it is concluded that the intake of aflatoxin B1 by nursery pigs has negative impacts on the health and, consequently, the animals' growth performance; however, the addition of the contaminated feed with an anti-mycotoxin blend was able to protect the pigs, minimizing the adverse effects caused by the mycotoxin.


Effects of Curcumin on the Oxidative Stress Response to a Dual Stress Challenge in Trained Men.
Firefighters and military personnel are exposed to a variety of stressors. The combination of mental and physical stress (i.e., dual stress challenges [DSCs]) results in significant oxidative stress (OS), which may contribute to cardiometabolic dysfunction. Curcumin (CUR) is an exogenous antioxidant that may attenuate such OS. Fourteen trained men participated in a randomized, cross-over design to investigate the impact of CUR on markers of OS resulting from DSC. CUR or placebo was ingested three days prior to, and the morning of, testing. The DSC involved 20 min of mental stress challenges during 35 min of cycling at 60% V̇O2 peak. Blood was sampled before, as well as immediately, 30 min, and 60 min after, exercise and analyzed for glutathione (GSH), superoxide dismutase (SOD), hydrogen peroxide (H2O2), and advanced oxidation protein products (AOPP). There was no treatment effect for any variable. However, the DSC resulted in significant reductions in SOD, H2O2, and AOPP at 30 and 60 min after exercise. Previous studies have shown that DSC results in significant OS compared to exercise alone. However, these data suggest the DSC was associated with reductions in postexercise markers of OS. Antioxidant therapy is likely not needed in trained men exposed to DSC.


Cannabinoid Compounds as a Pharmacotherapeutic Option for the Treatment of Non-Cancer Skin Diseases.
The endocannabinoid system has been shown to be involved in various skin functions, such as melanogenesis and the maintenance of redox balance in skin cells exposed to UV radiation, as well as barrier functions, sebaceous gland activity, wound healing and the skin's immune response. In addition to the potential use of cannabinoids in the treatment and prevention of skin cancer, cannabinoid compounds and derivatives are of interest as potential systemic and topical applications for the treatment of various inflammatory, fibrotic and pruritic skin conditions. In this context, cannabinoid compounds have been successfully tested as a therapeutic option for the treatment of androgenetic alopecia, atopic and seborrhoeic dermatitis, dermatomyositis, asteatotic and atopic eczema, uraemic pruritis, scalp psoriasis, systemic sclerosis and venous leg ulcers. This review provides an insight into the current literature on cannabinoid compounds as potential medicines for the treatment of skin diseases.


[Morphologic manifestations of the medicinal lysis of a coronary artery thrombus].
Morphologic studies of coronary arterial thrombi have shown immature fibrin fibres to prevail in those, with fibrin degradation products always present. This fact suggests that fibrinolytic components of hemostasis, limiting the rates of fibrin polymerization and maturation, may participate in thrombogenesis. At the same time, macrophages that phagocytose fibrin and blood cells (platelets and erythrocytes) become activated since the early hours of the thrombus' existence. Selective administration of fibrinolytic activators destroys the fibrin network of the thrombus, blood cells are washed away by the blood flow and the thrombus diminishes in volume. At the same time, its macrophagal response is activated, and fibrin and fibrin degradation products are eliminated from the vascular lumen.


Pathologic and Prognostic Implications of Incidental versus Nonincidental Gallbladder Cancer: A 10-Institution Study from the United States Extrahepatic Biliary Malignancy Consortium.
Most gallbladder cancers (GBCs) are discovered incidentally after routine cholecystectomy. The influence of timing of diagnosis on disease stage, treatment, and prognosis is not known. Patients with GBC who underwent resection at 10 institutions from 2000 to 2015 were included. Patients diagnosed incidentally (IGBC) and nonincidentally (non-IGBC) were compared. Primary outcome was overall survival (OS). Of 445 patients with GBC, 266 (60%) were IGBC and 179 (40%) were non-IGBC. Compared with IGBC, non-IGBC patients were more likely to have R2 resections (43% vs 19%; P < 0.001), advanced T-stage (T3/T4: 70% vs 40%; P < 0.001), high-grade tumors (50% vs 31%; P < 0.001), lymphovascular invasion (64% vs 45%; P = 0.01), and positive lymph nodes (60% vs 43%; P = 0.009). Receipt of adjuvant chemotherapy was similar between groups (49% vs 49%). Non-IGBC was associated with worse median OS compared with IGBC (17 vs 32 months; P < 0.001), which persisted among stage III patients (12 vs 29 months; P < 0.001), but not stages I, II, or IV. Despite accounting for other adverse pathologic factors (grade, T-stage, lymphovascular invasion, margin, lymph node), adjuvant chemotherapy was associated with improved OS only in stage III IGBC, but not in non-IGBC. Compared with incidental discovery, non-IGBC is associated with reduced OS, which is most evident in stage III disease. Despite being well matched for other adverse pathologic factors, adjuvant chemotherapy was associated with improved survival only in stage III patients with incidentally discovered cancer. This underscores the importance of timing of diagnosis in GBC and suggests that these two groups may represent a distinct biology of disease, and the same treatment paradigm may not be appropriate.


Uterus bicornis unicollis; Occurrence of consecutive viable pregnancies in separate horns.
A case of two-consecutive viable pregnancies in separate horns of bicornuate unicollis uterus of a Nigerian is presented. The problem of misdiagnosis associated with the anomaly is noted. This case further demonstrates that women with such anomaly may not have unhindered reproductive carrier and antenatal care will improve their chance.


Low dose intranasal oxytocin delivered with Breath Powered device dampens amygdala response to emotional stimuli: A peripheral effect-controlled within-subjects randomized dose-response fMRI trial.
It is unclear if and how exogenous oxytocin (OT) reaches the brain to improve social behavior and cognition and what is the optimal dose for OT response. To better understand the delivery routes of intranasal OT administration to the brain and the dose-response, we compared amygdala response to facial stimuli by means of functional magnetic resonance imaging (fMRI) in four treatment conditions, including two different doses of intranasal OT using a novel Breath Powered device, intravenous (IV) OT, which provided similar concentrations of blood plasma OT, and placebo. We adopted a randomized, double-blind, double-dummy, crossover design, with 16 healthy male adults administering a single-dose of these four treatments. We observed a treatment effect on right amygdala activation during the processing of angry and happy face stimuli, with pairwise comparisons revealing reduced activation after the 8IU low dose intranasal treatment compared to placebo. These data suggest the dampening of amygdala activity in response to emotional stimuli occurs via direct intranasal delivery pathways rather than across the blood-brain barrier via systemically circulating OT. This trial is registered at the U.S. National Institutes of Health clinical trial registry (www.clinicaltrials.gov; NCT01983514) and as EudraCT no. 2013-001608-12.


Gene expression profiling identifies emerging oncogenic pathways operating in extranodal NK/T-cell lymphoma, nasal type.
Biopsies and cell lines of natural killer/T-cell lymphoma, nasal type (NKTCL) were subject to combined gene expression profiling and array-based comparative genomic hybridization analyses. Compared with peripheral T-cell lymphoma, not otherwise specified, NKTCL had greater transcript levels for NK-cell and cytotoxic molecules, especially granzyme H. Compared with normal NKcells, tumors were closer to activated than resting cells and overexpressed several genes related to vascular biology, Epstein-Barr Virus-induced genes, and PDGFRA. Notably, platelet-derived growth factor receptor alpha and its phosphorylated form were confirmed at the protein level, and in vitro the MEC04 NKTCL cell line was sensitive to imatinib. Deregulation of the AKT, Janus kinase-signal transducers and activators of transcription, and nuclear factor-kappaB pathways was corroborated by nuclear expression of phosphorylated AKT, signal transducers and activators of transcription 3, and RelA in NKTCL, and several deregulated genes in these pathways mapped to regions of recurrent copy number aberrations (AKT3 [1q44], IL6R [1q21.3], CCL2 [17q12], TNFRSF21 [6p12.3]). Several features of NKTCL uncovered by this analysis suggest perturbation of angiogenic pathways. Integrative analysis also evidenced deregulation of the tumor suppressor HACE1 in the frequently deleted 6q21 region. This study highlights emerging oncogenic pathways in NKTCL and identifies novel diagnostic and therapeutic targets.


E-Learning for Medical Education in Sub-Saharan Africa and Low-Resource Settings: Viewpoint.
E-learning has been heralded as a revolutionary force for medical education, especially for low-resource countries still suffering from a dire lack of health care workers. However, despite over two decades of e-learning endeavors and interventions across sub-Saharan Africa and other low- and middle-income countries, e-learning for medical education has not gained momentum and continues to fall short of the anticipated revolution. Many e-learning interventions have been cul-de-sac pilots that have not been scaled up but rather terminated after the pilot phase. This is usually a result of not adopting a system-wide approach, which leads to insufficient scope of training, insufficient technological maintenance and user support, unattainably high expectations, and unrealistic financial planning. Thus, a multitude of e-learning evaluations have failed to provide scientifically sound evidence of the effectiveness of e-learning for medical education in low-resource countries. Instead, it appears that technological development has overwhelmed rather than revolutionized medical education. The question of how to push e-learning into a higher gear in low-resource countries persists. Provision of e-learning as a technology is insufficient. E-learning needs to be vigorously and sustainably integrated into the local educational setting and aligned with national strategies and other national endeavors and interventions. Adhering to a standardized framework for the implementation and evaluation of e-learning endeavors is key, especially to bridge the gap in robust evidence that should also guide e-learning implementations. The primary objective of e-learning for medical education is to strengthen the health system in order to serve the population's health care needs and expectations. Currently, medical e-learning does not measure up to its potential or do justice to medical students in low-resource countries. Technology may help unfold the potential of e-learning, but an all-encompassing change is needed. This can only be achieved through a joint effort that follows a systematic and standardized framework, especially for implementation and evaluation.


