An image dataset of cleared, x-rayed, and fossil leaves vetted to plant family for human and machine learning.
Leaves are the most abundant and visible plant organ, both in the modern world and the fossil record. Identifying foliage to the correct plant family based on leaf architecture is a fundamental botanical skill that is also critical for isolated fossil leaves, which often, especially in the Cenozoic, represent extinct genera and species from extant families. Resources focused on leaf identification are remarkably scarce; however, the situation has improved due to the recent proliferation of digitized herbarium material, live-plant identification applications, and online collections of cleared and fossil leaf images. Nevertheless, the need remains for a specialized image dataset for comparative leaf architecture. We address this gap by assembling an open-access database of 30,252 images of vouchered leaf specimens vetted to family level, primarily of angiosperms, including 26,176 images of cleared and x-rayed leaves representing 354 families and 4,076 of fossil leaves from 48 families. The images maintain original resolution, have user-friendly filenames, and are vetted using APG and modern paleobotanical standards. The cleared and x-rayed leaves include the Jack A. Wolfe and Leo J. Hickey contributions to the National Cleared Leaf Collection and a collection of high-resolution scanned x-ray negatives, housed in the Division of Paleobotany, Department of Paleobiology, Smithsonian National Museum of Natural History, Washington D.C.; and the Daniel I. Axelrod Cleared Leaf Collection, housed at the University of California Museum of Paleontology, Berkeley. The fossil images include a sampling of Late Cretaceous to Eocene paleobotanical sites from the Western Hemisphere held at numerous institutions, especially from Florissant Fossil Beds National Monument (late Eocene, Colorado), as well as several other localities from the Late Cretaceous to Eocene of the Western USA and the early Paleogene of Colombia and southern Argentina. The dataset facilitates new research and education opportunities in paleobotany, comparative leaf architecture, systematics, and machine learning.


Nucleotide sequence and T cell epitopes of a membrane protein of Francisella tularensis.
A 17-kDa major membrane protein of the facultative intracellular bacterium Francisella tularensis is recognized by T cells from individuals previously undergoing tularemia or tularemia vaccination. Here the nucleotide sequence of the encoding gene is presented. The A + T rich sequence deduced a protein of 149 amino acids with a predicted m.w. of 15,772. Evidence is presented suggesting that the 17-kDa protein is a lipoprotein. Also, homology was found to a peptidoglycan-associated lipoprotein of Escherichia coli. Thirteen overlapping synthetic peptides encompassing the entire deduced protein were tested on lymphocytes from F. tularensis-primed individuals. Three peptides induced a T cell response, as disclosed by lymphocyte proliferation and production of IL-2 and IFN-gamma. Out of five responding individuals, only one recognized more than one of the peptides. A murine mAb recognized an epitope separate from the T cell-reactive peptides. The identified T cell epitopes are presumably relevant to the host defense against F. tularensis, especially because IFN-gamma is known to enhance the antimicrobial activity of the host against intracellular bacteria.


In vitro and intracellular activities of frog skin temporins against Legionella pneumophila and its eukaryotic hosts.
Temporin-SHa (SHa) is a small cationic host defence peptide (HDP) produced in skin secretions of the Sahara frog Pelophylax saharicus. This peptide has a broad-spectrum activity, efficiently targeting bacteria, parasites and viruses. Noticeably, SHa has demonstrated an ability to kill Leishmania infantum parasites (amastigotes) within macrophages. Recently, an analog of SHa with an increased net positive charge, named [K3]SHa, has been designed to improve those activities. SHa and [K3]SHa were both shown to exhibit leishmanicidal activity mainly by permeabilization of cell membranes but could also induce apoptotis-like death. Temporins are usually poorly active against Gram-negative bacteria whereas many of these species are of public health interest. Among them, Legionella pneumophila, the etiological agent of Legionnaire's disease, is of major concern. Indeed, this bacterium adopts an intracellular lifestyle and replicate inside alveolar macrophages likewise inside its numerous protozoan hosts. Despite several authors have studied the antimicrobial activity of many compounds on L. pneumophila released from host cells, nothing is known about activity on intracellular L. pneumophila within their hosts, and subsequently mechanisms of action that could be involved. Here, we showed for the first time that SHa and [K3]SHa were active towards several species of Legionella. Both peptides displayed bactericidal activity and caused a loss of the bacterial envelope integrity leading to a rapid drop in cell viability. Regarding amoebae and THP-1-derived macrophages, SHa was less toxic than [K3]SHa and exhibited low half maximal lethal concentrations (LC50). When used at non-toxic concentration (6.25 µM), SHa killed more than 90% L. pneumophila within amoebae and around 50% within macrophages. Using SHa labeled with the fluorescent dye Cy5, we showed an evenly diffusion within cells except in vacuoles. Moreover, SHa was able to enter the nucleus of amoebae and accumulate in the nucleolus. This subcellular localization seemed specific as macrophages nucleoli remained unlabeled. Finally, no modifications in the expression of cytokines and HDPs were recorded when macrophages were treated with 6.25 µM SHa. By combining all data, we showed that temporin-SHa decreases the intracellular L. pneumophila load within amoebae and macrophages without being toxic for eukaryotic cells. This peptide was also able to reach the nucleolus of amoebae but was not capable to penetrate inside vacuoles. These data are in favor of an indirect action of SHa towards intracellular Legionella and make this peptide a promising template for further developments.


Death receptor apoptosis signaling mediated by FADD in CD30-positive lymphoproliferative disorders involving the skin.
The CD30-positive lymphoproliferative disorders lymphomatoid papulosis (LyP), primary cutaneous anaplastic large cell lymphoma (C-ALCL), and systemic anaplastic large cell lymphoma (S-ALCL) are lesions that overlap clinically, histopathologically, and immunophenotypically. Their biologic behaviors, however, vary considerably. In particular, lesions of LyP regress spontaneously while those of S-ALCL persist and often progress. Apoptosis has been suggested as the mechanism by which the lesions of LyP regress, but the underlying signaling pathways remain unclear. In this study, we used newly developed activation state-specific antibodies to demonstrate apoptosis signaling through the death receptor-mediated pathway regulated by FADD and caspase 3. Dual immunohistochemistry for CD30 and activated forms of FADD and caspase 3 was performed on cutaneous biopsy specimens from 27 patients with CD30-positive lymphoproliferative disorders involving the skin. The patients included 18 with primary cutaneous CD30-positive LPDs (15 with LyP and 3 with C-ALCL) and 9 with S-ALCL. The proportion of CD30-positive cells expressing activated FADD was significantly different between primary cutaneous CD30-positive lymphoproliferative disorders and S-ALCL (36.4% vs. 14.5%, P = 0.0083). Expression of cleaved caspase 3 was also significantly different between primary cutaneous lesions and S-ALCL (9.2% vs. 1.9%, P = 0.048). Although a larger number of cases should be studied to validate these results, these data provide evidence that differences in signaling through the death-receptor apoptosis pathway mediated by FADD may be responsible for the varying biologic behaviors of CD30-positive lymphoproliferative disorders involving the skin.


Characterising the spatial dynamics of sympatric Aedes aegypti and Aedes albopictus populations in the Philippines.
Entomological surveillance and control are essential to the management of dengue fever (DF). Hence, understanding the spatial and temporal patterns of DF vectors, Aedes (Stegomyia) aegypti (L.) and Ae. (Stegomyia) albopictus (Skuse), is paramount. In the Philippines, resources are limited and entomological surveillance and control are generally commenced during epidemics, when transmission is difficult to control. Recent improvements in spatial epidemiological tools and methods offer opportunities to explore more efficient DF surveillance and control solutions: however, there are few examples in the literature from resource-poor settings. The objectives of this study were to: (i) explore spatial patterns of Aedes populations and (ii) predict areas of high and low vector density to inform DF control in San Jose village, Muntinlupa city, Philippines. Fortnightly, adult female Aedes mosquitoes were collected from 50 double-sticky ovitraps (SOs) located in San Jose village for the period June-November 2011. Spatial clustering analysis was performed to identify high and low density clusters of Ae. aegypti and Ae. albopictus mosquitoes. Spatial autocorrelation was assessed by examination of semivariograms, and ordinary kriging was undertaken to create a smoothed surface of predicted vector density in the study area. Our results show that both Ae. aegypti and Ae. albopictus were present in San Jose village during the study period. However, one Aedes species was dominant in a given geographic area at a time, suggesting differing habitat preferences and interspecies competition between vectors. Density maps provide information to direct entomological control activities and advocate the development of geographically enhanced surveillance and control systems to improve DF management in the Philippines.


Effect of 5-hydroxytryptamine (serotonin) receptor inhibitors on the radiation-induced bystander effect.
To test the importance of serotonin as a signaling molecule involved in the production and response of radiation-induced bystander effects. HPV-G human keratinocyte cultures were spiked with various concentrations of Granisetron or Ketanserin and subject to either 0 Gy or 0.5 Gy X-irradiation to observe the inhibitor's effects on bystander signal production. Medium from these cultures was harvested and introduced to non- irradiated cultures of the same cell line to determine the clonogenic bystander response. Separate HPV-G cultures were set up for subsequent calcium measurements in response to irradiated cell conditioned medium (ICCM) in the presence or absence of Granisetron in an attempt to block bystander signal response. Granisetron and Ketanserin produced a dose-dependent propagation of the bystander effect in recipient cultures. Granisetron completely abolished the characteristic calcium pulse observed when non-irradiated cultures are exposed to irradiated cell medium in the presence of this drug. Serotonin-dependent mechanisms appear to be involved in bystander signal production and response to radiation in this system.


