Networks in Canadian paediatric surgery: Time to get connected.
There has been a recent trend of improved outcomes for most infants born with surgically correctable congenital malformations, despite the fact that current surgical treatment is not standardized, with wide variations in practice among institutions. Because care for these infants is multidisciplinary, it is difficult to ascertain with clarity the specific role of neonatal surgery in determining outcomes. Moreover, the lack of validated measures of illness severity for most complex congenital malformations makes risk adjustment difficult. For these reasons, the utility of randomized controlled trials in determining best surgical practice in neonatal surgery for congenital malformations is impractical, and another means of deriving medical evidence to justify 'optimal' treatment is necessary.The Canadian Paediatric Surgical Network (CAPSNet) was developed specifically to address these issues. Patterned after the highly successful Canadian Neonatal Network, CAPSNet collects standardized data on every case of gastroschisis and congenital diaphragmatic hernia evaluated in the 16 referral perinatal centres in Canada. These centres serve as provincial referral centres for perinatal care, and, therefore, the data set created is population-based for gastroschisis and congenital diaphragmatic hernia in Canada. In addition to neonatal data fields recorded in the Canadian Neonatal Network, CAPSNet collects specific prenatal data, and details on surgical treatment and outcomes within each of the 16 participating centres. It is hoped that by using advanced analytical techniques, including outcomes modelling and multiple logistic regression analysis of risk-adjusted outcome variations by type of surgery performed, optimal treatment paradigms will be identified that will lead to further outcome improvement in babies born with complex birth defects.


p62/sequestosome-1 associates with and sustains the expression of retroviral restriction factor TRIM5alpha.
TRIM5 proteins mediate a potent block to the cross-species transmission of retroviruses, the most well known being the TRIM5alpha protein from rhesus macaques, which potently inhibits human immunodeficiency virus type 1 (HIV-1) infection. This restriction occurs at an early stage in the replication cycle and is mediated by the binding of TRIM5 proteins to determinants present in the retroviral capsid. TRIM5alpha, as well as other TRIM family proteins, has been shown to be regulated by interferons (IFN). Here we show that TRIM5alpha associates with another IFN-induced gene, sequestosome-1/p62 (p62). p62 plays a role in several signal transduction cascades that are important for maintaining the antiviral state of cells. Here we demonstrate that p62 localizes to both human and rhesus macaque TRIM5alpha cytoplasmic bodies, and fluorescence resonance energy transfer (FRET) analysis demonstrates that these proteins closely associate in these structures. When p62 expression was knocked down via small interfering RNA (siRNA), the number of TRIM5alpha cytoplasmic bodies and the level of TRIM5alpha protein expression were reduced in cell lines stably expressing epitope-tagged versions of TRIM5alpha. In accordance with these data, p62 knockdown resulted in reduced TRIM5alpha-mediated retroviral restriction in cells expressing epitope-tagged TRIM5alpha or expressing endogenously expressed human TRIM5alpha. p62 may therefore operate to enhance TRIM5alpha-mediated retroviral restriction, contributing to the antiviral state of cells following IFN treatment.


Mixed allogeneic chimerism to induce tolerance to solid organ and cellular grafts.
Transplantation of solid organs and cellular grafts has become clinical routine in the last 30 years. However, the requirement for life-long immunosuppression is associated with infections, malignancies and end-organ toxicity. Moreover, the treatment fails to prevent chronic rejection. The induction of donor-specific transplantation tolerance would solve these problems, but has remained an elusive goal. One approach to achieve transplantation tolerance is through hematopoietic chimerism. This review outlines different concepts of hematopoietic chimerism focusing on macrochimerism. Mixed allogeneic chimerism, also known as macrochimerism, is defined as engraftment of hematopoietic stem cells achieved by bone marrow transplantation (BMT). It discusses the advantages and limitations of the BMT as well as approaches to overcome these limitations in the future.


Seeing eye-to-eye: do intergroup biases operate similarly for younger and older adults?.
Because of their relatively temporary group memberships, age groups represent an intriguing test of theories of intergroup relations. In spite of this unique feature, virtually no research has examined age group relations from an intergroup perspective. The present study investigated the role of two influential intergroup factors, degree of group identification and threats to group status, in younger and older adults' evaluations of their ingroup (own age group) and the outgroup (other age group). Participants were placed in situations in which their ingroup was either superior or inferior to the outgroup. Several measures of bias were then assessed, including ingroup favoritism, perceived similarity, social distance, outgroup homogeneity, and self-stereotyping. The results support the notion that age groups are unique from other groups, as age influenced all forms of bias. In particular, young adults exhibited more biases than older adults by perceiving less similarity and distancing themselves more from the outgroup. These findings suggest that older adults' greater familiarity with the outgroup might attenuate their age-based biases compared with younger participants.


A reproducible canine model of nonocclusive mesenteric ischemia.
A technique for producing a reliable, clinically applicable, and highly reproducible canine model of nonocclusive mesenteric ischemia was developed. Following left thoracotomy in 10 dogs, a 1 mm diameter soft polyethylene tube was inserted into the pericardial space via a small puncture site. This tube was sealed in place with cyanoacrylate tissue adhesive. A solution of 10% Dextran 40 in saline was infused into the pericardial space until a 50% reduction (as monitored by electromagnetic flowmeter) in superior mesenteric artery flow (SMAQ) was obtained. Without additional intrapericardial infusion of the Dextran solution, SMAQ was reduced 51 +/- 4% to 54 +/- 3% of control values during a 60 minute post-tamponade observation period. During the same time. Cardiac output was depressed between 40 +/- 8% and 54 +/- 3%, and right atrial pressure remained elevated between 164 +/- 15% and 171 +/- 15%. Systemic arterial pressure initially dropped 28 +/- 5% but compensated to within 11 +/- 5% of pre-tamponade level at 60 minutes. The stability of this model is well suited for evaluating new experimental diagnostic and therapeutic procedures.


Carbon Vacancy-Enhanced Activity of Fe-N-C Single Atom Catalysts toward Luminol Chemiluminescence in the Absence of H2O2.
The classic luminol-H2O2 chemiluminescence (CL) systems suffer from easy self-decomposition of H2O2 at room temperature, hindering the practical applications of the luminol-H2O2 CL system. In this work, unexpectedly, we found that the carbon vacancy-modified Fe-N-C single atom catalysts (VC-Fe-N-C SACs) can directly trigger a luminol solution to generate strong CL emission in the absence of H2O2. The Fe-based SACs were prepared through the conventional pyrolysis of zeolitic imidazolate frameworks. The massive carbon vacancies were readily introduced into Fe-N-C SACs through a tannic acid-etching process. Carbon vacancy significantly enhanced the catalytic activity of Fe-N-C SACs on the CL reaction of luminol-dissolved oxygen. The VC-Fe-N-C SACs performed a 13.4-fold CL enhancement compared with the classic luminol-Fe2+ system. It was found that the introduction of a carbon vacancy could efficiently promote dissolved oxygen to convert to reactive oxygen species. As a proof of concept, the developed CL system was applied to detect alkaline phosphatase with a linear range of 0.005-1 U/L as well as a detection limit of 0.003 U/L. This work demonstrated that VC-Fe-N-C SAC is a highly efficient CL catalyst that can promote the analytic application of the luminol CL system.


The Effects of Phosphate Impurity on Recovered LiNi0.6Co0.2Mn0.2O2 Cathode Material via a Hydrometallurgy Method.
From portable electronics to electric vehicles, lithium-ion batteries have been deeply integrated into our daily life and industrial fields for a few decades. The booming field of battery manufacturing could lead to shortages in resources and massive accumulation of battery waste, hindering sustainable development. Therefore, hydrometallurgy-based approaches have been widely used in industrial recycling to recover cathode materials due to their high efficiency and throughput. Impurities have always been a great challenge for hydrometallurgical recycling, introducing challenges to maintain the consistency of product quality because of potential unintended effects caused by impurities. Herein, after comprehensive investigation, we first report the impacts of phosphate impurity on a recycled LiNi0.6Co0.2Mn0.2O2 ("NCM622") cathode via a hydrometallurgy method. We demonstrate that a passivation layer of Li3PO4 is formed at grain boundaries during sintering, which significantly raises the activation barrier and hinders lithium diffusion. In addition, the distinct degradation of cathode electrochemical properties is observed from poor particle morphology and high cation mixing as a result of phosphate impurity. Cathode powders with 1 at. % phosphate impurity retain a capacity of 146 mAh/g after 100 cycles at 0.33C, 6% less than that of a virgin cathode. Furthermore, cathodes with higher phosphate concentrations perform even worse in electrochemical tests. Therefore, phosphate impurities are detrimental to the hydrometallurgical recycling of NCM cathode materials and need to be excluded from the recycling process.


Acne and sebaceous gland function.
The embryologic development of the human sebaceous gland is closely related to the differentiation of the hair follicle and the epidermis. The number of sebaceous glands remains approximately the same throughout life, whereas their size tends to increase with age. The development and function of the sebaceous gland in the fetal and neonatal periods appear to be regulated by maternal androgens and by endogenous steroid synthesis, as well as by other morphogens. The most apparent function of the glands is to excrete sebum. A strong increase in sebum excretion occurs a few hours after birth; this peaks during the first week and slowly subsides thereafter. A new rise takes place at about age 9 years with adrenarche and continues up to age 17 years, when the adult level is reached. The sebaceous gland is an important formation site of active androgens. Androgens are well known for their effects on sebum excretion, whereas terminal sebocyte differentiation is assisted by peroxisome proliferator-activated receptor ligands. Estrogens, glucocorticoids, and prolactin also influence sebaceous gland function. In addition, stress-sensing cutaneous signals lead to the production and release of corticotrophin-releasing hormone from dermal nerves and sebocytes with subsequent dose-dependent regulation of sebaceous nonpolar lipids. Among other lipid fractions, sebaceous glands have been shown to synthesize considerable amounts of free fatty acids without exogenous influence. Sebaceous lipids are responsible for the three-dimensional skin surface lipid organization. Contributing to the integrity of the skin barrier. They also exhibit strong innate antimicrobial activity, transport antioxidants to the skin surface, and express proinflammatory and anti-inflammatory properties. Acne in childhood has been suggested to be strongly associated with the development of severe acne during adolescence. Increased sebum excretion is a major factor in the pathophysiology of acne vulgaris. Other sebaceous gland functions are also associated with the development of acne, including sebaceous proinflammatory lipids; different cytokines produced locally; periglandular peptides and neuropeptides, such as corticotrophin-releasing hormone, which is produced by sebocytes; and substance P, which is expressed in the nerve endings at the vicinity of healthy-looking glands of acne patients. Current data indicate that acne vulgaris may be a primary inflammatory disease. Future drugs developed to treat acne not only should reduce sebum production and Propionibacterium acnes populations, but also should be targeted to reduce proinflammatory lipids in sebum, down-regulate proinflammatory signals in the pilosebaceous unit, and inhibit leukotriene B(4)-induced accumulation of inflammatory cells. They should also influence peroxisome proliferator-activated receptor regulation. Isotretinoin is still the most active available drug for the treatment of severe acne.