Bronchoalveolar lavage in mixed cryoglobulinaemia associated with hepatitis C virus.
In order to evaluate the presence of an inflammatory process of the lower respiratory tract in patients with mixed cryoglobulinaemia (MC) associated with hepatitis C virus (HCV), bronchoalveolar lavage (BAL) was performed in 16 non-smoking females free of clinical pulmonary symptoms and with normal chest roentgenograms. Pulmonary function tests including diffusion capacity for carbon monoxide (DLCO) were also carried out. Thirteen healthy subjects were evaluated as the control group. Patients with MC had a lower percentage of alveolar macrophages (75% vs 92%, P = 0.001) and a higher percentage of lymphocytes (19.7% vs 7%, P = 0.001) than healthy controls. The percentage of CD3+ lymphocytes was higher in MC patients than in controls (86.5% vs 70%, P = 0.004). No significant differences in the percentage of CD4+, CD8+ and CD19+ lymphocytes, neutrophils and eosinophils were found. Pulmonary function tests showed significantly lower values of forced expiratory flow (FEF) 25-75 (P = 0.05) and DLCO (P = 0.05) in MC patients than in healthy controls. No correlations between BAL results and pulmonary function tests were found. The 5 yr follow-up of five patients did not demonstrate deterioration in lung function. Thus, BAL results indicate a subclinical T-lymphocytic alveolitis in MC HCV+ patients that is not associated with a risk of deterioration in lung function.


MD and NMR studies of alpha-bungarotoxin surface accessibility.
Protein surface accessibility represents a dimension of structural biology which has not been discussed in details so far, in spite of its fundamental role in controlling the molecular recognition process. In the present report the surface accessibility of alpha-bungarotoxin, a small and well characterized protein, has been investigated by analyzing its interaction with solvent and paramagnetic molecules in an integrated way. The presence of strong hydration sites, identified by a combined analysis of MD simulation and NMR results, seems to prevent the access of Gd(III)DTPA-BMA to the protein surface. On the contrary, the limited hydration of the alpha-bungarotoxin active site favors frequent encounters between the paramagnetic probe and the protein in the latter region. All the data obtained here for alpha-bungarotoxin suggest that shape and stability of the solvation shell control its surface accessibility and, hence, intermolecular interactions in a way which could be common to many other proteins.


Recombinant adenovirus-mediated cardiac gene transfer of superoxide dismutase and catalase attenuates postischemic contractile dysfunction.
Coronary revascularization entails obligatory myocardial ischemia followed by reperfusion with occasional resultant postischemic contractile dysfunction, a state associated with significant morbidity and mortality. This injury is attributed in part to oxygen free radicals and has been partially ameliorated with exogenous antioxidants, a strategy limited by agent instability, low titer, and inadequate cardiomyocyte uptake. Cardiac gene transfer with antioxidant encoding vectors may significantly enhance intracellular free radical scavenger activity. C57/BL6 neonatal mice (age, 2 days; n = 131) underwent intrapericardial delivery of recombinant adenoviruses encoding superoxide dismutase (SOD) and catalase (Cat) (n = 76) or beta-galactosidase (LacZ) as a control (n = 55). After 3 days, hearts were explanted, and SOD and Cat transgene expression was detected by Western blot analysis. Spectrophotometric enzyme assays demonstrated enhanced SOD activity 1.6-fold (P < 0.0001) and Cat 3.6-fold (P < 0.00001) in experimental versus LacZ hearts. Isolated perfused hearts were subjected to 5 minutes of warm ischemia, and at 5, 10, and 15 minutes after initiation of reperfusion, LacZ controls lost 24%, 33%, and 41% of peak systolic apicobasal force, respectively, whereas experimental hearts lost 5%, 12%, and 20% (P < 0.001, each time point). In controls, rate of force generation diminished 8%, 17%, and 35%; in experimental hearts, it increased 1% at 5 minutes and decreased 5% and 15% and 10 and 15 minutes (P < 0.01, P < 0.05, P < 0.05). LacZ hearts exhibited dysfunction similar to hearts from uninjected animals (P = NS, each time point). Adenovirus-mediated cardiac gene transfer and expression of SOD and Cat augment antioxidant enzyme activity and minimize contractile dysfunction after ischemic reperfusion in the isolated perfused neonatal mouse heart.


High prevalence of the metabolic syndrome in patients with systemic lupus erythematosus: association with disease characteristics and cardiovascular risk factors.
The metabolic syndrome is an independent risk factor for ischaemic heart disease. Patients with systemic lupus erythematosus (SLE) have accelerated atherosclerosis; however, there are no controlled studies of the metabolic syndrome in patients with SLE. To compare the prevalence of the metabolic syndrome in patients with SLE and controls and to evaluate its relationship to other cardiovascular risk factors and inflammation. 102 patients with SLE and 101 controls were studied. The prevalence of the metabolic syndrome was compared in patients and controls using the National Cholesterol Education Program Adult Treatment Panel III (NCEP) and the World Health Organization (WHO) definitions, and associations with cardiovascular risk factors and lupus characteristics were examined. The metabolic syndrome was present in 32.4% of patients and in 10.9% of controls subjects (p<0.001) using the WHO definition that requires direct determination of insulin resistance, and in 29.4% of patients with SLE and in 19.8% of controls (p = 0.14) using the NCEP definition. Among patients with SLE, both definitions were significantly associated with higher concentrations of C reactive protein (p = 0.001) and the NCEP definition was significantly associated with higher concentrations of homocysteine (p<0.001), lipoprotein (a) (p = 0.02) and cholesterol (p = 0.04). Neither lupus disease activity nor damage scores were associated with the metabolic syndrome. Patients with SLE have a higher prevalence of insulin resistance and consequently of the WHO-defined metabolic syndrome than controls. In patients with SLE, the metabolic syndrome was associated with higher levels of inflammation and may provide a link between inflammation and increased cardiovascular risk.


Hematopoietic-to-mesenchymal transition of adipose tissue macrophages is regulated by integrin β1 and fabricated fibrin matrices.
Some bona fide adult adipocytes arise de novo from a bone marrow-derived myeloid lineage. These studies further demonstrate that adipose tissue stroma contains a resident population of myeloid cells capable of adipocyte and multilineage mesenchymal differentiation. These resident myeloid cells lack hematopoietic markers and express mesenchymal and progenitor cell markers. Because bone marrow mesenchymal progenitor cells have not been shown to enter the circulation, we hypothesized that myeloid cells acquire mesenchymal differentiation capacity in adipose tissue. We fabricated a 3-dimensional fibrin matrix culture system to define the adipose differentiation potential of adipose tissue-resident myeloid subpopulations, including macrophages, granulocytes and dendritic cells. Our data show that multilineage mesenchymal potential was limited to adipose tissue macrophages, characterized by the acquisition of adipocyte, osteoblast, chondrocyte and skeletal muscle myocyte phenotypes. Fibrin hydrogel matrices stimulated macrophage loss of hematopoietic cell lineage determinants and the expression of mesenchymal and progenitor cell markers, including integrin β1. Ablation of integrin β1 in macrophages inhibited adipocyte specification. Therefore, some bona fide adipocytes are specifically derived from adipose tissue-resident macrophages via an integrin β1-dependent hematopoietic-to-mesenchymal transition, whereby they become capable of multipotent mesenchymal differentiation. The requirement for integrin β1 highlights this molecule as a potential target for controlling the production of marrow-derived adipocytes and their contribution to adipose tissue development and function.


Threatening Beliefs About Self and Others Moderate the Association Between Psychoticism and Psychological Distress.
Psychoticism is a multidimensional personality construct involving odd or eccentric behavior, quasi-psychotic experiences, mistrust, interpersonal detachment, and liability for schizophrenia-spectrum disorders, as well as significant distress. Recent advances suggest it can be understood as a dimension that is continuously distributed in the population, leading to questions about factors that contribute to distress and dysfunction among people with a schizotypal liability. We investigated in a large nonclinical sample of young adults whether associations between psychoticism and psychological distress would increase in the presence of threatening beliefs. In our study ( N = 2127), we found that the association between psychoticism and psychological distress is moderated by threatening beliefs including self-criticism, fear of compassion, and socially prescribed perfectionism. These results suggest that distress increases among people with schizotypal traits in the context of negative beliefs about self and others. We discuss implications for clinical practice and directions for further research.