Pulsed versus continuous application of the prodrug 5-fluorocytosine to enhance the oncolytic effectiveness of a measles vaccine virus armed with a suicide gene.
Abstract Oncolytic virotherapy with measles vaccine virus (MeV) already has been demonstrated to be safe. However, early clinical results pointed out the necessity for an enhancement of oncolytic effectiveness of MeV-based virotherapeutics. In our work, we are developing an armed measles vaccine virus (MeV-SCD) encoding a suicide fusion gene of yeast cytosine deaminase/uracil phosphoribosyltransferase, converting the nontoxic prodrug 5-fluorocytosine (5-FC) to the chemotherapeutic drug 5-fluorouracil (5-FU). To preclinically investigate what an optimal prodrug-assisted therapeutic regimen might look like, we added 5-FC at various time points after infection with MeV-SCD and either let the prodrug remain in the tumor cell culture medium continuously for various time periods ("continuous" 5-FC application) or applied it only temporarily for defined shorter periods of time ("pulsed" 5-FC application); we also varied the time point at which 5-FC was added after infection with MeV-SCD. As a result, addition of the prodrug at early times postinfection (e.g., at 3 hr postinfection) was found to be inferior concerning the overall oncolytic effectiveness when compared with addition of 5-FC at later time points (e.g., at 24 hr postinfection). Next, oncolytic effectiveness was found to correlate positively with the overall duration of incubation of MeV-infected tumor cells with 5-FC. Of note, this was true despite our finding that addition of the prodrug could also exert an inhibitory effect on the generation of infectious progeny viral particles, that is, on virus replication. These findings should be helpful for the rational design of further trials (preclinical, clinical) using suicide gene armed virotherapeutics, such as MeV-SCD.


Impact of Urinary Incontinence on Physical Function and Respiratory Muscle Strength in Incontinent Women: A Comparative Study between Urinary Incontinent and Apparently Healthy Women.
Patients with stress urinary incontinence (SUI) may be afraid to increase intra-abdominal pressure to avoid incontinence. This could lead to weak expiratory muscles. The aim of this study was to investigate the association between respiratory muscle strength, physical function, and SUI in patients with SUI. A cross-sectional study was conducted in the Physical Medicine and Functional Rehabilitation Department. Thirty-one incontinent women (IG) and twenty-nine women in a control group (CG) were enrolled in this study. Anthropometric data, respiratory muscle strength (maximal inspiratory pressure; maximal expiratory pressure), SUI (Urogenital Distress Inventory-6; Incontinence Impact Questionnaire-7; Pad test), and physical function (waist circumference; timed-up-and-go test; abdominal muscle strength) were assessed. Body fat, body mass index, body weight, and waist circumference were higher in IG than CG (p < 0.01), while postural gait and abdominal muscles were lower (p < 0.001). Respiratory muscle strength displayed moderate correlations with SUI severity, especially for maximal expiratory pressure (p < 0.01). Maximal expiratory pressure was moderately associated with physical function. Deterioration in respiratory muscle strength is a characteristic of women with SUI. In this population, pelvic floor muscle training may be prescribed to improve continence. By feeling more confident about increasing intra-abdominal pressure, women with SUI would strengthen their expiratory muscles and eventually improve their physical function.


Extradural arteriovenous fistulas involving the vertebral artery in neurofibromatosis Type 1.
Spinal extradural arteriovenous fistulas (AVFs) are rare lesions that may be associated with neurofibromatosis Type 1 (NF1). In these patients, the shunt typically occurs between the V(2) segment of the vertebral artery and the epidural venous plexus. Previously, reported cases have been treated either by using endovascular embolization or, sporadically, by open surgery. In surgical reports, proximal deafferentation or manipulation of the venous portion of the shunt--including suture, resection, or open embolization of the epidural ectasia--was attempted with variable results. The authors report on a case of a young patient with NF1 who underwent emergency surgical disconnection of a cervical extradural AVF after previously unsuccessful endovascular and surgical therapy. The lesion drained into a giant intrathecal varix, causing severe myelopathy. After surgery, the patient recovered almost completely. This experience clarified the surgical anatomy of these malformations and showed that, when surgery is necessary, the optimal treatment providing complete and permanent cure of this condition is direct closure of the epidural shunt pedicle.


Modulation of cutaneous scavenger receptor B1 levels by exogenous stressors impairs "in vitro" wound closure.
Scavenger receptor B1 (SR-B1) is a trans-membrane protein, involved in tissue reverse cholesterol transport. Several studies have demonstrated that SR-B1 is also implicated in other physiological processes, such as bacteria and apoptotic cells recognition and regulation of intracellular tocopherol and carotenoids levels. Among the tissues where it is localized, SR-B1 has been shown to be significantly expressed in human epidermis. Our group has demonstrated that SR-B1 levels are down-regulated in human cultured keratinocytes by environmental stressors, such as cigarette smoke, via cellular redox imbalance. Our present study aimed to investigate whether such down-regulation was confirmed in a 3D skin model and under other environmental challengers such as particulate matter and ozone. We also investigated the association between oxidation-induced SR-B1 modulation and impaired wound closure. The data obtained showed that not only cigarette, but also the other environmental stressors reduced SR-B1 expression in epidermal cutaneous tissues and that this effect might be involved in impaired wound healing.


Cysts of mammarylike glands in the vulva.
A hidrocystoma which originated in a mammarylike gland (MLG) of the vulva is described. It involved the main collecting duct and was characterized by a peripheral basal layer of myoepithelium and a luminal layer of cuboidal to columnar cells with discrete cytoplasmic snouts and by lobules opening into the cavity. Adhering to it were cutaneous glands, including MLGs, and dartos muscle. These features distinguish it from the other cysts of the vulva, including vestibular, urogenital sinus, and keratinous cysts. Another cystic lesion of the MLGs was evidenced only microscopically and involved multiple whole glands. It resembled similar alterations in eccrine, apocrine, and mammary glands, and most likely represented involution cysts of MLGs.


[On a problem of syphilitic damage of the eye].
Clinical features and epidemiology of syphilitic damage of the eye in Smolensk region was studied in 1996-2008 period. 32 medical charts of patients with ophthalmosyphilis were analyzed. Ophthalmosyphilis is usually registered in patients with secondary syphilis with disease duration more than 6 months (56.3%) and in patients with late neurosyphilis (40.6%). The diagnosis was established in 24.5+4.8 (from 14 till 34) days after clinical presentation. Clinical forms of ophthalmosyphilis included bilateral uveitis (15.6%), optic neuritis (15.8%), iridocyclitis (12.5%) and choreoretinitis (12.5%). Complications of ophthalmosyphilis included optic nerve atrophy developed in 6.2%, cataract--6.2% and glaucoma--3.1%. In epidemiologically unfavorable situation caution should be taken by ophthalmologists in terms of syphilitic infection, appropriate laboratory tests should be considered.


The impact of conscientiousness, mastery, and work circumstances on subsequent absenteeism in employees with and without affective disorders.
High numbers of employees are coping with affective disorders. At the same time, ambitiousness, achievement striving and a strong sense of personal control and responsibility are personality characteristics that are nowadays regarded as key to good work functioning, whereas social work circumstances tend to be neglected. However, it is largely unkown how personality characteristics and work circumstances affect work functioning when facing an affective disorder. Given the high burden of affective disorders on occupational health, we investigate these issues in the context of affective disorders and absenteeism from work. The principal aim of this paper is to examine whether particular personality characteristics that reflect self-governance (conscientiousness and mastery) and work circumstances (demands, control, support) influence the impact of affective disorders on long-term absenteeism (>10 working days). Baseline and 1-year follow-up data from 1249 participants in the Netherlands Study of Depression and Anxiety (NESDA) in 2004-2006 was employed. Multivariate logistic regression analyses were performed, including interaction effects between depressive, anxiety, and comorbid disorders and personality and work circumstances. In general, mastery and conscientiousness increased nor diminished odds of subsequent long-term absenteeism, whereas higher job support significantly decreased these odds. Interaction effects showed that the impact of affective disorders on absenteeism was stronger for highly conscientious employees and for employees who experienced high job demands. Affective disorders may particularly severely affect work functioning of employees who are highly conscientious or face high psychological job demands. Adjusting working conditions to their individual needs may prevent excessive work absence.


[Experience in using a tomicide paste in the combined treatment of patients with pyoderma].
Tomicide paste is a highly effective agent in combined therapy of patients with primary and secondary pyoderma. Tomicide is recommended for practical dermatology in the liquid form for sanitization++ of infection foci in nasopharyngeal organs and in paste with a 10% concentration of the agent. This paste is also advised for cases with secondary pyoderma complicating the course of neurodermatitis and chronic eczema not liable to weeping.


[Post-pneumonectomic purulent bronchopleural complications in lung cancer: a solution of the problem].
A strategy providing for solution of a number of tactical and technical problems involved in prognosis, prevention and management of postoperative bronchopleural complication after pneumonectomy for lung cancer was suggested. It was followed by a significant decrease in the frequency of bronchopleural fistula, postoperative empyema and lethality from purulent bronchopleural complications.


Acupuncture for Treating Anxiety and Depression in Women: A Clinical Systematic Review.
Anxiety and depression are high in prevalence, especially in the female population, whose incidence is approximately double that of the male population. In addition, these conditions are difficult to treat and have high relapse rates and medication side-effects. There is evidence to suggest that acupuncture may be an effective treatment modality. The aim of this review is to summarize the existing evidence on acupuncture as a therapy for anxiety and depression in women and to present a novel method for assessing acupuncture trial quality. Published randomized controlled trials were included, whereby acupuncture was compared with any control procedure in subjects with anxiety and/or depression. Two authors extracted data independently. A novel acupuncture trial quality-assessment tool was developed to analyze the literature quality. Six articles used the desired inclusion and exclusion criteria. The quality of research varied heavily. Five studies were properly randomized. Three were double-blinded. Three used individualized acupuncture. Four studies were of at least reasonable quality. One was of marginal quality, and one was of poor quality. There was a significant difference between acupuncture and at least one control in all six trials. With respect to six reviewed studies, there is high-level evidence to support the use of acupuncture for treating major depressive disorder in pregnancy.


MusIC method enhancement by a sensitivity study of its performance: Application to a lower limbs musculoskeletal model.
Providing a biomechanical feedback during experimental sessions is a real outcome for rehabilitation, ergonomics or training applications. However, such applications imply a fast computation of the biomechanical quantities to be observed. The MusIC method has been designed to solve quickly the muscle forces estimation problem, thanks to a database interpolation. The current paper aims at enhancing its performance. Without generating any database, the method allows to identify optimal densities (number of samples contained in the database) with respect to the method accuracy and the off-line computation time needed to generate the database. On a lower limbs model (12 degrees of freedom, 82 muscles), thanks to this work, the MusIC method exhibits an accuracy error of 0.1% with an off-line computation time lower than 10 minutes. The on-line computation frequency (number of samples computed per second) is about 58 Hz. Thanks to these improvements, the MusIC method can be used to produce a feedback during an experimentation with a wide variety of musculoskeletal models or cost functions (used to share forces into muscles). The interaction between the subject, the experimenter (e.g. trainer, ergonomist or clinician) and the biomechanical data (e.g. muscle forces) in experimental sessions is a promising way to enhance rehabilitation, training or design techniques.


