The isolation and characterization of nuclear ghosts from cultured HeLa cells.
Macromolecular complexes, which appear as ghosts when viewed by phase contrast microscopy, have been isolated from the nuclei of HeLa cells grown in culture. The preparation of these ghosts involves a detergent wash which removes the unit membranes of the nuclear envelop structure but leaves intact both the nuclear pores and the dense structure conferring nuclear margins (possibly the dense lamella). Detergent-washed nuclei are subsequently treated with 0.5 M MgCl2 and fractionated on continuous sucrose gradients containing 0.5 M MgCl2. The ghosts are recovered as a sharp band at an apparent sucrose density of 47-52% and consist of 72% protein, 10% phospholipid, 14% DNA, And 4% RNA. The release of the majority of intranuclear components is indicated by the large loss of nuclear DNA (95%), RNA (71%), and protein (87%) contrasted to the small loss of phospholipid (27%) druing the conversion of detergent washed nuclei to isolated ghosts. Sodium dodecyl sulfate-polyacrylamide gel patterns of the ghost proteins consist of two major bands with approximate molecular weights of 20,000 and 35,000. The isolation of ghosts with a similar density and protein composition from nondetergent-washed nuclei indicates that the ghost is not an artifact induced by the detergent treatment. The absence of cytoplasmic contamination in the preparations of detergent washed nuclei and nuclear ghosts was demonstrated by chemical, enzymatic, and electron microscope studies. We suggest that the isolated ghosts represent a structural macromolecular complex which underlies and is probably attached to the inner nuclear membrane of intact nuclei. The possible additional presence of intranuclear network proteins has not been excluded.


Manic thinking: independent effects of thought speed and thought content on mood.
This experiment found that the speed of thought affects mood. Thought speed was manipulated via participants' paced reading of statements designed to induce either an elated or a depressed mood. Participants not only experienced more positive mood in response to elation than in response to depression statements, but also experienced an independent increase in positive mood when they had been thinking fast rather than slow--for both elation and depression statements. This effect of thought speed extended beyond mood to other experiences often associated with mania (i.e., feelings of power, feelings of creativity, a heightened sense of energy, and inflated self-esteem or grandiosity).


Differentiation- and apoptosis-inducing activities by pentacyclic triterpenes on a mouse melanoma cell line.
In a study to investigate the relationship between the chemical structure and the differentiation-inducing activity of pentacyclic triterpenes, several lupane, oleanane, and ursane triterpenes were prepared and their effects on B16 2F2 melanoma cell differentiation and growth were examined. Eleven lupane triterpenes used in this study acted on the melanoma cells as a melanogen, but no induction of melanogenesis of B16 2F2 cells by oleanane and ursane was detected. The differences at C-17 of the lupane series and acetylation of the OH group at C-3 did not markedly influence their activities. However, the ED(50) value for up-regulation of melanin biosynthesis was markedly decreased by the oxidation of the OH group at C-3 of lupeol (1). Betulinic acid (11), its methyl ester (12), lup-28-al-20(29)-ene-3beta-ol (9), and lup-28-al-20(29)-en-3-one (10) inhibited B16 2F2 cell proliferation by induction of apoptosis. These findings suggested that the carbonyl group at C-17 might be essential for the apoptotic effects of these compounds on B16 2F2 cells.


[Analysis of 1268 patients with chronic renal failure in childhood: a report from 91 hospitals in China from 1990 to 2002].
Chronic renal failure (CRF) of childhood is not rare. The prognosis of CRF is very poor because of severe systemic complications. A nation-wide survey was conducted and data of hospitalized children (younger than 14 years old) with CRF during the period of 1990 to 2002 were analyzed. The aim was to investigate the epidemiology, natural history, clinical-pathological characteristics, treatment and outcome of the hospitalized children with CRF. Questionnaires concerning children with CRF were designed and distributed to the doctors of 91 hospitals in China. The criterion of CRF was creatinine clearance (CCr) < 50 ml/(min x 1.73 m(2)). The data were collected and analyzed. From January 1, 1990 to December 31, 2002, 1658 hospitalized children were diagnosed as CRF. The average annual cases of childhood CRF accounted for 1.31% (ranged from 0.72% to 1.75%) of the hospitalized cases with urologic-kidney diseases. In a comparison between 1990 - 1996 and 1997 - 2002, there were significant increases in the average annual number of cases of childhood CRF and the case ratio of CRF to urologic-kidney diseases (82 +/- 27 vs. 181 +/- 45 and 0.98 +/- 0.21 vs. 1.56 +/- 0.17, respectively, P < 0.001). Complete records were available for 1268 patients. The male to female ratio was 1.49:1. The mean age at the disease onset was 8.18 years. The mean duration of pre-diagnosis of CRF was 2.53 years. In this study, the main primary renal diseases causing CRF were chronic glomerulonephritis and nephrotic syndrome (52.7%). One-fourth of all cases had congenital and hereditary renal diseases, and the majority were renal hypoplasia and dysplasia. The main manifestations of CRF were anemia, gastrointestinal disorders, edema, hypertension and growth retardation. The mean serum creatinine and BUN were 594.7 micromol/L and 39.1 mmol/L, respectively. The cases with renal function >or= grade IV accounted for 80% of all cases. By renal ultrasound scanning, one-third of CRF children were found to have renal atrophy and a part of patients had cystic disorder. Most of the cases received conservative treatment. Dialysis therapy (including 66.5% of hemodialysis and 33.5% of peritoneal) was given to 15.8% of the patients. Twenty-nine cases received renal transplantation. The rate of graft survival was 93.1%. Follow-up was carried out for to 230 cases, the mean duration of follow-up was 2.36 years. One hundred and sixty-seven patients died during hospitalization over the 13-year review period. The main causes of death were cardiac failure and infections in addition to uremia. The incidence of CRF in children showed an increasing trend year after year. The main age of onset of the disease was school-age. The main primary renal diseases causing CRF were acquired renal diseases. Conservative treatment was the main therapy of CRF, but renal replacement therapy was initiated in some of the cases. The obvious difference between follow-up cases and lost cases warrants the need to establish a management system of childhood CRF.


Prevalence of bone fractures among children and adolescents with attention-deficit/hyperactivity disorder: a systematic review and meta-analysis.
Attention-deficit/hyperactivity disorder (ADHD) is a significant neurodevelopment disorder among children and adolescents, with 5 % prevalence. Bone fractures account for 25 % of accidents and injuries among all children and adolescents. Considering the characteristics of inattention, hyperactivity, and impulsivity in children with ADHD, it is critical to examine bone fractures among these children. The objective of our meta-analysis was to determine the prevalence of bone fractures among children and adolescents with ADHD. We completed a systematic review and meta-analysis using an electronic search of the following databases: CINAHL, EMBASE, PsycINFO, PubMed, and Scopus. The search terms used were: "attention deficit hyperactivity disorder OR attention deficit disorder" and "bone fracture*." We included studies examining patients 18 years or younger who were diagnosed with ADHD and tracked (prospectively or retrospectively) for five or more years. Effect size (es), using a random effects model, was calculated. We registered the review protocol with PROSPERO (CRD42019119527). From 445 records retrieved, 31 full text articles were reviewed and 5 articles met inclusion criteria for meta-analysis. The summary es revealed the prevalence of bone fractures among children and adolescents with ADHD to be 4.83 % (95 % CI: 3.07-6.58 %). The location of bone fractures, using a subset of data, showed a distribution of 69.62 %, 22.85 %, and 7.53 % in the upper limbs, lower limbs, and other anatomical regions, respectively. Another subset of studies revealed a 2.55-fold increase in the prevalence of fractures among the children with ADHD compared to their counterparts. Awareness of these findings is critical to physicians, parents, and policy makers to create safe environments and provide supports in order to optimize the health and safety of children and adolescents with ADHD.


Hereditary hyperferritinaemia-cataract syndrome: a challenging diagnosis for the hepatogastroenterologist.
Hereditary hyperferritinaemia-cataract syndrome (HHCS) is a relatively rare disorder with an autosomal dominant trait. It can be caused by various mutations within the iron responsive element (IRE) of the L-ferritin gene. These mutations result in an increased translation of L-ferritin mRNA and consequently the accumulation of L-ferritin in different fluids and tissues. HHCS patients present with an isolated hyperferritinaemia in the absence of any sign of iron overload. Early onset bilateral cataract, probably due to accumulation of ferritin crystals in the lens, is the only presenting clinical manifestation. Internists, especially gastrohepatologists, should be aware of this syndrome and differentiate it from haemochromatosis which is much more frequent, in order to avoid unnecessary imaging procedures, liver biopsies and an eventual venesection therapy, which will only lead to microcytic anaemia. In the present paper we report the first cases with HHCS diagnosed in Belgium. At diagnosis, the seven known affected members of three different families had ferritin levels between 603 and 3432 microg/l (normal < 150 microg/l), and this in combination with normal iron and transferrin values. All of them were known with early-onset bilateral cataract and our postulated diagnosis of HHCS was confirmed after genetic sequencing of the L-ferritin gene, which showed a C39U point mutation in the first family, and an A40G point mutation in the IRE loop segment in the two other families. The other investigated members of the three families had normal ferritin values, no history of early-onset cataract and genetic analyses could not reveal a mutation in the IRE of their L-ferritin gene. In current clinical practice, gastroenterologists should remember that elevated ferritin levels in the absence of documented iron overload is not haemochromatosis.