Histologic evaluation of socket augmentation with mineralized human allograft.
Socket augmentation performed at the time of tooth extraction has been recommended by many authors, since successful socket augmentation may reduce or eliminate the need for future ridge grafts. An augmentation procedure is described here, along with histologic and histomorphometric findings. Five patients (three men, two women; mean age 56 years) were recruited for this pilot study, and seven sites were treated. Solvent-preserved mineralized cancellous allograft was used to fill each socket up to the bone crest (2 mm below soft tissue surface), and sites were covered with a bioabsorbable collagen wound dressing. Core biopsies were taken from the center of extraction sockets 5 to 6 months after augmentation. Histologic evaluation of the prepared biopsies showed formation and remodeling of trabecular bone in areas of mineralized cancellous allografts and no signs of inflammation. Histomorphometric analysis of the samples showed an average of 68.5% vital bone, 3.8% residual graft particles, and 27.7% of connective tissue/bone marrow. In addition, vital bone and connective tissues were seen in close contact with the remaining allograft. These data suggest that this combination of human mineralized bone and absorbable collagen wound dressing is a suitable technique for socket augmentation. Nevertheless, future controlled clinical trials with larger sample sizes are recommended to validate the findings of the current technique.


[Histochemical study of the enzymatic activity of cultivated human macroglial brain tumors].
A histichemical study is presented of the activity of some redox enzymes (succinate dehydrogenase, malate dehydrogenase, NAD-diaphorase and lactate dehydrogenase) in 37 cultured human glial brain tumours. The stages of cell activity at different periods of tumour cultivation and the level of their differentiation in the initial tissue were taken into consideration. The examined tumour cultures showed enzymatic cell polymorphizm. During of period of adaptation of explants, the activity of the Krebs cycle enzymes was low to increase during differentiation and proliferation of cultures. The activity of lactate dehydrogenase elevated in tumour cells from cultures of dedifferentiated astrocytomas and glioblastomas mith marked anaplasia. The activity of this enzyme increased also in the course of advanced necrobiotic changes in the tumour cells.


Assessment of ebola virus disease, health care infrastructure, and preparedness - four counties,Southeastern Liberia, august 2014.
Ebola virus disease (Ebola) is a multisystem disease caused by a virus of the genus Ebolavirus. In late March 2014, Ebola cases were described in Liberia, with epicenters in Lofa County and later in Montserrado County. While information about case burden and health care infrastructure was available for the two epicenters, little information was available about remote counties in southeastern Liberia. Over 9 days, August 6-14, 2014, Ebola case burden, health care infrastructure, and emergency preparedness were assessed in collaboration with the Liberian Ministry of Health and Social Welfare in four counties in southeastern Liberia: Grand Gedeh, Grand Kru, River Gee, and Maryland. Data were collected by health care facility visits to three of the four county referral hospitals and by unstructured interviews with county and district health officials, hospital administrators, physicians, nurses, physician assistants, and health educators in all four counties. Local burial practices were discussed with county officials, but no direct observation of burial practices was conducted. Basic information about Ebola surveillance and epidemiology, case investigation, contact tracing, case management, and infection control was provided to local officials.


The long-term outcomes of transcoronary ablation of septal hypertrophy compared to surgical myectomy in patients with symptomatic hypertrophic obstructive cardiomyopathy.
The aim of this study was to compare the long-term outcomes of transcoronary ablation of septal hypertrophy (TASH) with open surgical myomectomy (SM) in patients with symptomatic hypertrophic obstructive cardiomyopathy (HOCM). We reviewed patients who underwent either procedure at our institution. The demographics, clinical outcomes, echocardiographic parameters, and complications were compared. Seventy patients with HOCM were treated with either TASH (n = 47, 26 male) or SM (n = 23, 10 male). Compared to those treated with SM, patients undergoing TASH were older (57+/- 14.7 years versus 47 +/- 20.6 years, P = 0.021) and more symptomatic. A higher proportion of patients had syncope as a presenting feature in the TASH group compared to the SM group (57.5% vs. 17.4%, P = 0.002) respectively. They were also more likely to be in New York Heart Association (NYHA) class III/IV compared to the patients who underwent SM (85.1% vs. 39.1%; P < 0.001). Patients were followed for a mean period of 43 months (TASH) and 46 months (SM). Repeat procedures were more common in the TASH group (17% vs. 0%, P = 0.04) but mitral valve replacement was more common in the SM group (0% vs. 8.7%, P = 0.105). Symptom improvement, the rate of complications and all cause mortality rates were similar in both groups. TASH compares favorably with surgical myectomy with regard to symptom resolution, rate of complications and mortality in a tertiary referral centre and should be seen as an attractive alternative to surgical myectomy in the appropriate patient population.


A phage display selection of engrailed homeodomain mutants and the importance of residue Q50.
Mutants of engrailed homeodomain (HD) that retain DNA-binding activity were isolated using a phage display selection. This selection was used to enrich for active DNA-binding clones from a complex library consisting of over a billion members. A more focused library of mutant homeodomains consisting of all possible amino acid combinations at two DNA-contacting residues (I47 and Q50) was constructed and screened for members capable of binding tightly and specifically to the engrailed consensus sequence, TAATTA. The isolated mutants largely recapitulated the distribution of amino acids found at these positions in natural homeodomains thus validating the in vitro selection conditions. In particular, the unequivocal advantage enjoyed by glutamine at residue 50 is surprising in light of reports that minimize the importance of this residue. Here, the subtle contributions of residue Q50 are demonstrated to play a functionally important role in specific recognition of DNA. These results highlight the complex subtlety of protein-DNA interactions, underscoring the value of the first reported in vitro selection of a homeodomain.


Image Diagnostic Classification of Magnetic Resonance T2 Increased Signal Intensity in Cervical Spondylotic Myelopathy: Clinical Evaluation Using Quantitative and Objective Assessment.
A prospective imaging study. The study investigated whether the classification of increased signal intensity (ISI) using magnetic resonance imaging (MRI) reflects the severity of symptoms in patients with cervical spondylotic myelopathy (CSM). Although the ISI on MRI in patients with CSM is observed, the degree of ISI has not been examined. The association between ISI and the surgical outcomes in cervical myelopathy remains controversial. A total of 505 consecutive patients with CSM (311 males; 194 females) were enrolled. The mean age was 66.6 years (range, 41-91 yrs), with an average postoperative follow-up period of 26.5 ± 12.5 months. The ISI was classified into three groups based on sagittal T2-weighted MRI as follows: Grade 0, none; Grade 1, light (obscure); and Grade 2, intense (bright). Pre- and postoperative neurological status was evaluated using the Japanese Orthopedic Association scoring system for cervical myelopathy (JOA score) and quantifiable tests, including the 10-s grip and release test (10-s G&R test) and the 10-s step test. The preoperative MRI showed 168 patients in Grade 0, 169 patients in Grade 1, and 168 in Grade 2, with no age differences among three groups. Grade 2 patients had a longer duration of symptom compared with the other grades. Grade 0 patients had a better postoperative JOA score and recovery rate compared with the other grades. The preoperative and postoperative scores in the G&R test and steps were better in the Grade 0 patients compared with the other grades. Grade 1 and 2 patients had similar outcomes and recovery rates. ISI on MRI in patients with CSM was prospectively classified into three grades. The ISI grading was not associated with the preoperative severity of myelopathy and outcomes. 2.


Abrupt-onset severe headaches.
Thunderclap headache, a severe headache which is maximal in intensity at onset, is associated with numerous underlying disorders, including subarachnoid hemorrhage, unruptured intracranial aneurysm, cervical artery dissection, cerebral venous sinus thrombosis, stroke, intracranial hemorrhage, reversible cerebral vasoconstriction syndrome, and reversible posterior leukoencephalopathy. After exclusion of all possible causes, thunderclap headache may be considered a primary headache. This review summarizes the diagnostic considerations and clinical approach to thunderclap headache, with particular emphasis on the reversible cerebral vasoconstriction syndromes.


Network Compression: Worst Case Analysis.
We study the problem of communicating a distributed correlated memoryless source over a memoryless network, from source nodes to destination nodes, under quadratic distortion constraints. We establish the following two complementary results: 1) for an arbitrary memoryless network, among all distributed memoryless sources of a given correlation, Gaussian sources are least compressible, that is, they admit the smallest set of achievable distortion tuples and 2) for any memoryless source to be communicated over a memoryless additive-noise network, among all noise processes of a given correlation, Gaussian noise admits the smallest achievable set of distortion tuples. We establish these results constructively by showing how schemes for the corresponding Gaussian problems can be applied to achieve similar performance for (source or noise) distributions that are not necessarily Gaussian but have the same covariance.


Engineering the Substrate Specificity of a Modular Polyketide Synthase for Installation of Consecutive Non-Natural Extender Units.
There is significant interest in diversifying the structures of polyketides to create new analogues of these bioactive molecules. This has traditionally been done by focusing on engineering the acyltransferase (AT) domains of polyketide synthases (PKSs) responsible for the incorporation of malonyl-CoA extender units. Non-natural extender units have been utilized by engineered PKSs previously; however, most of the work to date has been accomplished with ATs that are either naturally promiscuous and/or located in terminal modules lacking downstream bottlenecks. These limitations have prevented the engineering of ATs with low native promiscuity and the study of any potential gatekeeping effects by domains downstream of an engineered AT. In an effort to address this gap in PKS engineering knowledge, the substrate preferences of the final two modules of the pikromycin PKS were compared for several non-natural extender units and through active site mutagenesis. This led to engineering of the methylmalonyl-CoA specificity of both modules and inversion of their selectivity to prefer consecutive non-natural derivatives. Analysis of the product distributions of these bimodular reactions revealed unexpected metabolites resulting from gatekeeping by the downstream ketoreductase and ketosynthase domains. Despite these new bottlenecks, AT engineering provided the first full-length polyketide products incorporating two non-natural extender units. Together, this combination of tandem AT engineering and the identification of previously poorly characterized bottlenecks provides a platform for future advancements in the field.


