Fluorodeoxyglucose-induced allergic reaction: a case report.
The number of diagnostic positron emission tomography/computed tomography (PET/CT) procedures performed in the USA and worldwide is rapidly increasing. Although the benefits of these procedures are obvious, the increasing use of radiopharmaceuticals requires a better understanding of potential adverse affects and their proper management. We present herein the first report of an allergic reaction to fluorodeoxyglucose in the setting of repeated PET/CT scans for restaging purposes in a patient with pyriform sinus cancer.


The legal status of the fetus: an international review.
The article examines the way that courts and legislatures in the United Kingdom, the United States of America, Canada and Australia have answered questions regarding the legal status of a fetus. These questions have arisen in a variety of legal situations: the article deals with succession, criminal, child protection and negligence law. The conclusion offered is that a fetus has a value and an existence that the law should recognise. This does not mean, however, that in all circumstances the law should protect the interests of the fetus. Law-makers will respond differently to claims made on behalf of a fetus, depending on the context. The fetus does not have a uniform value or character in the eyes of the law. The law makes choices as to the situations in which it will take account of actual or threatened antenatal harm.


[Internal hernia: a rare cause of intestinal obstruction. Apropos of 14 cases].
Internal hernia is an uncommon cause of acute intestinal obstruction. The aim of this study was to retrospectively evaluate the diagnosis, the management, and the follow-up of the internal hernias operated over a 10-year period in our department of visceral surgery. 14 spontaneous internal hernias were observed. The patients were evaluated with respect to symptoms, radiological findings, time elapsed between the onset of symptoms and surgery, type of operation performed, postoperative morbidity and mortality, postoperative stay, and follow-up. There were 8 men and 6 women. The preoperative diagnosis was evoked in only one case. The mean time elapsed between the onset of the symptoms and surgery was 31.1 hours (range 6 to 72 hours). Two intestinal resection were performed. Mean postoperative hospital stay was 11.3 days (range 6 to 22 days). The morbidity was 21.4% with no mortality. Mean follow-up was 7 months (range 3 to 15 months); one patient developed an incisional hernia. Since preoperative diagnosis of an internal hernia is difficult because of the lack of specific signs, morbidity and mortality can be decreased with early surgical intervention. Operative risks include vascular accidents, especially to hernia neck vessels.


Simplification of analyses of fatty acids in fish lipids and related lipid samples.
The longer chain, highly unsaturated fatty acids up to 22:6 and typical of fish lipids must be included in many current analyses of fatty acids of diets, blood, and eventually of organ lipids. The use of the GLC liquid phase Carbowax-20M in a bonded, or cross-linked form, wall-coated in glass or flexible fused silica capillary columns, eliminates the confusing overlap of component fatty acids of different chain lengths found with polar packed GLC columns. Either isothermal or programmed conditions yield comparable results illustrated with a fish oil analysis.


Topographic, corneal wavefront, and refractive outcomes 2 years after collagen crosslinking for progressive keratoconus.
The aim was to report the corneal higher-order aberrations (HOA), the topographic metrics, and the visual and refractive outcomes 2 years after performing collagen crosslinking (CXL) for progressive keratoconus. The correlation among corneal HOAs, topographic metrics, and visual acuity changes was also investigated. This is a prospective case series involving 42 eyes from 32 patients with progressive keratoconus treated with CXL. The main outcomes measured at baseline and 6, 12, and 24 months after treatment were uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), refractive changes, topographic data, and corneal aberrations. Two years after CXL treatment, the UDVA (P < 0.001), CDVA (P < 0.001), and spherical equivalent (P = 0.048) improved significantly. The corneal topographic data revealed significant decreases in apical keratometry (P < 0.001), differential keratometry (P = 0.031), and central keratometry (P = 0.003) compared with the baseline measurements. Aberration analyses revealed a significant reduction in coma (P = 0.016), trefoil (P = 0.018), secondary astigmatism (P < 0.001), quatrefoil (P = 0.031), secondary coma (P < 0.001), and secondary trefoil (P = 0.001). Corneal HOA (except quatrefoil) demonstrated a significant correlation with postoperative CDVA; the highest correlations were for coma (rho = 0.703, P < 0.001), secondary astigmatism (rho = 0.519, P = 0.001), and total HOA (rho = 0.487, P = 0.001). However, the corneal HOA changes were not statistically associated with improved visual acuity. After treatment, the reduction in apical keratometry was the only variable that correlated with the improvement in the CDVA (rho = 0.319, P = 0.042). After 2 years, CXL was found to be effective in improving the UDVA, CDVA, topographic metrics, and most corneal HOAs in eyes with progressive keratoconus. A significant reduction was observed in apical keratometry, and this reduction directly correlated with an improvement in visual acuity.


Redefined clinical features and diagnostic criteria in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy.
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare primary immunodeficiency disorder typically caused by homozygous AIRE mutations. It classically presents with chronic mucocutaneous candidiasis and autoimmunity that primarily targets endocrine tissues; hypoparathyroidism and adrenal insufficiency are most common. Developing any two of these classic triad manifestations establishes the diagnosis. Although widely recognized in Europe, where nonendocrine autoimmune manifestations are uncommon, APECED is less defined in patients from the Western Hemisphere. We enrolled 35 consecutive American APECED patients (33 from the US) in a prospective observational natural history study and systematically examined their genetic, clinical, autoantibody, and immunological characteristics. Most patients were compound heterozygous; the most common AIRE mutation was c.967_979del13. All but one patient had anti-IFN-ω autoantibodies, including 4 of 5 patients without biallelic AIRE mutations. Urticarial eruption, hepatitis, gastritis, intestinal dysfunction, pneumonitis, and Sjögren's-like syndrome, uncommon entities in European APECED cohorts, affected 40%-80% of American cases. Development of a classic diagnostic dyad was delayed at mean 7.38 years. Eighty percent of patients developed a median of 3 non-triad manifestations before a diagnostic dyad. Only 20% of patients had their first two manifestations among the classic triad. Urticarial eruption, intestinal dysfunction, and enamel hypoplasia were prominent among early manifestations. Patients exhibited expanded peripheral CD4+ T cells and CD21loCD38lo B lymphocytes. In summary, American APECED patients develop a diverse syndrome, with dramatic enrichment in organ-specific nonendocrine manifestations starting early in life, compared with European patients. Incorporation of these new manifestations into American diagnostic criteria would accelerate diagnosis by approximately 4 years and potentially prevent life-threatening endocrine complications.


C3-symmetrical supramolecular architectures: fibers and organic gels from discotic trisamides and trisureas.
Hydrogen bonded C(3)-symmetrical molecules that associate into supramolecular stacks are described. Structural mutation on these molecules has been performed to elucidate the contribution of the different secondary interactions (hydrogen bonding, pi-pi stacking) to the self-assembly of the disks into chiral stacks. Twelve C(3)-symmetrical molecules have been investigated, six of which contain three central amide functionalities (1a-f) and six of which contain three central urea groups (2a-f). Peripheral groups of the disks are "small", "medium", or "large", half of them being achiral and the other half being chiral, to enable investigation of the supramolecular architectures with CD spectroscopy. In all of the cases, elongated, helical stacks are formed in apolar solution, except for the "medium" amide disks 1c/d. The elongated stacks of the C(3)-symmetrical disks form gels, which are visualized by AFM and SANS, and this confirms the directionality of the interactions. For the "large" urea disk, 2f, fibers with a length of up to 2 microm are observed. Temperature dependent and "sergeants-and-soldiers" CD measurements reveal that the urea stacks are much more rigid than the corresponding amide ones. In case of the "medium" urea disks, 2c/d, a true rigid rod, is formed. Where amide disks immediately reach their thermodynamic equilibrium, kinetic factors seem to govern urea aggregation. In a number of experiments aimed at reversibility with the urea stacks, hysteresis is observed, implying that these urea disks initially form a poorly defined stack, which subsequently transforms slowly into a well-defined, chiral architecture.


Theoretical estimates for the largest Lyapunov exponent of many-particle systems.
The largest Lyapunov exponent of an ergodic Hamiltonian system is the rate of exponential growth of the norm of a typical vector in the tangent space. For an N-particle Hamiltonian system with a smooth Hamiltonian of the type p(2)+V(q), the evolution of tangent vectors is governed by the Hessian matrix V of the potential. Ergodicity implies that the Lyapunov exponent is independent of initial conditions on the energy shell, which can then be chosen randomly according to the microcanonical distribution. In this way, a stochastic process V(t) is defined, and the evolution equation for tangent vectors can now be seen as a stochastic differential equation. An equation for the evolution of the average squared norm of a tangent vector can be obtained using the standard theory in which the average propagator is written as a cumulant expansion. We show that if cumulants higher than the second one are discarded, the Lyapunov exponent can be obtained by diagonalizing a small-dimension matrix that in some cases can be as small as 3 x 3. In all cases, the matrix elements of the propagator are expressed in terms of correlation functions of the stochastic process. We discuss the connection between our approach and an alternative theory, the so-called geometric method.


Chronic lupus peritonitis with massive ascites at elderly onset: case report and review of the literature.
A 77-year-old Japanese woman with massive painless ascites caused by chronic lupus peritonitis is reported. Peritoneal effusion had been resistant to the administration of steroids during the whole treatment period. It was characteristic that the titers of anti-DNA antibodies and the level of immune complex were elevated in the peritoneal fluid with suppressed levels of complements in ascites, although serum immunological markers reflecting the activity of SLE presented improvement after initiation of the treatment. Fifteen patients with chronic lupus peritonitis were reported previously. We reviewed the literature and suggest that chronic lupus peritonitis at elderly onset may demonstrate a poor response to the glucocorticoid therapy because of persistent inflammation in the peritoneum and the presence of impaired vascular circulation in addition to immunological mechanisms.


Ethics and Moral Agency for a Postpandemic Era: Beyond the Storm.
Laura Lee (Dolly) Swisher, PT, MDiv, PhD, FAPTA, the 53rd Mary McMillan Lecturer, is professor emerita and former director of the school of physical therapy and rehabilitation sciences at the University of South Florida in the USF Health Morsani College of Medicine. Dr Swisher received a bachelor of arts degree from Wilson College and is a 1986 physical therapy graduate of the University of Tennessee Health Science Center, Memphis. She received the M.Div. from Andover Newton Theological School and a doctoral degree in public administration from Tennessee State University. Dr Swisher is a highly regarded expert on professionalism, ethics, and interprofessional education and has been a featured speaker at local, state, and national conferences. She is the coauthor of Rehabilitation Ethics for Professional Practice, Professionalism in Physical Therapy and Legal and Ethical Issues in Physical Therapy and is a lead author or coauthor of multiple peer reviewed articles and individual book chapters. She served as a member and chair of the Commission on Accreditation for Physical Therapy Education, was former chair and member of the APTA Ethics and Judicial Committee, and served as co-chair of the Task Force to Revise the Core Ethics Documents. Dr Swisher served on the Editorial Board of the Journal of Physical Therapy Education and is a member of the Editorial Board of the Journal of Humanities in Rehabilitation. She is the recipient of APTA's Lucy Blair Service Award and the Polly Cerasoli Lecture Award and is a Catherine Worthingham Fellow of the APTA.