Longitudinal associations between lead dose and renal function in lead workers.
Existing research on the lead dose range associated with nephrotoxicity in the occupational setting is inconsistent and primarily cross-sectional in design. To determine if lead dose predicts change in renal function in a large population of current and former lead workers. Three evaluations were performed between 1997 and 2001. Lead dose was assessed with blood and tibia lead. Renal outcomes included blood urea nitrogen, serum creatinine, and calculated creatinine clearance. We used generalized estimating equations to model change in renal function between each evaluation in relation to tibia lead at the beginning of each follow-up period and concurrent change in blood lead, while adjusting for baseline lead dose and other covariates. At baseline, mean (SD) age and duration of occupational lead exposure were 42.0 (9.3) and 8.8 (6.3) years, respectively, in 537 current and former lead workers followed over a mean of 2.1 years. Mean (SD) blood and tibia lead were 31.3 (14.4) microg/dl and 35.0 (37.8) microg/g bone mineral, respectively. Women (25.9%) were older and more likely to be former lead workers than men. In males, serum creatinine decreased and calculated creatinine clearance increased over the course of the study. Mean blood lead was not significantly different between evaluations 1 and 3 in either sex, however, tibia lead decreased in women. Blood and tibia lead were significantly associated with change in renal function. In males, serum creatinine decreases and calculated creatinine clearance increases were greatest in participants whose blood lead declined. Both acute and chronic occupational lead dose measures were associated with change in renal function measures prospectively.


[Laboratory and clinical studies of rokitamycin in pediatric fields].
We have carried out laboratory and clinical studies on rokitamycin (RKM, TMS-19-Q). The results are summarized as follows. Serum and urinary concentrations of RKM were determined in 6 children with ages between 6 and 12 years given single oral doses of 5, 10 and 15 mg/kg. Mean serum concentrations peaked at 30 minutes after administration of 5, 10 and 15 mg/kg, and respective peak values were 0.30 microgram/ml, 0.79 microgram/ml and 1.32 micrograms/ml. Biological half-lives for 5, 10 and 15 mg/kg were 2.0 hours, 1.65 hours and 1.36 hours. The 6-hour urinary recovery ranged from 1.11% to 2.58% after administration of 5 mg/kg, and the mean 6-hour urinary recoveries were 1.35% after administration of 10 mg/kg and 2.28% after administration of 15 mg/kg. Therapeutic responses were recorded as excellent or good in 22 (73.3%) of the children, comprising 6 with tonsillitis, 2 with pharyngitis, 4 with bronchitis, 1 with bronchopneumonia, 1 with Mycoplasma pneumonia, 2 with whooping cough, 5 with streptococcal infections, 5 with Campylobacter enteritis, 3 with impetigo and 1 with SSSS. The microbiological effectiveness of RKM on identified pathogens comprising 4 strains of Staphylococcus aureus, 1 strain of Streptococcus pneumoniae, 6 strains of Streptococcus pyogenes, 4 strains of Haemophilus influenzae and 5 strains of Campylobacter spp. was not so satisfactory as evidenced by a eradication rate of 50.0%. No significant side effect due to the drug was observed in any cases. In conclusion, RKM was found to be efficacious and safe for the treatment of bacterial infections in children.


The relationship of non-disclosure in therapy to shame and depression.
This study aimed to explore the relationship between shame-proneness, depression, and non-disclosure in therapy in 85 men and women who had received treatment for depression. Data were collected by means of a questionnaire, which assessed depressive symptoms, shame-proneness, non-disclosure in therapy, and reasons for non-disclosure. In total, 54% of the respondents reported concealing depression-related symptoms and behaviours or other distressing experiences from their therapist. Shame was the most frequently reported reason for non-disclosure overall, but was a more frequent reason for non-disclosure of symptoms than experiences. Similarly, shame-proneness was significantly related to non-disclosure of symptoms but not to non-disclosure of experiences. For participants no longer in therapy, non-disclosure of symptoms made a significant independent contribution to current level of depressive symptoms after controlling for demographic variables, worst depression, and shame-proneness. The hypothetical model put forward in this study predicting a significant relationship between shame, non-disclosure in therapy, and current depressive symptomatology was supported. The findings suggest that encouraging and facilitating the disclosure of shameful symptoms and related behaviours has positive implications for the effectiveness of treatment.


Temperature-dependent atomic B factor: an ab initio calculation.
The Debye-Waller factor explains the temperature dependence of the intensities of X-ray or neutron diffraction peaks. It is defined in terms of the B matrix whose elements Bαβ are mean-square atomic displacements in different directions. These quantities, introduced in several contexts, account for the effects of temperature and quantum fluctuations on the lattice dynamics. This paper presents an implementation of the B factor (8π2Bαβ) in the thermo_pw software, a driver of Quantum ESPRESSO routines that provides several thermodynamic properties of materials. The B factor can be calculated from the ab initio phonon frequencies and displacements or can be estimated, although less accurately, from the elastic constants, using the Debye model. The B factors are computed for a few elemental crystals: silicon, ruthenium, magnesium and cadmium; the harmonic approximation at fixed geometry is compared with the quasi-harmonic approximation where the B factors are calculated accounting for thermal expansion. The results are compared with the available experimental data.


Characteristics of palytoxin-induced depolarization in squid axons.
The effects of palytoxin on squid axon membranes have been studied by means of internal perfusion and voltage clamp techniques. When applied externally at a concentration ranging from 1 X 10(-8) to 1 X 10(-6) M, palytoxin caused a large depolarization of the membrane that was reversed slowly after washing with toxin-free solution. The toxin-induced depolarization disappeared quickly upon decreasing the external sodium concentration from 445 to 1 mM and the membrane was hyperpolarized beyond the original level. Palytoxin did not cause depolarization if both external and internal solutions were devoid of sodium. The toxin-induced depolarization was only reversed partially by external application of 1 X 10(-6) M tetrodotoxin. Palytoxin had no effect on the resting potential when perfused internally. These results indicate that palytoxin acts from outside of the nerve membrane to increase sodium permeability, thereby causing a depolarization. The palytoxin-poisoned membrane was also permeable to other cations with a permeability ratio of Na/Li/Cs/NH4 = 1:0.62:0.75:1.45. Under voltage clamp conditions, palytoxin shifted the voltage dependence of peak sodium current and steady-state potassium current in the direction of hyperpolarization and reduced markedly the maximum amplitude of peak sodium current. However, the kinetics of sodium current underwent little or no change except a shift of voltage dependence toward hyperpolarization. Leakage current increased markedly after application of palytoxin. In view of these observations and data from the literature, it was suggested that palytoxin creates a new channel in the membrane, thereby causing an increase in cation permeability, depolarization, and other effects such as muscle contraction.


Content Analysis of Nicotine Poisoning (Nic Sick) Videos on TikTok: Retrospective Observational Infodemiology Study.
TikTok is a microvideo social media platform currently experiencing rapid growth and with 60% of its monthly users between the ages of 16 and 24 years. Increased exposure to e-cigarette content on social media may influence patterns of use, including the risk of overconsumption and possible nicotine poisoning, when users engage in trending challenges online. However, there is limited research assessing the characteristics of nicotine poisoning-related content posted on social media. We aimed to assess the characteristics of content on TikTok that is associated with a popular nicotine poisoning-related hashtag. We collected TikTok posts associated with the hashtag #nicsick, using a Python programming package (Selenium) and used an inductive coding approach to analyze video content and characteristics of interest. Videos were manually annotated to generate a codebook of the nicotine sickness-related themes. Statistical analysis was used to compare user engagement characteristics and video length in content with and without active nicotine sickness TikTok topics. A total of 132 TikTok videos associated with the hashtag #nicsick were manually coded, with 52.3% (69/132) identified as discussing firsthand and secondhand reports of suspected nicotine poisoning symptoms and experiences. More than one-third of nicotine poisoning-related content (26/69, 37.68%) portrayed active vaping by users, which included content with vaping behavior such as vaping tricks and overconsumption, and 43% (30/69) of recorded users self-reported experiencing nicotine sickness, poisoning, or adverse events such as vomiting following nicotine consumption. The average follower count of users posting content related to nicotine sickness was significantly higher than that for users posting content unrelated to nicotine sickness (W=2350.5, P=.03). TikTok users openly discuss experiences, both firsthand and secondhand, with nicotine adverse events via the #nicsick hashtag including reports of overconsumption resulting in sickness. These study results suggest that there is a need to assess the utility of digital surveillance on emerging social media platforms for vaping adverse events, particularly on sites popular among youth and young adults. As vaping product use-patterns continue to evolve, digital adverse event detection likely represents an important tool to supplement traditional methods of public health surveillance (such as poison control center prevalence numbers).