Laser-Induced Microsphere Hammer-Hit Vibration in Liquid.
We demonstrate a new principle of the laser-induced hammer-hit vibration of a micron-sized black sphere in liquid glycerol with a single divergent Gaussian beam. The light-induced Δα-photophoretic force, which is significantly improved by the vibrating speed of the microparticle, is responsible for both the pushing and pulling force of the hammer-hit vibration. Our approach expands the optical manipulation of microparticle hammer-hit vibration to a liquid medium and provides full control over the trapped particles, including the adjustment of the vibration frequency, amplitude, and position.


Photocatalytic reduction of Cr(VI) from agricultural soil column leachates using zinc oxide under UV light irradiation.
The photocatalytic reduction of Cr(VI) from agricultural soil leachates irrigated with Cr(VI)-containing waste hydroponic solution was evaluated in this work. For this purpose, zinc oxide was used as a catalyst under UV irradiation (lambda = 365 nm). The reduction of Cr(VI) was preliminarily evaluated on synthetic solutions with a concentration of 15 mg L(-1) to optimize the catalyst loading and the solution pH and to determine the effect of organic matter. Greater removal of Cr(VI) was observed at pH 7, and the optimum catalyst loading was found to be 2 g L(-1), which achieved an 84% Cr(VI) reduction in 6 h. The influence of dissolved organic matter on the reduction of Cr(VI) was evaluated through the addition of different concentrations of humic acid (HA) to the chromium solution. The removal of Cr(VI) was continuously enhanced as the HA concentration gradually increased from 0 to 14 mg L(-1). The percentage of hexavalent chromium reduction from soil leachates was in the range of 13-99%, and the rate constant was significantly enhanced by the presence of organic compounds in the soil pore water. Thus, a marked synergistic effect between the photocatalytic reduction of Cr(VI) and the organic matter in soil (e.g. humic substances) was observed in real samples and was similar to that observed in the Cr(VI) synthetic solution that contained HA.


Changing concepts in urological management of the congenital anomalies of kidney and urinary tract, CAKUT.
Recent advancement in ultrasonographic evaluation has prompted early detection and diagnosis of congenital anomalies in the kidney and urinary tract (CAKUT) in the asymptomatic phase. Consequently, early surgical intervention has become possible in the asymptomatic phase for the purpose of controlling manifestations early, thereby avoiding renal functional deterioration. However, some lesions detected by ultrasonography have been shown to often resolve or disappear without intervention. Thus, it has become more important to identify and understand the natural history of CAKUT. For the precise evaluation of the results of surgical intervention, one must understand the maturational process of renal function during infancy. Without considering this process, we cannot differentiate the renal significance of the surgical management from the natural course of CAKUT. Recent advancement in the field of radioisotopic studies has also made a major contribution to the more precise assessment of renal function. Recent progress in the understanding of the pathophysiology and the natural history of CAKUT has helped rationalize its treatment and management. Improvement in the surgical techniques and tools, together with improvements in pediatric anesthesiology, have made an appreciably positive impact on the outcome. Herein, we present the emerging concepts in the urological management of CAKUT, specifically, multicystic dysplastic kidney, vesicoureteral reflux, congenital hydronephrosis, ectopic ureters and ureteroceles.


[Micronutrients and diabetes, the case of minerals].
Minerals are essential nutrients for the body, are of inorganic nature which gives them the characteristic of being resistant to heat, are involved in a lot of chemical reactions in metabolism, regulating electrolyte balance, in maintaining bone, in the process of blood clotting and the transmission of nerve impulses, particularly its role as enzyme cofactors confers a key role in various physiological processes. Glucose homeostasis involves a fine coordination of events where hormonal control by insulin plays a key role. However, the role of minerals like magnesium, zinc, chromium, iron and selenium in the diabetes is less obvious and in some cases may be controversial. This review shows the knowledge of these five elements and their correlation with diabetes.


TRAT1 overexpression delays cancer progression and is associated with immune infiltration in lung adenocarcinoma.
The roles and mechanisms of T-cell receptor (TCR)-associated transmembrane adaptor 1 (TRAT1) in lung adenocarcinoma (LAC) have not yet been reported in the relevant literature. Therefore, this study aimed to understand the roles and mechanisms of TRAT1 in LAC using bioinformatics and in vitro experiments. TRAT1 expression levels in LAC samples were analysed using various databases. TRAT1 co-expressed genes were acquired by the correlation analysis of LAC tissues. The functional mechanisms and protein network of TRAT1 co-expressed genes were analysed using bioinformatics analysis. The expression of TRAT1 was activated in LAC cells, and the roles of TRAT1 overexpression in the growth and migration of cancer cells was investigated using flow cytometry, Cell Counting Kit-8 (CCK-8), and migration and invasion assays. The relationship between TRAT1 overexpression, the immune microenvironment, and RNA modification was evaluated using correlation analysis. TRAT1 expression levels were significantly abnormal at multiple mutation sites and were related to the prognosis of LAC. TRAT1 co-expressed genes were involved in cell proliferation, adhesion, and differentiation, and TRAT1 overexpression significantly inhibited cell viability, migration, and invasion and promoted apoptosis of A549 and H1299 cells, which might be related to the TCR, B cell receptor (BCR), MAPK, and other pathways. TRAT1 expression levels were significantly correlated with the ESTIMATE, immune, and stromal scores in the LAC microenvironment. Additionally, TRAT1 expression levels were significantly correlated with the populations of B cells, CD8 T cells, cytotoxic cells, and other immune cells. TRAT1 overexpression was significantly correlated with the expression of immune cell markers (such as PDCD1, CD2, CD3E) and genes involved in RNA modification (such as ALKBH1, ALKBH3, ALKBH5). In conclusions, TRAT1 overexpression inhibited the growth and migration of LAC cells, thereby delaying cancer progression, and was correlated with the LAC microenvironment and RNA modifications.


Executive Dysfunction and Functional Impairment Associated With Sluggish Cognitive Tempo in Emerging Adulthood.
Research has identified a relationship between sluggish cognitive tempo (SCT) symptoms and symptoms of ADHD, anxiety, and depression; however, no study has controlled for symptoms of ADHD, anxiety, and depression when examining impairment related to SCT symptoms. This study aimed to examine (a) the extent to which functional impairment and executive function (EF) problems were accounted for by SCT symptoms when controlling for ADHD, anxiety, and depression symptoms, and (b) which type of symptoms were associated with the greatest amount of impairment. College students ( N = 458) completed self-report scales of ADHD, SCT, anxiety, and depression symptoms, as well as functional impairment and EF problems. Thirteen percent of the sample was found to have high levels of SCT symptoms. SCT symptoms showed a moderate to strong correlation with the other symptom sets; however, high levels of SCT symptoms often occurred separate from high levels of ADHD, anxiety, or depression symptoms. SCT symptoms accounted for the most unique variance for both EF problems and functional impairment. Students with high levels of SCT symptoms, with or without high levels of ADHD symptoms, exhibited more impairment and EF problems than the controls. SCT is a clinical construct worthy of additional study, particularly among college students.


Messenger ribonucleic acid transcripts of pea chloroplast deoxyribonucleic acid.
The total ribonucleic acid (RNA) from pea chloroplasts has been found to hybridize with 50% of the base sequences of pea chloroplast deoxyribonucleic acid (ctDNA). The specificity of hybridization has been analyzed by competition experiments and thermal stability studies of ctDNA-RNA hybrids. The ctDNA-specific RNA does not hybridize with the nuclear DNA. There is about 2-3% reduction in the total hybridization of ctDNA with RNA from the dark grown leaves. About 0.15-0.2% of the RNA from chloroplasts has been found to contain poly(A) tracts. About 20-25% of RNA. Poly(A-) RNA, however, has been found to hybridize with 50% of the ctDNA. The molecular sizes of the mRNA transcripts have been found to range from 0.3 X 10(6) to 3 X 10(6).


Molecular and phenotypic characteristics of RSV infections in infants during two nirsevimab randomized clinical trials.
Nirsevimab is a monoclonal antibody that binds to the respiratory syncytial virus (RSV) fusion protein. During the Phase 2b (NCT02878330) and MELODY (NCT03979313) clinical trials, infants received one dose of nirsevimab or placebo before their first RSV season. In this pre-specified analysis, isolates from RSV infections were subtyped, sequenced and analyzed for nirsevimab binding site substitutions; subsequently, recombinant RSVs were engineered for microneutralization susceptibility testing. Here we show that the frequency of infections caused by subtypes A and B is similar across and within the two trials. In addition, RSV A had one and RSV B had 10 fusion protein substitutions occurring at >5% frequency. Notably, RSV B binding site substitutions were rare, except for the highly prevalent I206M:Q209R, which increases nirsevimab susceptibility; RSV B isolates from two participants had binding site substitutions that reduce nirsevimab susceptibility. Overall, >99% of isolates from the Phase 2b and MELODY trials retained susceptibility to nirsevimab.


Flow-Based Spatio-Temporal Structured Prediction of Motion Dynamics.
Conditional Normalizing Flows (CNFs) are flexible generative models capable of representing complicated distributions with high dimensionality and large interdimensional correlations, making them appealing for structured output learning. Their effectiveness in modelling multivariates spatio-temporal structured data has yet to be completely investigated. We propose MotionFlow as a novel normalizing flows approach that autoregressively conditions the output distributions on the spatio-temporal input features. It combines deterministic and stochastic representations with CNFs to create a probabilistic neural generative approach that can model the variability seen in high-dimensional structured spatio-temporal data. We specifically propose to use conditional priors to factorize the latent space for the time dependent modeling. We also exploit the use of masked convolutions as autoregressive conditionals in CNFs. As a result, our method is able to define arbitrarily expressive output probability distributions under temporal dynamics in multivariate prediction tasks. We apply our method to different tasks, including trajectory prediction, motion prediction, time series forecasting, and binary segmentation, and demonstrate that our model is able to leverage normalizing flows to learn complicated time dependent conditional distributions.