Perspectives on Lower Extremity Peripheral Artery Disease: A Qualitative Study of Early Diagnosis and Treatment and the Impact of Health Disparities.
Lower-extremity peripheral artery disease (PAD), the accumulation of atherosclerotic plaque in the arteries of the legs, causes substantial morbidity and mortality. Frequent under- and delayed diagnosis result in poor outcomes, disproportionately affecting individuals from racial and ethnic minority groups. To understand barriers to early detection and treatment and factors contributing to disparities, American Medical Group Association (AMGA) conducted roundtable discussions and semistructured interviews in 2021. Eighteen participants discussed PAD evaluation, diagnosis, early medical management, and disparities in care. A qualitative case study approach and data reduction methods were used to generate themes, draw conclusions, and make actionable recommendations. Identified themes included lack of (1) prioritization of PAD for population health; (2) engagement of primary care providers in early evaluation and referral; (3) "ownership" of lower-extremity PAD within health systems; and (4) focus on disparities in care. Participant solutions included (1) financial impact of early PAD management, in the context of value-based payment; (2) embedding an advanced practice provider into a vascular surgery practice to facilitate evaluation and provide medical therapy; and (3) leveraging care coordination, multidisciplinary clinics, and telehealth technology to provide comprehensive care for patients with PAD and address disparities. A deliberate focused effort is necessary to close gaps and the accompanying disparities in early evaluation, diagnosis, and treatment for people with lower-extremity PAD. The authors describe 3 models that can be emulated to improve care for this high-risk population. With improved reimbursement and better medical therapies, now is the time to focus on early diagnosis and management of PAD.


Preliminary experience using the transcatheter mitral valve leaflet repair procedure.
Mitral regurgitation (MR) causes increased morbidity and mortality in heart failure patients and is often associated with augmented surgical risk. To assess the preliminary results oftranscatheter mitral valve leaflet repair (TMLR) in a single academic center. Data were collected prospectively in the cardiology department of Rabin Medical Center in 2012. Ten consecutive patients (age 69.3 +/- 15.9 years, ejection fraction 36.5 +/- 9.4) who were poor surgical candidates with severe functional MR underwent general anesthesia, followed by trans-septal puncture and a TMLR procedure using the MitraClip device. All 10 patients were considered to have severe functional MR prior to TMLR treatment and were all symptomatic; the mean New York Heart Association (NYHA) class was 3.4 +/- 0.5. The MR severity was 4 +/- 0. There were no immediate complications or failures of the procedure. One patient died on day 5 due to massive gastrointestinal bleeding. Immediately following TMLR all 10 patients showed a profound MR reduction to a mean severity grade of 1.6 +/- 0.6. At one month after the procedure, NYHA had decreased to an average of 1.7 +/- 1.0 and was at least grade 2 in all but one patient. After 6 months the MR remained < or = 2 in six of eight patients, with a NYHA average of 1.4 +/- 0.5. The MitraClip procedure was shown to be relatively safe, providing significant clinical benefit to a relatively sick population with severe MR. It is therefore an important alternative to surgery in these high risk patients.


Multigene Measurable Residual Disease Assessment Improves Acute Myeloid Leukemia Relapse Risk Stratification in Autologous Hematopoietic Cell Transplantation.
We report here the largest study to date of adult patients with acute myeloid leukemia (AML) tested for measurable residual disease (MRD) at the time of autologous hematopoietic cell transplantation (auto-HCT). Seventy-two adult patients who underwent transplantation between 2004 and 2013 at a single academic medical center (University of California San Francisco) were eligible for this retrospective study based on availability of cryopreserved granulocyte colony-stimulating factor (GCSF)-mobilized autologous peripheral blood progenitor cell (PBPC) leukapheresis specimens ("autografts"). Autograft MRD was assessed by molecular methods (real-time quantitative PCR [RQ-PCR] for Wilms tumor 1 (WT1) alone or a multigene panel) and by multiparameter flow cytometry (MPFC). WT1 RQ-PCR testing of the autograft had low sensitivity for relapse prediction (14%) and a negative predictive value of 51%. MPFC failed to identify MRD in any of 34 autografts tested. Combinations of molecular MRD assays, however, improved prediction of post-auto-HCT relapse. In multivariate analysis of clinical variables, including age, gender, race, cytogenetic risk category, and CD34+ cell dose, only autograft multigene MRD as assessed by RQ-PCR was statistically significantly associated with relapse. One year after transplantation, only 28% patients with detectable autograft MRD were relapse free, compared with 67% in the MRD-negative cohort. Multigene MRD, while an improvement on other methods tested, was however suboptimal for relapse prediction in unselected patients, with specificity of 83% and sensitivity of 46%. In patients with known chromosomal abnormalities or mutations, however, better predictive value was observed with no relapses observed in MRD-negative patients in the first year after auto-HCT compared with 83% incidence of relapse in the MRD-positive patients (hazard ratio, 12.45; P = .0016). In summary, increased personalization of MRD monitoring by use of a multigene panel improved the ability to risk stratify patients for post-auto-HCT relapse. WT1 RQ-PCR and flow cytometric assessment for AML MRD in autograft samples had limited value for predicting relapse after auto-HCT. We demonstrate that cryopreserved autograft material presents unique challenges for AML MRD testing because of the masking effects of previous GCSF exposure on gene expression and flow cytometry signatures. In the absence of information regarding diagnostic characteristics, sources other than GCSF-stimulated PBSC leukapheresis specimens should be considered as alternatives for MRD testing in AML patients undergoing auto-HCT.


Trans-arterial radioembolization in intermediate-advanced hepatocellular carcinoma: systematic review and meta-analyses.
Trans-arterial radioembolization (TARE) is a recognized, although not explicitly recommended, experimental therapy for unresectable hepatocellular carcinoma (HCC).A systematic literature review was performed to identify published studies on the use of TARE in intermediate and advanced stages HCC exploring the efficacy and safety of this innovative treatment.Twenty-one studies reporting data on overall survival (OS) and time to progression (TTP), were included in a meta-analysis. The pooled post-TARE OS was 63% (95% CI: 56-70%) and 27% (95% CI: 21-33%) at 1- and 3-years respectively in intermediate stage HCC, whereas OS was 37% (95% CI: 26-50%) and 13% (95% CI: 9-18%) at the same time intervals in patients with sufficient liver function (Child-Pugh A-B7) but with an advanced HCC because of the presence of portal vein thrombosis. When an intermediate and advanced case-mix was considered, OS was 58% (95% CI: 48-67%) and 17% (95% CI: 12-23%) at 1- and 3-years respectively. As for TTP, only four studies reported data: the observed progression probability was 56% (95% CI: 41-70%) and 73% (95% CI: 56-87%) at 1 and 2 years respectively. The safety analysis, focused on the risk of liver decompensation after TARE, revealed a great variability, from 0-1% to more than 36% events, influenced by the number of procedures, patient Child-Pugh stage and treatment duration.Evidence supporting the use of radioembolization in HCC is mainly based on retrospective and prospective cohort studies. Based on this evidence, until the results of the ongoing randomized trials become available, radioembolization appears to be a viable treatment option for intermediate-advanced stage HCC.


Alterations of the PPP2R1B gene located at 11q23 in human colorectal cancers.
In 1998 the PPP2R1B gene encoding the A subunit of the serine/threonine protein phosphatase was identified as a putative tumour suppressor gene in lung and colon cancer in the chromosome region 11q22-24. The aim of the present study was to determine the type of alterations in primary rectal cancers as well as colon cancers and the correlation between these alterations and clinicopathological data. Mutation analyses of the PPP2R1B gene sequence encoding the binding sites of the catalytic C subunit (Huntington elongation A subunit TOR (HEAT) repeats 11-15) and partial binding sites of the regulatory B subunit were carried out on cDNA samples from 30 primary colorectal cancer specimens and corresponding normal tissues using a combination of the polymerase chain reaction and subsequent direct DNA sequencing. Five missense mutations producing amino acid substitutions were detected in the four colon cancer cases (13.3%; four of 30 colorectal cancers): (15)glycine (GGT) to alanine (GCT) and (499)leucine (TTA) to isoleucine (ATA) in the same case, and (498)valine (GTG) to glutamic acid (GAG), (500)valine (GTA) to glycine (GGA), and (365)serine (TCT) to proline (CCT). Of these five mutations, three (60%) were located in HEAT repeat 13 and four (80%) showed T to other nucleotide substitutions. In addition, a normal polymorphism, (478)leucine, was found. No correlation was found between these mutations and clinicopathological data. Our results suggest that the PPP2R1B gene is one of the true targets at 11q23, and its inactivation is involved in the development of all types of colorectal cancers.


[Effectiveness of laser treatment of narrow-angle glaucoma].
Forty-eight patients with narrow-angle glaucoma were treated with M-900 argon laser (Coherent Radiation, USA). Reduction of intraocular pressure as low as 20 +/- 1.82 mm Hg on an average was achieved. Fluid discharge efficacy coefficient has improved. The authors claim that laser cyclotrabeculospasis a sufficiently effective method for the treatment of primary narrow-angle glaucoma.


High Resilience of Seed Dispersal Webs Highlighted by the Experimental Removal of the Dominant Disperser.
The pressing need to conserve and restore habitats in the face of ongoing species loss [1, 2] requires a better understanding of what happens to communities when species are lost or reinstated [3, 4]. Theoretical models show that communities are relatively insensitive to species loss [5, 6]; however, they disagree with field manipulations showing a cascade of extinctions [7, 8] and have seldom been tested under field conditions (e.g., [9]). We experimentally removed the most abundant seed-dispersing ant species from seed dispersal networks in a Mediterranean landscape, replicating the experiment in three types of habitat, and then compared these communities to un-manipulated control communities. Removal did not result in large-scale changes in network structure. It revealed extensive structural plasticity of the remaining community, which rearranged itself through rewiring, while maintaining its functionality. The remaining ant species widened their diet breadth in a way that maintained seed dispersal, despite the identity of many interactions changing. The species interaction strength decreased; thus, the importance of each ant species for seed dispersal became more homogeneous, thereby reducing the dependence of seed species on one dominant ant species. Compared to the experimental results, a simulation model that included rewiring considerably overestimated the effect of species loss on network robustness. If community-level species loss models are to be of practical use in ecology or conservation, they need to include behavioral and population responses, and they need to be routinely tested under field conditions; doing this would be to the advantage of both empiricists and theoreticians.