Cherubism with idiopathic gingival enlargement: A rare case report.
Cherubism is a congenital childhood disease of autosomal dominant inheritance. It is a benign, familial giant cell lesion characterized by gradually progressive painless swelling of the jaws. Idiopathic gingival enlargement is a rare condition and may be associated with some uncommon syndromes. This case report describes an 11-year-old patient with unusual clinical form of gingival enlargement, cherubic facial appearance. Clinical examination revealed the presence of the hyperplastic gingiva, which completely covered all teeth. The bilateral swelling of mandible and the appearance of the sclera beneath the iris suggested cherubism. The diagnosis was confirmed by histopathological examination, which revealed multinucleated giant cells. Computed tomography scan showed multiple osteolytic zones in the mandible. A full mouth gingivectomy was performed in four stages. Lesion healed successfully, and no recurrence observed after 1-year follow-up. There was a marked improvement in esthetics and function through the surgical excision of the overgrowth.


Myoepithelial carcinoma of the lung: a review.
Primary myoepithelial carcinoma of the lung is a rare neoplasm with only 8 cases reported in the English literature to date. Myoepithelial carcinomas of the lung are thought to arise from submucosal bronchial glands and have morphologic features similar to their salivary gland counterparts. The pathologic features and immunohistochemical profile of this tumor have not yet been summarized in the literature. Our objective is to review the clinicopathologic features and immunohistochemistry of these tumors.


Crosstalk between casein kinase II and Ste20-related kinase Nak1.
Although the sterile 20 (Ste20) serine/threonine protein kinase was originally identified as a component of the S. cerevisiae mating pathway, it has homologs in higher eukaryotes and is part of a larger family of Ste20-like kinases. Ste20-like kinases are involved in multiple cellular processes, such as cell growth, morphogenesis, apoptosis and immune response. Carrying out such a diverse array of biological functions requires numerous regulatory inputs and outputs in the form of protein-protein interactions and post-translational modifications. Hence, a thorough knowledge of Ste20-like kinase binding partners and phosphorylation sites will be essential for understanding the various roles of these kinases. Our recent study revealed that Schizosaccharomyces pombe Nak1 (a conserved member of the GC-kinase sub-family of Ste20-like kinases) is in a complex with the leucine-rich repeat-containing protein Sog2. Here, we show a novel and unexpected interaction between the Nak1-Sog2 kinase complex and Casein kinase 2 (Cka1, Ckb1 and Ckb2) using tandem-affinity purification followed by mass spectrometric analysis. In addition, we identify unique phosphosites on Nak1, Sog2 and the catalytic subunit of casein kinase 2, Cka1. Given the conserved nature of these kinases, we expect this work will shed light on the functions of these proteins both in yeast and higher eukaryotes.


The cognitive bases of human tool use.
This article has two goals. The first is to assess, in the face of accruing reports on the ingenuity of great ape tool use, whether and in what sense human tool use still evidences unique, higher cognitive ability. To that effect, I offer a systematic comparison between humans and nonhuman primates with respect to nine cognitive capacities deemed crucial to tool use: enhanced hand-eye coordination, body schema plasticity, causal reasoning, function representation, executive control, social learning, teaching, social intelligence, and language. Since striking differences between humans and great apes stand firm in eight out of nine of these domains, I conclude that human tool use still marks a major cognitive discontinuity between us and our closest relatives. As a second goal of the paper, I address the evolution of human technologies. In particular, I show how the cognitive traits reviewed help to explain why technological accumulation evolved so markedly in humans, and so modestly in apes.


The global structures of a wild-type and poorly functional plant luteoviral mRNA pseudoknot are essentially identical.
The helical junction region of a -1 frameshift stimulating hairpin-type mRNA pseudoknot from sugarcane yellow leaf virus (ScYLV) is characterized by a novel C27.(G7-C14) loop 2-stem 1 minor groove base triple, which is stacked on a C8+.(G12-C28) loop 1-stem 2 major groove base triple. Substitution of C27 with adenosine reduces frameshifting efficiency to a level just twofold above the slip-site alone. Here, we show that the global structure of the C27A ScYLV RNA is nearly indistinguishable from the wild-type counterpart, despite the fact that the helical junction region is altered and incorporates the anticipated isostructural A27.(G7-C14) minor groove base triple. This interaction mediates a 2.3-A displacement of C8+ driven by an A27 N6-C8+ O2 hydrogen bond as part of an A(n-1).C+.G-Cn base quadruple. The helical junction regions of the C27A ScYLV and the beet western yellows virus (BWYV) pseudoknots are essentially superimposable, the latter of which contains an analogous A25.(G7-C14) minor groove base triple. These results reveal that the global ground-state structure is not strongly correlated with frameshift stimulation and point to a reduced thermodynamic stability and/or enhanced kinetic lability that derives from an altered helical junction architecture in the C27A ScYLV RNA as a significant determinant for setting frameshifting efficiencies in plant luteoviral mRNA pseudoknots.


[A report of an atypical case of Degos' disease with multiple perforations of the stomach and small intestine].
A 47-year old male complaining of severe abdominal pain associated with distention was admitted to our department on August 5, 1986. His first admission to our hospital was 18 days previously for leg pain and fever. He underwent emergency operation with a preoperative diagnosis of acute peritonitis due to perforation of gastric ulcer. Operative findings showed one perforation of the stomach and two of the ileum. Distal gastrectomy, enterectomy and peritoneal drainage were carried out. Resected specimen revealed six ulcers, two of them in the stomach, four in the ileum. Microscopic examination disclosed intimal proliferations of small arteries in the mucosal layer. The vessels near the ulcers were most severely involved but the same changes were also found in the subserous layer and mesentery. It was suggested that the multiple ulcers were secondary to vascular lesions identical to the gastrointestinal lesion of Degos' disease. Postoperative examinations revealed one ulcer in the jejunum and another in the descending colon. Ten months after operation he lives with no complaint on the gastrointestinal tract. Only 80 cases of Degos' disease have been reported in the western countries and 10 cases in Japan. In those atypical cases of Degos' disease without papulosis were only Manuel's and ours.


Crystallization and preliminary diffraction studies of Escherichia coli lysyl-tRNA synthetase (LysU).
Crystals of Escherichia coli lysyl-tRNA synthetase (lysU gene product) have been obtained by vapour diffusion techniques. Three different crystal forms could be grown under similar conditions. The crystals that have been chosen for the structure determination belong to space group C222(1) with cell dimensions a = 144.3 A, b = 257.8 A, c = 182.1 A and contain three monomers in the asymmetric unit. They diffract to at least 2.1 A resolution, but are very sensitive to radiation damage.


[Emergency endoscopic sclerosis in active hemorrhage caused by esophageal varices: analysis of 31 cases].
We have reviewed our experience in urgent endoscopic sclerosis of bleeding esophageal veins in most patients (67.7%) secondary to alcoholic liver cirrhosis. Through the flexible gastroscope, 1% of polydocanol was injected intra and periveinaly for sclerosis. Initial and primary hemostasis was achieved in 90.3% and 87% of the cases respectively. Hemorrhage recurred in 14.2% of the patients. Hospital mortality was 38.7% (11 patients classified in Childs group C and 1 patient in group B), although only 19.3% of the patients died because of esophageal vein bleeding. These results suggest that in a satisfactory percentage of cases urgent sclerosis of esophageal veins controls active bleeding, and the hospital mortality depends mainly on the severeness of liver failure in these patients.