Comparison of vascular parameters between normal cynomolgus macaques and healthy humans by optical coherence tomography angiography.
The metabolic activity of retina is higher than other human tissues and is crucial to the vision. Cynomolgus macaques is widely used in ophthalmic disease research. The evaluation and comparison of macular and optic disc vascular circulation parameters between normal adult cynomolgus macaques and healthy adult humans using OCT-A can promote better use of nonhuman primate models in studies of ophthalmic vascular disease. Twelve normal adult cynomolgus macaques with a mean age of 4.91 ± 0.43 years were studied for data collection. The macula of 28 adult healthy humans (14 males and 14 females), with a mean age of 25.11 ± 6.21 years and the optic discs of 9 adult healthy humans (4 males and 5 females) with a mean age of 28.56 ± 6.78 years were measured. The vessel density (VD) was measured using an RTVue XR with AngioVue. The scan sizes of the macular and optic discs were 3 × 3 mm and 4.5 × 4.5 mm, respectively. OCT-A can image the superficial and deep capillary plexuses and radial peripapillary capillary network. In RPC layer of the optic disc, the VD in the nasal quadrant was lower than the VD in the inferior temporal quadrant. Similarities and significant differences in VD between healthy humans and cynomolgus macaques were obtained using OCT-A. This study provides normal vascular parameters for adult cynomolgus macaques using OCT-A to help establish an optical parameter database for cynomolgus macaques and compare VD between healthy humans and cynomolgus macaques to promote choroid-retinopathy research. Current Controlled Trials NCT03692169 , retrospectively registered on 26 sept 2018.


Late results with Dardik-biograft in peripheral arterial surgery.
A total of 117 vascular reconstructions below the inguinal ligament were performed using Dardik's human umbilical vein. The indication for surgery was limb salvage in 91.5%. In 61.5% a previous reconstruction had failed. The distal anastomosis was done with the popliteal artery above the knee in 9 cases, below the knee in 41, and with a tibial or the peroneal artery in 60 cases. The umbilical vein was combined with a prosthesis or the autologous saphenous vein in 20 cases. The cumulative patency rates of all reconstructions were 59.6% after 3, and 46.7% after 6 years. Crural reconstructions had a cumulative patency rate of 52% 3 years after surgery. The main factors influencing patency were the preoperative grade of ischemia, the site of the distal anastomosis and the angiographic run-off. It is concluded that the human umbilical vein is the graft material of choice in long length revascularization whenever the saphenous vein is not available.


[Local recurrence following anterior resection of rectal cancer. CEA-titer (author's transl)].
The records of 70 patients undergoing a curative anterior resection at the Surgical Department of the Academic Teaching Hospital in Herford for carcinoma of the rectum between January 1, 1974 and December 31, 1978 were reviewed. There were 6 cases (8,5%) developing suture line and local recurrence between 9 and 16.5 months after anterior resection. In this study a rising CEA-titer was the first evidence of recurrence in only 29% of our patients. Among 9 patients with confirmed local recurrence - 6 from our own and 3 from outside - only 2 (22%) showed an increase in CEA levels above normal. In the face of the poor 5-year survival with secondary abdomino-perineal resection following anterior resection one must ask if the significance of those operative procedures with their technical difficulty is justified. Our own experience of 9 patients with secondary abdominoperineal resection for local recurrence has changed our mind for a more palliative operative procedure in such cases.


[Molecular medicine].
The introduction of new methods into medicine, such as recombinant DNA, production of monoclonal antibodies, and particularly polymerase chain reactions, yielded much knowledge and information in fields like preventive medicine (prenatal screening), reproduction strategies (preimplantation diagnosis of genetic defects), molecular diagnosis (oncological and infectious diseases), gene therapy, etc. In many areas the practical use of these sophisticated approaches has become technically feasible yet due to the high cost involved it is still limited. The introduction of some screening programs will be associated with ethical problems of serious impact. To date we can already establish presymptomatic diagnosis of some progressive diseases for which however no therapy is available. Potential abuse of confidential genetic information as well as the possibilities of using gene therapy for "corrective eugenics" are loaded with serious ethical problems. Prospective doctors have to be prepared for this situation in the course of undergraduate studies of medicine. (Ref. 11.)


beta 2-Microglobulin clearance as measured by radioimmunoassay.
We describe a radioimmunoassay for beta 2-microglobulin (beta 2 mu) in serum and urine. We incubated aliquots of diluted samples at room temperature for 1 h with 125I-labeled beta 2 mu and a rabbit antiserum monospecific for human beta 2 mu, and separated the phases by the double-antibody technique. The logit-log transformed dose-response curve was linear in the range 2 to 64 ng, equivalent to 0.5 to 16 mg/L of serum and 0.5 to 320 mg/L of urine. Assay sensitivity was 2.4 ng of beta 2 mu. Validation studies included tests of precision, accuracy, antibody specificity, and parallelism of the dose-response curves for standard and unknown. In a study of 25 normal individuals, serum and urine beta 2 mu ranged from 1.1 to 2.3 mg/L and 40 to 360 micrograms/24 h; the clearance of beta 2 mu was 8 to 130 microL/min. In 21 renal allograft recipients tested one to five weeks after transplantation, serum and urine beta 2 mu ranged from 3.9 to 15.6 mg/L and 7.2 to 611 mg/24 h; beta 2 mu clearance was 0.60 to 33.3 mL/min. Values for both serum and urine correlated well with severity of allograft rejection.


Correlated versus uncorrelated frailty Cox models: A comparison of different estimation procedures.
In many studies in medicine, including clinical trials and epidemiological investigations, data are clustered into groups such as health centers or herds in veterinary medicine. Such data are usually analyzed by hierarchical regression models to account for possible variation between groups. When such variation is large, it is of potential interest to explore whether additionally the effect of a within-group predictor varies between groups. In survival analysis, this may be investigated by including two frailty terms at group level in a Cox proportional hazards model. Several estimation methods have been proposed to estimate this type of frailty Cox models. We review four of these methods, apply them to real data from veterinary medicine, and compare them using a simulation study.


Immune response to rabbit coccidiosis: a comparison between infections with Eimeria flavescens and E. intestinalis.
Seven- to eight-week-old rabbits were infected with Eimeria intestinalis Cheissin, 1948, a highly immunogenic coccidium, or Eimeria flavescens Marotel et Guilhon, 1941, which is weakly immunogenic. Immune response was investigated at 7, 14 and 21 days post inoculation (DPI). The level of serum immunoglobulins, lymphocyte proliferation stimulated by parasite antigens and weight of mesenteric lymph nodes (MLN) showed similar dynamics in rabbits inoculated with both coccidia species. The amount of serum IgG and IgM, but not IgA, was increased from 14 DPI. The lymphocytes from MLN of infected animals significantly reacted to stimulation with parasite antigen 14 and 21 DPI and MLN were enlarged at 14 DPI. Thus, both parasite species elicited immune response characterized by these parameters in a similar manner despite of their different immunogenicity. The only apparent difference in the responses was in the percentage of CD8+ lymphocytes in the specific site of parasite development (the last third of the small intestine in E. intestinalis, caecum in E. flavescens), which increased in rabbits infected with E. intestinalis but not with E. flavescens. This parameter reflects the status of local immunity and hence the results suggest that the local reaction plays an important role in induction of protective immunity to coccidia in rabbits.


Serotonin syndrome induced by the readministration of escitalopram after a short-term interruption in an elderly woman with depression: a case report.
Serotonin syndrome is a rare but potentially fatal side effect of antidepressants that results from the effects of drug activity on both central and peripheral serotonergic receptors. A 78-year-old Japanese female with a 2-year history of major depressive disorder was treated with escitalopram (10 mg/d), risperidone (1 mg/d), and nitrazepam (5 mg/d). One month after beginning this drug regimen, she was transferred to the emergency department and immediately hospitalized due to suspicion of a urinary tract infection and dehydration. All psychotropic drugs were discontinued. Five days later, the patient's physical condition had recovered; therefore, the same dose of escitalopram (10 mg/d) was readministered. The patient subsequently developed convulsions accompanied by impaired consciousness, high fever, and myoclonus of both upper extremities. The tendon reflexes of both lower extremities were enhanced. Based on these clinical signs and symptoms, we suspected serotonin syndrome; therefore, escitalopram was discontinued, and a fluid infusion was initiated. The patient recovered from all symptoms within 3 weeks without receiving additional antidepressants. This case suggests that the careless readministration of selective serotonin reuptake inhibitors (SSRIs) is harmful to at-risk patients, like those in poor physical condition and the elderly.


Granulomatosis with polyangiitis in Northeastern Brazil: study of 25 cases and review of the literature.
Little has been published about the epidemiology of Granulomatosis with polyangiitis (GPA) in South America, especially in the intertropical zone, and no epidemiological data from Brazil are available. The purpose of the present study was to draw a clinical and demographic profile of GPA patients living in Northeastern Brazil based on laboratory, histological and imaging findings, and evaluate the frequency of organic involvement. Clinical, epidemiological and treatment data of GPA patients were collected retrospectively and compared with the literature. The cohort included 25 GPA patients (84% female) aged 45.8 ± 16.1 years. Renal and ear-nose-throat (ENT) manifestations were the most common (both 64%). One third (32%) of the patients had 24-h proteinuria > 1 g, 50% had creatinine clearance < 50 mL/min at the time of diagnosis, and 33% had recurrent kidney damage during disease progress. The affected organs included lungs (60%), joints (44%), skin (32%), peripheral nervous system (28%), eyes (28%) and heart (16%). ENT involvement (n = 16/64%) was less frequent in our region than in São Paulo (n = 115/85.8%). Renal (n = 16/64%) and pulmonary (n = 15/60%) involvement was less frequent in our region than in the U.K. (renal n = 30/90%; pulmonary n = 28/84.8%). Most of our patients were female, presented the generalized form and were diagnosed late. The frequency of the main clinical manifestations (ENT, renal and pulmonary) was lower than that observed at higher latitudes, suggesting the existence of a Northeast Brazilian clinical and epidemiological profile and adding to our knowledge of this rare condition.


FMG-based body motion registration using piezoelectret sensors.
Body motion registration can provide plenty of muscle activity information of human beings, which is applicable in the control of human-computer interfaces or real devices. Forcemyography (FMG) is a method to register real-time body motions by measuring the radially directed force distributions that are generated by muscle contractions. In this work, we recorded FMG maps by using a novel type of sensor, the polymer-based piezoelectrets. With five piezoelectret sensor units attached on the surface of thigh muscles, four basic lower-limb motions, leg-raising, leg-dropping, knee-extension, and knee-flexion, were properly captured on four able-bodied subjects. Motion classification accuracies of 92.9%, 84.8%, and 88.1% were obtained by using different recognition algorithms of KNN, LDA, and ANN, respectively. The pilot experimental results demonstrated the feasibility of FMG recording by using piezoelectret sensors, which may provide an alternative method for body motion registration.