Phyllotactic pattern and stem cell fate are determined by the Arabidopsis homeobox gene BELLRINGER.
Lateral organs in plants arise from the meristem in a stereotypical pattern known as phyllotaxy. Spiral patterns result from initiation of successive organs at a fixed angle of divergence but variable patterns of physical contact. Such patterns ultimately give rise to individual leaves and flowers at positions related to each other by consecutive terms in the mathematical series first described by Leonardo Fibonacci. We demonstrate that a BELL1 related homeodomain protein in Arabidopsis, BELLRINGER, maintains the spiral phyllotactic pattern. In the absence of BELLRINGER, the regular pattern of organ initiation is disturbed and lateral organs are initiated more frequently. BELLRINGER is also required for maintenance of stem cell fate in the absence of the regulatory genes SHOOT MERISTEMLESS and ASYMMETRIC LEAVES1. We propose a model whereby BELLRINGER coordinates the maintenance of stem cells with differentiation of daughter cells in stem cell lineages.


Degradation by cultured fibroblasts and macrophages of unmodified and 1,2-cyclohexanedione-modified low-density lipoprotein from normal and homozygous familial hypercholesterolaemic subjects.
Monolayer cultures of human skin fibroblasts and monocyte-derived macrophages were used to examine the effect of cyclohexane-1,2-dione modification on the proteolytic degradation of 125I-labelled low-density lipoprotein (LDL) from normal subjects (NLDL) and homozygous familial hypercholesterolaemic subjects (FHLDL). Normal fibroblasts, pre-incubated in lipoprotein-deficient serum, and macrophages, pre-incubated in whole serum, exhibited both saturable and non-saturable degradation of LDL. In fibroblasts, the saturable receptor-mediated degradation of FHLDL was similar to that of NLDL and was abolished if the lipoproteins were modified with cyclohexanedione. The rate of non-saturable degradation of FHLDL was at least 3-fold higher than that of NLDL and each was decreased by approx. 60% after modification. In macrophages, saturable degradation was decreased but not abolished by modification. The apparent affinity for unmodified LDL was lower than that of the fibroblast receptor and was greater for NLDL than for FHLDL. Non-saturable degradation of FHLDL by macrophages was only slightly higher than that of NLDL. Modification with cyclohexanedione decreased the rate of non-saturable degradation of NLDL by 30%, but increased that of FHLDL by 75%. These experiments show differences between the degradation of 125I-labelled NLDL and FHLDL. They suggest that macrophages can degrade LDL by a saturable process with different properties from that mediated by the fibroblast receptor and that, in vitro, the rate of degradation of the modified LDL is not the same as the rate of non-receptor-mediated degradation of unmodified LDL.


Kruppel-like factor 4 induces p27Kip1 expression in and suppresses the growth and metastasis of human pancreatic cancer cells.
The zinc finger transcription factor Krüppel-like factor 4 (KLF4) has been implicated in both tumor suppression and progression. However, its function in pancreatic cancer has not been well characterized. Here, we show that pancreatic cancer cell lines expressed various levels of KLF4 RNA and protein. Ectopic expression of KLF4 by FG and BxPC-3 pancreatic cancer cells resulted in cell cycle arrest and marked inhibition of cell growth in vitro and attenuation of tumor growth and metastasis in an orthotopic mouse model. Overexpression of KLF4 also led to significant induction of p27(Kip1) expression, at both the RNA and protein levels, in a dose- and time-dependent manner, indicating that KLF4 transcriptionally regulates the expression of p27(Kip1). Chromatin immunoprecipitation assays consistently showed that KLF4 protein physically interacts with the p27(Kip1) promoter. Promoter deletion and point mutation analyses indicated that a region between nucleotides -435 and -60 of the p27(Kip1) promoter and intact of the three KLF4-binding sites within that region were required for the full induction of p27(Kip1) promoter activity by KLF4. Our findings suggest that KLF4 transactivates p27(Kip1) expression and inhibits the growth and metastasis of human pancreatic cancer.


Nuclear and mitochondrial DNA replication during zygote formation and maturation in yeast.
Nuclear and mitochondrial DNA replication were monitered during the development of synchronous yeast zygotes. Purified first zygotic buds were also analyzed. Nuclear DNA replicated discontinuously but coincidently with bud initiation, while mitochondrial DNA replicated throughout the zygotic formation and maturation period. First zygotic buds contained the diploid level of both nuclear and mitochondrial DNA.


Rehabilitation of the Atrophic Posterior Maxilla Using Splinted Short Implants or Sinus Augmentation with Standard-Length Implants: A Retrospective Cohort Study.
To retrospectively compare short implants (6 to 8 mm) (short group) to standard-length implants (≥ 11 mm) inserted in combination with a lateral sinus elevation procedure (sinus group), supporting partial fixed prostheses in the atrophic posterior maxilla. Records of 118 patients treated with fluoride-modified implants in the atrophic posterior maxilla between January 2009 and December 2011 were screened in two private practices. Two to four implants were placed in each patient and loaded after 5 to 6 months with partial fixed prostheses. Patients were followed for at least 3 years after implant placement. Patients were contacted and invited for clinical and radiologic follow-up examinations. Outcome measures were implant failures, complications, soft tissue parameters, and marginal bone levels. Fisher exact and unpaired t tests were used to compare proportions and means at the .05 level of significance. A total of 101 patients attended the examination: 53 (112 implants) in the sinus group and 48 (109 implants) in the short group. The mean observation period was 47.03 ± 7.46 months for the sinus group and 44.18 ± 6.42 months for the short group. Ten surgical complications occurred in nine patients of the sinus group versus only one complication in the short group; the difference was statistically significant (P = .01). Six implants failed in five patients of the sinus group versus two implants in two patients of the short group. At follow-up, mean marginal bone loss was 0.64 ± 0.58 mm in the sinus group vs 0.48 ± 0.5 mm in the short group. No significant difference was observed in terms of implant failures, prosthetic complications, soft tissue parameters, or marginal bone loss between the two groups. Within the limitations of this study, both techniques showed similar medium-term outcomes, but short implants provided advantages in terms of a reduced number of surgical complications.


Milrinone Dosing and a Culture of Caution in Clinical Practice.
Milrinone is an invaluable agent in the treatment of end-stage heart failure patients who are refractory to optimal medical therapy. In addition to its use in acute decompensated heart failure, milrinone can also be employed as a home infusion therapy or a bridge to cardiac transplant. Concerns about its adverse effects, such as an increased risk of arrhythmias and hypotension, often limit the doses of milrinone used in clinical practice. In addition, milrinone is infrequently used or avoided entirely in patients with acute renal failure or end-stage renal disease because the drug is primarily cleared by renal excretion. Despite these concerns, studies that comprehensively reconcile the dose-response relationship and adverse events are scarce, and no clear provisions exist to guide milrinone dosing. After a brief discussion of the pharmacokinetics of milrinone, this article examines milrinone dosing, observed hemodynamic benefits, and documented adverse events across different studies.


[Effects of allelochemical isolated from Phragmites communis on algal membrane permeability].
Efflux of K+, Mg2+, Ca2+ ions from algal cells as signals of cell membrane permeability, inductively coupled plasma mass spectrometry (ICP-MS) as detection method of ions, the present research investigated effects of allelochemical eathyl-2-methyl acetoacetate (EMA) isolated from Phragmites communis on cell membrane permeability of Microcystis aeruginosa, Chlorella pyrenoidosa and Chlorella vulagaris. The results showed that, when the cells were boiled for 10 min and the membrane was destroyed absolutely, the K+ efflux of M. aeruginosa and C. pyrenoidosa were 1.45 and 1.59 microg x (10(9) cell) (-1), respectively. When the concentration of EMA was 2 mg x L(-1), the K+ efflux of M. aeruginosa and C. pyrenoidosa were 1.38 and 1.40 microg x (10(9) cell)(-1), respectively. The K+ efflux of M. aeruginosa and C. pyrenoidosa reached 1.44 and 1.58 microg x (10(9) cell)(-1) while the EMA was 4 mg x L(-1). When the concentrations were 2 mg x L(-1) or 4 mg x L(-1) the K+ efflux reached more than 95% of the total ion amount in M. aeruginosa and C. pyrenoidosa cells. But when EMA concentration was 4 mg x L(-1), K+ efflux of C. vulagaris was 0.64 microg x (10(9) cell)(-1), which was only 31.5% of total K+ amount in C. vulagaris. Effects EMA on efflux of Mg2+ and Ca2+ were similar to those of K+. The results indicated that EMA destroyed the cell membrane of M. aeruginosa and C. pyrenoidosa but not C. vulagaris. This is one of the mechanisms of EMA species-selective antialgal.


The Directive Growth Approach for Nonsyndromic, Unicoronal Craniosynostosis: Patient and Clinical Outcomes.
Deformities of the cranium in patients with nonsyndromic single-suture synostosis occur because of growth restriction at fused sutures and growth over compensation at normal sutures. Traditional surgery includes ostectomies of the synostotic suture to release these restricted areas and osteotomies to enable immediate cranial remodeling. In the process of reshaping the cranium, traditional approaches usually involve obliteration of both the normal functioning suture and the pathologic suture. The directive growth approach (DGA) is a new, simpler, more natural way to repair deformities caused by single-suture cranial synostosis. The DGA works by reversing the original deforming forces by temporarily restricting growth in areas of over compensation and forcing growth in areas of previous synostotic restriction. Most importantly, it preserves a normal functioning suture to allow for improved future cranial growth. Eighteen consecutive nonsyndromic patients with unilateral coronal synostosis were used to illustrate the efficacy of the DGA. Ten patients who underwent DGA treatment were compared with a control group of 8 patients treated with traditional frontal orbital advancement. Postoperative three-dimensional computed tomography (CT) comparison measurements were taken, including bilateral vertical and transverse orbital dimensions, lateral orbital rim to external auditory canal, and forehead measurements from the superior aspect of the orbital rim to the pituitary fossa. The traditional treatment group showed absence of the coronal sutures bilaterally on long-term CT scans. The DGA group showed normal coronal sutures on the unaffected sides. Postoperative CT measurements showed no statistical difference between the 2 techniques (P < 0.05).