Coupling interaction between thromboxane A2 receptor and alpha-13 subunit of guanine nucleotide-binding protein.
G protein-coupled receptors (GPCRs) form a large superfamily of membrane proteins that play an essential role in modulating many vital physiological events, such as cell communication, neurotransmission, sensory perception, and chemotaxis. Understanding of the 3D (dimensional) structures of these receptors and their binding interactions with G proteins will help in the design of drugs for the treatment of GPCR-related diseases. By means of the approach of structural bioinformatics, the 3D structures of human alpha-13 subunit of guanine nucleotide-binding protein (G alpha 13) and human thromboxane A2 (TXA2) receptor were developed. The former plays an important role in the control of cell growth that may serve as a prototypical G protein; the latter is a target for nitric oxide-mediated desensitization that may serve as a prototypical GPCR. On the basis of the 3D models, their coupling interactions were investigated via docking studies. It has been found that the two proteins are coupled with each other mainly through the interaction between the minigene of G alpha 13 and the 3rd intracellular loop of the TXA2 receptor, consistent with the existing deduction in the literatures. However, it has also been observed via a close view that some residues of the TXA2 receptor that are sequentially far away but spatially quite close to the loop region are also involved in forming hydrogen bonds with the minigene of G alpha 13. These findings may provide useful information for conducting mutagenesis and reveal the molecular mechanism how the human TXA2 receptor interact with G alpha 13 to activate intracellular signaling. The findings may also provide useful insights for stimulating new therapeutic approaches by manipulating the interaction of the receptor with the relevant G proteins.


Intravenous immunoglobulin therapy in children with severe atopic dermatitis.
Children with severe atopic dermatitis (AD) can benefit from intravenous immunoglobulin (IVIG) therapy. This study aimed to identify the efficacy and safety of IVIG therapy in children with severe AD. Twenty pediatric AD patients were enrolled in this study. Patients with an Investigator's Global Assessment score of 0 or 1 or a reduction of 2 points after treatment were defined as high-responders (HRs), otherwise, they were defined as low-responders (LRs). Twelve patients (60%) achieved an excellent treatment response after 2 months, while eight (40%) had a low response. The Scoring Atopic Dermatitis index had improved significantly at 2 months post-treatment compared with baseline (p < 0.001). Baseline total serum IgE levels and eosinophil counts were elevated in all subjects and decreased significantly at 2 months post-treatment (p = 0.004 and 0.021, respectively). Baseline IgE levels were significantly higher in the HR group compared with the LR group (p = 0.020). The treatment was well tolerated. Fever was the most common adverse event and occurred in five patients (25%). In conclusion, IVIG could be a safe and effective therapy for children with severe AD and may be more effective in patients with higher IgE levels. Further studies are needed to investigate the different therapeutic responses in patients with different AD phenotypes.


Analysis of dentoalveolar structures with novel corticotomy-facilitated mandibular expansion: A 3-dimensional finite element study.
Surgically assisted mandibular arch expansion is an effective treatment modality for alleviating constriction and crowding. However, only mandibular symphyseal osteotomy is recommended for mandibular arch expansion. No relevant studies have compared the biomechanical responses of different corticotomy designs on mandibular expansion. Therefore, the aim of this study was to evaluate the effect of different corticotomy approaches and modes of loading on the expansion of adult mandibles using biomechanics. Nine finite element models including 2 novel corticotomy designs were simulated. Stress, strain, and displacement of crown, root, and bone were calculated and compared under different corticotomy approaches and loading conditions. The biomechanical response seen in the finite element models in terms of displacement on the x-axis was consistent from anterior to posterior teeth with parasymphyseal step corticotomy and tooth-borne force application. In addition, the amount of displacement predicted by parasymphyseal step corticotomy in the tooth-borne mode was greater compared with other models. These results suggest that parasymphyseal step corticotomy with tooth-borne force application is a viable treatment option for true bony expansion in an adult mandible.


Ethics constructed through the process of nurse training: conceptions, spaces and strategies.
to discuss the professors' conceptions about the ethical dimension of nurse training based on the relationships which this establishes with the competencies with the professional profile; and to identify the spaces and strategies for the teaching of ethics in this process. A qualitative study delineated as a case study. The data was collected based on focus groups with professors from six undergraduate nursing courses in the state of Santa Catarina, Brazil, totaling 50 subjects. Based on the professors' discourse, the conceptions and mutual relations between professional competencies, the formative process and ethics were analyzed. The results were organized and the discussion explored through the thematic categories: The ethics constructed in the process of training nurses - the professors' conceptions, and spaces and strategies for the teaching of ethics in nurse training. The issue of ethics was shown to be transversal in the formative process. The study evidenced the challenge of creating spaces and strategies for teaching and fosters discussion about the new demands for changes placed upon the nursing schools, about the suitability of the care setting, and about the exercising of critical and problem-based education.


Wartime scars or reservoirs of biodiversity? The value of bomb crater ponds in aquatic conservation.
Considering the ongoing loss of aquatic habitats, anthropogenic ponds are gaining importance as substitute habitats. It is therefore important to assess their functioning in comparison to their natural precursors. Here we assess the biodiversity value of sodic bomb crater ponds by comparing their gamma diversity to that of natural reference habitats, astatic soda pans, and assess their importance on the landscape level by studying alpha and beta diversity. We studied aquatic organisms ranging from algae to vertebrates in a dense cluster of 54 sodic bomb crater ponds in Central Europe. Despite the overall small area of the pond cluster, gamma diversity was comparable to that found in surveys of natural habitats that encompassed much wider spatial and temporal scales. We also found a considerable number of species shared with reference habitats, indicating that these anthropogenic habitats function as important refuge sites for several species that are associated with the endangered soda pans. Moreover, we found a number of regionally or worldwide rare species. Among the components of beta diversity, species replacement dominated community assembly. Individual ponds contributed similarly to beta diversity in terms of replacement, being equally important for maintaining high gamma diversity and emphasising the role of the pond network rather than individual ponds. This pattern was seen in all studied groups. Bomb crater ponds therefore acted as important contributors to aquatic biodiversity. Considering the tremendous losses of ponds throughout Europe, anthropogenic ponds should be taken into consideration in nature conservation, especially when occurring in pond networks.


Primary hepatic lymphoma with spindle cell components: a case report.
Diffuse large B-cell lymphoma (DLBCL) with spindle cell components is extremely rare and often misdiagnosed as carcinoma or sarcoma. Here, we present a case of primary DLBCL with spindle cell components arising in the liver, for which a preoperative diagnosis by needle biopsies was unsuccessful. The patient was a 70-year-old man with a continuous cough. Thoracic computed tomography incidentally detected a mass of 5 cm in diameter in his liver. The initial and second needle biopsies from the liver mass were pathologically diagnosed as suspicious for sarcomatoid hepatocellular carcinoma. He underwent an extended left hepatectomy. Histological examination revealed a diffuse or epithelioid arrangement of round and polygonal cells, mixed with the fascicles of spindle-shaped cells. Immunohistochemically, all the morphological types of tumor cells showed positive reactions for a lymphocytic marker (CD45RB) and B-cell markers (CD20 and CD79a). Double-immunostaining revealed that the spindle-shaped tumor cells expressed CD20, but never expressed alpha-smooth muscle actin. Malignant lymphoma with a spindle cell morphology is quite uncommon, and this variant can be a diagnostic pitfall, especially in tiny biopsy specimens. We emphasize that pathologists should be reminded of lymphoma as a differential diagnosis of spindle cell tumors.


High rates of superoxide production in skeletal-muscle mitochondria respiring on both complex I- and complex II-linked substrates.
Despite the considerable interest in superoxide as a potential cause of pathology, the mechanisms of its deleterious production by mitochondria remain poorly understood. Previous studies in purified mitochondria have found that the highest rates of superoxide production are observed with succinate-driven reverse-electron transfer through complex I, although the physiological importance of this pathway is disputed because it necessitates high concentrations of succinate and is thought not to occur when NAD is in the reduced state. However, very few studies have examined the rates of superoxide production with mitochondria respiring on both NADH-linked (e.g. glutamate) and complex II-linked substrates. In the present study, we find that the rates of superoxide production (measured indirectly as H2O2) with glutamate+succinate (approximately 1100 pmol of H2O2 x min(-1) x mg(-1)) were unexpectedly much higher than with succinate (approximately 400 pmol of H2O2 x min(-1) x mg(-1)) or glutamate (approximately 80 pmol of H2O2 x min(-1) x mg(-1)) alone. Superoxide production with glutamate+succinate remained high even at low substrate concentrations (<1 mM), was decreased by rotenone and was completely eliminated by FCCP (carbonyl cyanide p-trifluoromethoxyphenylhydrazone), indicating that it must in large part originate from reverse-electron transfer through complex I. Similar results were obtained when glutamate was replaced with pyruvate, alpha-ketoglutarate or palmitoyl carnitine. In contrast, superoxide production was consistently lowered by the addition of malate (malate+succinate approximately 30 pmol of H2O2 x min(-1) x mg(-1)). We propose that the inhibitory action of malate on superoxide production can be explained by oxaloacetate inhibition of complex II. In summary, the present results indicate that reverse-electron transfer-mediated superoxide production can occur under physiologically realistic substrate conditions and suggest that oxaloacetate inhibition of complex II may be an adaptive mechanism to minimize this.