The quiet-Sun photosphere and chromosphere.
The overall structure and the fine structure of the solar photosphere outside active regions are largely understood, except possibly the important roles of a turbulent near-surface dynamo at its bottom, internal gravity waves at its top and small-scale vorticity. Classical one-dimensional static radiation-escape modelling has been replaced by three-dimensional time-dependent magento-hydrodynamic simulations that come closer to reality. The solar chromosphere, in contrast, remains little understood, although its pivotal role in coronal mass and energy loading makes it a principal research area. Its fine structure defines its overall structure, so that hard-to-observe and hard-to-model small-scale dynamical processes are key to understanding. However, both chromospheric observation and chromospheric simulation presently mature towards the required sophistication. Open-field features seem of greater interest than easier-to-see closed-field features.


Excited State Dipole Moments in Solution: Comparison between State-Specific and Linear-Response TD-DFT Values.
We compare different response schemes for coupling continuum solvation models to time-dependent density functional theory (TD-DFT) for the determination of solvent effects on the excited state dipole moments of solvated molecules. In particular, linear-response (LR) and state-specific (SS) formalisms are compared. Using 20 low-lying electronic excitations, displaying both localized and charge-transfer character, this study highlights the importance of applying a SS model not only for the calculation of energies, as previously reported ( J. Chem. Theory Comput. , 2015 , 11 , 5782 , DOI: 10.1021/acs.jctc.5b00679 ), but also for the prediction of excited state properties. Generally, when a range-separated exchange-correlation functional is used, both LR and SS schemes provide very similar dipole moments for local transitions, whereas differences of a few Debye units with respect to LR values are observed for CT transitions. The delicate interplay between the response scheme and the exchange-correlation functional is discussed as well, and we show that using an inadequate functional in a SS framework can yield to dramatic overestimations of the dipole moments.


Synovial membrane microarthroscopy of the equine midcarpal joint.
To evaluate the value of microarthroscopy in the equine midcarpal joint using the vital stains methylene blue, trypan blue, neutral red, and Janus green B to observe components of the synovial lamina propria, vascular architecture, and synoviocytes. Experimental. Ten horses. Microarthroscopy of left and right midcarpal joints was performed with and without vital staining of the synovium. Four vital stains (methylene blue, trypan blue, neutral red, and Janus green B) were evaluated, with each stain used in 5 joints. Synovial biopsy specimens were collected from the dorsomedial and dorsolateral aspects of the joint. All dyes were biocompatible. At x 60 without vital staining, synovial surface topography, vascular network, and translucency were observed. Intra-articular vital dyes improved evaluation of synovial surface topography. At x 150 with vital staining, individual synoviocytes were clearly identified with all dyes, except neutral red. Although methylene blue provided the best in vivo microscopic differentiation of the structure of the intima, trypan blue had superior retention in conventionally processed synovial biopsies. Methylene blue, trypan blue, neutral red, and Janus green B stains can be used safely for microarthroscopy. Good visualization of cells and vascular network can be obtained by microarthroscopy, and microarthroscopic evaluation of the synovium compares favorably with conventional histologic evaluation of biopsy specimens. Microarthroscopy may be beneficial in both research and clinical diagnosis of equine articular diseases.


Influence of prosthesis-related factors on the occurrence of early leaflet thrombosis after transcatheter aortic valve implantation.
Early leaflet thrombosis (LT) is a well-described phenomenon after transcatheter aortic valve implantation (TAVI) with an incidence around 15%. Data about predictors of LT are scarce. The purpose of the study was to investigate the influence of prosthesis-related factors on the occurrence of LT. Fusion imaging of pre- and post-procedural computed tomography angiography was performed in 55 TAVI patients with LT and 140 selected patients as control groups (85 patients in an unmatched and 55 in a matched control) to obtain a 3D reconstruction of the transcatheter heart valve (THV) within the native annulus region. All patients received a balloon-expandable Sapien 3 THV. The THV length above and below the native annulus was measured within the fused images to assess the implantation depth. The deployed THV area was quantified on three heights (left ventricular outflow tract end, stent centre, and aortic end) to determine the average expansion of the prosthesis as percent of the nominal area. We also calculated the extent of prosthesis waist in percent of maximum area. After multivariate adjustment, the extent of THV waist [odds ratio (OR) per 10% (confidence interval, CI) 0.636 (0.526-0.769), P < 0.001] as prosthesis-related factor and previous oral anticoagulation [OR (CI) 0.070 (0.020-0.251), P < 0.001] had significant, independent influence on the occurrence of LT. The implantation depth showed no influence on LT manifestation (P = 0.704). Besides the absence of previous oral anticoagulation, a less pronounced waist of the implanted THV was a prosthesis-position-related independent predictor of LT after TAVI using the Sapien 3.


[Regularities of fixation of brain serum antibodies from patients with lateral amyotrophic sclerosis in rabbit CNS].
Kuhns' indirect immunofluorescent test was used to study fixation of serum brain antibodies (Ab) of patients with bulbar, cervicothoracic, lumbosacral lateral amyotropic sclerosis (LAS) on brain sections of rabbits. The disease is characterized by formation of brain Ab complementary to various structures of nervous and glial cells, myelin of fibers from different conducting systems, vessels which exhibit both common and individual antigenic properties. It was found that fixation of antineuronal, antimyelin brain Ab of patients with bulbar, cervicothoracic and lumbosacral LAS in different CNS structures varies.


Reactivity differences of Sc3N@C(2n) (2n = 68 and 80). Synthesis of the first methanofullerene derivatives of Sc3N@D(5h)-C80.
Using a purification method introduced earlier based on redox properties it was possible to isolate Sc3N@I(h)-C80 and Sc3N@D(3h)-C78 and a mixture of Sc3N@D(5h)-C80 and Sc3N@D3-C68. Taking advantage of their chemical reactivity differences, Sc3N@D(5h)-C80 was isolated from Sc3N@D3-C68 followed by further functionalization, giving rise to five new methano-derivatives of Sc3N@D(5h)-C80.


Societal and commercial issues affecting the future of biotechnology in the United States: a survey of researchers' perceptions.
A 1995 survey of 1,257 U.S. recombinant DNA researchers assessed how they view outside factors affecting their work, including public and media attention; regulation; funding; international competition; commercialization of research and university/ industry collaboration; health care reform efforts; and patenting laws and policies. Generally, respondents view public attention as-having had positive effects on biotechnology progress, but they are concerned about the decrease in R&D funding, especially from government; the loss of scientific openness and basic-research quality caused by academic/industrial collaboration; international competition, particularly from Japan and Germany; overly stringent regulations that control R&D processes rather than products; inefficient regulatory agencies focused on irrelevant criteria; and threats to basic biomedical research from the short-term cost focus of managed-care companies.


hTERT-Immortalized Bone Mesenchymal Stromal Cells Expressing Rat Galanin via a Single Tetracycline-Inducible Lentivirus System.
The use of human telomerase reverse transcriptase-immortalized bone marrow mesenchymal stromal cells (hTERT-BMSCs) as vehicles to deliver antinociceptive galanin (GAL) molecules into pain-processing centers represents a novel cell therapy strategy for pain management. Here, an hTERT-BMSCs/Tet-on/GAL cell line was constructed using a single Tet-on-inducible lentivirus system, and subsequent experiments demonstrated that the secretion of rat GAL from hTERT-BMSCs/Tet-on/GAL was switched on and off under the control of an inducer in a dose-dependent manner. The construction of this cell line is the first promising step in the regulation of GAL secretion from hTERT-immortalized BMSCs, and the potential application of this system may provide a stem cell-based research platform for pain.


Issues in conducting research in nursing homes.
Anticipation of increased numbers of older persons throughout the coming decades who will require care and assistance with chronic illnesses and functional deficits has correspondingly increased awareness of the need for nursing research to support best geriatric nursing practices. Although badly needed, research in nursing homes presents challenges. This article discusses issues and challenges of ethically acceptable and rigorous research in nursing homes that are related to the dependency and institutionalization of older persons and to setting, staff, and resident characteristics. Strategies for easing the challenges of nursing research in nursing homes are offered.


Fear of the unknown: ultrasound and anxiety about fetal health.
Using a qualitative approach, this study sought to explore the role of ultrasound in fetal health anxiety. One semi-structured interview was conducted with 30 pregnant women. Data analysis was inductive, following the principles of the template and editing organizing styles of coding and analysis. Overall, 93 percent of the women reported anxiety over fetal health, with 96.5 percent of these women indicating that ultrasound played a role in their anxiety. The women reported heightened fetal health anxiety in anticipation of the ultrasound, as well as during the ultrasound due to the sonographer's behavior and an inability to see the monitor. Findings indicated that fetal health anxiety was relieved by the ultrasound, particularly when women had access to the visual image and received encouraging verbal feedback. The findings are discussed with regard to their implications for policy and obstetric practice.


Postoperative Cardiovascular Surgery Delirium: Interrater Agreement Between Nurses and Clinical Nurse Specialist and Factors Associated With Prevalence.
The aims of this study were to examine interrater agreement of delirium between clinical nurses and a clinical nurse specialist, determine delirium subtype prevalence, and examine associated patient, procedure, and hospital factors. A descriptive cross-sectional design and a convenience sample of nurses and patients on progressive care units were used in this study. Clinical nurse specialist data were collected on a case report form, and clinician and patient data were obtained from electronic databases. Interrater agreement of delirium prevalence was assessed by κ statistic, and logistic regression models were used to determine patient factors associated with delirium. Of 216 patients, 23 had delirium; clinical nurses identified fewer cases than the clinical nurse specialist: 1.8% versus 10.7%; κ agreement, 0.27 (0.06, 0.49). By delirium subtype, hypoactive delirium was more frequent (n = 10). Factors associated with delirium were history of cerebrovascular disease (odds ratio [95% confidence interval], 2.8 [1.01-7.7]; P = .044), history of mitral valve disease (odds ratio [95% confidence interval], 0.31 [0.09-0.90]; P = .041), and longer perfusion time (odds ratio [95% confidence interval], 1.7 [1.1-2.7]; P = .016). One factor was associated with hypoactive delirium, longer perfusion time (odds ratio [95% confidence interval], 2.2 [1.3-4.2]; P = .008). Because clinician-clinical nurse specialist delirium agreement was low and hypoactive delirium was common, clinical interventions are needed.