Visual contrast processing in migraine.
Some migraine sufferers report certain visual patterns can reliably trigger a migraine attack, such as high contrast striped patterns or flickering lights. Differences between people with and without migraine on tasks that involve these patterns have been attributed to abnormal cortical processing in migraine, although the locus and extent of the abnormality remains unclear, as is any relationship between impairment on various visual tasks. In this study 58 migraine sufferers and 61 control subjects participated in three visual tasks involving striped patterns. One assessed pattern sensitivity with high contrast patterns, the second detection thresholds for low contrast patterns and the third supra-threshold contrast scaling. With each measure, the performance of migraine sufferers as a group differed to the performance of non-migraine control subjects. There were no significant differences between the migraine subgroups when classified according to the presence or absence of aura. Cross-correlating the results from the three tasks, however, revealed consistent associations: impaired or extreme responses on one task were associated with impaired or extreme responses on the others. There were no overall effects due to migraine duration, the frequency of migraine attacks or the time since the last attack. These results are discussed in the context of visually induced migraine, proposed causes of abnormal cortical function in migraine and the prospects for developing clinically useful tests of visual function.


Light of Two Atoms in Free Space: Bunching or Antibunching?
Photon statistics divides light sources into three different categories, characterized by bunched, antibunched, or uncorrelated photon arrival times. Single atoms, ions, molecules, or solid state emitters display antibunching of photons, while classical thermal sources exhibit photon bunching. Here we demonstrate a light source in free space, where the photon statistics depends on the direction of observation, undergoing a continuous crossover between photon bunching and antibunching. We employ two trapped ions, observe their fluorescence under continuous laser light excitation, and record spatially resolved the autocorrelation function g^{(2)}(τ) with a movable Hanbury Brown and Twiss detector. Varying the detector position we find a minimum value for antibunching, g^{(2)}(0)=0.60(5) and a maximum of g^{(2)}(0)=1.46(8) for bunching, demonstrating that this source radiates fundamentally different types of light alike. The observed variation of the autocorrelation function is understood in the Dicke model from which the observed maximum and minimum values can be modeled, taking independently measured experimental parameters into account.


ZIEL: Internet-Based Self-Help for Adjustment Problems: Results of a Randomized Controlled Trial.
Adjustment Disorder (AjD) represents a healthcare paradox. On the one hand, it is one of the most diagnosed mental disorders worldwide. On the other hand, AjD and its possible treatment options remain a severely neglected field of research. In this context, we developed a self-guided online intervention for adjustment problems, named ZIEL, and tested its efficacy. It is based on and extends a bibliotherapeutic treatment approach for symptoms of AjD. In our study, a total of 98 individuals who had experienced a life event in the last two years, were randomly assigned to care as usual (CAU) or an online intervention group (CAU + online intervention). The primary endpoint was AjD symptom severity measured by Adjustment Disorder-New Module 20 (ADNM-20). Secondary endpoints were depressive symptoms, quality of life and other variables such as satisfaction and usability. Both the intervention and the control group improved comparably well regarding the severity of adjustment disorder symptoms post-treatment. However, participants in the intervention group showed significantly fewer depressive symptoms and a significantly higher quality of life (Cohen's d: 0.89 (BDI) and -0.49 (SF-12)). The intervention was well-received by users with an above average usability rating. Overall, the results suggest that the ZIEL intervention has the promise to contribute to the treatment of AjD and reduce symptom burden by means of a scalable low-barrier approach.


Psychodynamic psychotherapy for the depressive syndrome.
Historical approaches of psychotherapy for depression are contrasted with current psychotherapeutic strategies. Now more strategies are focused, structured, time-limited, observable, testable, researchable and data based. The following depressive syndromes are reviewed in terms of the literature that demonstrates the effectiveness of psychotherapy: major depressive disorder, bipolar depressive disorder, depression associated with medical illness such as cancer, myocardial infarction and stroke, resistant depression post-traumatic stress disorder, grief reactions and depression during adolescence, mid-life and the geriatric period of the life cycle. A conceptual model favoring tripartite focus of intervention is recommended. Psychodynamic psychotherapy for depression must consider intrapsychic, interpersonal and family dynamics as well as social supports. A model for each population needs to be studied and developed further. Recommendations for current research are suggested. In the individual modification of psychotherapeutic approaches we must consider the varying maturity of ego defenses and the ego strength of the individual patient. Forty well-designed studies that demonstrate the effectiveness of psychotherapy in the depressive syndromes are quoted in this paper.


Steroid cell tumor of the ovary associated with endometrial adenocarcinoma--a rare case report.
Endometrial carcinoma is the most common invasive neoplasm of the female genital tract and is associated to the elevated levels of unopposed estrogen, especially in postmenopause. Ovarian Steroid cell tumors are rare tumors and they are named according to the origin of cell. The most common cancer of the female genital tract is the endometrial adenocarcinoma and it accounts for 7% of all invasive cancers in women. In the present case report, the authors present a 59-year-old multiparous woman with a postmenopausal bleeding complaint and they discuss the case of ovarian steroid cell tumor associated with endometrioid adenocarcinoma of endometrium. Endometrial adenocarcinoma is the most common cancer of female genital tract and its contemporarity with an ovarian steroid cell tumor is extremely rare.


Basic science curriculum in vascular surgery residency.
Recognizing the importance of basic science teaching in surgical education, the leadership of the Association of Program Directors in Vascular Surgery (APDVS) appointed a panel to gather information and to present its findings at the 1999 annual fall meeting of the Apdvs. A questionnaire was distributed to the program directors present. In addition, information was gathered from the American Board of Surgery regarding the basic science content in the vascular surgery item pool on the vascular surgery qualifying examination (VQE). The vascular surgery unit of the surgical resident curriculum was also analyzed. Fifty-three program directors (64%) completed the questionnaire. Although only two program directors felt that their residents were better prepared to answer basic science questions, the results of the Vqe showed that the examinees do not, as a group, perform differently on basic science items than on clinical management questions. In addition, only a minority of program directors (15%) use a specific method to monitor the learning process of their residents. The majority of the program directors responding (75%) felt that they were capable of teaching basic science to residents. Interestingly, almost half the 53 respondents (47%) said that a basic science curriculum should be comprehensive, not exclusively relevant to the clinical setting. Vqe content outline and the vascular surgery unit of the surgical resident curriculum revealed great emphasis on clinically relevant basic science information. The Apdvs panel recommends that a basic science curriculum should be comprehensive, yet clinically pertinent, and completely integrated with the clinical curriculum. In terms of how to teach basic science in vascular residencies, the panel supports teaching conferences that are problem-based with a faculty member acting as the "resource person" and with specific goals set for the conferences. The panel also suggested establishing a Web site that provides a series of questions, the answers of which could be readily available to trainees and program directors. such immediate feedback could be of great help to program directors to focus the learning process of their residents and monitor its progress.


Comparative study of immunodeficient rat strains in engraftment of hiPSC-derived airway epithelia.
The airway epithelia (AE) play a role in the clearance of foreign substances through ciliary motility and mucus secreted. We developed an artificial trachea that is made of collagen sponges and polypropylene mesh for the regeneration of the tracheal defect, and it was used for a clinical study. Then, a model in which the luminal surface of an artificial trachea covered with a human-induced pluripotent stem cell-derived AE (hiPSC-AE) was transplanted into the tracheal defect of nude rats to promote epithelialization. In the future, this model was expected to be applied to research on infectious diseases and drug discovery as a trachea-humanized rat model. However, at present, sufficient engraftment has not been achieved to evaluate functional recovery in transplanted cells. Therefore, this study focused on immunosuppression in recipient rats. Nude rats lack T-cell function and are widely used for transplantation experiments; however, more severe immunosuppressed recipients are preferred for xenotransplantation. Several strains of immunodeficient rats were created as rats that exhibit more severe immunodeficiency until now. In this study, to establish a trachea-humanized rat model in which human AE function can be analyzed to improve engraftment efficiency, engraftment efficiency in nude rats and X-linked severe combined immunodeficiency (X-SCID) rats following hiPSC-AE transplantation was compared. In the analysis of the proportion of engrafted cells in total cells at the graft site, the engraftment efficiency of epithelial cells tended to be high in X-SCID rats, although no statistical difference was found between the two groups, whereas the engraftment efficiency of mesenchymal cells was higher in X-SCID rats. Furthermore, the number of immune cells that accumulated in the grafts showed that a pan T-cell marker, i.e., CD3-positive cells, did not differ between the two strains; however, CD45-positive cells and major histocompatibility complex (MHC) class II-positive cells significantly decreased in X-SCID rats. These results indicate that X-SCID rats are more useful for the transplantation of hiPSC-AE into the tracheae to generate trachea-humanized rat models.


Three-Dimensional Live Imaging of Bovine Preimplantation Embryos: A New Method for IVF Embryo Evaluation.
Conception rates for transferred bovine embryos are lower than those for artificial insemination. Embryo transfer (ET) is widely used in cattle but many of the transferred embryos fail to develop, thus, a more effective method for selecting bovine embryos suitable for ET is required. To evaluate the developmental potential of bovine preimplantation embryos (2-cell stage embryos and blastocysts), we have used the non-invasive method of optical coherence tomography (OCT) to obtain live images. The images were used to evaluate 22 parameters of blastocysts, such as the volume of the inner cell mass and the thicknesses of the trophectoderm (TE). Bovine embryos were obtained by in vitro fertilization (IVF) of the cumulus-oocyte complexes aspirated by ovum pick-up from Japanese Black cattle. The quality of the blastocysts was examined under an inverted microscope and all were confirmed to be Code1 according to the International Embryo Transfer Society standards for embryo evaluation. The OCT images of embryos were taken at the 2-cell and blastocyst stages prior to the transfer. In OCT, the embryos were irradiated with near-infrared light for a few minutes to capture three-dimensional images. Nuclei of the 2-cell stage embryos were clearly observed by OCT, and polynuclear cells at the 2-cell stage were also clearly found. With OCT, we were able to observe embryos at the blastocyst stage and evaluate their parameters. The conception rate following OCT (15/30; 50%) is typical for ETs and no newborn calves showed neonatal overgrowth or died, indicating that the OCT did not adversely affect the ET. A principal components analysis was unable to identify the parameters associated with successful pregnancy, while by using hierarchical clustering analysis, TE volume has been suggested to be one of the parameters for the evaluation of bovine embryo. The present results show that OCT imaging can be used to investigate time-dependent changes of IVF embryos. With further improvements, it should be useful for selecting high-quality embryos for transfer.