Mood disturbance versus other symptoms of depression in multiple sclerosis.
We administered the Multiscale Depression Inventory (MDI) and the Beck Depression Inventory (BDI) to 84 multiple sclerosis (MS) patients, 101 patients diagnosed with major depression and 87 nonmedical, nonpsychiatric controls. The MDI consists of three separate depression scales measuring mood, vegetative, and evaluative symptoms. We found that: (a) MS patients did not significantly differ from the controls in mood symptoms, (b) the depression prevalence rate in MS patients was significantly lower when measured by the mood scale (17.7%) than by the BDI (30.5%) or MDI total score (26.6%), and (c) MS patients showed significantly less mood disturbance than a non-MS comparison group matched on BDI measured depression severity. We suggest that the inclusion of nonmood symptoms in self-report depression scales may artificially raise both prevalence rates and severity ratings of MS related depression and that the most valid measure of depression in MS is mood disturbance.


Genetic identification of novel poxviruses of cetaceans and pinnipeds.
Novel poxviruses were identified in skin lesions of several species of cetaceans and pinnipeds using polymerase chain reaction targeting DNA polymerase and DNA topoisomerase I genes of members of the subfamily Chordopoxvirinae. With the exception of parapoxviruses, no molecular data of marine mammal poxviruses were available to infer genetic and evolutionary relatedness to terrestrial vertebrate poxviruses. Viruses were assigned to a cetacean poxvirus 1 (CPV-1) group based on nucleotide and amino acid identities of gene fragments amplified from skin lesions of Asian bottlenose (Tursiops aduncus), Atlantic bottlenose (Tursiops truncatus), rough-toothed (Steno bredanensis), and striped (Stenella coeruleoalba) dolphins. A different poxvirus was detected in skin lesions of a bowhead whale (Balaena mysticetus) and provisionally assigned to a CPV-2 group. These viruses showed highest identity to terrestrial poxviruses of the genera Orthopoxvirus and Suipoxvirus. A novel species-specific poxvirus was also identified in skin lesions of Steller sea lions (Eumetopias jubatus). None of these poxviruses were found to have amplifiable hemagglutinin gene sequences. Novel parapoxviruses were also identified in skin lesions of Steller sea lions and spotted seals (Phoca largha). A significant degree of divergence was observed in sequences of Steller sea lion parapoxviruses, while those of spotted seals and harbor seals (Phoca vitulina) were highly conserved.


[Health service's responsibility for sexually abused victims].
The abuse of women is a global problem, a women's health problem, and an egalitarian issue. In Sweden alone, 15,000 cases of the abuse of women, where victim and perpetrator were acquainted, were reported in 1994. In 1995, the National Women's Centre was inaugurated at the University Hospital, Uppsala, for the care of woman exposed to assault, abuse and sexual violence. Both care, research and training of personnel are carried out at the centre. Every abused woman coming to the hospital is now taken care of by specially trained personnel. The centre works in close cooperation with the police and the voluntary crisis centre, where battered women can receive support and help--for instance with temporary accommodation.


Detection of Leishmania within sand flies by kinetoplast DNA hybridization.
A kinetoplast DNA hybridization probe method was used to detect Leishmania within sand flies and to distinguish it from the non-pathogenic flagellate, Endotrypanum. Eighty-one sand flies (74 Lutzomyia umbratilis, 1 Lu. anduzei, and 6 Lu. shannoni) collected outside Manaus, Brazil were dissected. Forty-four of these were found to be infected with flagellates, and 2 hybridized with a Leishmania braziliensis probe. Thirty-three of sixty-one flies reprobed with an Endotrypanum probe were positive.


Preparation of a highly active cell-free translation system from immature Xenopus laevis oocytes.
Understanding mechanisms of post-transcriptional control of gene expression has come under much scrutiny in recent years. A key question in this field is how the translation of specific mRNAs is activated or repressed both spatially and temporally in a given cell. In oocytes of the frog Xenopus laevis a number of mRNAs are localized early in oogenesis and subsequently translated at later stages. We have developed a highly active cell-free translation system from oocytes in the early stages of oogenesis that is applicable to the study of translation and translational control of both endogenous and exogenous mRNAs.


Increased frequency of cells secreting interleukin-6 and interleukin-10 in peripheral blood of patients with primary Sjögren's syndrome.
Sjögren's syndrome (SS) is a chronic autoimmune disease of exocrine glands. There is increasing evidence that interferon-gamma (IFN-gamma) plays a role in the pathogenesis of SS. It has also been suggested that other type 1 cytokines, as well as interleukin-6 (IL-6), IL-10 and transforming growth factor-beta, are important in the induction and/or maintenance of SS. The aim of this study was to investigate the type 1/type 2 cytokine pattern in peripheral blood of primary SS patients. The enzyme-linked immunospot (ELISPOT) assay was performed to quantify the number of mononuclear cells (MNC) secreting IFN-gamma, IL-6 and IL-10 in peripheral blood samples from 33 patients with primary SS and 12 healthy controls. The mean number of cells secreting IFN-gamma was 9/105 MNC in the SS patient group, and 4/105 MNC in the control group (P = 0.73). Fifteen of the SS patients had anti-Ro 52 kDa antibodies in serum. In this patient group the mean number of cells secreting IFN-gamma was 4/105 MNC, while in the patient group without such antibodies the mean number of cells secreting IFN-gamma was 14/105 MNC (P = 0.04). The mean number of cells secreting IL-6 was 12 000/105 MNC in the SS patient group, and 5000/105 MNC in the control group (P = 0.01). The mean number of cells secreting IL-10 was 270/105 MNC in the SS patient group, and 180/105 MNC in the control group (P = 0.04). The SS patients had a significantly higher number of cells secreting IL-6 and IL-10 in peripheral blood than the healthy controls, which may facilitate B-cell activation and production of autoantibodies.


Increased CCR4 expression on circulating CD4(+) T cells in ankylosing spondylitis, rheumatoid arthritis and systemic lupus erythematosus.
Previous studies have suggested that CCR4 is particularly important in the selective recruitment of various subsets of leucocytes in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). In this study, we examined the percentage of CD4(+)/CCR4(+) T cells within circulating lymphocytes in active ankylosing spondylitis (AS), RA and SLE patients. The clinical significance of CCR4 expression as well as possible associations between the expression and serum levels of tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma and interleukin (IL)-10 were also examined. Our results showed that the percentage of CD4(+)/CCR4(+) T cells was significantly elevated in AS and RA patients as compared with normal controls. The percentage was also significantly higher in SLE patients who had received no treatment with glucocorticoids or cytotoxic drugs (untreated SLE) than that in controls. In addition, the percentage of CD4(+)/CCR4(+) T cells showed significant positive correlations with the Bath ankylosing spondylitis disease activity index (BASDAI) in AS and with the SLE disease activity index (SLEDAI) in untreated SLE. Of all the cytokines examined, the elevated serum IL-10 level was closely correlated with the percentage of CD4(+)/CCR4(+) T cells in AS, RA and untreated SLE. These results suggest that CCR4 may be crucial in the pathogenesis of AS, RA and SLE. The percentage of CD4(+)/CCR4(+) T cells can serve as a useful marker for the activity of AS and untreated SLE.


The graduate nurse experience: qualitative residency program outcomes.
Graduate nurses experience role conflict and stress as they begin practice in work environments of high complexity, nurse shortages, and expectations to become competent rapidly. The authors report outcomes from a study that evaluated qualitative responses to the Casey-Fink Graduate Nurse Experience Survey administered to graduate nurse residents in the University HealthSystem Consortium/American Association of Colleges of Nursing postbaccalaureate nurse residency program at 12 academic hospital sites. Qualitative analysis provided sufficient evidence to convert specific open-ended questions on the Casey-Fink Graduate Nurse Experience Survey instrument to a quantitative format for ease of administration and analysis.


Normal mode solutions for seismo-acoustic propagation resulting from shear and combined wave point sources.
Normal mode solutions to range-independent seismo-acoustic problems are benchmarked against elastic parabolic equation solutions and then used to benchmark the shear elastic parabolic equation self-starter [Frank, Odom, and Collis, J. Acoust. Soc. Am. 133, 1358-1367 (2013)]. The Pekeris waveguide with an elastic seafloor is considered for a point source located in the ocean emitting compressional waves, or in the seafloor, emitting both compressional and shear waves. Accurate solutions are obtained when the source is in the seafloor, and when the source is at the interface between the fluid and elastic layers.


Developing a survival strategy for rural hospitals.
As rural hospitals grapple with falling utilization and increasing competition, many are realizing that their viability is in question. This article reviews the issues most critical to the survival of the rural hospital and offers a two stage business planning process to address these issues. In the first stage, the hospital defines its role in the delivery of health care. The second stage requires developing a business plan that improves the hospital's resource management.


The role of ethnic relations and education systems in migration from Southeast Asia to Australia.
"After a brief discussion of the geographical, cultural, and historical characteristics of Southeast Asia [and Hong Kong], a review is provided of the evolution of Australian immigration policy which, in our view, is a strong pull factor. This is followed by stock and flow analyses of Asian-born residents in Australia. The motivations for emigration in countries which exhibit substantial emigration rates are considered next and the article ends with the conclusion that demand factors and social networks play a decisive role in the decision to emigrate." Factors affecting migration significantly include political conditions and ethnic relations in countries of origin, and educational and career opportunities in the country of destination.


Expedited Transition in the Wettability Response of Metal Meshes Structured by Femtosecond Laser Pulses for Oil-Water Separation.
Oil-water separation using super-wetting and the selective permeability of membranes for oil or water has great ecological and economic significance. We report on the transition of wettability response, from superhydrophilic underwater-superoleophobic to superhydrophobic-superoleophilic state, by nanostructuring stainless steel and copper meshes using ultrashort femtosecond laser pulses. Our approach is environment-friendly, chemical free, and efficient as it exploits the benefit of aging the processed samples in a high vacuum environment. We optimized the laser scanning parameters, mesh pore size, and aging conditions to produce membranes exhibiting an extraordinary separation efficiency of 98% for the oil-water mixture. A variation in the water and oil contact angles for different meshes is presented as a function of the laser scanning speed. Stainless steel meshes with 150 μm pore size and copper meshes with 100 μm pore size have demonstrated an excellent wettability response for oil and water phases. Vacuum aging causes rapid chemisorption of hydrocarbons on laser-structured surfaces in the absence of water molecules, rapidly transforming the wetting state from superhydrophilic to superhydrophobic.