How redesigning AD clinical trials might increase study partners' willingness to participate.
Timely recruiting and retaining participants into Alzheimer disease (AD) clinical trials is a challenge. We used conjoint analysis to identify how alterations in attributes of clinical trial design improve willingness to participate: risk, home visits, car service, or increased chance of receiving intervention. A total of 108 study partners of patients with very mild to severe stage AD rated willingness to allow their relative to participate in eight clinical trials that varied combinations of the four attributes. The highest utility was for home visits (0.89) which essentially compensated for the disutility of high risk (-0.85). The combination of home visits and car service was redundant, with almost no increase in utility over home visits alone. Seventeen percent were willing to participate in a trial with no amenities; the addition of home visits increased predicted willingness to participate to 27%; low risk, home visits, and higher chance of active treatment increased predicted willingness to 60%. The value of reducing the hassles of travel correlated well with measures of AD severity (activities of daily living r = 0.41, p < 0.001; basic activities of daily living r = 0.38, p < 0.001; Neuropsychiatric Inventory severity p = 0.24, p = 0.01; Neuropsychiatric Inventory distress r = 0.23, p < 0.02). No association was found between degree of study partner burden and willingness to tolerate risk of an intervention. Clinical trials that reduce travel inconvenience may offset the disincentive of study features such as the risk of intervention and may also increase willingness to participate. Redesigning trials may also help recruit patients with more severe Alzheimer disease. Shorter recruitment periods and increased retention rates may offset costs of these changes.


2nd BSPR London Regional Meeting and 6th Annual Imperial Proteomics Day. November 2007, Imperial College London, London, UK.
The 2(nd) BSPR London Regional Meeting held at Imperial College London focused on nanoproteomics and single cell proteomics, the solutions to many of the technical challenges in proteomics and protein based molecular diagnostics. This one day meeting included presentations from leading scientists within and outside of Imperial College who share a common interest in novel solutions for the identification and characterization of proteins from a single cell. The conclusion was that nanomaterials are delivering enhanced reagents and have been tested at the proof-of-concept level, but have yet to be incorporated into routine proteomic workflows.


Microfungi on the Pandanaceae: Linocarpon lammiae sp. nov., L. siamensis sp. nov. and L. suthepensis sp. nov. are described with a key to Linocarpon species from the Pandanaceae.
Linocarpon species are reported from Pandanaceae in Australia, Brunei, Hong Kong, Nepal, New Zealand, Philippines, Seychelles, Thailand and Vanuatu. Linocarpon lammiae sp. nov. were collected on decaying leaves of Pandanus tectorius in Hong Kong. Linocarpon siamensis sp. nov. and L. suthepensis sp. nov. were collected from decaying leaves of P. penetrans in Thailand. These taxa are described, illustrated and compared with Linocarpon species with similar ascospore morphology and dimensions. Included are a synoptic table, which compares the new species to similar known species, and a dichotomous key to species of Linocarpon known from members of the Pandanaceae.


Is medical treatment for angina the most cost-effective option?
A meta-analysis of the benefits of coronary artery bypass graft (CABG) surgery has been used as the basis of a model for comparing the costs and benefits of surgical and medical treatment of angina pectoris. In order to allow for the results of recent research, the economic model included the addition of aspirin and aspirin plus an HMG-CoA reductase inhibitor (statin) to medical management. The analysis indicates that in unselected patients the cost-effectiveness of CABG vs initial standard medical therapy over 5 years is towards the upper limit of what can be considered a cost-effective treatment both in terms of its effect on mortality (life-years gained) and morbidity (quality adjusted life-years). Addition of a statin to medical therapy reduced mortality and made coronary artery bypass graft surgery an expensive option in terms of improvement of quality of life. In patients with three-vessel disease or left ventricular dysfunction surgery appears fairly cost-effective in comparison with standard medical therapy but becomes relatively expensive when the benefits of aspirin or lipid-lowering therapy are added to medical treatment.


Idiopathic Polymorphic Ventricular Tachycardia: a "Benign Disease" with a Touch of Bad Luck?
Ventricular extrasystole originating from the right ventricular outflow tract or the left ventricular outflow tract are the most commonly encountered ventricular arrhythmias recorded in ostensibly healthy individuals with no evidence of heart disease. These ventricular arrhythmias have a distinctive electrocardiographic morphology. The morphology is so distinctive that it is common practice to accept the diagnosis of "idiopathic benign ventricular arrhythmias from the outflow tract" based on this unique morphology when the electrocardiogram during sinus rhythm and the echocardiogram are normal, sometimes removing the need to perform invasive tests in patients. Even if the outflow ventricular extrasystole ultimately triggers sustained ventricular arrhythmia, the resulting ventricular tachycardia (VT) will be a monomorphic VT originating from the outflow tract, which is known to be hemodynamically well tolerated. Thus, idiopathic ventricular arrhythmias originating from outflow tracts are universally considered benign. In 2005, we described a rare form of malignant polymorphic VT resulting in syncope or cardiac arrest. Here, we review the literature on this topic since the emergence of initial descriptions of this intriguing phenomenon.


From condemnation to understanding: Views on suicidal behavior in Ghana in transition.
The cultural context in which suicide occurs has been emphasized as critical in understanding the act and informing prevention. Yet the penchant of psychiatrizing suicidality in mainstream suicidology relegates cultural issues to the background. Through the lenses of critical cultural suicidology, the authors have re-emphasized the importance of culture by reviewing the two major meanings of suicide as observed in our 8-year study in Ghana: moral transgression and life crisis. They have also showed the usefulness of the life crisis perspective of suicidality in reducing stigma and sustaining advocacy in decriminalizing attempted suicide in the country.


Effect of larval thermal conditions on limb regeneration in a ladybird beetle, Cheilomenes sexmaculata.
In view of global environmental change, ecological factors especially temperature, affect development of the poikilotherms like insects. Since ladybirds are at risk of injury under mass-rearing conditions, their ability to regenerate injured limbs is highly crucial for their survival. Therefore, the effect of limb regeneration in relation to temperature forms the basis of the present study. The immature stages of insects, being more vulnerable to the surrounding temperature, were considered to study the effect of the prior thermal experience of larvae on regeneration. We exposed the early larval stages of the ladybird beetle, Cheilomenes sexmaculata, to different temperature conditions pre- and postamputation. Exposure of immature stages to extreme temperatures did not affect the ability to regenerate and regeneration occurred at given temperature conditions. However, the regenerated legs were smaller in size across given temperatures as compared to unamputated legs. Body weights in amputated treatments showed no difference and remained unchanged across temperatures when compared to unamputated treatments. Postamputation developmental duration, equivalent to recovery time postlimb amputation, was found to be affected by larval thermal conditions. Recovery was faster in larval treatments exposed to higher temperatures. Thus, larval thermal conditions though did not affect the ability to regenerate lost limbs directly, it does modulate the time taken to regenerate.


Poly (l-γ-glutamylglutamine) Polymer Enhances Doxorubicin Accumulation in Multidrug Resistant Breast Cancer Cells.
Drug resistance is one of the bottlenecks of cancer chemotherapy in the clinic. Polymeric nanomedicine is one of the most promising strategies for overcoming poor chemotherapy responses due to the multidrug resistance (MDR). In this study, a new polymer-based drug delivery system, poly (l-γ-glutamylglutamine)-doxorubicin (PGG-Dox) conjugate, was studied in both drug-induced resistant human breast cancer MDA-MB-231/MDR cells and their parent human breast cancer MDA-MB-231 cells. The effect of PGG on facilitating the growth inhibition of Dox against multidrug resistant cells were investigated by evaluating the cytotoxicity of PGG-Dox conjugate, PGG/Dox unconjugated complex and free Dox on both cells. The underlying mechanisms in resistant cells were further studied via the intracellular traffic studies. Both conjugated and unconjugated PGG significantly increased Dox uptake, prolonged Dox retention and reduced Dox efflux in the MDA-MB-231/MDR cells. The PGG-Dox conjugate is taken up by tumor cells mainly by pinocytosis pathway, in which PGG-Dox conjugate-containing vesicles are formed and enter the cells. This study indicated that both polymer-drug conjugate and unconjugated complex are promising strategies of overcoming resistance of anti-tumor drugs.


Macrophage Gal/GalNAc lectin 2 (MGL2)+ peritoneal antigen presenting cells during Fasciola hepatica infection are essential for regulatory T cell induction.
Fasciola hepatica, one of the agents that causes fasciolosis, modulates the host immune system to allow parasite survival in the host. F. hepatica expresses carbohydrate-containing glycoconjugates that are decoded by C-type lectin receptors, such as Dectin-1, mannose receptor, DC-SIGN and MGL, that are mainly present on myeloid antigen presenting cells (APCs) and can mediate immunoregulatory properties on T cells. In particular, Macrophage Gal/GalNAc lectin 2 (MGL2) expands modified Th2 immune responses, while suppressing Th1 polarization, upon recognition of GalNAc-glycosylated parasite components. In this study, by using MGL2-DTR transgenic mice that encode human diphtheria toxin receptor in MGL2+ cells, we demonstrate the role of peritoneal APCs during F. hepatica infection in favoring parasite survival. This process might be mediated by the induction of splenic Tregs in vivo, since the depletion of MGL2+ cells conferred mice with partial resistance to the infection and abrogated the increase of CD4+/CD25+ FoxP3+ Tregs induced by the parasite. Therefore, MGL2+ cells are critical determinants of F. hepatica infection and could constitute immune checkpoints to control parasite infection.


Assessment of safe bioactive doses of Foeniculum vulgare Mill. essential oil from Portugal.
This study was designed to evaluate the antifungal activity of Foeniculum vulgare essential oil; concomitantly, the safety of bioactive doses was also unveiled, for the first time, in several mammalian cells. The chemical characterisation was made by GC and GC-MS. Antifungal activity was evaluated against yeasts, dermatophytes and Aspergillus strains and germ tube inhibition assay was evaluated using Candida albicans. Cell viability was assessed by the MTT assay. The main constituents of the oil are E-anetol (47%), α-phellandrene (11%), α-pinene (10.1%) and fenchone (10.8%). The oil was more active against Cryptococcus neoformans and C. albicans (MICs 0.32-0.64 μL/mL) and the filamentation of C. albicans was totally inhibited with 0.08 μL/mL. The oil is safe for keratinocytes, hepatocytes and fibroblasts in concentrations up to 1.25 μL/mL, and to macrophages up to 0.64 μL/mL. These findings highlight safe bioactive concentrations that should be deeper investigated for further application in pharmaceutical industry.