Structure and composition of a family of human cytomegalovirus glycoprotein complexes designated gC-I (gB).
Murine monoclonal antibodies (MAbs) were made to the 52,000 (gp52) and the 93,000 to 130,000 Mr (gp93-130) glycoproteins from a human cytomegalovirus (HCMV) glycoprotein complex designated gC-I or the gB homologue. MAbs recognizing either gp52 or gp93-130 could immunoprecipitate unreduced gC-I complexes from non-ionic detergent extracts of HCMV. Western blotting was performed with immunoaffinity-purified gC-I complexes which were reduced prior to analysis. MAbs made against gp52 recognized gp52 and a 158,000 Mr glycoprotein (gp158). MAbs which recognized gp93-130 in a Western blot also reacted with gp158, which is a gC-I precursor glycoprotein. The origin of gp93-130 was demonstrated by the reactivity of our gp93-130 MAbs with a recombinant protein containing the N-terminal portion of the gB gene. These data are consistent with the hypothesis that gp52 and gp93-130 are generated from the same high Mr precursor by proteolysis. MAbs recognizing either gp52 or gp93-130 neutralized Towne strain HCMV, but MAbs recognizing gp52 required complement to neutralize whereas MAbs recognizing gp93-130 did not. It was also determined that gp93-130 and gp 158 have detectable amounts of O-linked glycans but gp52 does not, showing a difference in the glycosylation of these glycoproteins. Analysis of gC-I disulphide bonds showed that two types were present, one which was very susceptible to reduction and a second which was less susceptible. These complexes could consist of very susceptible inter-complex disulphide bonds and less susceptible intra-complex disulphide bonds.


Thermodynamics of apoplastocyanin folding: comparison between experimental and theoretical results.
It has been experimentally shown that the folding of apoplastocyanin (apoPC) accompanies a very large enthalpic loss [N. Baden et al., J. Chem. Phys. 127, 175103 (2007)]. This implies that an even larger entropic gain occurs in stabilizing the folded structure to overcome the enthalpic loss. Here, we calculate the water-entropy gain upon the folding of apoPC using the angle-dependent integral equation theory combined with the multipolar water model and the recently developed morphometric approach. It is demonstrated that the calculated value is in quantitatively good accord with the value estimated from the experimental data by accounting for the conformational-entropy loss. According to a prevailing view, the water adjacent to a hydrophobic group is unstable especially in terms of the rotational entropy and the folding is driven primarily by the release of such unfavorable water to the bulk through the burial of nonpolar side chains. We show, however, that the resultant entropic gain is too small to elucidate the experimental result. The great entropic gain observed is ascribed to the reduction in the restriction for the translational motion of water molecules in the whole system.


Polytype and stacking faults in the Li2CoSiO4 Li-ion battery cathode.
Atomic-resolution imaging of the crystal defects of cathode materials is crucial to understand their formation and the correlation between the structure, electrical properties, and electrode performance in rechargeable batteries. The polytype, a stable form of varied crystal structure with uniform chemical composition, holds promise to engineer electronic band structure in nanoscale homojunctions.1-3 Analyzing the exact sites of atoms and the chemistry of the boundary in polytypes would advance our understanding of their formation and properties. Herein, the polytype and stacking faults in the lithium cobalt silicates are observed directly by aberration-corrected scanning transmission electron microscopy. The atomic-scale imaging allows clarification that the polytype is formed by stacking of two different close-packed crystal planes in three-dimensional space. The formation of the polytype was induced by Li-Co cation exchange, the transformation of one phase to the other, and their stacking. This finding provides insight into intrinsic structural defects in an important Li2 CoSiO4 Li-ion battery cathode.


Bidirectional influence between African American mothers' and children's racial centrality from elementary through high school.
For many African Americans, racial identity is an important aspect of their individual identity. We explored developmental change and stability of individual differences in the racial centrality of African American youths and their mothers as well as the relation between maternal and child racial centrality across time. African American youths (N = 380) and mothers completed surveys when youths were in grades 5, 7, 10, and 12. Mean levels of youths' racial centrality did not increase or decrease across the 7 years of the study. The stability of individual differences in youths' racial centrality increased across time, reaching adult levels by high school. Cross-lagged panel analyses showed relations between mothers' and children's racial centrality in middle adolescence but not in early and late adolescence. Results document that the importance of race to the personal identities of African American youths does not show normative developmental change across adolescence, and only minimal change is linked to maternal influence. (PsycINFO Database Record


Improving xylem hydraulic conductivity measurements by correcting the error caused by passive water uptake.
Xylem hydraulic conductivity (K) is typically defined as K = F/(P/L), where F is the flow rate through a xylem segment associated with an applied pressure gradient (P/L) along the segment. This definition assumes a linear flow-pressure relationship with a flow intercept (F(0)) of zero. While linearity is typically the case, there is often a non-zero F(0) that persists in the absence of leaks or evaporation and is caused by passive uptake of water by the sample. In this study, we determined the consequences of failing to account for non-zero F(0) for both K measurements and the use of K to estimate the vulnerability to xylem cavitation. We generated vulnerability curves for olive root samples (Olea europaea) by the centrifuge technique, measuring a maximally accurate reference K(ref) as the slope of a four-point F vs P/L relationship. The K(ref) was compared with three more rapid ways of estimating K. When F(0) was assumed to be zero, K was significantly under-estimated (average of -81.4 ± 4.7%), especially when K(ref) was low. Vulnerability curves derived from these under-estimated K values overestimated the vulnerability to cavitation. When non-zero F(0) was taken into account, whether it was measured or estimated, more accurate K values (relative to K(ref)) were obtained, and vulnerability curves indicated greater resistance to cavitation. We recommend accounting for non-zero F(0) for obtaining accurate estimates of K and cavitation resistance in hydraulic studies.


Effects of carbendazim and astaxanthin co-treatment on the proliferation of MCF-7 breast cancer cells.
There has been a controversy in the oncology field about the use of antioxidants along with chemotherapeutics in cancer treatment. This study aimed to investigate the effects of a potent antioxidant (astaxanthin) co-treatment with a promising anti-cancer drug (carbendazim), which is in phase I clinical trials, on MCF-7 breast cancer cell proliferation. MCF-7 cells were treated with carbendazim, astaxanthin, or their combinations and incubated for 24 h. After the incubation, each treatment group was evaluated for proliferation, cell cycle progression, and production of reactive oxygen species (ROS) using WST-1, flow cytometry, and CM-H2DCFDA, respectively. All tested carbendazim and astaxanthin combinations increased the anti-proliferative effect of Carb treatment alone and increased the G2/M phase cell cycle arrest compared to the DMSO-treated control. Astaxanthin, at all concentrations tested, reduced the elevated intracellular ROS levels induced by the carbendazim treatment. Our data suggest that astaxanthin and carbendazim co-treatment enhances the anti-proliferative effect of carbendazim as a single agent, while alleviating the carbendazim treatment-associated ROS production in MCF-7 cells. These findings may contribute to the current debate on the use of antioxidants along with anti-cancer drugs in cancer chemotherapy.


ts BCR-ABL kinase activation confers increased resistance to genotoxic damage via cell cycle block.
Using a temperature-sensitive mutant of the p210 BCR-ABL gene, transfected into a growth factor-dependent cell line (BaF3), we show that transient BCR-ABL kinase expression increases single cell and clonogenic resistance to apoptosis arising from genotoxic damage induced by ionizing radiation and VP-16/etoposide. This effect is achieved in the absence of any detectable changes in the levels of BCL-2, BAX or BCL-x proteins and is independent of proliferative, MAP kinase-dependent effects of BCR-ABL kinase. In contrast to parental cells that transiently arrest in G2 and then apoptose, p210 BaF3 cells show a pronounced and sustained G2 arrest following radiation coupled with enhanced phosphorylation of cdc2. A cell cycle block in early M phase induced by the mitotic spindle poison, nocodazole, does not provide protection from apoptosis. Reversal of G2 arrest by caffeine abolishes the protective effect of BCR-ABL kinase. These data provide further insight into the transforming properties of BCR-ABL and are relevant to the clinical intransigence of Ph-positive leukaemias.


Gallic Acid Attenuates Dimethylnitrosamine-Induced Liver Fibrosis by Alteration of Smad Phosphoisoform Signaling in Rats.
Dimethylnitrosamine (DMN) is a potent hepatotoxin, carcinogen, and mutagen. In our previous study, a candidate gallic acid (GA) that widely exists in food and fruit was selected for its capability to alleviate DMN toxicity in vivo. We aimed to investigate the therapeutic potential of GA against DMN-induced liver fibrosis. During the first four weeks, DMN was administered to rats via intraperitoneal injection every other day, except the control group. GA or silymarin was given to rats by gavage once daily from the second to the sixth week. GA significantly reduced liver damage in serum parameters and improved the antioxidant capacity in liver and kidney tissues. Cytokines involved in liver fibrosis were measured at transcriptional and translational levels. These results indicate that GA exhibits robust antioxidant and antifibrosis effects and may be an effective candidate natural medicine for liver fibrosis treatment.


Exploring the evolution of circular polarized light backscattered from turbid tissue-like disperse medium utilizing generalized Monte Carlo modeling approach with a combined use of Jones and Stokes-Mueller formalisms.
Phase retardation of circularly polarized light (CPL), backscattered by biological tissue, is used extensively for quantitative evaluation of cervical intraepithelial neoplasia, presence of senile Alzheimer's plaques, and characterization of biotissues with optical anisotropy. The Stokes polarimetry and Mueller matrix approaches demonstrate high potential in definitive non-invasive cancer diagnosis and tissue characterization. The ultimate understanding of CPL interaction with tissues is essential for advancing medical diagnostics, optical imaging, therapeutic applications, and the development of optical instruments and devices. We investigate propagation of CPL within turbid tissue-like scattering medium utilizing a combination of Jones and Stokes-Mueller formalisms in a Monte Carlo (MC) modeling approach. We explore the fundamentals of CPL memory effect and depolarization formation. The generalized MC computational approach developed for polarization tracking within turbid tissue-like scattering medium is based on the iterative solution of the Bethe-Salpeter equation. The approach handles helicity response of CPL scattered in turbid medium and provides explicit expressions for assessment of its polarization state. Evolution of CPL backscattered by tissue-like medium at different conditions of observation in terms of source-detector configuration is assessed quantitatively. The depolarization of light is presented in terms of the coherence matrix and Stokes-Mueller formalism. The obtained results reveal the origins of the helicity flip of CPL depending on the source-detector configuration and the properties of the medium and are in a good agreement with the experiment. By integrating Jones and Stokes-Mueller formalisms, the combined MC approach allows for a more complete representation of polarization effects in complex optical systems. The developed model is suitable to imitate propagation of the light beams of different shape and profile, including Gaussian, Bessel, Hermite-Gaussian, and Laguerre-Gaussian beams, within tissue-like medium. Diverse configuration of the experimental conditions, coherent properties of light, and peculiarities of polarization can be also taken into account.