Measuring and Assessing Kidney Function.
Assessment of kidney function is important for the detection and management of chronic kidney disease. The glomerular filtration rate (GFR) and level of albuminuria are two frequently used indices of kidney function assessment. Administration of an exogenous filtration marker to measure GFR and collection of urine for 24 hours to measure albumin excretion generally are considered the gold standard for GFR and albuminuria, respectively, but they are time consuming and onerous for the patient. Thus, in routine clinical practice, other methods are used more frequently to assess GFR and albuminuria. In this review, we discuss the role of GFR and albuminuria in staging of chronic kidney disease as well as the pros and cons and prognostic implications of various methods of assessment of GFR and albuminuria.


Immuno-cytological blood tests in cases of sarcoidosis.
Monocytosis, occurring in the majority of sarcoidosis cases in the bloodstream, and an increased number of natural killer cells are a manifestation of an increased cellular defence by bone marrow cells. The antigen-offering function of natural killer cells, macrophages and monocytes, should be specially emphasized. While the majority of sarcoidosis patients show an absolute lymphocyte count of less than 1500 cells/microliter during the usual clinical blood tests, the determination of lymphocyte subpopulations by means of monoclonal antibodies displayed a different behaviour of the lymphocyte subpopulations, especially a substantial reduction of T-cells, while B-lymphocytes were at normal levels. The assumption, that sarcoidosis immunology is characterized by an imbalanced homeostasis in the sense of a decrease in cellular and an increase in humoral immune defence, can no longer be maintained. We are rather dealing with an increased immunological activity of the cellular and humoral immune defence. In addition, the investigation of the lymphocyte subpopulations in the blood allows a judgement on the existing activity of the disease. The statement of a helper-suppressor ratio of less than 2.0 suggests progress of disease and indicates therefore drug therapy. Our immunological findings also explain the difference of the prognosis, which is more favourable for women than for men.


Immunomodulatory Effects of the Water-soluble Lectin from Moringa oleifera Seeds (WSMoL) on Human Peripheral Blood Mononuclear Cells (PBMC).
Moringa oleifera is used in traditional medicine as well as in food, cosmetic, and pharmaceutical industries. Water-soluble M. oleifera lectin (WSMoL) is an anionic protein isolated from the seeds of this tree. Until now, immune responses promoted by this lectin in human PBMC have not been investigated. The main objective of this study was to investigate the immunomodulatory effects of WSMoL on human PBMC through measurement of lymphocytes subsets, cytokine and nitric oxide levels. Human peripheral blood mononuclear cells (PBMC) were isolated through Ficoll technique, were incubated with WSMoL (10 µg/mL) for 24, 48 and 72 hours, and was performed immunophenotyping assay of lymphocytes and monocytes. Culture supernatants were used to determined cytokine and nitric oxide levels. Assays with cells subsets and cytokine production were performed through cytometry. Nitric oxide release assay was determinate by spectrophotometry. WSMoL induced the release of the cytokines TNF-α, IL-2, IL-6, IL-10 as well as nitric oxide. Incubation of PBMC with this lectin also led to activation of CD8+ T lymphocytes. WSMoL promotes immunomodulation in human PBMC inducing a potential wound healing profile and, in future in vivo assays, can be evaluated as adjuvant in immunosuppressive diseases and wound repair.


Iron overload inhibits osteogenic commitment and differentiation of mesenchymal stem cells via the induction of ferritin.
Osteogenic differentiation of multipotent mesenchymal stem cells (MSCs) plays a crucial role in bone remodeling. Numerous studies have described the deleterious effect of iron overload on bone density and microarchitecture. Excess iron decreases osteoblast activity, leading to impaired extracellular matrix (ECM) mineralization. Additionally, iron overload facilitates osteoclast differentiation and bone resorption. These processes contribute to iron overload-associated bone loss. In this study we investigated the effect of iron on osteogenic differentiation of human bone marrow MSCs (BMSCs), the third player in bone remodeling. We induced osteogenic differentiation of BMSCs in the presence or absence of iron (0-50μmol/L) and examined ECM mineralization, Ca content of the ECM, mRNA and protein expressions of the osteogenic transcription factor runt-related transcription factor 2 (Runx2), and its targets osteocalcin (OCN) and alkaline phosphatase (ALP). Iron dose-dependently attenuated ECM mineralization and decreased the expressions of Runx2 and OCN. Iron accomplished complete inhibition of osteogenic differentiation of BMSCs at 50μmol/L concentration. We demonstrated that in response to iron BMSCs upregulated the expression of ferritin. Administration of exogenous ferritin mimicked the anti-osteogenic effect of iron, and blocked the upregulation of Runx2, OCN and ALP. Iron overload in mice was associated with elevated ferritin and decreased Runx2 mRNA levels in compact bone osteoprogenitor cells. The inhibitory effect of iron is specific toward osteogenic differentiation of MSCs as neither chondrogenesis nor adipogenesis were influenced by excess iron. We concluded that iron and ferritin specifically inhibit osteogenic commitment and differentiation of BMSCs both in vitro and in vivo.


Highly potent antioxidant Olea europaea L. leaf extract affects carotid and renal haemodynamics in experimental hypertension: The role of oleuropein.
Haemodynamic alterations in carotid and renal arteries are associated with the severity of target organ damage in patients with hypertension. Dietary habits, such as the Mediterranean diet, regulate blood pressure and oxidative stress, thus reduce the mortality rate due to cardiovascular diseases. In this study, our aim was to evaluate the reducing activity, antioxidant capacity and metal chelating ability of standardized Olea europaea L. leaf extract (OLE), and to test its (5, 25, 50 mg/kg) acute in vivo effects, as well as oleuropein's (OP, 10 mg/kg) on oxidative stress, carotid, renal and systemic haemodynamic parameters (blood pressure, heart rate, cardiac output, peripheral resistance) in spontaneously hypertensive rats (SHR). OLE has a higher antioxidative capacity than BHT, higher reducing ability than vitamin C, and 23 times lower capacity for metal ion chelation than EDTA. All three doses of OLE, and OP, improved oxidative stress in SHR. OLE5 improved carotid and renal haemodynamics, without significant effects on systemic haemodynamics. Two different mechanisms of antihypertensive responses to OLE were observed, OLE25 was most effective in reducing cardiovascular risks by improving systemic and regional (carotid and renal) haemodynamics, peripheral and regional vascular resistance. OLE50 causes the improvement of blood pressure and cardiac performances, but tends to retain elevated vascular resistance, therefore, reducing the inflow of blood into the brain and kidneys of the SHR. The OP did not alter systemic or regional haemodynamics, suggesting others constituents responsible for changes of cardiac function, as well as carotid and renal haemodynamics in response to OLE50.


News in the treatment of axial spondyloarthritis.
Axial spondyloarthritis is a rheumatic disease characterized by inflammation and bone formation causing impaired function of the spine and affected joints. Basic research has highlighted the key role of dysregulation of tumor necrosis factor α, interleukin- 23 and interleukin-17 cytokine production in the etiology of axial spondyloarthritis. Tumor necrosis factor α and interleukin-17 inhibitors have been shown to be effective in clinical trials and are currently approved biological disease-modifying drugs for all disease subgroups. The presumed efficacy of IL-23 blockade has not been confirmed in two clinical trials with anti-IL-23 monoclonal antibodies. Janus kinase inhibitors appear to be a new treatment option.


Interaction between the sequence of feeding of hay and concentrate, and boiling of barley on feed intake, the activity of hydrolytic enzymes and fermentation in the hindgut of Arabian mares.
The interaction between the sequence of feeding of hay and concentrate and the hydrothermal processing of barley in alleviating concentrate effects on intake, and hindgut fermentation in horses was tested. Six Arabian mares (4-10 years of age, 410 ± 35 kg body weight) were used to evaluate the effects of feeding sequence (FS) and type of barley (TB) on intake, and faecal volatile fatty acids (VFA), activities of α-amylase (AA: EC 184.108.40.206), carboxymethyl cellulase (CMCase: EC 188.8.131.52), microcrystalline cellulase (MCCase: EC 22.214.171.124) and general filter paper degrading activity (FPD). Mares were offered a ration of air-dried alfalfa and concentrate (70:30 as-fed) in four subsequent periods of 14 days including 8 days of adaptation and 6 days of sampling. In each period and each meal, mares received concentrate either 30 min after (HC) or 30 min before (CH) alfalfa hay. Barley was either milled or boiled in water. Rectal samples were grabbed directly from rectum once per period. Mares subjected to CH had higher dry matter intakes than mares under HC regime. The acetate:propionate ratio (A:P ratio) in rectal content was higher with CH than HC. The AA activity was higher under CH than under HC. Mares fed boiled barley had lower rectal concentrations of VFA and propionate and a higher A:P ratio than mares fed milled barley. Furthermore, the rectal content showed a higher MCCase activity but a lower AA activity when mares were fed boiled compared with milled barley. Interactions between FS and TB were observed with respect to CMCase activity, and concentrations of propionate and valerate. In conclusion, the present results suggest that both, feeding concentrate before hay and boiling the barley, might improve the hindgut environment in Arabian mares, and that the two measures were mostly additive and sometimes even synergistic.