Formulating a role for occupational therapy in child psychiatry: a clinical application.
Occupational therapy is in need of role clarification within the specialty of child psychiatry. The literature reveals that occupational therapy is often undelineated or unrecognized by child psychiatry, has limited efficacy research, and may be at risk for losing its practice with children hospitalized for psychiatric disturbances. This paper outlines steps for the formulation of a specialized role for occupational therapy within this specialty. The Model of Human Occupation (Kielhofner, 1985) is suggested as a basis for conceptualizing this role. A clinical study focused on the evaluation of adaptive functioning with use of the Vineland Adaptive Behavior Scales (Sparrow, Balla, & Cicchetti, 1984, 1985) is presented as an example of a way in which occupational therapy can provide assessment data valuable to the interdisciplinary clinical team. The role of occupational therapy in both short-term and long-term hospitalization of children with psychiatric disturbances is described.


Estimation of growth parameters for some oral bacteria grown in continuous culture under glucose-limiting conditions.
The coexistence of bacteria in natural environments can often be explained in terms of competition for a growth-limiting substrate(s), and the outcome of such competition depends upon relevant growth parameters such as substrate affinity and yield. Dental plaque bacteria are frequently carbon and energy limited. Growth parameters for seven oral Streptococcus species and one Actinomyces viscosus strain were estimated under glucose-limited conditions in continuous culture. In all strains, mixed-acid fermentation occurred at low growth rates, while amounts of lactate increased at higher growth rates. Two important growth parameters, mumax and Y glucose, were very similar in the two serotype c Streptococcus mutans strains (T8 and Ingbritt), one of the serotype d/g Streptococcus mutans strains (OMZ65), and the two Streptococcus milleri strains (699B3 and B448). Two other serotype d/g S. mutans strains (KIR and B13) were divergent from this group and had lower mumax values and a lower Y glucose. The maintenance energy coefficients were lower in the S. mutans serotype c strains, and the highest values were observed in the S. milleri strains. While A. viscosus had a lower mumax, its lower maintenance rate and significantly higher yield indicate that it deals much more efficiently with glucose than do the streptococci. The most striking feature of amino acid utilization was that arginine was completely consumed by S. milleri strains; similarly, A. viscosus used up all available asparagine as did one of the S. milleri strains at faster growth rates. It is suggested that the ability of strains of S. milleri and S. sanguis to utilize arginine in addition to carbohydrate as a source of energy may explain why such organisms increase in proportion in the plaque of subjects consuming diets almost devoid of fermentable carbohydrate.


[Arbovirus causing hemorrhagic fever at IMSS].
To know the arbovirus causing hemorrhagic fever in patients at the Mexican Institute of Social Security. A follow-up study was made in patients with probable diagnosis of hemorrhagic dengue. Blood samples were taken to look for dengue fever, yellow fever and San Luis, Tonate and Mayaro encephalitis viruses. Frequencies and proportions of the interest variables were analyzed. 35 patients were studied. Isolation and PCR results of the 13 samples were negative in 12 of them and positive to denguevirus-3 in one of them. The determination of IgM was positive for dengue fever in 25 cases; 2 were positive to Mayaro virus and 8 were negative to what was looked for. Hemorrhages and thrombocytopenia were more frequent in patients infected with dengue and Mayaro viruses; jaundice and encephalopathy were more frequent in the latter, and renal dysfunction, in patients with a negative result. Evolution was satisfactory in all cases, except for one (Mayaro), which presented hemorrhages, thrombocytopenia, jaundice and encephalopathy that lead to death. The results show the risk of appearance and dissemination of several vector-born diseases in Mexico. Thus, they require intensive epidemiological surveillance to identify them and to know their real occurrence and specific clinical profile.


Somatic mosaicism for maternal uniparental disomy 15 in a girl with Prader-Willi syndrome: confirmation by cell cloning and identification of candidate downstream genes.
Although uniparental disomy often results from the postzygotic rescue of a meiotic non-disjunction event, mosaicism is usually confined to the placenta. We describe a girl with Prader-Willi syndrome (PWS) who is mosaic for normal cells and cells with maternal uniparental disomy 15 [upd(15)mat] in blood and skin. Somatic mosaicism was confirmed by cloning and genotyping of skin fibroblasts. X inactivation studies indicated that upd occurred prior to X inactivation. RNA samples from the cloned cells were used in DNA microarray experiments to study the effect of upd(15)mat on the gene expression pattern of fibroblasts. Proof of principle was obtained by detecting several chromosome 15 genes known to be imprinted. We did not obtain any evidence for novel 15q genes showing imprinted expression in fibroblasts. Differentially expressed genes on other chromosomes are candidates for downstream genes regulated by an imprinted gene and may play a role in the pathogenesis of PWS. The finding of strongly reduced mRNA levels in upd(15)mat cells of the gene encoding secretogranin II (SCG2), which is a precursor of the dopamine releasing factor secretoneurin, raises the question whether hyperphagia in patients with PWS might be due to a defect in dopamine-modulated food reward circuits.


Hyperbetaglobulinemia, anaemia and thrombocytopenia in a domestic ferret (Mustela putorius furo) associated to Leishmania infantum.
Leishmaniosis in domestic ferrets is a vector-borne disease caused in Europe by the protozoan parasite Leishmania infantum. There is limited information on clinical signs and laboratory abnormalities in ferrets due to leishmaniosis. This clinical case report described a domestic ferret (Mustela putorius furo) with severe hyperbetaglobulinemia, anaemia, thrombocytopenia, and abnormal renal parameters. A good clinical response following an anti-Leishmania infantum treatment protocol was achieved. However, the presence of pain at the site of injection was the main side effect due to meglumine antimoniate administration. Xanthine crystalluria was not observed in urine sediment with no other urine alterations detected by urine analysis during the follow-up. Initially, clinical signs noted in this ferret could not initially be attributed to leishmaniosis. However, no causes were found that could have caused the hyperglobulinemia in this patient. A reduction of the levels of anti-L. infantum serum antibodies and the concentrations of beta-globulin fraction was detected in this patient after anti-Leishmania treatment administered as well as the disappearance of thrombocytopenia. To extent of the knowledge of leishmaniosis in ferrets, this is the fourth case report of leishmaniosis documented in this species.


Toxin from Fusarium moniliforme: Effects on Plants and Animals.
A mycotoxin-producing strain of Fusarium moniliforme was isolated from southern leaf blight-damaged corn seed. A water-soluble toxin, subsequently purified from the fungus, had an oral median lethal dose of 4.0 milligrams per kilogram in 1-day-old cockerels. The toxin also produced plant growth-regulating and phytotoxic effects on plant systems. Physical and chemical data presented for the toxin suggest a structurally new toxin. The trivial name "moniliformin" has been assigned to the toxin.


"I Am the Home Care Agency": The Dementia Family Caregiver Experience Managing Paid Care in the Home.
As the locus of long-term care in the United States shifts from institutions to the community, paid caregivers (i.e., home health aides, personal care attendants) are providing more hands-on care to persons with dementia living at home. Yet, little is known about how family caregivers engage with paid caregivers. We conducted in-depth, semi-structured interviews (n = 15) with family caregivers, of persons living at home with severe dementia, and enriched our findings with data from a second cohort of family caregivers of persons with dementia (n = 9). Whether paid caregivers were hired privately or employed via a Medicaid-funded agency, family caregivers reported that they needed to manage paid caregivers in the home. Core management tasks were day-to-day monitoring and relationship building with family caregivers; training paid caregivers and coordinating care with homecare agencies was also described. In order to support family caregivers of individuals with dementia at home, it is important consider their preferences and skills in order to effectively manage paid caregivers. Support of efforts to build a high-quality paid caregiving workforce has the potential to improve not only care delivered to persons with dementia, but the experiences of their family caregivers.


Self-Assembly of Perylenediimide-Single-Strand-DNA Conjugates: Employing Hydrophobic Interactions and DNA Base-Pairing To Create a Diverse Structural Space.
The self-assembly behavior of DNA conjugates possessing a perylenediimide (PDI) head group and an N-oligonucleotide tail has been investigated using a combination of optical spectroscopy and cryogenic transmission electron microscopy (cryo-TEM) imaging. To obtain insight into the interplay between PDI hydrophobic interactions and DNA base-pairing we employed systematic variation in the length and composition of the oligo tails. Conjugates with short (TA)n or (CG)n oligo tails (n≤3) form helical or nonhelical fibers constructed from π-stacked PDI head groups with pendent oligo tails in aqueous solution. Conjugates with longer (TA)n oligo tails also form stacks of PDI head groups, which are further aggregated by base-pairing between their oligo tails, leading to fiber bundling and formation of bilayers. The longer (CG)n conjugates form PDI end-capped duplexes, which further assemble into PDI-stacked arrays of duplexes leading to large scale ordered assemblies. Cryo-TEM imaging reveals that (CG)3 gives rise to both fibers and large assemblies, whereas (CG)5 assembles preferentially into large ordered structures.