[Refractory ascites in hemodialysis: treatment by paracentesis- reinjection during dialysis].
Two hemodialysis patients, one male and one female, aged 46 and 54 years, were treated with preceed respectively for refractory ascites secondary to hepatic cirrhosis and for large polycystic liver. Preceed was decided because of the rapid reappearance of effusion following repeated puncture and albumin infusion, the poor tolerance to ultrafiltration (UF) and the poor nutritional status of the patients, with severe hypoalbuminemia. Abdominal paracentesis was performed on initiation of the dialysis session. Reinjection of the ascites fluid was made into the arterial line, allowing its UF and control of its flow. The procedure was performed whenever necessary, i.e., when inter-dialysis weight gain and ascites volume were high. In both cases, improvement was quickly obtained, with less rapid and less severe reappearance of the effusion and correction of albuminemia. Dialysis sessions with UF were better tolerated. No notable side effect was observed. The first patient was treated for 2 months, when he died of an unrelated cause. The other patient was treated for 6 months and then could be transferred to a dialysis center near her home. Twenty five months after start of dialysis treatment, kidney and liver transplantation were performed in this same patient. After transplantation, reappearance of moderate ascites and oedema is attributed to e degradation of renal function, without liver dysfunction. Five weeks after transplantation, improvement of renal function and ascites regression were noted. Preceed is an effective method of treating refractory ascites in the hemodialysis patient. Compared to classical paracentesis, it has the advantage of good tolerance, patient comfort and moderate cost.


Conditioned pharmacotherapeutic effects: a preliminary study.
To test the hypothesize that psoriasis patients treated under a partial schedule of pharmacologic (corticosteroid) reinforcement would show less severe symptoms and relapse than those given the same amount of drug under standard conditions. Behavioral conditioning as an inherent component of many pharmacotherapeutic protocols has never been examined. A double-blind, simple randomization intervention was conducted with 46 patients from California and New York. Initially, lesions were treated with 0.1% acetonide triamcinolone under standard treatment conditions. Thereafter, a Standard Therapy group continued on continuous reinforcement (active drug every treatment) with 100% of the initial dose; Partial Reinforcement patients received a full dose 25% to 50% of the time and placebo medication other times; Dose Control patients received continuous reinforcement with 25% to 50% of the initial dose. Severity of disease scores in California neither supported nor refuted the hypothesis. In New York, where there was no difference between Partial Reinforcement and Dose Control groups at baseline, partial reinforcement effected a greater reduction in lesion severity than Dose Control conditions and did not differ from Standard Therapy patients receiving two to four times more drug. For the entire population, the frequency of relapse under partial reinforcement (26.7%) was lower than in Dose Control patients (61.5%) and did not differ from full-dose treatment (22.2%). A partial schedule of pharmacotherapeutic reinforcement could maintain psoriasis patients with a cumulative amount of corticosteroid that was relatively ineffective when administered under standard treatment conditions. Conceivably, corticosteroid administration only one quarter or half as frequently as currently prescribed is sufficient to treat psoriasis. We posit, however, that these preliminary observations implicate conditioning processes in-and for the design of-regimens of pharmacotherapy.


Clinical characteristics of HTLV-1 associated dermato-polymyositis. Seven cases from Martinique.
Myositis linked to HTLV-1 is unfrequent. Over a period of 8 years, 14 patients with inflammatory myopathy were diagnosed in Martinique. Seven were seropositive for HTLV 1 antibody; the clinical and pathological data of whom are presented herein. Five patients presented with polymyositis, two with dermatomyositis. All seven patients had extra-muscular clinical features including neuropathy (4/7) and myelopathy (6/7), resulting in a quite peculiar clinical picture. Muscle biopsy showed a neurogenic process combined with myositic changes in 3/7 patients. Corticotherapy led to dramatic improvement in only one case, but with no sustained effect. HTLV 1 may be considered the etiological agent of this form of dermato-polymyositis, characterized by a clearly distinctive clinico-pathological picture, and a poor response to corticotherapy. As in the case of tropical spastic paraparesis/HTLV 1 associated myelopathy, careful assessment of non-steroidal therapy is now warranted.


I2O5-Mediated Iodocyclization Cascade of N-(1-Arylallyl)pyridine-2-amines with Concomitant C═C Bond Cleavage: A Synthesis of 3-Iodoimidazo[1,2- a]pyridines.
A facile method for the synthesis of 3-iodoimidazo[1,2- a]pyridines has been successfully developed involving an I2O5-mediated iodocyclization cascade of N-(1-arylallyl)pyridin-2-amines with concomitant C═C bond cleavage. Preliminary mechanistic studies reveal that this protocol might undergo an oxidative cyclization/decarboxylation/iodination sequence in which I2O5 is used as both an oxidant and an iodine source. The present protocol has advantages of wide substrate scope, simple operation, and metal-free conditions.


Clinical features of patients with diabetes mellitus presenting with their first episode of uveitis.
Little is known about uveitis in patients with diabetes mellitus (DM). The authors studied diabetic patients with their first episode of uveitis. Cross-sectional, case note study documenting the uveitis, underlying cause/syndrome, treatment, type of DM and treatment, and any diabetic retinopathy. There were 34 patients (M/F: 17/17, 48 eyes) with their first uveitis episode (33 had type 2 DM). Mean age of onset of DM 49 years and uveitis 56 years. Uveitis was bilateral in 14 (45%), with most having idiopathic anterior uveitis. Visual acuity 6/18-6/60 in 15 eyes, and worse than 6/60 in 11 eyes. There was 3-4+ flare in 16 eyes, 3-4+ anterior chamber cells in 13 eyes. Diabetic retinopathy was seen in 20 (42%) eyes, and mean blood glucose was 13.64 mmol/L in 11 patients. Diabetic patients presenting with uveitis, whatever the aetiology, may have severe inflammation, reduced vision, and poor glycaemic control.


Multiple mechanisms of soy isoflavones against oxidative stress-induced endothelium injury.
Diabetic vascular complications are related to a combination of oxidative stress and hyperglycemia. Here we investigate the effect and mechanism of soy isoflavones on oxidative stress-induced endothelial cell injury. Oxidative stress was modeled in primary cultured human umbilical vein endothelial cells by incubation with H(2)O(2) and high glucose. Genistein and daidzein protected the cells against H(2)O(2)-induced apoptosis and their protective actions were abolished by ICI 182780, an estrogen receptor antagonist. The inhibition of cell proliferation by oxidative stress was prevented by genistein and daidzein under normal glucose conditions, but they were less effective at high glucose levels. Genistein and daidzein upregulated the estrogen receptor ERbeta and increased Bcl-2 expression. Silencing of Bcl-2 with siRNA abolished the protection of genistein. Moreover, inhibition of the PI3K and Rho A/Rho kinase pathways by wortmannin and Y-27632 altered the effects of genistein and daidzein on cell survival. We conclude that oxidative stress-induced apoptosis and cell proliferation inhibition can be prevented by soy isoflavones via the regulation of ERbeta and Bcl-2/Bax expression and modulation of cell survival signaling, such as the PI3K pathway. These findings imply that multiple mechanisms are involved in the beneficial effects of soy isoflavone supplements for diabetic endothelial injury.


The genome sequence of the clay, Mythimna ferrago (Fabricius, 1787).
We present a genome assembly from an individual female Mythimna ferrago (the clay; Arthropoda; Insecta; Lepidoptera; Noctuidae). The genome sequence is 861 megabases in span. The majority of the assembly (99.98%) is scaffolded into 32 chromosomal pseudomolecules, with the W and Z chromosomes assembled. The complete mitochondrial genome was also assembled and is 15.3 kilobases in length. Gene annotation of this assembly on Ensembl has identified 14,075 protein coding genes.


[Overview of models on spoken word recognition].
Models of spoken word recognition, such as logogen model, cohort model, new cohort model, trace model, shortlist model, and neighborhood activation model, were examined from the viewpoints of lexical processing. Although none of these models were good enough to explain all the results of studies on activation, competition, and composition of word candidates, the trace and shortlist models were less problematic than the other models.


Structural analysis of a hepatitis B virus genome integrated into chromosome 17p of a human hepatocellular carcinoma.
Hepatitis B virus (HBV) is clearly a factor in the development of hepatocellular carcinoma, but its mechanism of action remains obscure. One possibility is that the HBV integration event alters the expression of a nearby growth-regulatory cellular gene. A 9-kilobase (kb) DNA fragment containing an HBV insert plus flanking cellular sequences was cloned from a hepatoma specimen from Shanghai, People's Republic of China. Restriction mapping of the insert revealed a large inverted repeat structure consisting of both viral sequences (encompassing all of the core and pre-S regions and portions of the X and S genes) and at least 3 kb of unique cellular sequences. The virus-cell junction mapped 11 nucleotides from the DR1 region, in a position within the HBV X gene and included in the cohesive overlap region. A probe generated from 1.0 kb of the flanking cellular DNA mapped the viral insert to chromosome 17 in the region designated 17p11.2-17p12, which is near the human proto-oncogene p53. Sequence data from a portion of the flanking cellular DNA revealed a stretch of approximately 70 base pairs that showed highly significant homology with a conserved region of a number of functional mammalian DNAs, including the human autonomously replicating sequence 1 (ARS1).


Lymphatic Pathways on Indocyanine Green Lymphography in Patients with Labia Minora Hypertrophy.
Labia minora hypertrophy (LH) is a growing aesthetic concern, yet its etiology and local lymphatic anatomy remain unclear. This study aimed to use indocyanine green (ICG) lymphography to investigate evidence of lymphedema in LH and clarify the anatomy of lymph vessels from labia minora. Thirty-five patients with LH underwent preoperative ICG lymphography of their bilateral labia minora. The study reviewed demographic, ICG imaging, and measurement data to identify the characteristics of the superficial lymphatic anatomy in labia minora. The ICG lymphography findings revealed that 97.1% of the observed patterns were linear, and 2.9% were dermal backflow patterns. Further analysis of the linear patterns revealed the presence of three main superficial pathways originating from the labia minora and connecting to the labia majora and clitoral hood. These pathways were identified as the superior, median, and inferior channels. Based on the observed lymphatic mapping in the labia minora, three types were classified: type 1 (Superior + Inferior channels) accounted for 75.0% (51 sides), type 2 (Median + Inferior channels) accounted for 8.8% (6 sides), and type 3 (Superior + Median + Inferior channels) accounted for 16.2% (11 sides). The study demonstrates that ICG lymphography enables clear visualization of superficial lymph flow from labia minora. It also suggests that lymphedema is not a common pathologic feature of LH. Understanding the lymphatic anatomy of the labia minora can provide valuable guidance for surgical interventions involving the female external genitalia.