3D Bioprinting tissue analogs: Current development and translational implications.
Three-dimensional (3D) bioprinting is a promising and rapidly evolving technology in the field of additive manufacturing. It enables the fabrication of living cellular constructs with complex architectures that are suitable for various biomedical applications, such as tissue engineering, disease modeling, drug screening, and precision regenerative medicine. The ultimate goal of bioprinting is to produce stable, anatomically-shaped, human-scale functional organs or tissue substitutes that can be implanted. Although various bioprinting techniques have emerged to develop customized tissue-engineering substitutes over the past decade, several challenges remain in fabricating volumetric tissue constructs with complex shapes and sizes and translating the printed products into clinical practice. Thus, it is crucial to develop a successful strategy for translating research outputs into clinical practice to address the current organ and tissue crises and improve patients' quality of life. This review article discusses the challenges of the existing bioprinting processes in preparing clinically relevant tissue substitutes. It further reviews various strategies and technical feasibility to overcome the challenges that limit the fabrication of volumetric biological constructs and their translational implications. Additionally, the article highlights exciting technological advances in the 3D bioprinting of anatomically shaped tissue substitutes and suggests future research and development directions. This review aims to provide readers with insight into the state-of-the-art 3D bioprinting techniques as powerful tools in engineering functional tissues and organs.


Assessing the Knowledge and Practices of Burn First Aid in Al-Baha Region, Saudi Arabia.
Background Burns are a prevalent type of injury that can result in substantial morbidity and mortality. Burn first aid knowledge is essential for reducing its complications and improving outcomes. However, evidence of the amount of burn first aid knowledge among the general population in many nations is sparse. Methodology A cross-sectional survey was conducted among 346 persons over the age of 18 from the Al-Baha region of Saudi Arabia. The participants' knowledge of first aid for burns, including the appropriate steps to take in the event of a burn, the types of burns, and the proper application of burn dressings was assessed using a structured questionnaire. Results The majority of participants (73.6%) had inadequate knowledge of first aid for burns, while only 26.4% had adequate knowledge. The most common misconception among participants was the use of toothpaste, honey, or ice for burn treatment, which is not recommended. Additionally, hot water was the main cause of burning in this study. Conclusions This study underscores the necessity for targeted education and awareness-raising activities to improve the general population's knowledge and habits about first aid for burns. Such programs can be tailored to clarify myths and misunderstandings regarding burn treatment and encourage evidence-based strategies for preventing and treating burns.


[Exploring and analyzing Wang Qishi's academic thoughts on the spleen and stomach].
There are several academic characteristics about the spleen and the stomach which could be used when identifying and treating the consumption diseases in Li xu yuan jian (Mirror to Manage the Vacuity Pattern), which was written by Wang Qishi, a doctor of the Ming dynasty. About the cause of illness and patho - mechenism, he attached importance to the relation among the essence, Qi and fire (spirit). And he considered that the three sides of the Yang vacuity were belonged to the spleen. About the differentiation of syndromes for treatment, he emphasized the whole connection among treasures and houses. He put forward that the treatment with the vacuity pattern should have three bases: the spleen, the lung and the kidney, in which he especially stressed the spleen, fully reflecting the important academic viewpoint of "the spleen is the mother of body".


Dual mobility acetabular cup for total hip arthroplasty: use with caution.
Dual-mobility cups were introduced to reduce the incidence of dislocation after total hip arthroplasty (THA). The biomechanics of dual-mobility cups allow for greater range of motion, jump distance and better stability when compared to conventional cups in THA. These cups can be very beneficial in THA particularly when the hip instability is a concern such as elderly patients, obese, hip fracture patients, those with neuromuscular diseases, or patients undergoing revision THA for instability. Areas covered: An extensive search is conducted in PubMed and Google scholar to find past five years publications relevant to dual-mobility cups in THA. 225 articles were found which many of those were excluded because of: written in other languages, nearly same cohort in different journals, unavailable full text, and were not covering main fields of this article. We categorized the articles to four different aspects of the biomechanics, outcomes in primary, revision, and after hip fracture THA. Expert commentary: While the important role of the dual-mobility in addressing recurrent instability and reduction of instability in high risk patients undergoing primary THA has been demonstrated, the concern regarding the release of metal ion release, particularly in the younger and active patients, and prosthetic malfunction are worrisome.


Antioxidant activities and bioactive compound determination from caps and stipes of specialty medicinal mushrooms Calocybe indica and Pleurotus sajor-caju (higher Basidiomycetes) from India.
In this study, we evaluated total phenolics, condensed tannins, ascorbic acid, lycopene, β-carotene, total antioxidant activity, reducing power, ferric-reducing antioxidant power, and radical scavenging activity (RSA) on ABTS and DPPH as well as metal chelating activity of methanolic and aqueous extract from caps and stipes of Calocybe indica and Pleurotus sajor-caju mushrooms. Per gram of extract, the different mushroom extracts contained 18.09-27.47 mg gallic acid equivalent of phenolics, 5.06-8.89 mg catechins of tannins, and 0.15-0.21 mg ascorbic acid. Principal component analysis (PCA) revealed that methanolic extract from caps of C. indica and P. sajor-caju contained higher ascorbic acid, total antioxidant activity, β-carotene and radical scavenging activity (RSA) on 2,2-diphenyl-1-picrylhydrazyl (DPPH) than did the stipes. The aqueous extract from cap and stipe of P. sajor-caju had higher total phenolics and RSA on 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) as well as higher metal-chelating activity and ferric-reducing antioxidant power. The antioxidant potential is higher in the caps of P. sajor-caju and C. indica than in the stipes; the cap contributes most to antioxidant activity.


Corrections and clarifications.
In the 3 September Random Samples item "Processing the New Coke fiasco" (p. 1271), Daniel Levine's collaborator should have been listed as Samuel Leven of the Center for Brain Research at Radford University in Radford, Virginia.


Lack of gastric effects of S-(carboxy-methyl)-L-cysteine.
In 10 male subjects, the effects of oral S-(carboxy-methyl)-L-cysteine (SCMC) -- a mucolytic agent useful in the treatment of chronic obstructive bronchitis -- on gastric secretion of acid and N-acetylneuraminic acid (NANA) containing glycoproteins were investigated. Gastric acid outputs and mucus secretory rates remained unchanged during a 10-day period of daily administration of SCMC. Thus, the receptors of SCMC in the bronchial system appear to differ basically from those in the stomach.


Surface characteristics of resin-coated composite restorations.
Twenty-four maxillary anterior composite restorations from a clinical study of resin coating were examined at the time of baseline evaluation and at 23 months; electroplated positive replicas, impression negative replicas, and SEMs were used for evaluation. Coated restorations had smooth surfaces after 23 months, in comparison with rough surfaces of uncoated restorations. Defects in some of the resin coatings were found at the time of baseline evaluation; these included isolated areas of the composite or etched enamel that were not covered by the resin. Later examinations showed cracking of part of the edges of resin coating, development of bare areas, thinning of the coating edges, or generalized loss of the protective coating. The defects seen immediately after placement of the coatings were probably caused by errors in technique that include: application of the resin in a layer that was too thin; surface contaminants in the area of application; moisture on the surface of the composite or enamel; and areas of inadequate enamel etching were adjacent to the cavosurface margin of the composite. The appearance of bare spots or total loss or thinning of the resin coating edges during the later examinations is caused by wearing or abrading of the resin coatings from natural or mechanical causes. This seems to be a function of the initial coating thickness and its location on the tooth.