Wide mass range trapping using a 7-T internal source matrix-assisted laser desorption/ionization Fourier transform mass spectrometer.
A wide mass range trapping experiment using internal source matrix-assisted laser desorption-Fourier transform mass spectrometry (MALDI-FTMS) was evaluated. In this method, the front trap plate potential is ramped up and the rear trap plate potential is simultaneously decreased using a cubic cell to trap ions over a wide range of mass-to-charge ratios. To apply this to MS/MS experiments, a second ion ejection procedure would remove unwanted ions, with the selected remaining ions then fragmented by collision-induced dissociation. In measurements using a 7.2-T unshielded magnet presented here, an approximately equimolar mixture of a set of poly(ethylene glycol) (PEG) species for the ramped measurements had peak areas of 1.0:1.0:1.0:1.0, as did the previously described integral method which gave peak areas of 1.0:1.1:1.0:1.0, in good agreement with the known composition of the samples deposited on the MALDI probe tip. Comparative MALDI-TOF in reflectron mode results were of similar quality for the equimolar mixture, giving a ratio of 1.0:1.0:1.2:0.9. All methods failed to varying degrees when individual PEG compositions of the trial mixture were changed. However, the previously described integral method showed relatively better results for all but the PEG 8000 doubled mixture.


The role of ATP in the differential ability of Sr2+ to trigger Ca2+ oscillations in mouse and human eggs.
At fertilization in mice and humans, the activation of the egg is caused by a series of repetitive Ca2+ oscillations which are initiated by phospholipase-C(zeta)ζ that generates inositol-1,4,5-trisphophate (InsP3). Ca2+ oscillations and egg activation can be triggered in mature mouse eggs by incubation in Sr2+ containing medium, but this does not appear to be effective in human eggs. Here, we have investigated the reason for this apparent difference using mouse eggs, and human eggs that failed to fertilize after IVF or ICSI. Mouse eggs incubated in Ca2+-free, Sr2+-containing medium immediately underwent Ca2+ oscillations but human eggs consistently failed to undergo Ca2+ oscillations in the same Sr2+ medium. We tested the InsP3-receptor (IP3R) sensitivity directly by photo-release of caged InsP3 and found that mouse eggs were about 10 times more sensitive to InsP3 than human eggs. There were no major differences in the Ca2+ store content between mouse and human eggs. However, we found that the ATP concentration was consistently higher in mouse compared to human eggs. When ATP levels were lowered in mouse eggs by incubation in pyruvate-free medium, Sr2+ failed to cause Ca2+ oscillations. When pyruvate was added back to these eggs, the ATP levels increased and Ca2+ oscillations were induced. This suggests that ATP modulates the ability of Sr2+ to stimulate IP3R-induced Ca2+ release in eggs. We suggest that human eggs may be unresponsive to Sr2+ medium because they have a lower level of cytosolic ATP.


Intrarenal mechanisms mediating pressure natriuresis: role of angiotensin and prostaglandins.
The ability of the kidney to increase sodium and water excretion in response to increases in perfusion pressure has been recognized for more than 50 years. Because glomerular filtration rate is tightly autoregulated, pressure natriuresis occurs as the result of decreased tubular sodium reabsorption rather than increased filtered load. Micropuncture and microperfusion data support the contention that acute changes in arterial pressure can alter proximal tubule reabsorption; however, studies have failed to show a consistent association between changes in sodium excretion and peritubular, interstitial, or tubular pressures. Thus, the specific intrarenal mechanism for the change in tubular reabsorption in response to an acute change in arterial pressure does not appear to be related to the peritubular physical factors at the level of outer cortical nephrons. The possible roles of angiotensin and prostaglandins as humoral mediators of pressure natriuresis are considered in this report. Although angiotensin II is a powerful modulator of the slope of the pressure natriuresis relationship, the responsiveness of sodium excretion to arterial pressure is actually enhanced by angiotensin-converting enzyme inhibitors. These data suggest that angiotensin does not mediate the basic phenomenon. Recent experiments indicate that intrarenal prostaglandins also modulate the magnitude of the pressure natriuresis relationship, but these hormones do not appear to be essential for its basic manifestation.


Cost of Exempting Sole Orphan Drugs From Medicare Negotiation.
The Inflation Reduction Act (IRA) requires Medicare to negotiate prices for some high-spending drugs but exempts drugs approved solely for the treatment of a single rare disease. To estimate Medicare spending and global revenues for drugs that might have been exempt from negotiation from 2012 to 2021. This cross-sectional study analyzed drugs that met the IRA threshold for price negotiation (Medicare spending >$200 million/y) in any year from 2012 to 2021 and had an Orphan Drug Act designation. We stratified drugs into 4 mutually exclusive categories: approved for a single rare disease (sole orphan), approved for multiple rare diseases (multiorphan), initially approved for a rare disease and subsequently approved for a nonrare disease (orphan first), and initially approved for a nonrare disease and subsequently approved for a rare disease (non-orphan first). The primary outcomes were the number of sole orphan drugs, estimated Medicare spending on those drugs from 2012 to 2021, and global revenue since launch. Among 282 drugs, 95 (34%) were approved to treat at least 1 rare disease, including 25 sole orphan drugs (26%), 20 multiorphan drugs (21%), 13 orphan first drugs (14%), and 37 non-orphan first drugs (39%). From 2012 to 2021, Medicare spending on sole orphan drugs increased from $3.4 billion to $10.0 billion. Each year, a median (IQR) of $2.5 ($1.9-$2.6) billion in Medicare spending would have been excluded from price negotiation because of the sole orphan exemption. The cumulative global revenue of the median (IQR) sole orphan drug was $11 ($6.6-$19.2) billion. The sole orphan exemption will exclude billions of dollars of Medicare drug spending from price negotiation. The high level of global revenues achieved by these drugs, however, suggests that special exemption is unnecessary for them to achieve financial success. Congress could consider removing the sole orphan exemption to obtain additional savings for patients and taxpayers and to eliminate any potential disincentive for developing additional indications for these drugs.


Ratiometric Sensing of Glyphosate in Water Using Dual Fluorescent Carbon Dots.
Glyphosate is a broad-spectrum pesticide used in crops and is found in many products used by industry and consumers. Unfortunately, glyphosate has been shown to have some toxicity toward many organisms found in our ecosystems and has been reported to have carcinogenic effects on humans. Hence, there is a need to develop novel nanosensors that are more sensitive and facile and permit rapid detection. Current optical-based assays are limited as they rely on changes in signal intensity, which can be affected by multiple factors in the sample. Herein, we report the development of a dual emissive carbon dot (CD) system that can be used to optically detect glyphosate pesticides in water at different pH levels. The fluorescent CDs emit blue and red fluorescence, which we exploit as a ratiometric self-referencing assay. We observe red fluorescence quenching with increasing concentrations of glyphosate in the solution, ascribed to the interaction of the glyphosate pesticide with the CD surface. The blue fluorescence remains unaffected and serves as a reference in this ratiometric approach. Using fluorescence quenching assays, a ratiometric response is observed in the ppm range with detection limits as low as 0.03 ppm. Our CDs can be used to detect other pesticides and contaminants in water, as cost-effective and simple environmental nanosensors.


Structural correlates of spoken language abilities: A surface-based region-of interest morphometry study.
Brain structure can predict many aspects of human behavior, though the extent of this relationship in healthy adults, particularly for language-related skills, remains largely unknown. The objective of the present study was to explore this relation using magnetic resonance imaging (MRI) on a group of 21 healthy young adults who completed two language tasks: (1) semantic fluency and (2) sentence generation. For each region of interest, cortical thickness, surface area, and volume were calculated. The results show that verbal fluency scores correlated mainly with measures of brain morphology in the left inferior frontal cortex and bilateral insula. Sentence generation scores correlated with structure of the left inferior parietal and right inferior frontal regions. These results reveal that the anatomy of several structures in frontal and parietal lobes is associated with spoken language performance. The presence of both negative and positive correlations highlights the complex relation between brain and language.


Mu opioid transactivation and down-regulation of the epidermal growth factor receptor in astrocytes: implications for mitogen-activated protein kinase signaling.
Astroglia are a principal target of long-term mu antiproliferative actions. The mitogen-activated protein (MAP) kinase known as extracellular signal-regulated kinase (ERK), is a key mediator of cell proliferation. In studies on the mechanism of short- and long-term mu opioid regulation of the ERK signaling pathway, we show that the mu opioid agonist [d-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO), acting via the endogenous mu opioid receptor (MOR), induced sequential epidermal growth factor receptor (EGF) receptor (EGFR) Tyr phosphorylation, Ser phosphorylation, and down-regulation in immortalized rat cortical astrocytes. The short-term action of DAMGO resulted in the stimulation of ERK phosphorylation. 4(3-Chlorophenylamino)-6,7-dimethoxyquinazoline (Tyrphostin AG1478), a selective inhibitor of EGFR Tyr kinase activity, blocked EGFR and ERK activation by short-term DAMGO administration, implicating EGFR transactivation in its stimulation of ERK activity. Inhibitors of matrix metalloproteinases attenuated MOR-mediated ERK phosphorylation, suggesting that shedding of EGF-like ligands from the plasma membrane may be involved in the EGFR transactivation process. Prolonged DAMGO exposure induced EGFR internalization/down-regulation, did not activate ERK, and inhibited exogenous EGF-stimulated ERK phosphorylation. MOR-mediated EGFR down-regulation seems to be MAP kinase-dependent, because it was inhibited by the ERK kinase inhibitor 1,4-diamino-2,3-dicyano-1,4-bis(2-aminophenylthio) butadiene (U0126), and tyrphostin AG1478. The kappa opioid agonist (5alpha,7alpha,8beta)-(-)-N-methyl-N-(7-(1-pyrrolidinyl)-1-oxaspiro(4,5)dec-8-yl) benzeneacetamide (U69,593) induced Tyr and Ser phosphorylation of EGFR and activation of ERK. However, long-term application of U69,593 neither down-regulated EGFR nor inhibited EGF-induced ERK activation. Instead, it engendered a sustained activation of ERK. Collectively, our data suggest that long-term application of DAMGO initiates heterologous down-regulation of EGFR via a mechanism involving ERK in astrocytes.