Using qualitative research in radiologic technology.
Qualitative research is an underused methodology in radiologic technology that has valid applications for patient care, professional practice and education. This article discusses uses of qualitative methodology in the health professions and describes specific applications for the radiologic sciences.


Over- and under-representation of short oligonucleotides in DNA sequences.
Strand-symmetric relative abundance functionals for di-, tri-, and tetranucleotides are introduced and applied to sequences encompassing a broad phylogenetic range to discern tendencies and anomalies in the occurrences of these short oligonucleotides within and between genomic sequences. For dinucleotides, TA is almost universally under-represented, with the exception of vertebrate mitochondrial genomes, and CG is strongly under-represented in vertebrates and in mitochondrial genomes. The traditional methylation/deamination/mutation hypothesis for the rarity of CG does not adequately account for the observed deficiencies in certain sequences, notably the mitochondrial genomes, yeast, and Neurospora crassa, which lack the standard CpG methylase. Homodinucleotides (AA.TT, CC.GG) and larger homooligonucleotides are over-represented in many organisms, perhaps due to polymerase slippage events. For trinucleotides, GCA.TGC tends to be under-represented in phage, human viral, and eukaryotic sequences, and CTA.TAG is strongly under-represented in many prokaryotic, eukaryotic, and viral sequences. The CCA.TGG triplet is ubiquitously over-represented in human viral and eukaryotic sequences. Among the tetranucleotides, several four-base-pair palindromes tend to be under-represented in phage sequences, probably as a means of restriction avoidance. The tetranucleotide CTAG is observed to be rare in virtually all bacterial genomes and some phage genomes. Explanations for these over- and under-representations in terms of DNA/RNA structures and regulatory mechanisms are considered.


Use of a subcutaneous implantable pleural port in the management of recurrent malignant pleurisy: five-year experience based on 168 subcutaneous implantable pleural ports.
The authors report their experience in the use of subcutaneous implantable pleural port (SIPP) catheters for the treatment of symptomatic recurrent malignant pleurisy. Single-center, prospective follow-up of 137 patients (168 SIPPs). No SIPP placement failures were observed. All but 3 of the 125 evaluable patients obtained complete or partial relief of their dyspnea. Seventy-six patients (60.3%) were receiving chemotherapy. Spontaneous pleurodesis was observed within 2 months in 46 patients (36.8%). Twenty-six patients (20.8%) died during the month following SIPP placement. Forty-one patients (32%) survived for more than 6 months. The overall median survival time was 344 days. Three infectious complications (1 empyema, 2 cellulitis) and 3 mechanical complications were observed. The role of pleurodesis as prognostic factor was assessed. Seventy-one patients survived for more than 2 months, 36 with pleurodesis, 35 without pleurodesis, requiring repeated pleural aspiration. The difference observed between the two groups by the 120th day was no longer significant when chemotherapy was taken into account. SIPP is a safe and effective option for the outpatient management of recurrent malignant effusions and could be considered as first-line treatment in all patients with bilateral, compressive pleural effusion or poor lung reexpansion.


Temporal lobe epilepsy: differential pattern of damage in temporopolar cortex and white matter.
Our purpose was to quantify structural changes of the temporopolar cortex (TPC) and its white matter (TPWM) in temporal lobe epilepsy (TLE) using MRI volumetry and texture analysis. We studied 23 patients with hippocampal atrophy, and 20 healthy controls. Gradient magnitude and entropy were calculated to model signal intensity blurring on T1-MRI. Two observers assessed signal changes and atrophy visually. Compared to controls, TLE patients had a decrease in TPC and TPWM volume ipsilateral to the seizure focus. The gradient magnitude and entropy were decreased ipsilateral to the focus only in TPWM, indicating blurring of this compartment. Eighty-seven percent of TLE patients had at least one volumetric or textural abnormality. Although sensitivity of visual and quantitative assessment of TPC atrophy was comparable (43 and 39%), specificity was higher for volumetry (54% vs. 95%). Compared to visual analysis of signal changes in TPWM on T1-MRI, texture metrics had higher sensitivity (65% vs. 17%) and specificity (100% vs. 69%). The proportion of patients with blurring of TPWM as determined by texture analysis was higher than that seen on visual inspection of T2 images (78% vs. 43%). We found no clear association between volumetric or textural changes of TPC and TPWM and outcome after surgery. Structural changes of the anatomically distinct TPC and TPWM are found ipsilateral to the seizure focus in the majority of TLE patients with hippocampal sclerosis. MRI post-processing allows dissociating different pathological tissue characteristics and shows that atrophy involves gray and white matter, whereas blurring is confined to white matter.


Attentional function in fibromyalgia and rheumatoid arthritis.
Concentration difficulties, forgetfulness and mental slowness are common in fibromyalgia syndrome (FMS); initial findings suggest that rheumatoid arthritis (RA) may also be accompanied by cognitive impairments. This study aimed to compare attentional performance between patients with FMS and RA. Attention was quantified in the domains of alerting, orienting and executive control using the Attentional Network Test-Interaction (ANT-I) in 56 women with FMS, 41 women with RA and 50 healthy women. Pain severity was statistically controlled in the group comparison. While FMS patients exhibited longer reaction times and made more errors on the ANT-I than RA patients and healthy women, performance did not differ between RA patients and healthy women. The magnitude of group differences did not vary by the experimental conditions of the ANT-I, suggesting a general attentional deficit in FMS rather than specific impairments in the domains of alerting, orienting and executive control. Differences between patient groups may relate to the different pathogenetic mechanisms involved in the disorders, i.e. inflammatory processes in RA and central nervous sensitization in FMS. In FMS, heightened activity in the pain neuromatrix may interfere with attention, because it requires enhanced neural resources in brain areas that are involved in both pain and attentional processing.


[Therapy of hypertensive coronary patients. Open long-term study with a combination of atenolol and nifedipine].
In the present study, 20 patients with both hypertension and stabile angina pectoris were treated twice daily for 6 months with 50 mg atenolol and 20 mg retard-formulation nifedipine. The effect of this treatment on blood pressure and heart rate was investigated at rest and under standardized ergometric conditions, and by means of a 24 h Holter ECG. The frequency of angina pectoris episodes in 6-week periods was reduced by 34% over 6 months. The initial decrease in systolic and diastolic blood pressure (by 25%) was maintained over the long term at rest and under exercise. Patient exercise tolerance with reduced oxygen utilization, as represented by the product of pressure x rate, showed a lasting improvement. After 6 months, monotopic ventricular premature beats in particular were reduced significantly (46%) as compared with the initial situation.


Recent advances in the pharmacological management of hypercholesterolaemia.
The recent developments in pharmacological interventions that reduce LDL cholesterol have been remarkable, coming more than a decade after the approval of the last LDL-cholesterol-lowering drug, the cholesterol absorption inhibitor ezetimibe. Within just a few years, four new LDL-cholesterol-lowering agents have received regulatory approval. Lomitapide and mipomersen inhibit the production of LDL, but also increase hepatic fat and are licensed specifically for homozygous familial hypercholesterolaemia. Alirocumab and evolocumab are monoclonal antibodies that bind to proprotein convertase subtilisin/kexin type 9 (PCSK9), lowering LDL by about 50-60%. These drugs are approved for use in patients with cardiovascular disease or familial hypercholesterolaemia whose LDL cholesterol levels are insufficiently controlled on standard agents. Although definitive clinical efficacy and long-term safety data are still needed, antibody-based PCSK9 inhibitors promise to meet much of the unmet medical need in the treatment of raised LDL cholesterol. However, several additional approaches to inhibiting PCSK9, as well as other classes of LDL-lowering therapies, are in clinical development. Here we summarise the science behind the development of the newly approved LDL-cholesterol-lowering drugs and critically review their efficacy and safety data, highlighting unanswered research questions. Finally, we discuss emerging LDL-lowering therapies in clinical development.


Parenteral nutrition in adults during acute illness: a clinical perspective for clinicians.
Parenteral nutrition (PN) is the administration of a nutritional formula by means other than the gastrointestinal (GI) tract. The formula may include carbohydrates, amino acids, lipids, electrolytes and/or micronutrients. The primary indications for PN are intestinal failure (IF) due to an underlying disease or treatment, or if the GI tract is not accessible. The goals of PN should be to ensure adequate nutrition provision to meet patient needs while minimising the risk of complications. PN should be commenced in <48 h in patients who are malnourished or otherwise within 7 days if oral or enteral nutrition is not possible or insufficient. There has been evolution in PN techniques and technology, and the risks associated with PN administration have been reduced. Monitoring clinical, laboratory and metabolic parameters in acute IF is essential to provision of safe nutritional support. When provided to appropriate patients with IF in a timely and considered manner, PN has been shown to be safe, improve nutritional parameters and reduce complications associated with malnutrition. This review aims to provide clinicians a practical guide for the management of PN in adult patients within the acute setting.


Bupropion metabolism by human placenta.
Smoking during pregnancy is the largest modifiable risk factor for pregnancy-related morbidity and mortality. The success of bupropion for smoking cessation warrants its investigation for the treatment of pregnant patients. Nevertheless, the use of bupropion for the treatment of pregnant smokers requires additional data on its bio-disposition during pregnancy. Therefore, the aim of this investigation was to determine the metabolism of bupropion in placentas obtained from nonsmoking and smoking women, identify metabolites formed and the enzymes catalyzing their formation, as well as the kinetics of the reaction. Data obtained revealed that human placentas metabolized bupropion to hydroxybupropion, erythro- and threohydrobupropion. The rates for formation of erythro- and threohydrobupropion exceeded that for hydroxybupropion by several folds, were dependent on the concentration of bupropion and exhibited saturation kinetics with an apparent K(m) value of 40microM. Human placental 11beta-hydroxysteroid dehydrogenases were identified as the major carbonyl-reducing enzymes responsible for the reduction of bupropion to threo- and erythrohydrobupropion in microsomal fractions. On the other hand, CYP2B6 was responsible for the formation of OH-bupropion. These data suggest that both placental microsomal carbonyl-reducing and oxidizing enzymes are involved in the metabolism of bupropion.