The Pharmacologic and Clinical Effects of Illicit Synthetic Cannabinoids.
This article presents information on illicitly used synthetic cannabinoids. Synthetic cannabinoids are structurally heterogeneous and commonly used drugs of abuse that act as full agonists of the cannabinoid type-1 receptor but have a variety of additional pharmacologic effects. There are numerous cases of patient harm and death in the United States, Europe, and Australia with many psychological, neurological, cardiovascular, pulmonary, and renal adverse events. Although most users prefer using cannabis, there are convenience, legal, and cost reasons driving the utilization of synthetic cannabinoids. Clinicians should be aware of pharmacologic and clinical similarities and differences between synthetic cannabinoid and cannabis use, the limited ability to detect synthetic cannabinoids in the urine or serum, and guidance to treat adverse events.


Sternotomy approach for modified Blalock-Taussig shunt: is it a safe option?
Central aorta-pulmonary artery shunts have fallen into disfavor because of shunt thrombosis and congestive heart failure, and a modified Blalock-Taussig shunt via thoracotomy can lead to pulmonary artery hypoplasia and distortion. We reviewed the outcomes of a modified Blalock-Taussig shunt by a sternotomy approach in 20 infants from July 2007 to October 2009. Their mean age was 5.79 months, and median weight was 5.4 kg. A 4-mm graft was placed in 11 patients, a 5-mm graft in 8, and a 3.5-mm graft in 1. There was no incidence of sepsis, seroma, or phrenic nerve palsy. There was one hospital death. The mean hospital stay was 10.4 +/- 4.3 days (range, 8-15 days). The mean oxygen saturation at discharge was 89% (range, 81%-93%). The sternotomy approach is technically easier to perform, cosmetically preferable, and probably hemodynamically superior. Correction of branch pulmonary stenosis is easily incorporated into this procedure. The theoretical disadvantage of this method is a potential technical difficulty with sternal reentry for subsequent procedures.


The detection of multiply charged dyes using matrix-assisted laser desorption/ionization mass spectrometry for the forensic examination of pen ink dyes directly from paper.
Laser desorption mass spectrometry (LDMS) is emerging as a technique for questioned document examination. Its use is limited to detecting ink dyes that are neutral or singly charged. Several inks contain dyes that are multiply charged and LDMS cannot be employed for their identification. We have successfully detected >20 polyionic dyes that can be used in the manufacture of inks using matrix-assisted laser desorption/ionization (MALDI) MS, directly from paper, with the matrix, 2-(4-hydroxyphenylazo)benzoic acid (HABA), and the additive, diammonium hydrogen citrate (DAHC). For example, Acid Violet 49, a charged dye containing one positively-charged site and two negatively charged sulfonate groups, cannot be detected by LDMS, but forms intact, singly charged ions in the MALDI MS experiment. The method described is also useful for identifying multiply charged dye mixtures that are used in modern pen inks.


Silicon-Enhanced Adipogenesis and Angiogenesis for Vascularized Adipose Tissue Engineering.
The enhancement of adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and sufficient vascularization remain great challenges for the successful reconstruction of engineered adipose tissue. Here, the bioactive effects of silicon (Si) ions on adipogenic differentiation of human BMSCs (HBMSCs) and the stimulation of vascularization during adipose tissue regeneration are reported. The results show that Si ions can enhance adipogenic differentiation of HBMSCs through the stimulation of the expression of adipogenic differentiation switches such as peroxisome proliferator-activated receptor γ and CCAAT/enhancer-binding protein α. Furthermore, Si ions can enhance both angiogenesis and adipogenesis, and inhibit dedifferentiation of cocultured adipocytes by regulating the interactions between HBMSC-derived adipocytes and human umbilical vein endothelial cells, in which the promotion of the expression of insulin-like growth factor 1 and vascular endothelial growth factor plays vital roles. The in vivo studies further demonstrate that the designed composite hydrogel with the ability to release bioactive Si ions clearly stimulates neovascularization and adipose tissue regeneration. The study suggests that Si ions released from biomaterials are important chemical cues for adipogenic differentiation and biomaterials with the ability to release Si ions can be designed for adipose tissue engineering.


Immune Responses to the ChAdOx1 nCoV-19 and BNT162b2 Vaccines and to Natural Coronavirus Disease 2019 Infections Over a 3-Month Period.
There are limited data directly comparing immune responses to vaccines and to natural infections with coronavirus disease 2019 (COVID-19). This study assessed the immunogenicity of the BNT162b2 and ChAdOx1 nCoV-19 vaccines over a 3-month period and compared the immune responses with those to natural infections. We enrolled healthcare workers who received BNT162b2 or ChAdOx1 nCoV-19 vaccines and patients with confirmed COVID-19 and then measured S1 immunoglobulin (Ig) G and neutralizing antibodies and T-cell responses. A total of 121 vaccinees and 26 patients with confirmed COVID-19 were analyzed. After the second dose, the BNT162b2 vaccine yielded S1 IgG antibody responses similar to those achieved with natural infections (mean IgG titer [standard deviation], 2241 [899] vs 2601 [5039]; P = .68) but significantly stronger than responses to the ChAdOx1 vaccine (174 [96]; P < .001). The neutralizing antibody titer generated by BNT162b2 was 6-fold higher than that generated by ChAdOx1 but lower than that by natural infection. T-cell responses persisted for 3 months with BNT162b2 and natural infection but decreased with ChAdOx1. Antibody responses after the second dose of BNT162b2 are higher than after the second dose of ChAdOx1 and like those occurring after natural infection. T-cell responses are maintained longer in BNT162b2 vaccinees than in ChAdOx1 vaccinees.


Mosquito species and their densities in some Egyptian governorates.
The present work studied the mosquito's identification, distribution and densities in fourteen Egyptian Governorates. The abundance and distribution of mosquito species monitored by three phases. The first was carried out in 1999 in five governorates, Qalyobia, Menoufia, Behaira, Fayium and Assuit. The second was in the year 2000 in Kafr El Sheikh, Giza, Sharkia, Menia and Aswan. The third was in the year 2001 in Kena, El Wady El Gadeed, Dakahlia and South Sinai. Culex species were the commonest mainly C. pipiens, C. antennatus and C. univittatus. C. thelerei was found only in El Kharga Oasis. Culiseta sp. was found in Qalyobia, Menofia, Behaira, Fayium, El Wady El Gadeed, Dakahlia and South Sinai and as larvae in Kafr El Sheikh, Giza, and Menia. Aedes detritus was found in Assiut, Fayium, Giza, Aswan, El Wady El Gadeed and South Sinai. Ae. caspius was found in Assiut and Aswan and as larvae in Kena and El Wady El Gadeed. Anopheles pharoensis was found in Behaira and Fayium, while A. algeriensis in Aswan. A. multicolor and A. sergentii were found in Fayium, Aswan and El Wady El Gadeed; but in Kena A. sergentii was found as larvae and A. multicolor as adults.


[Differential diagnosis in cholestatic liver diseases].
Causes of cholestasis include disturbed bile flow out of the hepatocyte into the biliary capillaries, or obstruction (stone, tumor, inflammation) of small or larger intrahepatic or extrahepatic. In the event of acute or subacute onset, Cholestatic liver disease becomes manifest by its clinical presentation; in the case of a chronic course it tends to be an incidental finding based on liver parameters. For the differential diagnosis, the history (duration of symptoms, general symptoms, family history, drug history), clinical picture, laboratory investigations (alkaline phosphatase, g-GT, possibly specific autoantibodies) and imaging procedures (in particular ultrasonography and ERCP) point in the right direction. The present article provides an overview of the major differential diagnoses of intrahepatic and extrahepatic cholestasis. A diagnostic algorithm is presented.


Primary sequence heterogeneity and tissue expression of glutathione S-transferases of Fasciola hepatica.
Glutathione S-transferases (GSTs) from Fasciola hepatica have been purified by glutathione affinity chromatography. Two closely migrating species of Mr 26,000 and 26,500 were identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and several species resolved by two-dimensional gel analysis, indicating substantial heterogeneity among the GSTs. N-terminal amino acid sequencing revealed one core sequence containing three polymorphisms, whereas the sequence of GST peptides implied a minimum of three different GSTs. The amino acid sequence data assigned the F. hepatica GSTs to the mu class of GSTs with high similarities to these proteins in other helminths and mammals. The native GSTs of F. hepatica appeared to behave as dimers as determined by molecular sieving chromatography. The observation that the GSTs of F. hepatica are heterogeneous in sequence and behave as dimers in the native state suggest that these isoenzymes may exhibit considerable functional heterogeneity which may be of importance to the parasite. Immunocytochemical studies suggest that the main source of GST in F. hepatica are the parenchymal cells and peripheral tissues of the parasite. Some extracellular GST is associated with the lamellae of the intestinal epithelium. The identification of an intestinal GST is unique among trematodes studied to date.


Targeting thermogenesis in brown fat and muscle to treat obesity and metabolic disease.
Brown fat is emerging as an interesting and promising target for therapeutic intervention in obesity and metabolic disease. Activation of brown fat in humans is associated with marked improvement in metabolic parameters such as levels of free fatty acids and insulin sensitivity. Skeletal muscle is another important organ for thermogenesis, with the capacity to induce energy-consuming futile cycles. In this Review, we focus on how these two major thermogenic organs - brown fat and muscle - act and cooperate to maintain normal body temperature. Moreover, in the light of disease-relevant mechanisms, we explore the molecular pathways that regulate thermogenesis in brown fat and muscle. Brown adipocytes possess a unique cellular mechanism to convert chemical energy into heat: uncoupling protein 1 (UCP1), which can short-circuit the mitochondrial proton gradient. However, recent research demonstrates the existence of several other energy-expending 'futile' cycles in both adipocytes and muscle, such as creatine and calcium cycling. These mechanisms can complement or even substitute for UCP1-mediated thermogenesis. Moreover, they expand our view of cold-induced thermogenesis from a special feature of brown adipocytes to a more general physiological principle. Finally, we discuss how thermogenic mechanisms can be exploited to expend energy and hence offer new therapeutic opportunities.