Are surgical and non-operating room intervention safe in the COVID-19 pandemic? A retrospective study.
Little is known about the impact of COVID-19 on the outcomes of patients undergoing surgery and intervention. This study was conducted between 20 March and 20 May 2020 in six hospitals in Istanbul, and aimed to investigate the effects of surgery and intervention on COVID-19 disease progression, intensive care (ICU) need, mortality and virus transmission to patients and healthcare workers. Patients were examined in three groups: group I underwent emergency surgery, group II had an emergency non-operating room intervention, and group III received inpatient COVID-19 treatment but did not have surgery or undergo intervention. Mortality rates, mechanical ventilation needs and rates of admission to the ICU were compared between the three groups. During this period, patient and healthcare worker transmissions were recorded. In total, 1273 surgical, 476 non-operating room intervention patients and 1884 COVID-19 inpatients were examined. The rate of ICU requirement among patients who had surgery was nearly twice that for inpatients and intervention patients, but there was no difference in mortality between the groups. The overall mortality rates were 2.3% in surgical patients, 3.3% in intervention patients and 3% in inpatients. COVID-19 polymerase chain reaction positivity among hospital workers was 2.4%. Only 3.3% of infected frontline healthcare workers were anaesthesiologists. No deaths occurred among infected healthcare workers. We conclude that emergency surgery and non-operating room interventions during the pandemic period do not increase postoperative mortality and can be performed with low transmission rates.


Mining heterogeneous causal effects for personalized cancer treatment.
Cancer is not a single disease and involves different subtypes characterized by different sets of molecules. Patients with different subtypes of cancer often react heterogeneously towards the same treatment. Currently, clinical diagnoses rather than molecular profiles are used to determine the most suitable treatment. A molecular level approach will allow a more precise and informed way for making treatment decisions, leading to a better survival chance and less suffering of patients. Although many computational methods have been proposed to identify cancer subtypes at molecular level, to the best of our knowledge none of them are designed to discover subtypes with heterogeneous treatment responses. In this article we propose the Survival Causal Tree (SCT) method. SCT is designed to discover patient subgroups with heterogeneous treatment effects from censored observational data. Results on TCGA breast invasive carcinoma and glioma datasets have shown that for each subtype identified by SCT, the patients treated with radiotherapy exhibit significantly different relapse free survival pattern when compared to patients without the treatment. With the capability to identify cancer subtypes with heterogeneous treatment responses, SCT is useful in helping to choose the most suitable treatment for individual patients. Data and code are available at https://github.com/WeijiaZhang24/SurvivalCausalTree . firstname.lastname@example.com. Supplementary data are available at Bioinformatics online.


A carbohydrate-rich diet increases social immunity in ants.
Increased potential for disease transmission among nest-mates means living in groups has inherent costs. This increased potential is predicted to select for disease resistance mechanisms that are enhanced by cooperative exchanges among group members, a phenomenon known as social immunity. One potential mediator of social immunity is diet nutritional balance because traits underlying immunity can require different nutritional mixtures. Here, we show how dietary protein-carbohydrate balance affects social immunity in ants. When challenged with a parasitic fungus Metarhizium anisopliae, workers reared on a high-carbohydrate diet survived approximately 2.8× longer in worker groups than in solitary conditions, whereas workers reared on an isocaloric, high-protein diet survived only approximately 1.3× longer in worker groups versus solitary conditions. Nutrition had little effect on social grooming, a potential mechanism for social immunity. However, experimentally blocking metapleural glands, which secrete antibiotics, completely eliminated effects of social grouping and nutrition on immunity, suggesting a causal role for secretion exchange. A carbohydrate-rich diet also reduced worker mortality rates when whole colonies were challenged with Metarhizium. These results provide a novel mechanism by which carbohydrate exploitation could contribute to the ecological dominance of ants and other social groups.


Digital and interdigital corns: a report of two cases with use of hyaluronic acid gel filler.
Digital and interdigital corns are common painful foot conditions encountered by podiatrists during the course of their practice. These corns can often be treated with conservative techniques, although they tend to eventually recur. Currently, no single treatment exists that is efficient, long-lasting, minimally invasive, and easy to administer. This article describes two cases where hyaluronic acid gel injections were used to improve symptoms associated with digital and interdigital corns located in a nonweightbearing area. Both patients tolerated the intervention well and showed considerable improvement of their condition for a substantial period of time after the intervention without developing adverse reactions. Hyaluronic acid gel injections could very well represent an interesting therapeutic alternative for digital and interdigital corns located in nonweightbearing areas.


Reproducibility of semiautomated body composition segmentation of abdominal computed tomography: a multiobserver study.
Segmentation of computed tomography (CT) images provides quantitative data on body tissue composition, which may greatly impact the development and progression of diseases such as type 2 diabetes mellitus and cancer. We aimed to evaluate the inter- and intraobserver variation of semiautomated segmentation, to assess whether multiple observers may interchangeably perform this task. Anonymised, unenhanced, single mid-abdominal CT images were acquired from 132 subjects from two previous studies. Semiautomated segmentation was performed using a proprietary software package. Abdominal muscle compartment (AMC), inter- and intramuscular adipose tissue (IMAT), visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were identified according to pre-established attenuation ranges. The segmentation was performed by four observers: an oncology resident with extensive training and three radiographers with a 2-week training programme. To assess interobserver variation, segmentation of each CT image was performed individually by two or more observers. To assess intraobserver variation, three of the observers did repeated segmentations of the images. The distribution of variation between subjects, observers and random noise was estimated by a mixed effects model. Inter- and intraobserver correlation was assessed by intraclass correlation coefficient (ICC). For all four tissue compartments, the observer variations were far lower than random noise by factors ranging from 1.6 to 3.6 and those between subjects by factors ranging from 7.3 to 186.1. All interobserver ICC was ≥ 0.938, and all intraobserver ICC was ≥ 0.996. Body composition segmentation showed a very low level of operator dependability. Multiple observers may interchangeably perform this task with highly reproducible results.


Rapidly diminishing sensitivity and discrete sensitivity: Explaining people's sensitivity to outcomes across decisions.
Classic theories of perception, cognition, judgment, and decision making assert that people exhibit diminishing sensitivity to magnitude changes. For instance, according to the value function of prospect theory (Kahneman & Tversky, 1979), the pleasure of moving from 0 to $1000 is larger than the pleasure of moving from $1000 to $2000, whereas the pleasure of moving from $1000 to $2000 is larger than the pleasure of moving from $2000 to $3000. In this article, I call into question how much diminishing sensitivity actually impacts choice and the nature of the value function. I advance a special form of diminishing sensitivity that I have termed rapidly diminishing sensitivity, which postulates that people are sensitive to the presence versus the absence of outcomes but are less sensitive to the scope of the outcomes when the latter differ from zero. Rapidly diminishing sensitivity yields a value function that flattens out rapidly as values move away from zero. In the special case where the value function flattens out immediately after zero, rapidly diminishing sensitivity assumes a discrete form that I have termed discrete sensitivity. I propose that rapidly diminishing sensitivity and discrete sensitivity are typically observed in experimental studies that involve extensive manipulations of the size of the outcomes across decisions, holding everything else constant. I provide evidence for my hypothesis in eight well-powered preregistered experiments across a wide range of domains, such as financial decisions, valuations of human lives, purchase decisions, judgments of goal-related performance, intertemporal choices, and moral decisions. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


[Switch in the synthesis of IgM--IgG antibodies. I. Ratio of allelic variants of light rat immunoglobulin chains in antilactoside antibodies of different classes].
Ratio of allelic variants was studied of the rat immunoglobulin light chains in IgM and IgG fractions of anti-lactoside antibodies isolated from the sera of immune heterozygous rats (WAGXMSU)F1 and (AugustXMSU)F1. For MSU rat strain, RL1 allelic variant of light chains is typical whereas WAG and August strains possess the RL2 variant. Anti-lactoside antibodies isolated from sera of F1 rats were separated into high affinity and low affinity fractions. Thereafter each fraction was divided into IgG and IgM classes and each preparation was tested for the content of the molecules of the antibodies with light chains of RL1 and RL2 type. It has been shown that the ratio of allelic variants coincides in IgM and IgG antibody fractions. It follows from this fact that the IgG switch of antibody synthesis may process in the same cell during development of the given population of antibody-producing cells.


v-Src enhances phosphorylation at Ser-282 of the Rous sarcoma virus integrase.
The Rous sarcoma virus (RSV) integrase (IN) and the beta polypeptide (beta) of the reverse transcriptase are posttranslationally modified by phosphorylation on Ser at amino acid position 282 of IN. When IN was immunoprecipitated from RSV (Prague A strain) virions, approximately 30 to 40% of the IN molecules were phosphorylated. When IN was immunoprecipitated from a v-src deletion mutant (delta Mst-A) of RSV or from avian myeloblastosis virus (AMV), the percentage of IN molecules that were phosphorylated was significantly reduced. This reduction in phosphorylation of IN between virions was verified by [35S]Met-[35S]Cys or 32P labeling of IN, followed by immunoprecipitation analysis using antisera directed to the amino or carboxyl terminus of IN. In delta Mst-A or AMV, a nonphosphorylated, slightly truncated (at the carboxyl terminus) polypeptide was the major species of IN. The enhanced phosphorylation of IN does not appear to be a general function of transformed cells, since enhanced phosphorylation was not detected in AMV derived from viremic chickens or from a v-src deletion mutant of RSV propagated in a chemically transformed quail cell line, QT6. From these data, we conclude that v-Src is necessary for efficient phosphorylation of IN and beta.