New Star Observations with NuSTAR: Flares from Young Stellar Objects in the ρ Ophiuchi Cloud Complex in Hard X-Rays.
We study the structure and dynamics of extreme flaring events on young stellar objects (YSOs) observed in hard X-rays by the Nuclear Spectroscopic Telescope Array (NuSTAR). During 2015 and 2016, NuSTAR made three observations of the star-forming region ρ Ophiuchi, each with an exposure ~50 ks. NuSTAR offers unprecedented sensitivity above ~7 keV, making this data set the first of its kind. Through improved coverage of hard X-rays, it is finally possible to directly measure the high-energy thermal continuum for hot plasmas and to sensitively search for evidence of nonthermal emission from YSO flares. During these observations, multiple flares were observed, and spectral and timing analyses were performed on three of the brightest flares. By fitting an optically thin thermal plasma model to each of these events, we found flare plasma heated to high temperatures (~40-80 MK) and determined that these events are ~1000 times brighter than the brightest flares observed on the Sun. Two of the studied flares showed excess emission at 6.4 keV, and this excess may be attributable to iron fluorescence in the circumstellar disk. No clear evidence for a nonthermal component was observed, but upper limits on nonthermal emission allow for enough nonthermal energy to account for the estimated thermal energy in the flare on protostar IRS 43, which is consistent with the standard model for solar and stellar flares.


SIRT1-FOXO3a regulate cocaine actions in the nucleus accumbens.
Previous studies have shown that chronic cocaine administration induces SIRT1, a Class III histone deacetylase, in the nucleus accumbens (NAc), a key brain reward region, and that such induction influences the gene regulation and place conditioning effects of cocaine. To determine the mechanisms by which SIRT1 mediates cocaine-induced plasticity in NAc, we used chromatin immunoprecipitation followed by massively parallel sequencing (ChIP-seq), 1 d after 7 daily cocaine (20 mg/kg) or saline injections, to map SIRT1 binding genome-wide in mouse NAc. Our unbiased results revealed two modes of SIRT1 action. First, despite its induction in NAc, chronic cocaine causes depletion of SIRT1 from most affected gene promoters in concert with enrichment of H4K16ac (itself a deacetylation target of SIRT1), which is associated with increased expression of these genes. Second, we deduced the forkhead transcription factor (FOXO) family to be a downstream mechanism through which SIRT1 regulates cocaine action. We proceeded to demonstrate that SIRT1 induction causes the deacetylation and activation of FOXO3a in NAc, which leads to the induction of several known FOXO3a gene targets in other systems. Finally, we directly establish a role for FOXO3a in promoting cocaine-elicited behavioral responses by use of viral-mediated gene transfer: we show that overexpressing FOXO3a in NAc enhances cocaine place conditioning. The discovery of these two actions of SIRT1 in NAc in the context of behavioral adaptations to cocaine represents an important step forward in advancing our understanding of the molecular adaptations underlying cocaine action.


The antiplatelet effects of organic nitrates and related nitroso compounds in vitro and in vivo and their relevance to cardiovascular disorders.
Organic nitrates, cornerstones of antianginal therapy, are believed to exert their principal anti-ischemic benefit by relaxing vascular smooth muscle. Recent evidence suggests that these compounds and related nitro(so) vasodilators are also potent platelet inhibitors. In view of the well recognized role of thrombotic events mediated by platelets in acute coronary syndromes, the antiplatelet effect of nitrates may also be of mechanistic importance in the treatment of these disorders. This review details the biochemical mechanism by which nitro(so) compounds inhibit platelet function and summarizes the in vitro and in vivo evidence that supports their antithrombotic effects.


Evaluating the Portability of an NLP System for Processing Echocardiograms: A Retrospective, Multi-site Observational Study.
While natural language processing (NLP) of unstructured clinical narratives holds the potential for patient care and clinical research, portability of NLP approaches across multiple sites remains a major challenge. This study investigated the portability of an NLP system developed initially at the Department of Veterans Affairs (VA) to extract 27 key cardiac concepts from free-text or semi-structured echocardiograms from three academic edical centers: Weill Cornell Medicine, Mayo Clinic and Northwestern Medicine. While the NLP system showed high precision and recall easurements for four target concepts (aortic valve regurgitation, left atrium size at end systole, mitral valve regurgitation, tricuspid valve regurgitation) across all sites, we found moderate or poor results for the remaining concepts and the NLP system performance varied between individual sites.


Steroid therapy can modulate gut barrier function, host defense, and survival in thermally injured mice.
Prednisone may be immunosuppressive and dehydroepiandrosterone may stimulate the immune response, but their effect on gut-origin sepsis caused by bacterial translocation has not been studied. Balb/c mice were treated orally with prednisone (1 or 10 mg/kg/day) or saline for 4 days before receiving gavage with 10 (10) 14 C-labeled Escherichia coli and a 20% thermal injury. Mice were transfused with allogeneic blood and given dehydroepiandrosterone (5 or 25 mg/kg/day) or vehicle subcutaneously for 4 days before bacterial gavage and thermal injury. Some groups in each experiment were observed 10 days for mortality and others were sacrificed 4 hr postburn to measure translocation and survival of translocated bacteria. Survival in prednisone treated animals was 25% (10 mg/kg/day) and 75% (1 mg/kg/day) versus 80% for controls. Following dehydroepiandrosterone administration, survival was 72% (25 mg/kg/day/group) and 30% (5 mg/kg/day/group) versus 16% for controls. High dose prednisone increased bacterial translocation to the intestinal wall and mesenteric lymph nodes and greatly impaired killing of translocated E. coli. In contrast, dehydroepiandrosterone (25 mg/kg) did not affect translocation but significantly improved bacterial killing. Prednisone and dehydroepiandrosterone exert opposite effects during gut-derived sepsis.


Paleoecology and paleoceanography of the Athel silicilyte, Ediacaran-Cambrian boundary, Sultanate of Oman.
The Athel silicilyte is an enigmatic, hundreds of meters thick, finely laminated quartz deposit, in which silica precipitated in deep water (>~100-200 m) at the Ediacaran-Cambrian boundary in the South Oman Salt Basin. In contrast, Meso-Neoproterozoic sinks for marine silica were dominantly restricted to peritidal settings. The silicilyte is known to contain sterane biomarkers for demosponges, which today are benthic, obligately aerobic organisms. However, the basin has previously been described as permanently sulfidic and time-equivalent shallow-water carbonate platform and evaporitic facies lack silica. The Athel silicilyte thus represents a unique and poorly understood depositional system with implications for late Ediacaran marine chemistry and paleoecology. To address these issues, we made petrographic observations, analyzed biomarkers in the solvent-extractable bitumen, and measured whole-rock iron speciation and oxygen and silicon isotopes. These data indicate that the silicilyte is a distinct rock type both in its sedimentology and geochemistry and in the original biology present as compared to other facies from the same time period in Oman. The depositional environment of the silicilyte, as compared to the bounding shales, appears to have been more reducing at depth in sediments and possibly bottom waters with a significantly different biological community contributing to the preserved biomarkers. We propose a conceptual model for this system in which deeper, nutrient-rich waters mixed with surface seawater via episodic mixing, which stimulated primary production. The silica nucleated on this organic matter and then sank to the seafloor, forming the silicilyte in a sediment-starved system. We propose that the silicilyte may represent a type of environment that existed elsewhere during the Neoproterozoic. These environments may have represented an important locus for silica removal from the oceans.


[A survey of the current status of the differential diagnosis of amoebas in Mexico].
The differential diagnostic criteria for the amebas parasitizing the human colon are described. The results of epidemiological studies carried out published in Mexico are discussed and the results of a survey performed in some hospitals in Mexico City on the current differential diagnosis of these parasites are reported. The findings showed that no carriers of E. hartmanni have been reported in the studies published in Mexico so far. However, no differentiation between E. histolytica and E. hartmanni is made in those hospitals according to the survey results. The possibility that in Mexico E. hartmanni is probably diagnosed as E. histolytica is discussed and as result the prevalence as asymptomatic intestinal amoebiasis is overestimated. The necessity of making the differential diagnosis between these parasites is emphasized.


Surgical radiofrequency ablation of both atria for atrial fibrillation: results of a multicenter trial.
The Cox maze procedure has shown to be effective in treating atrial fibrillation. Radiofrequency ablation, with a similar objective, has been used as an adjunct to conventional cardiac surgery for the treatment of atrial fibrillation in more than 20 centers in Australia and New Zealand since March 2000. This is a report of those results. One hundred thirty-two patients in 20 centers underwent radiofrequency ablation as an adjunct to conventional cardiac surgery, with a standardized lesion set created with a flexible, 7-electrode, temperature-controlled probe (Cobra; EPTechnologies, San Jose, Calif). All data were entered into a central registry, with regular follow-up prompted by the registry cocoordinator. Each radiofrequency scar was made with standard parameters requiring 2 minutes of tissue coagulation at 80 degrees C to 85 degrees C. Patients undergoing mitral procedures had radiofrequency ablation performed in the left atrium endocardially. Patients undergoing aortic valve replacement or coronary artery bypass surgery underwent epicardial radiofrequency ablation of the left atrium. Epicardial radiofrequency ablation lesions on the right atrium were common to both groups of patients. Preoperatively, 75% of the patients had chronic atrial fibrillation, 21% had paroxysmal atrial fibrillation, and 4% had flutter. Surgical procedures performed included mitral valve procedure in 60%, coronary artery bypass grafting in 14%, aortic valve replacement in 7%, and coronary artery bypass grafting plus aortic valve replacement in 4%. There were no major complications related to the use of radiofrequency ablation. There were no soft tissue or cardiac perforations. Ten patients were defibrillated into sinus rhythm within 3 months postoperatively. The freedom from atrial fibrillation was 84% at 3 months, 90% at 6 months, and 100% at 12 months. All patients at 12 and 18 months' follow-up were in sinus rhythm. There were no thromboembolic complications. Surgical radiofrequency ablation can be performed safely as an adjunct to conventional cardiac surgery. A standardized lesion set created by using similar temperature settings can be adopted in multiple centers and might be effective in treating atrial fibrillation. Data collection through a central registry has helped in monitoring the effectiveness of this new technique in a scattered population.