Outcome of Selective Laser Trabeculoplasty in Young Patients with Primary Open-Angle Glaucoma and Ocular Hypertension.
To determine the effectiveness and safety of selective laser trabeculoplasty (SLT) in young patients with primary open-angle glaucoma (POAG) and ocular hypertension (OHT). This was a retrospective clinical study. Fifty-six eyes from 56 young (age ≤ 40 y) patients with POAG or OHT treated with SLT were included. According to age, patients were divided into group 1 and group 2. Patients in group 1 were younger than 18 years old, and patients in group 2 were between 18 and 40 years old. Patients were evaluated before treatment and at 1 hour, 1 day, 1 week, 1 month, 3 months, 6 months, and 1 year after treatment. We also collected older patients (age ≥ 60 y) who received SLT during the same period for comparison at 1-year follow-up. Possible factors affecting the success of SLT, including baseline IOP, age, sex, diagnosis (POAG or OHT), and whether or not use of antiglaucoma medication before treatment, were analyzed. SLT treatment produced significant reduction in IOP in the young patients with POAG or OHT during the 1-year follow-up period(P < 0.05). Mean IOP at 1 hour after SLT was lower in group 1 than in group 2 (P < 0.01), but at other follow-up time points, IOP values were not different (P > 0.05). IOP reduction and success rate were not significantly different between young and old patients at 1 year after treatment. IOP measurements over a 24-hour period were recorded before and after the SLT in 20 young adult patients. IOP values were significantly lower in the treated patients at all time points than at pretreatment (P < 0.05), and 24-hour mean IOP, peak IOP, valley IOP, and fluctuation in IOP were also lower in SLT-treated patients (P < 0.05). Baseline IOP was found as a predictor of SLT success in young patients (OR = 1.895, P=0.003), whereas age, gender, diagnosis, and whether or not use of antiglaucoma medication were not correlated with SLT success (P=0.725, P=0.750, P=0.061, and P=0.201, respectively). In this study, SLT was found as an effective and safe treatment for young patients with POAG and OHT. High baseline IOP predicted high SLT success.


Lipid diffusion and swelling in a phase separated biocompatible thermoplastic elastomer.
Lipid uptake was analyzed via gravimetric measurements in a biocompatible poly(styrene-block-isobutylene-block-styrene) (SIBS) copolymer. Absorption followed Fickian diffusion behavior very closely, although some deviation was noticed once saturation was reached. Diffusion parameters of three different SIBS formulations were calculated and used to predict the behavior of a fourth type based on molecular weight and relative polystyrene content. SIBS with lower polystyrene content and molecular weight showed lower physical stability and developed surface cracks that propagated with exposure to the lipid medium. Saturation lipid content varied from 45% to 63% by weight and was inversely related to polystyrene content, suggesting most of the plasticization is occurring in the isobutylene phase of SIBS. Moreover, swelling of specimens was monitored throughout the immersion in the lipid medium and ranged from 32% to 58%. Swelling in formulations with lower hard phase (polystyrene) was significantly higher than the swelling in SIBS with higher hard phase content. This is consistent with lipid-induced plasticization occurring in the soft (polyisobutylene) segments, relaxing the polymer network and leading to increased swelling and lipid uptake. The biocompatibility and tailorability of SIBS through control of hard/soft phase ratio offer significant advantages for in vivo applications. However, the lipophilic nature of the material and the associated degradation may render the polymer unusable in certain applications. The predictive model of lipid uptake introduced here will allow more accurate evaluation of lipid susceptibility during the preliminary design phase of SIBS-based in vivo structures.


Identification of compounds that inhibit late steps of peptidoglycan synthesis in bacteria.
A screening system is described that can detect and confirm inhibitors of the late steps of cell wall biosynthesis. The primary high through-put screen monitors induction of beta-lactamase following exposure to samples, in an Escherichia coli envA- strain that carries the beta-lactamase gene from Citrobacter freundii on a plasmid. Positive samples were detected from compound libraries, from natural products libraries, and from fractions of natural products crude preparations. These samples were then subjected to in vitro assays that could detect the incorporation of soluble cell wall precursor into Lipid I, Lipid II, and polymerized cell wall, using a TLC system that was very accurate and unambiguous in detecting known cell wall inhibitors. One partially purified sample containing a novel antibacterial agent derived from natural products was found to inhibit the formation of Lipid I (50% inhibition at < or = 62.5 ng/ml), whereas another partially purified sample also derived from natural products inhibited transglycosylation into cell wall polymer (50% inhibition at < or = 10 microg/ml). This screening system proved to be especially useful because it was sufficiently sensitive and robust to detect inhibitors among samples of crude preparations or varying states of purity.


[Short-term treatment with leuprolide acetate depot before surgical intervention for uterine leiomyomatosis].
It has been amply demonstrated that uterine leiomyoma possess estrogen receptors. On the basis of this presupposition, it is considered logical to use GnRH-agonists which, by reducing the level of estrogen, also reduce the volume of the leiomyoma, although to a varying extent. The maximum reduction which can be obtained occurs, according to published data, between 3 and 6 months of treatment, attaining mean values of approximately 50%. In the author's experience the treatment period was shortened even further by administering only 2 vials of leuprolide depot each month to women who subsequently underwent hysterectomy. The sample group comprised 30 women with uterine leiomyomatosis, of whom 15 were treated with a GnRH analogue and 15 with placebo. The reduction of uterine volume was evaluated by echography and was found to be 40% in the treated group, whereas non change was detected in the "placebo-group".


A single in vivo cocaine administration impairs 5-HT(1B) receptor-induced long-term depression in the nucleus accumbens.
The nucleus accumbens (NAc) is a crucial forebrain nucleus implicated in reward-based decision-making. While NAc neurons are richly innervated by serotonergic fibers, information on the functional role of serotonin 5-hydroxytryptamine (5-HT) in the NAc is still sparse. Here, we demonstrate that brief application of 5-HT or 5-HT1B receptor agonist CP 93129 induced a long-term depression (LTD) of glutamatergic transmission in NAc neurons. This LTD was presynaptically mediated and inducible by endogenous 5-HT. Remarkably, a single cocaine exposure impaired the induction of LTD by 5-HT or CP 93129. The inhibition was blocked when a selective dopamine D1 receptor antagonist SCH23390 was coadministered with cocaine. Cocaine treatment resulted in increased phosphorylation of presynaptic proteins, rabphilin 3A and synapsin 1, and significantly attenuated CP 93129-induced decrease in rabphilin 3A and synapsin 1 phosphorylation. Application of cAMP-dependent protein kinase inhibitor KT5720 caused a prominent synaptic depression in NAc neurons of mice with a history of cocaine exposure. Our results reveal a novel 5-HT1B receptor-mediated LTD in the NAc and suggest that cocaine exposure may result in elevated phosphorylation of presynaptic proteins involved in regulating glutamate release, which counteracts the presynaptic depressant effects of 5-HT1B receptors and thereby impairs the induction of LTD by 5-HT.


Progress in the development of a heat-stable recombinant rinderpest vaccine using an attenuated vaccinia virus vector.
Rinderpest is a fatal infectious disease of cattle and buffalo, and is prevalent in many parts of the developing world. Eradication campaigns are at present under way in Africa, the Middle East and South Asia. As these regions have very hot climates, it is difficult and expensive to establish reliable cold chains to deliver heat-sensitive vaccines and, for this reason, many previous vaccination/eradication campaigns have been ineffective. To overcome the problem of vaccine heat-lability, a recombinant rinderpest vaccine (RRV) has been developed by inserting the haemagglutinin gene of rinderpest virus into the attenuated smallpox vaccine (vaccinia virus) and using this as heat-stable vaccine vector system to deliver the foreign antigens. This rinderpest vaccine, as with the smallpox vaccine, could be used for the global eradication campaign, without the need to establish a cold chain. Both the efficacy and the safety of the RRV have been confirmed in experiments in cattle. In addition to heat stability, the RRV has several other advantages over the current rinderpest tissue-culture vaccine. DNA viruses have greater genetic stability than RNA viruses (this may be easily checked by restriction enzyme analysis), and the use of RRV enables vaccinated animals to be distinguished from naturally-infected animals, as the vaccine generates a more restricted antigenic response to rinderpest virus. The current situation in relation to the efficacy and safety of the RRV is discussed.


Multiplex immunohistochemistry elucidates increased distance between cytotoxic T cells and plasma cells in relapsed myeloma, and identifies Lag-3 as the most common checkpoint receptor on cytotoxic T cells of myeloma patients.
A dysfunctional immune tumour microenvironment facilitates disease progression in multiple myeloma (MM). Using multiplex immunohistochemistry (mIHC), we described the quantitative and qualitative changes in CD3+ CD8+ cytotoxic T-cells and assess their proximity to malignant plasma cells (PCs) in patients with monoclonal gammopathy of undetermined significance (MGUS), newly diagnosed (ND) and relapsed/refractory (RR) MM. Formalin-fixed, paraffin-embedded trephine sections from patients with MGUS (n=32), NDMM (n=65) and RRMM (n=59) were sequentially stained for CD138, CD3, CD8, and checkpoint receptors (CPR) Tim-3, Lag-3, and PD-1. Halo® image analysis platform was used for cell segmentation and phenotyping, facilitating enumeration of cytotoxic T-cells and analysis of proximity to PCs. The percentage of CD8+ cytotoxic T-cells in proximity to PCs is greater in patients with NDMM than patients with RRMM (at 50gm distance 90.8% vs. 81.5%, p=0.038). There is a trend for more CD3+ T-cells in MGUS (p=0.08) but no difference was observed in the prevalence of CD8+ cytotoxic T-cells (p=0.48). Lag-3 is the most common CPR expressed on cytotoxic T-cells in myeloma (p.