[Osteosynthetically-treated intracapsular femoral neck fractures].
Treatment of intracapsular femoral neck fractures, especially in elder patients, has been a topic of ongoing discussion. This study analyzes the results of 97 osteosynthetically-treated femoral neck fractures. It had to be proved whether the Dynamic Martin Screw (DMS) represents an alternative to the already existing implantation devices. Until now no systematic results have been reported on this topic. Over a period of seven years, 389 patients with femoral neck fractures were treated. In 101 of these patients operations with preserved femoral heads were carried out. In order to ensure stabilization, compression screw stabilization (3 AO cancellous screws) was performed in 4 cases, the Dynamic Hip Screw (DHS) in 34 cases and the DMS in 63 cases. Observation criteria used in this retrospective study were osseous consolidation, pseudarthritis rate, complications involved with implantations, aseptic femoral head necrosis, as well as operating time. Period of observation was on average 8.5 years, with 65 years being the average age of the patients. Head necrosis was identified in 6 of 34 cases (17.6%) for the DHS group and 12 of 63 cases (19%) for the DMS group (p=0.95). Operating time was significantly reduced with the DMS procedure (p=0.035). The DMS can be seen as an alternative implantation device for stabilizing medial intracapsular femoral neck fractures. In comparison with the DHS, the operating time could be significantly reduced.


[Surgical treatment of herniation of a lumbar intervertebral disk in young people (author's transl)].
Among 2755 patients operated on for nerve-root compression there were 38 children and juveniles (aged 11-22 years). Average interval between onset of symptoms and operation was 14 1/2 months and often involved considerable diagnostic effort. 36 of the 38 patients were re-examined an average of 11 years after operation: 15 were free of symptoms, 18 had occasional mild symptoms, two had continuous mild pain and one had occasional severe pain. Re-operation was necessary in six. All patients are able to work. A connection between an accident and the herniation was demonstrated in only two instances.


Impacts of urbanization on West Nose Creek: a Canadian experience.
The lower reaches of West Nose Creek have been subject to urbanization since the 1970s, leading to channel widening and excessive erosion. This paper discusses what would likely happen if urbanization were allowed to continue in the same manner. Comparisons are presented of the channel width and depth for both the upstream rural and downstream urbanizing reaches. Estimates of the evolution of the creek were generated by linking the dominant discharge to the entire shape and volume of the hydrograph that the creek is subjected to rather than solely considering peak discharges. otential remedial measures and stormwater management philosophies are discussed in relationship to instream flow needs (IFNs) initiatives. IFNs are generally developed by relating the amount of suitable aquatic habitat to the quantity of flow. The emphasis has so far been on IFNs for large river systems. Unfortunately, none of the IFN approaches cover streams that are subject to significant urbanization. In urbanized streams the issue is not as much the impacts due to withdrawals but due to significantly increased runoff rates and volumes generated within the urban areas. Examples are provided how fisheries habitat is impacted by the changed hydrologic regime and changed stream morphology.


Cross-border care and healthcare quality improvement in Europe: the MARQuIS research project.
Citizens are increasingly crossing borders within the European Union (EU). Europeans have always been free to travel to receive care abroad, but if they wished to benefit from their statutory social protection scheme, they were subject to their local or national legislation on social protection. This changed in 1991 with the European Court of Justice defining healthcare as a service, starting a debate on the right balance between different principles in European treaties: movement of persons, goods and services, versus the responsibility of member states to organise their healthcare systems. Simultaneously, cross-border cooperation has developed between member states. In this context, patient mobility has become a relevant issue on the EU's agenda. The EU funded a number of Scientific Support to Policies (SSP) activities within the Sixth Framework Programme, to provide the evidence needed by EU policy makers to deal with issues that European citizens face due to enhanced mobility in Europe. One SSP project "Methods of Assessing Response to Quality Improvement Strategies" (MARQuIS), focused on cross-border care. It aimed to assess the value of different quality strategies, and to provide information needed when: (1) countries contract care for patients moving across borders; and (2) individual hospitals review the design of their quality strategies. This article describes the European context related to healthcare, and its implications for cross-border healthcare in Europe. The background information demonstrates a need for further research and development in this area.


Rapid and sensitive detection of hepatitis B virus 1762T/1764A double mutation from hepatocellular carcinomas using LNA-mediated PCR clamping and hybridization probes.
The 1762T/1764A double mutation of the hepatitis B virus (HBV) basal core promoter has been suggested to be a potential biomarker for hepatocellular carcinoma (HCC) among individuals with chronic HBV infection. In this study, a real-time PCR assay is established using the hybridization probes and an oligonucleotide clamp containing locked nucleic acids (LNAs). The LNA-containing oligonucleotide clamp specific for the wild type HBV is able to suppress the amplification of the wild type HBV templates. In addition, the clamp can inhibit the binding of the WT templates to the fluorescence probes thereby suppress the wild type HBV signals during the melting curve analyses. These effects facilitated the detection of HBV double mutation in the presence of 3000-fold excess of the wild type genome. Thus PCR amplification coupled with the melting curve analyses provides a quick, simple, and highly sensitive tool for the detection of this HBV double mutation.


[Effect of antilymphocyte globulin on growth and erythroid differentiation of K-562 cells].
The influence of antilymphocytic globulin (ALG) on the proliferative activity and erythroid differentiation of erythromyeloid K-562 cells was studied. It has been established that ALG produces a dose-dependent inhibiting effect (20-150 micrograms of ALG/ml) on the proliferative activity of K-562 cells and induces erythroid differentiation of these cells that does not depend on the concentration of ALG used in the test. Pretreatment of K-562 cells with ALG increases their sensitivity to the following growth-inhibiting action of cytosine-arabinoside.


Distal hypospadias repair with or without foreskin reconstruction: A single-surgeon experience.
Dartos flap coverage is routinely used as a protective layer during tubularized incised plate urethroplasty (TIPU) except when an associated foreskin reconstruction (FSR) precludes its use. In this study we compare the outcome of distal hypospadias repair with and without foreskin reconstruction by the same surgeon. Between September 2002 and June 2007, 215 children with distal hypospadias underwent stented TIPU by a single surgeon. Of these, 25 (glanular 8, coronal 17) underwent a two-layer FSR without dartos flap coverage. An age- and time-matched group of 49 patients (glanular 10, coronal 39) who underwent TIPU with dartos flap coverage without foreskin reconstruction (NoFSR) were selected for comparison. Operative time and complications were recorded. There was no significant difference in severity of hypospadias and follow-up duration (mean 17 vs 19 months, P=0.57) between the two groups. Operative time ranged between 30 and 86min (mean 57) in the FSR group and 35 and 113min (mean 75) in the NoFSR group (P</=0.01). Initial retraction of the foreskin by the surgeon at 6-8 weeks was successful in 15; five of the six who failed initial retraction responded to steroid cream. Four (16%) children underwent redo surgery in the FSR group (urethrocutaneous fistula in three, circumcision for recalcitrant phimosis in one). In the NoFSR group, six (12.2%) underwent redo surgery (urethrocutaneous fistula in four, removal of redundant skin in two). There was no significant difference in the need for redo surgery (P=0.45) or incidence of fistula (P=0.43) between the groups. There was no statistical difference in outcome between the two techniques, particularly regarding fistula complication. The complication particular to FSR, namely initial failure of foreskin retraction, responds adequately to steroid cream application. Foreskin reconstruction is a surgical alternative in selected patients, particularly those with distal hypospadias and a personal preference of no circumcision. Larger prospective studies are needed to ascertain similarity in outcome between FSR urethroplasty and the conventional urethroplasty with dartos coverage.