Impact of Pharmacist Interventions at an Outpatient US Coast Guard Clinic.
US Coast Guard (USCG) active-duty service members (ADSMs) are required to maintain medical readiness to maximize operational success. USCG pharmacists serve the traditional pharmacist role while maintaining oversight of regional pharmaceutical services. This study aimed to quantify the number, duty status impact, and replicability of medication interventions made by one pharmacist at the USCG Base Alameda clinic in California over 6 months. Medication interventions made at the USCG Base Alameda clinic from July 1, 2021, to December 31, 2021, were categorized as a drug therapy problem (DTP) or non-DTP. Each DTP was further evaluated in a retrospective record review by a panel of USCG pharmacists to assess 2 additional factors: duty status severity (potential to affect duty status) and replicability (potential for the same intervention to be made in the absence of access to the patient health record). USCG Base Alameda pharmacy dispensed 1751 prescriptions and made 116 interventions (7%), of which 111 (96%) were accepted by the prescriber. Of the interventions, 64 (55%) were DTPs, and 14 of those (22%) had potential to change duty status, and 18 DTPs (28%) were made because the pharmacist had access to the health record. Pharmacists' role in USCG clinics includes collaborating with the patient care team to make medication interventions that have significant impact on ADSMs' wellness and the USCG mission.


Stage 2 Registered Report: There is no appreciable relationship between strength of hand preference and language ability in 6- to 7-year-old children.
Background: Weak or inconsistent hand preference has been postulated to be a risk factor for developmental language delay. Following on from our Registered Stage 1 report this study assessed the extent to which variations in language skills are associated with the strength of hand preference. Methods: Data are drawn from a large sample ( N = 569) of 6- to 7-year-old children unselected for ability, assessed at two time points, 6 months apart. Hand preference was assessed using the Quantitative Hand Preference (QHP) task and five uni-manual motor tasks. Language skills (expressive and receptive vocabulary, receptive grammar, and morphological awareness) were assessed with standardized measures. Results: We found QHP scores did not distinguish children with weaker language skills from those with stronger language skills and the correlation between QHP scores and language ability was negligible in this study. Hand preference on the QHP task was significantly stronger among right-handed than left-handed children and left-handed children were typically inconsistent in the hand used across different tasks. Conclusions: The findings presented here fail to provide any support for the theory that weak cerebral lateralisation (as assessed here by the QHP task) places children at risk of language difficulties . Stage 1 report: https://doi.org/10.12688/wellcomeopenres.15077.1.


[μ-Bis(diphenyl-arsanyl)methane-1:2κAs:As']nona-carbonyl-1κC,2κC,3κC-(triisoprop-yl phos-phite-3κP)-triangulo-triruthenium(0).
The asymmetric unit of the title triangulo-triruthenium compound, Ru(3)(CO)(9)(μ-Ph(2)AsCH(2)AsPh(2))(P[OCH(CH(3))(2)](3)) or [Ru(3)(C(25)H(22)As(2))(C(9)H(21)O(3)P)(CO)(9)], contains two mol-ecules of the triangulo-triruthenium complex. The bis-(diphenyl-arsanyl)methane ligand bridges an Ru-Ru bond and the monodentate phosphite ligand binds to the third Ru atom. Both the arsine and phosphite ligands are equatorial with respect to the Ru(3) triangle. Additionally, each Ru atom carries one equatorial and two axial terminal carbonyl ligands. The dihedral angles between the pairs of benzene rings bound to individual As atoms are 85.67 (8) and 75.91 (8) in the first independent mol-ecule and 74.64 (8) and 70.76 (9) in the second. In the crystal, mol-ecules are linked into a three-dimensional framework by inter-molecular C-H⋯O hydrogen bonds.


Primary osteosarcoma of the breast: a case report.
Primary osteosarcomas of the breast are extremely uncommon. Here we describe a case of a 77-year-old woman who presented with a hard mass on her right breast. Mammography and breast ultrasound demonstrated a round-shaped calcified mass on the right breast but the features were not definitely diagnostic. For diagnostic purposes, an excisional biopsy was performed and the mass proved to be a primary osteosarcoma of the breast by pathologic findings. PET-CT and whole body bone scan showed neither evidence of metastasis nor underlying bone lesions. Wide excision without axillary lymph node dissection was performed after diagnosis. Further treatment such as adjuvant chemotherapy or radiation therapy was not performed. We discuss proper treatment of this rare type of breast cancer.


Recycling plastic: diagnosis and management of plastic bronchitis among adults.
Plastic bronchitis is a rare, underdiagnosed and potentially fatal condition. It is characterised by the formation and expectoration of branching gelatinous plugs that assume the shape of the airways. These airway plugs differ from the allergic mucin that characterises allergic bronchopulmonary aspergillosis and mucoid impaction of the bronchi. Plastic bronchitis is most often encountered in the paediatric population following corrective cardiac surgery, such as the Fontan procedure. It also occurs in adults. Plastic bronchitis in adults is rare, heterogeneous in its aetiology, and can lead to respiratory distress or even life-threatening airway obstruction. Plastic bronchitis in adulthood should not be overlooked, particularly in patients with chronic inflammatory lung diseases. This review presents current understanding of the presentation, aetiology, pathogenesis, pathology and management of plastic bronchitis in adults.


Validity, trustworthiness and rigour: reasserting realism in qualitative research.
This paper challenges recent sceptical approaches to the possibility of validating qualitative research and underlines the benefits of adopting a realist approach to validity. In recent discussion about the methodological bases for qualitative research it has been argued that, because different methodologies take different approaches to validity, attempts to develop a common set of validation criteria are futile. On the basis of this sceptical view, a number of strategies for judging qualitative research have been proposed. These include suggestions that: it should be judged according to aesthetic or rhetorical criteria, rather than epistemological validity; responsibility for appraisal should move from researchers to readers; each methodology should be assessed individually according to its own merits. None of these suggestions provide a viable alternative to validity, defined as the extent to which research reflects accurately that to which it refers. Because the form of research does not determine its content, replacement of epistemology by aesthetics is unsustainable. Because research reports mediate between writer and reader, a one-sided approach to this relationship constitutes a false dichotomy. If we accept the criterion of practitioner confidence as a means of judging methodological approaches, this involves rejection of judgement according to a methodology's own merits. If qualitative research is actually about something, and if it is required to provide beneficial information, then a realist approach to validity holds out greatest promise.


Use of dietary mannanoligosaccharides during rabbit fattening period: effects on growth performance, feed nutrient digestibility, carcass traits, and meat quality.
This study was conducted to compare the effects of mannanoligosaccharides (MOS) and antibiotics as a dietary supplement on ADG, ADFI, G:F, and feed nutrient digestibility of rabbits during the fattening period, as well as on carcass traits and meat quality. A total of 512, sixty-day-old hybrid Hyla rabbits were randomly divided into 4 treatment groups based on BW and sex. The 4 treatment groups consisted of a control group and 3 MOS groups. The control group was fed a diet that contained apramycin (50 mg/kg), but diets for the 3 MOS groups contained 0.5, 1.0, or 1.5 g/kg of MOS instead of apramycin. The rabbits were fed experimental diets for 22 d and all rabbits were slaughtered at the end of the experiment when they were 82 d old. Individual BW and feed intake per cage were recorded weekly for 32 cages randomly chosen per group (64 rabbits) to calculate ADG, ADFI, and G:F. The apparent digestibility values of OM, CP, ether extract, crude fiber, NDF, ADF, cellulose, and hemicellulose were measured using AIA as an inert marker. Carcass data were collected from 16 randomly chosen rabbits (8 males and 8 females) per group. The control group had less G:F (P < 0.001) than the MOS groups and a linear increase (P < 0.001) in G:F was observed as the concentration of MOS increased from 0.5 to 1.0 and 1.5 g/kg. The apparent digestibility of DM, OM, crude fiber, NDF, ADF, cellulose, and hemicellulose increased (quadratic, P < 0.05) as the concentration of MOS in the diets increased. The apparent digestibility of DM, OM, CP, crude fiber, NDF, ADF, cellulose, and hemicellulose was also greater (P < 0.05) in the diets containing MOS than in the control diet and the digestibility of these nutrients was greater (P < 0.05) in the diet containing 1.5 g/kg of MOS compared with the control diet. The concentration of palmitic acid, stearic acid, and SFA was greater (P < 0.05) in the meat from rabbits fed the control diet than rabbits fed the MOS diets. The concentration of stearic acid decreased (quadratic, P < 0.05) in the meat of rabbits as the concentration of MOS in the diet increased. Meat from rabbits fed diets containing MOS also had greater contents of oleic acid (P < 0.05) and MUFA (P < 0.001) than those rabbits fed the diet containing apramycin. The thrombogenic index was greater (P < 0.05) in the meat from the control group rabbits than the MOS group rabbits. In conclusion, the inclusion of MOS in diets fed to rabbits during the fattening period may improve G:F and modify the fatty acid profile of meat.


Evolution of large-scale flow from turbulence in a two-dimensional superfluid.
Nonequilibrium interacting systems can evolve to exhibit large-scale structure and order. In two-dimensional turbulent flow, the seemingly random swirling motion of a fluid can evolve toward persistent large-scale vortices. To explain such behavior, Lars Onsager proposed a statistical hydrodynamic model based on quantized vortices. Here, we report on the experimental confirmation of Onsager's model. We dragged a grid barrier through an oblate superfluid Bose-Einstein condensate to generate nonequilibrium distributions of vortices. We observed signatures of an inverse energy cascade driven by the evaporative heating of vortices, leading to steady-state configurations characterized by negative absolute temperatures. Our results open a pathway for quantitative studies of emergent structures in interacting quantum systems driven far from equilibrium.


[Corrective strategies in treatment of postoperative hemodynamic dysfunctions in patients with chronic cholelithiasis in combination with the heart ischemic disease].
132 patients with complicated forms of chronic calculous cholecystitis combined with heart ischemia and postinfarctial cardiosclerosis were investigated. In preoperative period besides the clinical instrumental and laboratory investigations condition of cardiovascular system with the use of physical exertion -treadmill test and echocardiography was done in order to find the heart's working regime. The analysis of the treadmill tests results with the central and peripheral hemodynamic data changes, the level of myocardial oxygen contribution, metabolic changes has shown that their connection is widely varied. This is explained by inflammatory processes spreading which formed the pathological connection of the whole biliary system and inflammatory focuses with pain sinchrone. Preoperative conservative treatment, including individual mechanisms of heart dysfunction based on treadmill and EchoCG, for the correction of hemodynamic is not necessary on the background of pain, cholemia, pancreas induration which forces myocardium up to the liquidation of pathogenetic mechanism of hepatoduodenal zone. That's why the methods of small invasive endosurgery are used in the complex conservative preoperative treatment.