Glucuronyl C5-epimerase an enzyme converting glucuronic acid to iduronic acid in heparan sulfate/heparin biosynthesis.
The glucuronyl C5 epimerase (HSepi) is one of the modification enzymes involved in biosynthesis of heparan sulfate (HS) and heparin, catalyzing the epimerization of D-glucuronic acid (GlcA) to L-iduronic acid (IdoA) at polymer level. IdoA is critical for HS and heparin to interact with protein ligands, because of its flexible conformation. Although the enzyme recognizes both GlcA and IdoA as substrates catalyzing a reversible reaction of the hexuronic acids in vitro, the reaction appears irreversible in vivo. Targeted interruption of the gene, Glce, in mice resulted in neonatal lethality accompanied with kidney agenesis, premature lung, and skeletal malformations, demonstrating that the single gene coded enzyme is essential for animal development. Elimination of the enzyme resulted in abnormal HS and heparin structure that completely lacks IdoA residues. Loss of 2-O-sulfation due to lacking IdoA in HS chains appears compensated by increased N- and O-sulfation of the glucosamine residues. Recombinant HSepi is used to generate HS/heparin related compounds having potential to be used for therapeutic purposes.


Bullying Perpetration and Victimization: A Test of Traditional and Cyber-Behaviors as Latent Constructs.
The current investigation hypothesized and tested latent bully/victim traits for physical, verbal, or relational bullying/victimization, both cyber and traditional behaviors. Data were collected from 1,356 German students who attended Grades 5 to 10: 48.4% males, 49.3% females from eight different schools in Northern Germany. Based on two samples for cross-validation (Ntraining set = 525, Nvalidation set = 525), study findings provided strong evidence of adequate model fit, both for traditional and cyber behaviors. Consistent with the current state of knowledge, bullying and victimization latent traits highly associated, more so for cyber behaviors than traditional ones. Thus, both the theoretical plausibility as well as statistical evidence support the application of latent modeling to these behaviors. Further research is needed to replicate the applied measurement models proposed in this work and to reveal moderators or measurement invariance across diverse populations. Nevertheless, the current evidence substantiates the importance of the application of a latent modeling approach to overcome known psychometric challenges of reliability and validity in bullying research.


Strong Metal-Support Interaction Boosts Activity, Selectivity, and Stability in Electrosynthesis of H2O2.
Noble metals have an irreplaceable role in catalyzing electrochemical reactions. However, large overpotential and poor long-term stability still prohibit their usage in many reactions (e.g., oxygen evolution/reduction). With regard to the low natural abundance, the improvement of their overall electrocatalytic performance (activity, selectivity, and stability) was urgently necessary. Herein, strong metal-support interaction (SMSI) was modulated through an unprecedented time-dependent mechanical milling method on Pd-loaded oxygenated TiC electrocatalysts. The encapsulation of Pd surfaces with reduced TiO2-x overlayers is precisely controlled by the mechanical milling time. This encapsulation induced a valence band restructuring and lowered the d-band center of surface Pd atoms. For hydrogen peroxide electrosynthesis through the two-electron oxygen reduction reaction (ORR), these electronic and geometric modifications resulted in optimal adsorption energies of reaction intermediates. Thus, SMSI phenomena not only enhanced electrocatalytic activity and selectivity but also created an encapsulating oxide overlayer that protected the Pd species, increasing its long-term stability. This SMSI induced by mechanical milling was also extended to other noble metal systems, showing great promise for the large-scale production of highly stable and tunable electrocatalysts.


Predictors of Stress in College Students.
University students often face different stressful situations and preoccupations: the first contact with the university, the freedom of schedule organization, the selection of their master's degree, very selective fields, etc. The purpose of this study is to evaluate a model of vulnerability to stress in French college students. Stress factors were evaluated by a battery of six scales that was accessible online during 3 months. A total of 483 students, aged between 18 and 24 years (Mean = 20.23, standard deviation = 1.99), was included in the study. The results showed that 72.9, 86.3, and 79.3% of them were suffering from psychological distress, anxiety and depressive symptoms, respectively. More than half the sample was also suffering from low self-esteem (57.6%), little optimism (56.7%), and a low sense of self-efficacy (62.7%). Regression analyses revealed that life satisfaction, self-esteem, optimism, self-efficacy and psychological distress were the most important predictors of stress. These findings allow us to better understand stress-vulnerability factors in students and drive us to substantially consider them in prevention programs.


Interleukin-6 is a direct mediator of T cell migration.
Interleukin (IL)-6 is a pleiotropic cytokine involved in the differentiation and proliferation of hematopoietic cells. Hepatocytes respond to IL-6 with the synthesis and secretion of acute-phase proteins. In addition, IL-6 plays a role as a migration factor in vivo. In the present paper, we studied the potential of IL-6 to mediate migration of human primary T cells and T cell-derived cell lines. IL-6 was found to induce migration only in the presence of extracellular matrix, suggesting a cross-talk between the IL-6- and integrin signal transduction pathways. Furthermore, an IL-6 gradient is required for chemotactic migration. This activity is not due to the release of secondary chemotactic activities, but is a direct response to IL-6. T cell migration could also be observed in response to IL-11, but no migration was found after stimulation with leukemia inhibitory factor or oncostatin M, although these cytokines signal through gp130-containing receptor complexes. Finally, we present evidence that activation of the mitogen-activated protein kinase (MAPK) cascade, the phosphatidylinositol 3-kinase as well as the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway is crucial for IL-6-induced migration. Selective activation of the JAK/STAT or the MAPK cascade by mutated receptor proteins shows a crucial role of IL-6-initiated SH2 domain-containing tyrosine phosphatase 2/MAPK activity for migration.


Outcomes of Resectability Assessment of the Dutch Colorectal Cancer Group Liver Metastases Expert Panel.
Decision making on optimal treatment strategy in patients with initially unresectable colorectal cancer liver metastases (CRLM) remains complex because uniform criteria for (un)resectability are lacking. This study reports on the feasibility and short-term outcomes of The Dutch Colorectal Cancer Group Liver Expert Panel. The Expert Panel consists of 13 hepatobiliary surgeons and 4 radiologists. Resectability assessment is performed independently by 3 randomly assigned surgeons, and CRLM are scored as resectable, potentially resectable, or permanently unresectable. In absence of consensus, 2 additional surgeons are invited for a majority consensus. Patients with potentially resectable or unresectable CRLM at baseline are evaluated every 2 months of systemic therapy. Once CRLM are considered resectable, a treatment strategy is proposed. Overall, 398 panel evaluations in 183 patients were analyzed. The median time to panel conclusion was 7 days (interquartile range [IQR] 5-11 days). Intersurgeon disagreement was observed in 205 (52%) evaluations, with major disagreement (resectable vs permanently unresectable) in 42 (11%) evaluations. After systemic treatment, 106 patients were considered to have resectable CRLM, 84 of whom (79%) underwent a curative procedure. R0 resection (n = 41), R0 resection in combination with ablative treatment (n = 26), or ablative treatment only (n = 4) was achieved in 67 of 84 (80%) patients. This study analyzed prospective resectability evaluation of patients with CRLM by a panel of radiologists and liver surgeons. The high rate of disagreement among experienced liver surgeons reflects the complexity in defining treatment strategies for CRLM and supports the use of a panel rather than a single-surgeon decision.


From lecture to learning tasks: use of the 4C/ID model in a communication skills course in a continuing professional education context.
This article describes the use of four-component instructional design (4C/ID), a model to plan educational interventions for complex learning. This model was used to design a continuing education course on communication skills for health professionals in a context that is hierarchical and communal. The authors describe the 4C/ID model and provide an example of its application in designing the course. In the 4C/ID model, learning tasks serve as the backbone of the course, with lectures and other supportive information organized around them. The 4C/ID model is different from traditional models that base the course on lectures on different topics and connect part-task assignments to these topics. The use of the 4C/ID model to develop the educational intervention moves the paradigm from lectures to learning tasks to better prepare learners for real practice.


Targeted antibiotic discovery through biosynthesis-associated resistance determinants: target directed genome mining.
Intense competition between microbes in the environment has directed the evolution of antibiotic production in bacteria. Humans have harnessed these natural molecules for medicinal purposes, magnifying them from environmental concentrations to industrial scale. This increased exposure to antibiotics has amplified antibiotic resistance across bacteria, spurring a global antimicrobial crisis and a search for antibiotics with new modes of action. Genetic insights into these antibiotic-producing microbes reveal that they have evolved several resistance strategies to avoid self-toxicity, including product modification, substrate transport and binding, and target duplication or modification. Of these mechanisms, target duplication or modification will be highlighted in this review, as it uniquely links an antibiotic to its mode of action. We will further discuss and propose a strategy to mine microbial genomes for these genes and their associated biosynthetic gene clusters to discover novel antibiotics using target directed genome mining.


Phospha-Michael addition reaction of maleimides employing N-heterocyclic phosphine-thiourea as a phosphonylation reagent: synthesis of 1-aryl-2,5-dioxopyrrolidine-3-yl-phosphonate derivatives.
N-Heterocyclic phosphine (NHP)-thiourea as a novel phosphonylation reagent has been successfully applied for the phospha-Michael reaction of maleimides under catalyst and additive free reaction conditions. This methodology enables desymmetrization of a variety of maleimide derivatives to provide 1-aryl-2,5-dioxopyrrolidine-3-yl-phosphonates in up to 92% yield. Synthetic manipulation of this Michael adduct afforded an ethylphosphonate and a phosphino lactam. Furthermore, a scale-up experiment for its practical usage as a versatile precursor in organic synthesis was readily demonstrated.


Comparative studies of bile salts. Bile salts of the lamprey Petromyzon marinus L.
1. Bile salts of Petromyzon marinus L. ammocoetes appeared to consist solely or chiefly of a crystalline substance, whose chromatographic and i.r.-spectral characteristics suggested that it was a monosulphate ester of a bile alcohol having the 3alpha,7alpha,12alpha-trihydroxy pattern of substitution in a 5alpha-steroid nucleus. 2. This substance on cleavage with dioxan-trichloroacetic acid gave petromyzonol, n.m.r. and mass-spectral examination of which suggested the structure 5alpha-cholane-3alpha,7alpha,12alpha,24-tetrol. 3. 3alpha,7alpha,12alpha-Trihydroxy-5alpha-cholanoic acid (allocholic acid) from the lizards Anolis lineatopus lineatopus Gray and Cyclura carinata Harlan (family Iguanidae) was esterified with propan-1-ol and reduced by lithium aluminium hydride to 5alpha-cholane-3alpha,7alpha,12alpha,24-tetrol, identical with petromyzonol. 4. Chromic acid oxidation of petromyzonol sulphate from lamprey bile, followed by acid hydrolysis, gave 24-hydroxy-5alpha-cholane-3,7,12-trione; hence the sulphate ester group is at C-24. 5. Petromyzonol sulphate is both primitive and unique: a study of its biogenesis might improve our understanding of evolution at the molecular level.