Epidemiology of nosocomial infection in 125 Italian intensive care units.
A continuous infection surveillance program was conducted by GiViTI throughout 2006 in Intensive Care Units (ICUs). This was a prospective epidemiological study carried out in 125 Italian intensive care units. All patients have been included in the study. Aside from the detailed clinical information collected for all patients, in cases of infection upon ICU admission and for the first site-specific episode that occurred during the patient's stay, the following data were collected: severity upon admission, micro-organisms and their antibiotic resistance patterns, subsequent multiple episodes in the same site, origin of infections and maximum severity reached. The diagnostic criteria for all infections are explicitly stated. A total of 34,472 patients entered the study. Infection upon admission was present in 12.6% of patients, with a high level of ICU and hospital mortality (29.4% and 38.7%, respectively). In 3148 patients one or more infections were reported as ICU-acquired with an overall incidence of 9.1% and an ICU and hospital mortality of 27.2% and 35.1%, respectively. Out of the device-related infections, ventilator-associated pneumonia was the most frequently diagnosed (8.9/1000 days on ventilator). Catheter-related blood stream infection was reported with a low incidence (1.9/1000 central venous catheter days). Nearly 20% of more than 5000 isolated microorganisms were classified as multi-drug resistant, with methicillin-resistant Staphylococcus aureus as the most frequently reported bug. The ad hoc expanded GiViTI software "Margherita2" allows continuous infection surveillance in Italian ICUs, annually providing an extensive and updated database. Interventions to improve infection prevention and patient safety should be tailored to accommodate these data.


Dynamic repositioning of CD4 and CD8 genes during T cell development.
Although stable repression of CD4 and CD8 genes is a central feature of T cell lineage commitment, we lack detailed information about the timing and mechanism of this repression. Stable gene repression has been linked to the position of genes within the nucleus. Therefore, information about the nuclear position of CD4 and CD8 genes during T cell development could provide insights into both the mechanism of regulation of CD4 and CD8 genes, and the process of lineage commitment. Here, we report that lineage-specific repression of CD4 and CD8 genes is associated with the repositioning of alleles close to heterochromatin. We also provide evidence that the relocalization of CD4 and CD8 genes to heterochromatin can occur as an early response to positive selection signals. We discuss our results in terms of our current knowledge of CD4 and CD8 gene regulation and CD4 versus CD8 lineage commitment.


Optimized multi-site local orbitals in the large-scale DFT program CONQUEST.
We introduce numerical optimization of multi-site support functions in the linear-scaling DFT code CONQUEST. Multi-site support functions, which are linear combinations of pseudo-atomic orbitals on a target atom and those neighbours within a cutoff, have been recently proposed to reduce the number of support functions to the minimal basis while keeping the accuracy of a large basis [J. Chem. Theory Comput., 2014, 10, 4813]. The coefficients were determined by using the local filter diagonalization (LFD) method [Phys. Rev. B: Condens. Matter Mater. Phys., 2009, 80, 205104]. We analyse the effect of numerical optimization of the coefficients produced by the LFD method. Tests on crystalline silicon, a benzene molecule and hydrated DNA systems show that the optimization improves the accuracy of the multi-site support functions with small cutoffs. It is also confirmed that the optimization guarantees the variational energy minimizations with multi-site support functions.


[Primary (idiopathic) cardiomyopathies].
The lecture gives the clinical and morphological characteristics of different forms of primary (idiopathic) cardiomyopathies. It presents macroscopic, histological, and ultrastructural changes in primary cardiomyopathies.


Deleterious effects of Schinus terebinthifolius Raddi seed flour on cowpea weevil, Callosobruchus maculatus (F.), larval development.
Schinus terebinthifolius, Raddi, has been extensively studied due to its anti-inflammatory and antibiotic properties. S. terebinthifolius was also toxic to some insects, however little has been explored about the nature of its insecticide compounds or the toxicity of this plant to insect species. In this work, we investigate the toxicity of S. terebinthifolius seed flour against the insect C. maculatus. S. terebinthifolius seed flour interfered with the post hatch development of the C. maculatus larvae, decreasing larval survival, mass and length. Using DEAE-cellulose chromatography, five protein fractions were isolated, a non-retained fraction (NRF) and four retained fractions, eluted with 0.25, 0.5, 0.7 and 1.0 M NaCl. Proteins with varying molecular masses were observed in all fractions. The majority protein bands were identified by mass spectrometry analysis and among the main identified proteins are 11S globulins (such glycinin), lipoxygenase, chitinases, 7S globulins (vicilins, canavalin and β conglycinin), annexin, catalase and sucrose binding protein. All DEAE-protein fractions were toxic to the insect, interfering with the post hatch larval development and survival. Decreases greater than 90% were observed in the larval mass and length at 20 days after oviposition (DAO) for larvae raised on diet containing 0.5% of some fractions. Alterations in the level of proteins, glucose and in the activity of the enzymes lipases and cysteine proteases were also detected in these larvae. Our results show that seeds of S. terebinthifolius have an arsenal of toxic proteins with potential for the control of the insect C. maculatus.


Stimulus content and the neural correlates of source memory.
It has been suggested that several regions of the brain, including subregions of the medial temporal lobe (MTL) and the posterior parietal cortex, contribute to source memory success in a material-general manner, with most models highlighting the importance of memory process rather than material type. For the MTL in particular, however, increasing evidence suggests that MTL subregions may be specialized for processing different materials, raising the possibility that source memory-related activity may be material-sensitive. Previous fMRI studies have not directly compared source memory activity for different categories of stimuli, and it remains unclear whether source memory effects, in the MTL or elsewhere, are influenced by material. To investigate this issue, young participants were scanned during study while they made semantic judgments about words, pictures of objects and scenes, and during test when they retrieved the context (source) in which these items were studied. Several regions, including the hippocampi, medial and lateral parietal cortex, exhibited source memory effects common to words, objects and scenes, at both study and test. Material-dependent source memory effects were also identified in the left posterior inferior frontal and left perirhinal cortex for words and objects, respectively, at study but not test. These results offer direct support for the hypothesis that the MTL and posterior parietal cortex make material-general contributions to recollection. These results also point to a dissociation between encoding and retrieval with regard to the influence of material on the neural correlates of source memory accuracy, supporting the idea that a relatively small proportion of the activity elicited by a stimulus during encoding is incorporated into an episodic memory representation of the stimulus.


Effect of skeletal muscle fiber type on the pressor response evoked by static contraction in rabbits.
The purpose of this study was to determine whether the reflex hemodynamic responses to static contraction of predominately glycolytic muscle are greater than the changes elicited by primarily oxidative muscle. Low-frequency electrical stimulation (continuous 21 days) of the tibial nerve of one hindlimb of adult rabbits converted the metabolic characteristics of the predominately glycolytic gastrocnemius to a muscle that was primarily oxidative. After 21 days of stimulation, the rabbits were decerebrated, and static contraction of the glycolytic muscle (unstimulated gastrocnemius) initially decreased heart rate (HR; -16 +/- 3 beats/min) and mean arterial pressure (MAP; -17 +/- 3 mmHg). Thereafter, MAP increased 13 +/- 3 mmHg above baseline. Static contraction of the oxidative muscle (stimulated gastrocnemius) produced similar decreases in HR and MAP (-12 +/- 4 beats/min and -12 +/- 3 mmHg, respectively). However, the subsequent increase in MAP (8 +/- 3 mmHg; above baseline) was less than that evoked by contraction of the glycolytic muscle. The responses evoked by stretch of each muscle and high-intensity electrical stimulation were the same, indicating that the afferents from the muscle were not destroyed by the chronic-stimulation technique. These results support the hypothesis that metabolic by-products play a role in the pressor response to static contraction of skeletal muscle. In addition, these data confirm that contraction of predominately oxidative muscle can evoke a reflex pressor response, albeit smaller than the change elicited from primarily glycolytic muscle.


Group occupational health service in a developing country.
In 1967 an experimental group occupational health service was set up in Dar es Salaam to provide direct service to industrial firms. Larger companies were visited by a doctor, smaller firms in rotation by auxiliaries. After three years 65 companies had joined with over 15,000 employees, and workers were attending the group dispensaries at a rate of over 250,000 visits a year. Such an approach through direct service to the working community appears to be more appropriate to a developing country than a purely advisory central occupational health unit.


Facilitating Healthier Eating at Restaurants: A Multidisciplinary Scoping Review Comparing Strategies, Barriers, Motivators, and Outcomes by Restaurant Type and Initiator.
Restaurants are understudied yet increasingly important food environment institutions for tackling diet-related diseases. This scoping review analyzes research and gray literature (n = 171 records) to assess which healthy eating promotion strategies have been implemented in restaurants and the associated motivations, barriers, and outcomes, compared by restaurant type (corporate/chain vs. independently owned restaurants) and initiator (restaurant-initiated vs. investigator-initiated). We found that the most commonly reported strategy was the increase of generally healthy offerings and the promotion of such offerings. Changes in food availability were more common among corporate restaurants and initiated by restaurants, while environmental facilitators were more commonly initiated by investigators and associated with independently owned restaurants. Aside from those associated with revenue, motivations and barriers for healthy eating promoting strategies varied by restaurant type. While corporate restaurants were also motivated by public health criticism, independently owned restaurants were motivated by interests to improve community health. Revenue concerns were followed by food sourcing issues in corporate restaurants and lack of interest among independently owned restaurants. Among reporting sources, most outcomes were revenue positive. This study shows the need for practice-based evidence and accounting for restaurant business models to tailor interventions and policies for sustained positive changes in these establishments.