Vitalizing the group--and me.
Emotional liveliness in a psychotherapy group can take various forms. Maintaining this liveliness can be a challenging task in a group, particularly when both the patients and the therapist face deeply rooted inhibitions, including fears about competition, being judged, and being destructive. The author of this paper, a candidate and group member in a postdoctoral group psychotherapy training program, recounts some of her experiences as the leader of a newly formed and developing group, particularly as they relate to her efforts to become and remain a "libidinal" (i.e., life or vital force) leader, despite the impact of the group members' and her own anxieties. Clinical anecdotes and insights about the author's own growth, both personally and professionally, as they relate to establishing and maintaining vitality are presented.


Bariatric surgery in individuals with liver cirrhosis: A narrative review.
Bariatric surgery has become the gold standard treatment for morbid obesity, but there is no consensus regarding its safety and efficacy among individuals with chronic liver diseases. To critically evaluate the existing evidence on literature about bariatric surgery in individuals with liver cirrhosis. Narrative review performed by means of an online search in the MEDLINE and LILACS databases. Bariatric surgery is safe and effective in individuals with chronic liver disease without clinical decompensation or significant portal hypertension. Individuals with severe liver function impairment present significantly higher surgical morbidity and mortality. Among candidates to liver transplantation, surgery may be performed before, after and even during transplantation, and there is a predominant trend to perform it after. Vertical sleeve gastrectomy seems to be the most adequate technique in this group of subjects. Bariatric surgery is safe and effective in individuals with compensated cirrhosis without significant portal hypertension, but presents higher morbidity. Among candidates to liver transplantation and/or individuals with severe portal hypertension, morbidity and mortality are significantly higher.


Status of urea and related enzymes during Plasmodium yoelii infection and pyrimethamine treatment in mice.
Plasmodium yoelii infection alters the hepatic levels of key enzymes of urea cycle, viz.carbamoyl phosphates synthetase (EC 184.108.40.206) and ornithine transcarbamoylase (EC 18.104.22.168) and urea levels in mice. The urea level was found elevated in liver, brain and plasma during P. yoelii infection. However, carbamoyl phosphate synthetase and ornithine transcarbamoylase were noticeably decreased during P. yoelii infection. Pyrimethamine treatment (10 mg/kg body weight for 4 days) brought back the altered parameters to normal a week after cessation of drug treatment.


Comparison of myocardial perfusion 82Rb PET performed with CT- and transmission CT-based attenuation correction.
CT-based attenuation correction (AC) for myocardial perfusion PET studies is challenging because of respiratory motion. Our study aimed to compare the transmission CT (TCT)-based and CT-based AC for myocardial perfusion PET/CT images with a direct semiquantitative approach comparing differences in segmental count distribution. Stress and rest (82)Rb PET scans from 54 consecutive patients acquired on a PET/CT scanner with dual CT-based and TCT-based AC were considered. TCT- and CT-based AC images were automatically registered to each other, and direct voxel-based and American Heart Association segment-based estimation of positive and negative changes between these scans was performed. Additionally, visual quality control (QC) of CT map alignment with PET emission data was performed by 2 expert observers, and studies with significant (>/=5 mm) misalignment were reprocessed with corrected CT alignment. We used the 17-segment American Heart Association model for TCT-to-CT regional change analysis in all patients and found that 4 segments on rest and 4 segments on stress scans differed more than 3% between CT- and TCT-corrected images for studies without significant misalignments (<5 mm); only 1 differed by more than 5%. In cases with significant misalignment of greater than or equal to 3% TCT-CT AC, changes were observed on 14 rest and 10 stress segments; after alignment, these differences were still seen in 13 rest segments and 11 stress segments. Visual QC revealed that 46% of rest and 54% of stress PET scans were misaligned by greater than or equal to 5 mm with the CT maps acquired during normal breathing. The range of the reported PET/CT misalignment was 0-15 mm in x, 0-16 mm in y, and 0-20 mm in z directions. The overall agreement in visual QC of PET/CT alignment between the observers was 72.2% There are significant differences between TCT and CT AC applied to cardiac PET/CT studies, which remain after alignment of CT maps to emission data.


P069 The Unrelenting Ulcer.
Inflammatory Bowel Disease (IBD) is becoming more common in an increasingly diverse population. Exposure history is important, especially when prescribing immunosuppressive therapy. We present a case of suspected disseminated histoplasmosis in a gentleman with longstanding Ulcerative Colitis (UC) on anti-TNF with an atypical, large, non-healing duodenal ulcer. We aim to highlight risks, presentation, and management of histoplasmosis in IBD patients on immunosuppression with anti-TNFs. A 49-year-old-male with a 21-year history of left sided UC in remission on Infliximab (10 years) presented to our ED with orthostatic symptoms and melena. He reported two months of heartburn and epigastric pain refractory to acid suppression. In the ED, vitals were unremarkable. Labs showed BUN 38 mg/dL, hemoglobin 13.3 g/dL, and abnormal AST/ALT. Evaluation of mild chest discomfort revealed normal EKG and calcified nodule in the left lower lobe on chest X-ray. Tuberculosis testing was negative. EGD found a massive, 3-4cm, cratered, medial wall, hemi-circumferential ulcer from duodenal apex into the second duodenal segment (D2). Biopsies revealed acute inflammation, without CMV, dysplasia, malignancy or helicobacter pylori. CT identified a large mass 5x3.1x3.2cm in the pancreaticoduodenal groove from D2 without pancreatic duct dilation. There were prominent right axillary and sub-pectoral lymph nodes and the calcified granuloma seen on X-ray. He denied NSAID use. Symptomatic improvement occurred on aggressive acid suppression. EGD a month later showed persistent ulcer with unchanged pathology. EUS showed significant peri-duodenal thickening without malignant findings. IgG/IgG4 immunostains were negative. CEA and CA 19-9 were normal. Subsequent EGDs and imaging showed no changes. He developed duodenal stenosis requiring dilation. Hematology/Oncology evaluation was unrevealing and hyper-secretory disorder was ruled out. Lack of healing over seven months prompted referral to Infectious Disease. They identified bird dropping exposure with repeated deck pressure washing. Positive Histoplasma immunodiffusion M band indicated prior infection. Given exposure, lab, chest imaging and endoscopic findings, treatment for disseminated histoplasmosis (DH) with Itraconazole was initiated. Infliximab was held and mesalamines were restarted. Histoplasmosis is endemic to the Ohio/Mississippi River Valley and other countries. Disseminated histoplasmosis, typically found in the immunocompromised, presents in many ways with GI involvement in 70%. Diagnosis can be difficult as histoplasmosis mimics other diseases, including IBD. Prognosis is poor if left untreated. Endoscopically, ulcerations, mass-like lesions, or strictures are seen. Aside from identifying yeast, pathology is nonspecific. Severity guides treatment, classically involving Itraconazole. In IBD and diseases managed with immunosuppression (e.g. anti-TNFs), stopping therapy during infections is standard of care. Therapy may resume after treatment response. Treatment may be a year for DH. Prophylaxis for histoplasmosis, the most common fungal infection with anti-TNF use, is controversial. Literature exists where anti-TNF was continued during treatment of histoplasmosis with good outcomes. There were no recurrences with continuation or re-initiation of anti-TNF after treatment. However, many patients switched therapies. Though histoplasmosis rarely causes infection in IBD patients, outcomes can be poor. We must be aware of possible exposures, atypical or presentations mimicking IBD to identify infection early, stop immunosuppression and provide timely treatment.


Rovibrational energy transfer in ortho-H2+para-H2 collisions.
We present the results of a full-dimensional quantum mechanical study of the rovibrational energy transfer in the collision between ortho-H2 and para-H2 in the energy range of 0.1-1.0 eV. The multiconfiguration time-dependent Hartree algorithm has been used to propagate the wave packets on the global potential energy surface by Boothroyd et al. [J. Chem. Phys. 116, 666 (2002)] and on a modification of this surface where the short range anisotropy is reduced. State-to-state attributes such as probabilities or integral cross sections are obtained using the formalism of Tannor and Weeks [J. Chem. Phys. 98, 3884 (1993)] by Fourier transforming the correlation functions. The effect of initial rotation of the diatoms on the inelastic and de-excitation processes is investigated.


Mammographic breast density--evidence for genetic correlations with established breast cancer risk factors.
Previous twin and family studies indicate that the familial aggregation of breast density is due (in part) to genetic factors. Whether these genetic influences are shared with other breast cancer risk factors, however, is not known. Using standard film-screen mammography, we screened 550 women, including 611 pairs of sisters, from the Old Order Amish population of Lancaster County, Pennsylvania. We digitized mammograms and quantified the dense and nondense areas of the breast using a computer-assisted method. Information about other breast cancer risk factors was collected via questionnaires and a physical exam. Using pedigree-based variance component methods, we estimated the genetic contributions to several breast cancer risk factors, including breast density, and evaluated the evidence for shared genetic influences between them. After adjusting for covariates, genetic effects accounted for >33% of the total variance of each risk factor (P < 0.001), including breast density, and the dense and nondense areas of the breast were significantly genetically correlated with parity [genetic correlation (rho(G)) = -0.47; P = 0.013] and age at menarche (rho(G) = -0.38; P = 0.008), respectively. The nondense area of the breast and, in turn, breast density, expressed as a ratio of dense area to total area, were also genetically correlated with most measures of adiposity but in opposite directions (rho(G) > or = 0.75; P < 10(-7) for nondense area). We conclude that the genetic components that influence breast density are not independent of the genetic components that influence other breast cancer risk factors. This shared genetic architecture should be considered in future genetic studies of breast density.


Giant lymph node hyperplasia with unusual clinicopathologic features.
This report describes two cases of giant lymph node hyperplasia (GLNH) with unusual clinicopathologic features, both studied with immunohistochemical techniques. In the first case, mesenteric GLNH was associated with amyloidosis and the nephrotic syndrome. In the second, GLNH developed in a patient with previously treated Hodgkin's disease. In both cases, the GLNH was of the plasma cell variant. The plasma cells of the first case contained both kappa and lambda light chains, while those in the second case contained only the lambda light chain. The presence or absence of monoclonality was not predictable from the morphology alone. Cases of GLNH with unusual clinicopathologic features are reviewed and the significance of immunohistochemical studies discussed.