[Candiduria! What now? : Therapy of urinary tract infections with Candida].
Yeasts are found in urine specimens relatively often, especially in the elderly and patients under treatment with broad spectrum antibiotics, i. e. especially in intensive care unit (ICU) patients. In some cases, the number of pathogens is very high, i. e. >105/ml. The clinical relevance of detecting Candida in urine is difficult to assess. In the German S3 guidelines it is apodictically stated that an ascending infection of the urinary tract by yeasts does not occur but this may undoubtedly happen in certain instances in patients at risk, for example in the elderly, in diabetic persons and in the case of foreign bodies in the urinary tract. A hematogenous spread of yeasts can lead to pyelonephritis, which accompanies candiduria. In rare cases this can be induced by prostatitis and epididymitis. Therapy is indicated in all cases when a urological manipulation is planned, particularly those with injury to the mucosal barrier, in order to prevent an intraoperative spread of pathogens. The antimicrobial agents suitable for therapy of candiduria are limited, namely flucytosine, amphotericin B, which is also used for irrigation and fluconazole. The in vitro effect of nitroxoline on 100 isolates of yeasts from urine was tested by an agar diffusion test. Nitroxoline exerted a good activity against all yeast isolates. The antibiotic nitroxoline has a good antifungal activity. It achieves high concentrations in urine and in addition, it is effective at low pH as well as against pathogens in biofilms, which most antimycotics cannot achieve. Hence, nitroxoline is suitable for termination of candiduria. Foreign bodies in the urinary tract, on which biofilms are formed, should be removed whenever possible.


Sporadic and familial cases of aquagenic keratoderma.
Aquagenic keratoderma is a dermatosis characterized by transient whitish and transluscent hyperwrinkling after water exposure. The aim of the current report was to present a sporadic and familial cases of aquagenic keratoderma. Sporadic Case: A 38-year-old female patient presented with eruption in the right hand after exposure to water. The patient was placed on systemic acitretin therapy with the diagnosis of idiopathic acquired aquagenic keratoderma. No recurrence occurred during a 6-month follow-up period. Familial Cases: A 55-year-old male patient, who was engaged in fishery, presented to the outpatient clinics of the department of dermatology due to whitish vesicles in the palms of both hands. It was realized that the father, sister, and brother of the patient had similar complaints. The cases were thought to have familial aquagenic keratoderma; however acitretin therapy could not be initiated due to elevated alanine aminotransferase and triglyceride levels. Topical application of salicylic acid 10% and 10% urea containing lotions was effective but did not prevent recurrence. Systemic acitretin may be an effective agent in the treatment of aquagenic keratoderma, and topical application of 10% salicylic acid and 10% urea-containing lotion did not prevent recurrence.


Did it move? Humans use spatio-temporal landmark permanency efficiently for navigation.
Visual landmarks provide crucial information for human navigation. But what characteristics define a landmark? To be uniquely recognized, a landmark should be distinctive and salient, while providing precise and accurate positional information. It should also be permanent. For example, to find back to your car, a nearby church seems a better landmark compared with a distinct truck or bicycle, because you learned that there is a chance that these objects might move. To this end, we investigated human learning of landmark permanency for navigation while treating spatiotemporal permanency as a probabilistic property. We hypothesized that humans will be able to learn the probabilistic nature of landmark permanency and assign higher weight to more permanent landmarks. To test this hypothesis, we designed a homing task where participants had to return to a position that was surrounded by three landmarks. In the learning phase we manipulated the spatiotemporal permanency of one landmark by secretly repositioning it before participants returned home. In the test phase, we investigated the weight allocated to the nonpermanent landmark by analyzing its influence on the navigational performance during homing. We conducted four experiments: In the first two experiments we altered the statistics of permanency and accordingly found an influence on participants' behavior, nonpermanent objects were used less for finding home. In the last two experiments we investigated the role of short-term learning of novel statistics versus long-term knowledge about such statistics. No carry-over effects in Experiment 3 and very little influence of object identity with different long-term permanency characteristics in Experiment 4 revealed a dominance of short-term learning over the use of long-term a priori knowledge about object permanency. This indicates that long-term prior beliefs are quickly updated by the current permanency statistics. Taken together, consistent with a Bayesian account for navigation these results indicate that humans quickly learn and update the statistics of landmark permanency and use it in an effective way, assigning gradually more weight to the more permanent landmark and making it more important for navigation. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Development of a Transitional Care Model Program for Patients with Pneumonia, Asthma, and Chronic Obstructive Pulmonary Disease: In-depth Interviews with Readmitted Patients.
Community-based health management policies are needed considering societal aging. We aimed to develop a transitional care model (TCM) program for patients with pneumonia, asthma, and chronic obstructive pulmonary disease. First, we conducted in-depth interviews with patients who were hospitalized, released, and readmitted for those three conditions to identify issues with the current hospitalization/discharge system and post-discharge processes. Next, we developed a new TCM program suited to the realities of the current medical environment. Interviews revealed problems including inadequate awareness of disease and health management; insufficient information exchange between patients, caregivers, and primary medical institutions; and absence/low usage of community-based care services. The investigation applying the new TCM program to patients and following up on readmission rates and life satisfaction after discharge is ongoing. Reviewing these results and conducting further studies in the future will allow improvements to the model.


[Systematic review and Meta-analysis of efficacy and safety of Biyuan Tongqiao Granules in treatment of chronic sinusitis].
The present study conducted a systematic review and Meta-analysis on the efficacy and safety of Biyuan Tongqiao Granules in the treatment of chronic sinusitis. CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, EMbase, and Web of Science were searched for randomized controlled trials(RCTs) of Biyuan Tongqiao Granules in the treatment of chronic sinusitis. The quality of the included RCTs was assessed according to the Cochrane risk-of-bias assessment tool and the final included trials underwent Meta-analysis with RevMan 5.4.1. Fifty-four RCTs were included, with a total sample size of 7 278 cases. The results of Meta-analysis showed that the clinical efficacy of Biyuan Tongqiao Granules alone or in combination in the experimental group in the treatment of chronic sinusitis was superior to that in the control group with conventional western medicine, Chinese medicinal preparations, or surgery only(RR=1.19, 95%CI[1.15, 1.24], P<0.000 01). The combined use of Biyuan Tongqiao Granules on the basis of the control group was superior to the control group in improving the main symptoms and signs of chronic sinusitis [RR_(nasal congestion)=1.33, 95%CI[1.21, 1.45], P<0.000 01, RR_(runny nose)=1.28, 95%CI[1.18, 1.40], P<0.000 01, RR_(turbinate congestion or swelling)=1.28, 95%CI[1.16, 1.41], P<0.000 01]. Biyuan Tongqiao Granules alone or in combination could effectively reduce the Snot-20 score, which was superior to the control group(MD=-2.94, 95%CI[-3.60,-2.28], P<0.000 01). Biyuan Tongqiao Granules alone and in combination could effectively reduce the VAS score, which was superior to the control group(MD_(total score)=-4.44, 95%CI[-6.05,-2.82], P<0.000 01; MD_(nasal congestion VAS score)=-0.99, 95%CI[-1.38,-0.60], P<0.000 01; MD_(runny nose VAS score)=-1.19, 95%CI[-1.62,-0.76], P<0.000 01; MD_(dysosmia VAS score)=-0.96, 95%CI[-1.26,-0.65], P<0.000 01; MD_(head and face pain VAS score)=-0.73, 95%CI[-0.98,-0.47], P<0.000 01). The combined use of Biyuan Tongqiao Granules could effectively reduce the sinus CT score and the Lund-Mackey score of the endoscopic mucosal morphology(MD_(sinus CT score)=-3.68, 95%CI[-5.47,-1.88], P<0.000 1, MD_(endoscopic mucosal morphology score)=-3.06, 95%CI[-5.53,-0.59], P=0.02). Compared with the control group with conventional western medicine, Chinese medicinal preparations, or surgery only, combined use of Biyuan Tongqiao Granules did not increase the occurrence of adverse reactions(RR=0.68, 95%CI[0.26, 1.77], P=0.43). As demonstrated by the existing evidence, Biyuan Tongqiao Granules can improve the clinical efficacy of chronic sinusitis, relieve the clinical symptoms and signs, and reduce the Snot-20 score, VAS score, and Lund-Mackey score, without inducing serious adverse reactions, indicating that Biyuan Tongqiao Granules alone or in combination are more effective and safe in the treatment of chronic sinusitis than conventional western medicine, Chinese medicinal preparations, or surgical treatment. Since the quality of the included trials was generally low, large-scale, high-quality, rigorous, multi-center, and blinded-designed RCTs that meet international standards should be adopted in the future to increase the strength and level of evidence.


Facilitating partner notification through an online messaging service: Let Them Know.
Let Them Know (www.letthemknow.org.au) is an Australian internet based service designed to support individuals diagnosed with an STI to notify sexual partners using anonymous or personal text messages. A review of user activity and acceptability of the website was performed. Between 17 March 2010 and 31 March 2011, of 13?024 website visits, 4863 (37%) visits resulted in a text message being sent. From 3 December 2010, of 1383 consecutive users, 963 (70%) indicated they were more likely to contact a partner because of the website. A short period of misuse was identified and controlled, and additional measures to monitor for and prevent misuse were subsequently implemented. Web-based notification systems such as the Let Them Know website can help to facilitate partner notification for individuals who may be reluctant to do this in person.


Toward a systems level view of the ECM and related proteins: a framework for the systematic definition and analysis of biological systems.
Advances in high throughput 'omic technologies are starting to provide unprecedented insights into how components of biological systems are organized and interact. Key to exploiting these datasets is the definition of the components that comprise the system of interest. Although a variety of knowledge bases exist that capture such information, a major challenge is determining how these resources may be best utilized. Here we present a systematic curation strategy to define a systems-level view of the human extracellular matrix (ECM)--a three-dimensional meshwork of proteins and polysaccharides that impart structure and mechanical stability to tissues. Employing our curation strategy we define a set of 357 proteins that represent core components of the ECM, together with an additional 524 genes that mediate related functional roles, and construct a map of their physical interactions. Topological properties help identify modules of functionally related proteins, including those involved in cell adhesion, bone formation and blood clotting. Because of its major role in cell adhesion, proliferation and morphogenesis, defects in the ECM have been implicated in cancer, atherosclerosis, asthma, fibrosis, and arthritis. We use MeSH annotations to identify modules enriched for specific disease terms that aid to strengthen existing as well as predict novel gene-disease associations. Mapping expression and conservation data onto the network reveal modules evolved in parallel to convey tissue-specific functionality on otherwise broadly expressed units. In addition to demonstrating an effective workflow for defining biological systems, this study crystallizes our current knowledge surrounding the organization of the ECM.