A novel high-throughput vaccinia virus neutralization assay and preexisting immunity in populations from different geographic regions in China.
Pre-existing immunity to Vaccinia Tian Tan virus (VTT) resulting from a large vaccination campaign against smallpox prior to the early 1980s in China, has been a major issue for application of VTT-vector based vaccines. It is essential to establish a sensitive and high-throughput neutralization assay to understand the epidemiology of Vaccinia-specific immunity in current populations in China. A new anti-Vaccinia virus (VACV) neutralization assay that used the attenuated replication-competent VTT carrying the firefly luciferase gene of Photinus pyralis (rTV-Fluc) was established and standardized for critical parameters that included the choice of cell line, viral infection dose, and the infection time. The current study evaluated the maintenance of virus-specific immunity after smallpox vaccination by conducting a non-randomized, cross-sectional analysis of antiviral antibody-mediated immune responses in volunteers examined 30-55 years after vaccination. The rTV-Fluc neutralization assay was able to detect neutralizing antibodies (NAbs) against Vaccinia virus without the ability to differentiate strains of Vaccinia virus. We showed that the neutralizing titers measured by our assay were similar to those obtained by the traditional plaque reduction neutralization test (PRNT). Using this assay, we found a low prevalence of NAb to VTT (7.6%) in individuals born before 1980 from Beijing and Anhui provinces in China, and when present, anti-VTT NAb titers were low. No NAbs were detected in all 222 samples from individuals born after 1980. There was no significant difference observed for titer or prevalence by gender, age range and geographic origin. A simplified, sensitive, standardized, reproducible, and high-throughput assay was developed for the quantitation of NAbs against different Vaccinia strains. The current study provides useful insights for the future development of VTT-based vaccination in Beijing and Anhui provinces of China.


Detection of equine arteritis virus (EAV)-specific cytotoxic CD8+ T lymphocyte precursors from EAV-infected ponies.
Equine arteritis virus (EAV) causes a systemic infection in equids with variable outcome, ranging from subclinical infections to severe disease, and also has the capacity to induce abortion in pregnant mares and persistent infections in stallions. The serum virus-neutralizing antibody response that invariably develops in the infected animal lasts for many months or years and is believed to play an important role in virus clearance. However, very little is known about cellular immunity against EAV because of a lack of methods for evaluating these immune responses. In the present study, we describe methods for detecting cytotoxic T lymphocyte (CTL) precursors in the peripheral blood of EAV-convalescent ponies using a (51)Cr release cytolysis assay. Primary equine dermal cells, used as CTL targets, were shown to express MHC I but not MHC II and to retain (51)Cr efficiently and support EAV replication. Peripheral blood mononuclear cells (PBMC) collected from EAV-convalescent ponies that had been incubated with or without live EAV were used as effectors. EAV-induced PBMC cultures showed evidence of expansion and activation of lymphoblasts, with an increase in the CD8(+)/CD4(+) ratio in comparison with mock-induced PBMC. The cytotoxicity induced by EAV-stimulated PBMC was virus specific, showed genetic restriction, was mediated by CD8(+) T lymphocytes and could be detected for periods of 4 months to more than 1 year post-infection. These findings and methods will hopefully contribute to an understanding of virus-host interactions in horses, in particular the mechanisms of virus clearance occurring during EAV infection.


Deep whole-genome sequencing of multiple proband tissues and parental blood reveals the complex genetic etiology of congenital diaphragmatic hernias.
The diaphragm is critical for respiration and separation of the thoracic and abdominal cavities, and defects in diaphragm development are the cause of congenital diaphragmatic hernias (CDH), a common and often lethal birth defect. The genetic etiology of CDH is complex. Single-nucleotide variants (SNVs), insertions/deletions (indels), and structural variants (SVs) in more than 150 genes have been associated with CDH, although few genes are recurrently mutated in multiple individuals and mutated genes are incompletely penetrant. This suggests that multiple genetic variants in combination, other not-yet-investigated classes of variants, and/or nongenetic factors contribute to CDH etiology. However, no studies have comprehensively investigated in affected individuals the contribution of all possible classes of variants throughout the genome to CDH etiology. In our study, we used a unique cohort of four individuals with isolated CDH with samples from blood, skin, and diaphragm connective tissue and parental blood and deep whole-genome sequencing to assess germline and somatic de novo and inherited SNVs, indels, and SVs. In each individual we found a different mutational landscape that included germline de novo and inherited SNVs and indels in multiple genes. We also found in two individuals a 343 bp deletion interrupting an annotated enhancer of the CDH-associated gene GATA4, and we hypothesize that this common SV (found in 1%-2% of the population) acts as a sensitizing allele for CDH. Overall, our comprehensive reconstruction of the genetic architecture of four CDH individuals demonstrates that the etiology of CDH is heterogeneous and multifactorial.


Early post-cardiac surgery delirium risk factors.
The purpose of this study was to identify the post-cardiac surgery delirium risk factors and to evaluate clinical outcomes. Data on 90 patients with postoperative delirium after cardiac surgery on cardiopulmonary bypass (CPB) were analyzed retrospectively. The patients were divided into two groups by evaluating the severity of the delirium: light and moderate delirium group (n=74) and severe delirium group (n=16). We found that the rate of early post-cardiac surgery delirium was low (4.17%). We have determined that post-cardiac surgery delirium prolonged the length of stay in the Intensive Care Unit (ICU) by (8.4 (8.6)) and the hospital stay by (23.6 (13.0)) days. The patients had higher preoperative risk scores, their age was 71.5 (8.9) years, the body mass index was 28.8 (4.4) kg/m(2), the majority were male (72.2%), and the left ventricular ejection fraction was 46.1(11.9) %. Statistical analysis by multivariable logistic regression has indicated that increasing the dose of fentanyl administered during surgery over 1.4 mg also increased the possibility of developing a severe delirium (OR=29.4, CI 4.1-210.3) and longer aortic clamping time could be independently associated with severe postoperative delirium (OR=8.0, CI 1.7-37.2). After surgery, new atrial fibrillation (AF) episodes amounted to 53.3% and, after distinguishing the delirium severity groups, AF developed in the patients belonging to the severe delirium groups statistically significantly more frequently, 81.8 vs 47.3, where p=0.01. Our data suggest that early post-cardiac surgery delirium is not a common complication, but it prolonged the length of stay at the ICU and in the hospital. The delirium risk factors, such as longer aortic clamping time, the dose of fentanyl and new atrial fibrillation episodes occurring after cardiac surgery, are associated statistically significantly with the development of severe post-cardiac surgery delirium.


[Supra-fascial elevated free forearm flap--indications, surgical technique and follow-up examination of the donor site defect].
From March 1995 to May 1997, 66 free radial forearm flaps were used for orofacial reconstructions. All flaps were elevated following the suprafascial technique. Donor-site closure was performed with split-thickness skin grafts in 54 cases, and with full-thickness skin grafts in 12 patients. Investigations after six months included grip strength, pulp-to-pulp pinch strength, range of motion as compared to preoperative values, aesthetical self-assessment, cold intolerance, and dysesthesias. The latter evaluation could be performed in 42 patients, whereas the complete follow-up protocol included 36 patients. Primary wound healing with immediate complete take of skin grafts was achieved in 93.9%. Grip strength and pulp-to-pulp pinch strength showed no decrease postoperatively. An impairment of range of motion of the wrist was observed in 2.8%. There was no cold intolerance. Aesthetical outcome was rated as good or fair in 97.3%. Slight numbness distally to the donor-site was found in 59.5%. The results of this prospective study show a superiority of suprafascial elevation of the radial foream flap as compared to the classic elevation technique, particularly in a higher rate of primary wound healing, thus avoiding impairment of range of motion and strength of the donor hand.


Immature Platelet Dynamics in Immune-Mediated Thrombocytopenic States.
A major challenge encountered by clinicians is differentiating presentations characterized by significant thrombocytopenia due to overlapping clinical symptoms and signs in the setting of ambiguous laboratory results. Immature platelets represent the youngest platelets that can be measured in peripheral blood by current hematology analyzers. These young platelets are larger, with higher RNA content recently released from the bone marrow. Thrombocytopenic presentations caused directly or indirectly by immune responses can lead to compensatory bone marrow responses seeking to normalize the platelet count; thus obtaining absolute immature platelet counts may be informative while triaging patients. Over the last decade, their use has expanded beyond being an early biomarker of bone marrow reconstitution post-hematopoietic stem cell transplantation to being used to establish bone marrow responses to infection and thrombocytopenias due to immune etiologies. Its accessibility as part of more detailed platelet indices obtained with routine laboratories makes it a promising option to understand the bone marrow's real-time response to disease states characterized by thrombocytopenia. This review will look at the immature platelet count as a biomarker, while presenting current attempts trying to understand how it could be used in thrombocytopenias occurring secondary to a given immune etiology.