[Percutaneous renal biopsy in children: use of a fine needle].
Percutaneous renal biopsies were performed on native kidneys in 40 children and adolescent, aged 1.7-13 (mean 6.7) years. Bleeding diatheses were excluded by the determination of Hb, blood platelets, PT, PTI and fibrinogen. Biopsies were performed under ultrasound imaging, using a semiautomated and thin needle (20 gauge in children with age under 5 years and 18 gauge for those over 5 years). All the patients were lightly sedated, except for 3 ones who received a general anesthesia. Diagnostically adequate tissue was retrieved in 38 of 40 biopsy procedures (95%). A macro-haematuria was observed with elimination of haematic coagula in 3 children (7.5%) and 24-h post-biopsy ultrasonography disciosed a small haematoma of the biopsied kidney in 2 one (5%). No mayor complications occurred. We conclude that the use of ultrasound imaging and a semiautomated needle is a safe and efficient method for performing renal biopsies in paediatric patients. The use of smaller (18 or 20-gauge) cutting needles would reduce the complications rate while allowing retrieval of sufficient tissue for histologic diagnosis.


SHP-2 is a dual-specificity phosphatase involved in Stat1 dephosphorylation at both tyrosine and serine residues in nuclei.
Signal transducer and activator of transcription (STAT) proteins are both tyrosine- and serine-phosphorylated, mediating signal transduction and gene regulation. Following gene regulation, STAT activity in the nucleus is then terminated by a nuclear protein phosphatase(s), which remains unidentified. Using novel antibody arrays to screen the Stat1-specific protein phosphatase(s), we identified a SHP-2-Stat1 interaction in the A431 cell nucleus. SHP-2 and Stat1 nuclear localization and their association in response to either epidermal growth factor or interferon-gamma (IFNgamma) were confirmed by immunofluorescent staining and affinity precipitation assays. The SHP-2 C-terminal region containing protein-tyrosine phosphatase activity interacted with the C-terminal SH2 transcriptional activation domain of Stat1. In SHP-2-/- mouse fibroblast cells, Stat1 phosphorylation at both the tyrosine residue Tyr(701) and the serine residue Ser(727) by IFNgamma was enhanced and prolonged. Consistently, purified GST-SHP-2 dephosphorylated Stat1 at both tyrosine and serine residues when immunoprecipitated phospho-Stat1 or a peptide corresponding to the sequence surrounding Tyr(P)(701) or Ser(P)(727) of Stat1 was used as the substrate. Overexpression of SHP-2 in 293T cells inhibited IFNgamma-dependent Stat1 phosphorylation and suppressed Stat1-dependent induction of luciferase activity. Our findings demonstrate that SHP-2 is a dual-specificity protein phosphatase involved in Stat1 dephosphorylation at both tyrosine and serine residues and plays an important role in modulating STAT function in gene regulation.


Synthesis and evaluation of hydroxycamptothecin-encapsulated chitosan nanospheres for the treatment of liver cancer.
Hydroxycamptothecin-encapsulated chitosan (HC) nanospheres were prepared by Shirasu porous glass (SPG) membrane emulsification technique. The properties and morphology of HC nanospheres were characterized. The diameter of the nanospheres could be controlled within a narrow distribution according to the pore-size of SPG membrane. Hydroxycamptothecin (HCPT) encapsulation efficiency could reach to 81.3%. The long-term drug release of HCPT could be presented by an accumulated drug release of 85.4% in 15 days with an initial burst effect. In vitro study, HC showed its anti-tumor ability to human hepatoma (HepG2) cells. In vivo study, HC could reduce tumor weight and growth rate. The results indicated that HC nanospheres prepared by SPG had potential application as a sustained drug delivery system for the treatment of liver cancer.


Identification, Analysis, and Confirmation of Seed Storability-Related Loci in Dongxiang Wild Rice (Oryza rufipogon Griff.).
Dongxiang wild rice (Oryza rufipogon Griff.) (DXWR) has strong seed storability and identifying its elite gene resources may facilitate genetic improvements in rice seed storability. In this study, we developed two backcross inbred lines (BILs) populations, with DXWR as a common donor parent and two rice varieties (F6 and R974) as recipient parents. Bulked segregant analysis via whole genome sequencing (BSA-seq) was used to identify seed storability-related loci in the DXWR and F6 population. Two main genomic regions containing 18,550,000-20,870,000 bp on chromosome 4 and 7,860,000-9,780,000 bp on chromosome 9 were identified as candidate loci of DXWR seed storability; these overlapped partially with seed storability-related quantitative trait loci (QTLs) discovered in previous studies, suggesting that these loci may provide important regions for isolating the responsible genes. In total, 448 annotated genes were predicted within the identified regions, of which 274 and 82 had nonsynonymous and frameshift mutations, respectively. We detected extensive metabolic activities and cellular processes during seed storability and confirmed the effects of the seed storability-related candidate loci using four BILs from DXWR and R974. These results may facilitate the cloning of DXWR seed storability-related genes, thereby elucidating rice seed storability and its improvement potential.


Synthesis of dihydrodiol metabolites implicated in the mechanism of carcinogenesis of phenanthro[4,3-b][1]benzothiophene and phenanthro[3,4-b][1]benzothiophene, the polycyclic sulfur heterocycles with a "Fjord" structure.
Dihydrodiols, which are potential proximate carcinogens of phenanthro[4,3-b][1]benzothiophene (3) and phenanthro[3,4-b][1]benzothiophene (4) and possess a "fjord" structure, were synthesized. The dihydrodiols synthesized were trans-3,4-dihydroxy-3,4-dihydrophenanthro[4,3-b][1]benzothiophene (5) and trans-3,4-dihydroxy-3,4-dihydrophenanthro[3,4-b][1]benzothiophene (6). The precursors to the dihydrodiols 5 and 6 were 3-methoxyphenanthro[4,3-b][1]benzothiophene (11) and 3-methoxyphenanthro[3,4-b][1]benzothiophene (16). Compound 11 was obtained via Suzuki cross-coupling reaction of easily accessible starting materials. However, this synthetic strategy utilizing Suzuki reaction for the preparation of 16 was comparatively less productive than that described previously due to time-consuming synthesis of the starting material(s), and extremely poor yield associated with cyclization of the epoxide 15 to 16. The methoxy derivatives 11 and 16 were converted to the corresponding dihydrodiols 5 and 6 by a sequence involving demethylation, oxidation, and reduction. The trans-stereochemistry of the dihydrodiols was established by (1)H NMR, which indicated a large coupling constant between vicinal carbinol protons. The UV spectra of the dihydrodiols 5 and 6 are presented.


Mercury-induced Ethylene Formation and Abscission in Citrus and Coleus Explants.
Mercury vapor induces ethylene formation and abscission in Citrus and Coleus explants. Both responses are markedly greater in the absence of CO(2). The stimulation of these metabolically complex processes indicates that the action of mercury vapor is not consistent with the more popular conception of mercury toxicity. This was manifested in its complete failure to disturb respiratory gas exchange, and in the total absence of any necrosis. Accordingly, the effect of mercury appears to be highly specific. The overall significance of these findings is discussed with respect to physiological, environmental, and methodological aspects.


Real-world management of advanced prostate cancer: A description of management practices of community-based physicians and prostate cancer specialists.
The Canadian Genitourinary Research Consortium (GURC) conducted a consensus development conference leading to 31 recommendations. Using the GURC consensus development questionnaire, we conducted a survey to measure the corresponding community-based practices on the management of metastatic castration-sensitive prostate cancer (mCSPC), metastatic castration-resistant prostate cancer (mCRPC) and non-metastatic castration-resistant prostate cancer (nmCRPC). An 87-item online questionnaire was sent to 600 community urologists and oncologists involved in the treatment of prostate cancer. Seventy-two community physicians responded to the survey. Of note, 50% community physicians indicated they would treat nmCRPC with agents approved for this indication if advanced imaging showed metastases. Radiation to the prostate for low-volume mCSPC was identified as a treatment practice by 27% of community physicians, and 35% indicated docetaxel as the next line of treatment after use of apalutamide. Use of genetic testing was reported in 36% of community physicians for newly diagnosed metastatic prostate cancer. There are several areas of community-based management of advanced prostate cancer that could represent potential areas for education, practice tools, and future research.


Signals from type 1 sphingosine 1-phosphate receptors enhance adult mouse cardiac myocyte survival during hypoxia.
Sphingosine 1-phosphate (S1P) is a biologically active lysophospholipid that serves as a key regulator of cellular differentiation and survival. Immune stimuli increase S1P synthesis and secretion by mast cells and platelets, implicating this molecule in tissue responses to injury and inflammation. Binding of S1P to G(i) protein-coupled receptors activates phosphatidylinositol 3-kinase and Akt in a variety of tissues. To elucidate the mechanisms by which S1P enhances adult cardiac myocyte survival during hypoxia, we used a mouse cell culture system in which S1P(1) receptors were observed to transduce signals from exogenous S1P, an S1P(1) receptor antibody with agonist properties, and the pharmacological agents FTY720 and SEW2871. S1P(1) receptor mRNA and protein were abundantly expressed by adult mouse cardiac myocytes. S1P-S1P(1) receptor axis enhancement of myocyte survival during hypoxia was abolished by phosphatidylinositol 3-kinase inhibition. S1P(1) receptor function was closely associated with activation of Akt, inactivation of GSK-3beta, and reduction of cytochrome c release from heart mitochondria. These observations highlight the importance of S1P(1) receptors on ventricular myocytes as mediators of inducible resistance against cellular injury during severe hypoxic stress.


Ligand-Controlled Synthesis of Azoles via Ir-Catalyzed Reactions of Sulfoxonium Ylides with 2-Amino Heterocycles.
An iridium-catalyzed method was developed for the synthesis of imidazo-fused pyrrolopyrazines. The presence or absence of a nitrogenated ligand controlled the outcome of the reaction, leading to simple β-keto amine products in the absence of added ligand and the cyclized 7- and 8-substituted-imidazo[1,2-a]pyrrolo[2,3-e]pyrazine products in the presence of ligand. This catalyst control was conserved across a variety of ylide and amine coupling partners. The substrate was shown to act as a ligand for the iridium catalyst in the absence of other ligands via NMR spectroscopy. Kinetic studies indicated that formation of the Ir-carbene was reversible and the slow step of the reaction. These mechanistic investigations suggest that the β-keto amine products form via an intramolecular carbene N-H insertion, and the imidazopyrrolopyrazines form via an intermolecular carbene N-H insertion.


The cost-effectiveness of lung transplantation. A pilot study. University of Washington Medical Center Lung Transplant Study Group.
Lung transplantation is one of the fastest-growing solid organ transplant procedures in the world, yet its cost-effectiveness is unknown. We compared the costs and outcomes of the first 25 patients who received lung transplants at the University of Washington with 24 patients currently on the lung transplant waiting list. Inpatient and outpatient charges were obtained from the hospital billing service and home health agencies. Quality-adjusted life year scores (QALYs) were computed from the following: (1) utility scores obtained through standard gamble interviews, and (2) published survival data from an international lung transplant registry and from studies of patients on lung transplant waiting lists. Transplantation charges averaged $164,989 (median, $152,071). Average monthly charges posttransplant were $11,917 in year 1 and $4,525 thereafter, vs $3,395 for waiting-list patients. Posttransplant utility scores were significantly higher than waiting-list scores (0.80 vs 0.68; p < 0.001). Life expectancy was not greater for lung transplant vs waiting-list patients (5.89 vs 5.32 years; p > 0.05), although quality-adjusted life expectancy did improve significantly. After converting charges to costs, the incremental cost per QALY gained for posttransplant compared with waiting-list patients was $176,817. Lung transplantation is very expensive, although it can substantially improve quality of life. Two-thirds of care costs are incurred after transplantation. The principal barriers to cost-effectiveness at present are the high cost of postrecovery care and marginal gains in life expectancy compared with conservative care.


MARTA: a suite of Java-based tools for assigning taxonomic status to DNA sequences.
We have created a suite of Java-based software to better provide taxonomic assignments to DNA sequences. We anticipate that the program will be useful for protistologists, virologists, mycologists and other microbial ecologists. The program relies on NCBI utilities including the BLAST software and Taxonomy database and is easily manipulated at the command-line to specify a BLAST candidate's query-coverage or percent identity requirements; other options include the ability to set minimal consensus requirements (%) for each of the eight major taxonomic ranks (Domain, Kingdom, Phylum, ...) and whether to consider lower scoring candidates when the top-hit lacks taxonomic classification.


Interferometric technique for measuring the refractive index variation of a liquid with temperature.
A technique for measuring the variation of refractive index of a liquid as a function of temperature or solute concentration using a Mach-Zender interferometer is described. The principal difficulty of obtaining a uniform temperature along the optical path in the sample liquid while simultaneously varying the temperature at a reasonable rate is overcome by heating the liquid in a separate vessel and injecting the heated fluid into the test vessel as a series of jets to encourage turbulent mixing. An equivalent resolution in the refractive index variation of 2x10(-6) was obtained. The above method was used to determine the variation of refractive index in a 0.1% NaCl/H(2)O solution in the temperature range 23 degrees -33 degrees C.


Sensory receptors as a special class of hormonal cells.
Classically, sensory receptors are specialized cells which detect specific environmental disturbances and send out neural signals for the integration, control and/or regulation of effector organs. Recently, a special class of sensory receptors called sensori-hormonal cells which employ hormones as their means of flux of biological information has been proposed. These sensori-hormonal cells are capable of detecting and transducing environmental signals directly into the secretion of hormones within the same cells. Theoretically, all sensory receptors may have examples capable of direct sensori-hormonal transduction. However, only one group of sensori-hormonal cells, the photoendocrine cells, have so far been studied. The photoendocrine cells including the photoreceptors of fish retinas and pinealocytes of bird pineals are capable of detecting light and/or darkness and transducing the electromagnetic radiation energy into a hormonal output. Generally, light suppresses and darkness stimulates the biosynthesis and secretion of melatonin by these photoendocrine cells. Contrary to many hormonal systems which employ principally the feedback mechanism for regulation, the sensori-hormonal cells are predominantly controlled by the feedforward mechanism. However, other factors may serve as additional means of regulation by influencing the system and affecting the transduction processes and/or the synthesis and secretion of the hormone. The ability of sensori-hormonal transduction is suggested to be important for the survival of the organism itself and/or its species and sensori-hormonal cells or their equivalent should appear early in the course of animal evolution. It is further suggested that the sequence of appearance of melatonin functions in the course of evolution would be: hormone--humoral factor--neuromodulator--neurotransmitter.


An epidemiological study of paratuberculosis in dairy cattle in Ontario: study design and prevalence estimates.
An observational study involving 304 dairy herds and three abattoirs was conducted between 1986 and 1989 to investigate the epidemiology of paratuberculosis in dairy cattle in Ontario. The objectives of this paper were to describe the method of data collection for the study, to present descriptive production statistics and to present estimates of the prevalence of paratuberculosis among dairy cattle in Ontario. Mycobacterium paratuberculosis was isolated from the distal ileum and/or the ileocecal lymph node of 5.5% of 400 cull cows. Based on a lipoarabinomannan antigen enzyme-linked immunosorbent assay (LAM-ELISA) on sera, the predicted true prevalence of paratuberculosis among 14,923 dairy cattle from 304 herds, was 6.1%. Nineteen percent of 2,943 fecal cultures were uninterpretable because of overgrowth with contaminating bacteria or fungi. It was concluded that the true prevalence of paratuberculosis among dairy cattle in Ontario was no greater, and may be less than the true prevalence among dairy cattle from various regions of the United States. However, at a practical level, for the purposes of trade policy, the present study suggests that the functional prevalence is very similar in the two countries.


Stachydrine Relieved the Inflammation and Promoted the Autophagy in Diabetes Retinopathy Through Activating the AMPK/SIRT1 Signaling Pathway.
Diabetes retinopathy (DR) is a chronic, progressive, and potentially harmful retinal disease associated with persistent hyperglycemia. Autophagy is a lysosome-dependent degradation pathway that widely exists in eukaryotic cells, which has recently been demonstrated to participate in the DR development. Stachydrine (STA) is a water-soluble alkaloid extracted from Leonurus heterophyllus. This study aimed to explore the effects of STA on the autophagy in DR progression in vivo and in vitro. High glucose-treated human retinal microvascular endothelial cells (HRMECs) and STA-treated rats were used to establish DR model. The reactive oxygen species (ROS) and inflammatory factor levels (TNF-α, IL-1β, and IL-6) were determined using corresponding kits. Additionally, the cell growth was analyzed using CCK-8 and EdU assays. Besides, LC3BII, p62, p-AMPKα, AMPKα, and SIRT1 protein levels were measured using Western blot. The LC3BII and SIRT1 expressions were also determined using immunofluorescence. The results showed that STZ decreased the ROS and inflammatory factor levels in the HG-treated HRMECs. Besides, after STA treatment, the beclin-1, LC3BII, p-AMPKα, and SIRT1 levels were increased, and p62 was decreased in the HG-treated HRMECs and the retinal tissue of STZ-treated rats. In conclusion, this study demonstrated that STA effectively relieved the inflammation and promoted the autophagy in DR progression in vivo and in vitro through activating the AMPK/SIRT1 signaling pathway.


Nutrient Intake and Nutritional Status in Adult Patients with Inherited Metabolic Diseases Treated with Low-Protein Diets: A Review on Urea Cycle Disorders and Branched Chain Organic Acidemias.
Low-protein diets (LPDs) are the main treatment for urea cycle disorders (UCDs) and organic acidemias (OAs). In most cases, LPDs start in childhood and must be continued into adulthood. The improved life expectancy of patients with UCDs and OAs raises the question of their consequences on nutritional status in adult subjects. As this topic has so far received little attention, we conducted a review of scientific studies that investigated the nutrient intake and nutritional status in adult patients with UCDs and branched chain organic acidemias (BCOAs) on LPD. The literature search was conducted in PubMed/MEDLINE, Scopus, EMBASE and Google Scholar from 1 January 2000 to 31 May 2020, focusing on nutrient intake and nutritional status in UCD and OA adult patients. Despite protein restriction is recommended as the main treatment for UCDs and OAs, in these patients, protein intake ranges widely, with many patients who do not reach safety levels. When evaluated, micronutrient intake resulted below recommended values in some patients. Lean body mass resulted in most cases lower than normal range while fat body mass (FM) was often found normal or higher than the controls or reference values. Protein intake correlated inversely with FM both in adult and pediatric UCD patients. The clinical management of adult patients with UCDs and BCOAs should include an accurate assessment of the nutritional status and body composition. However, as little data is still available on this topic, further studies are needed to better clarify the effects of LPDs on nutritional status in adult UCD and BCOA patients.


New taxane diterpenoids from the roots of Taiwanese Taxus mairei.
Five new taxane diterpenoids, taxumairols G (1), H (2), I (3), J (4), and L (5) were isolated from extracts of the roots of Taiwanese Taxus mairei (LEMEE & LEVL.) S. Y. Hu. Compounds 1-4 belong to the new 11(15-->1)-abeo-taxene system, having a tetrahydrofuran ring along carbons C-2, C-3, C-4 and C-20. Compounds 3 and 4 contain an isopropenyl group at C-1 while compounds 1 and 2 are attached with a benzoxyl group at C-15. The structures of compounds 1-5 were determined on the basis of two-dimensional (2D)-NMR techniques including correlation spectroscopy (COSY), heteronuclear single quantum coherence (HSQC), heteronuclear multiple bond correlation (HMBC), and nuclear Overhauser effect spectroscopy (NOESY) experiments.


Water quality trend analysis in a citywide water distribution system.
Rapid urbanization poses challenges to meet the increased water supply demands. Apart from the quantity, the distributed water quality often fails to meet the permissible level. This study aimed to conduct a citywide spatio-temporal variation of water quality parameters. Water sampling points were selected by applying the Analytical Hierarchical Process (AHP) technique using ArcGIS considering pipe leakage, source water quality, pipe age, and pipe materials. The Chattogram city comprises 397 km of pipes; pipe material distribution shows 71.28% PVC, 20.94% asbestos, 5.16% mild steel, 2.17% ductile, and 0.45% cast iron. The citywide pipe network was established in 1963; 20.87% of pipes aged over 30 years, 15.07% 20-30 years, 26.38% 10-20 years, and 37.68% pipelines are relatively new, i.e., within 0-10 years. Eight water quality parameters, i.e., pH, temperature, turbidity, biochemical oxygen demand after five days (BOD5), total coliform, fecal coliform, chloride, and residual chlorine, were collected from the secondary source cross-checked by field survey. Computation of the Water Quality Index (WQI) was interpolated using Inverse Distance Weighted (IDW) method to generate a WQI map. Thus, this study could be a basis to improve the treatment system and proper distribution network maintenance.