Report from the first snake genomics and integrative biology meeting.
This report summarizes the proceedings of the 1st Snake Genomics and Integrative Biology Meeting held in Vail, CO USA, 5-8 October 2011. The meeting had over twenty registered participants, and was conducted as a single session of presentations. Goals of the meeting included coordination of genomic data collection and fostering collaborative interactions among researchers using snakes as model systems.


Sexual Fluidity and Psychological Distress: What Happens When Young Women's Sexual Identities Change?
The sexual identities of young women today are less binary and more fluid than ever before. Several theoretical perspectives imply that this fluidity could be accompanied by distress. To examine this, we analyzed four waves of data from Australian women born 1989 to 1995 (n = 11,527). We found no evidence of a universal association between sexual identity change and psychological distress. Instead, psychological distress was elevated when women changed their identity away from the heterosexual norm and lowered when they changed their identity toward it. Social stress partly attenuated these associations. In addition, women unsure of their identity at multiple assessment points reported significantly greater psychological distress in the final assessment than women who were never unsure. Our findings suggest that greater support should be offered to women who are questioning their sexual identity or developing a minority identity.


Multimedia Data-Based Mobile Applications for Dietary Assessment.
Diabetes mellitus (DM) and obesity are chronic medical conditions associated with significant morbidity and mortality. Accurate macronutrient and energy estimation could be beneficial in attempts to manage DM and obesity, leading to improved glycemic control and weight reduction, respectively. Existing dietary assessment methods are subject to major errors in measurement, are time consuming, are costly, and do not provide real-time feedback. The increasing adoption of smartphones and artificial intelligence, along with the advances in algorithms and hardware, allowed the development of technologies executed in smartphones that use food/beverage multimedia data as an input, and output information about the nutrient content in almost real time. Scope of this review was to explore the various image-based and video-based systems designed for dietary assessment. We identified 22 different systems and divided these into three categories on the basis of their setting for evaluation: laboratory (12), preclinical (7), and clinical (3). The major findings of the review are that there is still a number of open research questions and technical challenges to be addressed and end users-including health care professionals and patients-need to be involved in the design and development of such innovative solutions. Last, there is a clear need that these systems should be validated under unconstrained real-life conditions and that they should be compared with conventional methods for dietary assessment.


[Safety of solifenacin and tolterodine in the treatment of overactive bladder: a meta-analysis].
To evaluate the safety of solifenacin and tolterodine in the treatment of overactive bladder (OAB). Studies on the solifenacin, tolterodine and OAB were searched and those fulfilling the inclusion criteria were selected. RevMan 5.0 software was used to perform meta-analysis. Three studies were included with an overall sample size of 1013 cases. The experimental group of solifenacin contained 517 cases while the control group had 496 cases. The incidence rates of overall adverse event, dry mouth, constipation and blurred vision of the experimental group (solifenacin 5 mg once per day) was 26.69% (138/517), 10.64% (55/517), 5.42% (28/517) and 6.55% (26/397) while those of the control group (tolterodine 2 mg twice per day) 33.27% (165/496), 16.73% (83/496), 2.22% (11/496) and 4.20% (16/381) respectively. There was no statistically significant difference in overall adverse event (RR = 0.76, 95%CI: 0.52 - 1.12, P = 0.170) and blurred vision (RR = 1.59, 95%CI: 0.88 - 2.90, P = 0.130) between two groups. However, the incidence rate of key antimuscarinic adverse events such as dry mouth (RR = 0.63, 95%CI: 0.46 - 0.87, P = 0.005) and constipation (RR = 2.38, 95%CI: 1.21 - 4.66, P = 0.010) showed statistically significant difference. Dry mouth is the most common adverse event of solifenacin (5 mg once per day) and tolterodine (2 mg twice per day). Solifenacin has a lower incidence rate of dry mouth and a higher rate of constipation than tolterodine. A clinical physician should consider the incidence of adverse events during treating OAB, especially for those patients prone to constipation.


Characterization of pellet morphology during submerged growth of Streptomyces tendae by image analysis.
Many filamentous bacteria and fungi tend to form pellets, or mixtures of dispersed mycelium and pellets in liquid fermentation broths. In some cases, a specific kind of morphology is required for optimum product yield. When quantitative analysis and characterization of the pellet morphology are needed, an image processing system can be used. It allows a fast and reproducible analysis of the frequency distribution of pellet size, mean pellet size, contents of pellets, or their shape. The use of such a system allows for an on-line analysis. For a demonstration of the method, results of two fermentations of Streptomyces tendae are shown.


Talquetamab in multiple myeloma.
Initial results of the Phase 1 trial of talquetamab, a bispecific antibody targeting GPRC5D and CD3, were reported in December of 2022 for the treatment of relapsed or refractory multiple myeloma in the fourth line or later setting. It demonstrated a similar efficacy profile and durability of response to teclistamab, the first bispecific antibody therapy to be approved in multiple myeloma. Additionally, it has less infections than teclistamab but demonstrates unique class specific side effects including skin, oral, and nail-related adverse events. Despite this, it is still a highly efficacious and well-tolerated therapy that will add to the armamentarium of therapeutics against heavily pretreated multiple myeloma.


Composite gastric carcinoid and adenocarcinoma.
The light microscopical, histochemical and ultrastructural features of an unusual gastric tumour are presented. Microscopically, the neoplasm showed the features of both a conventional carcinoid tumour and of a mucin-producing adenocarcinoma. The ultrastructural demonstration of individual cells containing both endocrine granules and mucin globules supports the view that gastric enterochromaffin cells are of endodermal origin.


Activity of the 2013 Geminid meteoroid stream at the Moon.
The Lunar Dust Experiment (LDEX) onboard the Lunar Atmosphere and Dust Environment Explorer mission orbited the Moon from 2013 October to 2014 April and detected impact ejecta generated by the continual bombardment of meteoroids to the lunar surface. While the Moon transited the Geminid meteoroid stream, LDEX observed a large enhancement in the lunar impact ejecta cloud, particularly above the portion of lunar surface normal to the Geminids radiant. Here, we present the LDEX measurements during the Geminids, using the surface density of impact ejecta at the Moon as a proxy for meteoroid activity. We find two peaks during the Geminids, a smaller peak at solar longitude λ⊙ = 261°.3 ± 0°.12 followed by a larger peak at λ⊙ = 262°.2 ± 0°.12, with a surface density ratio of 2.6 between the two. Both peaks coincide with radar observations of shallower mass indices than most of the Geminids, suggesting an enhancement of larger particles during the two peaks. The total duration of the 2013 Geminid meteoroid shower at the Moon measured by LDEX is Δλ⊙ = 1°.7 for activity >10 per cent of the peak value, corresponding to a width of 1.9 × 106 km normal to the Geminids velocity vector. The timing of the main observed peak matches ground-based visual observations of meteors with magnitude of -1 to -3 and suggests LDEX is detecting ejecta from primary impactors with radii ~2 mm to 2 cm during this time.


Carcinoembryonic antigen, a human tumor marker, cooperates with Myc and Bcl-2 in cellular transformation.
Carcinoembryonic antigen (CEA) is a tumor marker that is overexpressed in many human cancers and functions in vitro as a homotypic intercellular adhesion molecule. We have investigated the possibility of synergy between CEA, v-Myc, and Bcl-2 in the transformation of cells with differentiation capacity. We find that v-Myc increases the cell division rate and maximum density of rat L6 myoblasts but also markedly stimulates both apoptosis and surprisingly, differentiation, thus preventing transformation. The superposition of Bcl-2 blocks the apoptotic stimulation of v-Myc and independently promotes further cell division at confluence, but still allows differentiation. The further expression of CEA has a dominant effect in blocking differentiation, regardless of the presence of the other activated oncogenes, generating cells that enter a reversible quiescent G0-like state in medium promoting differentiation. Transfectants expressing CEA with or without v-myc and bcl-2 allow the emergence of cells with the property of heritable, efficient, anchorage-independent growth in soft agar and the ability to markedly reduce the latency for tumor formation in nude mice. We propose that by prolonging cell survival in the presence of differentiation signals, CEA represents a novel class of dominant differentiation-blocking oncogene.


SMART DOCS: a new patient-centered outcomes and coordinated-care management approach for the future practice of sleep medicine.
The practice of medicine is currently undergoing a transformation to become more efficient, cost-effective, and patient centered in its delivery of care. The aim of this article is to stimulate discussion within the sleep medicine community in addressing these needs by our approach as well as other approaches to sleep medicine care. The primary goals of the Sustainable Methods, Algorithms, and Research Tools for Delivering Optimal Care Study (SMART DOCS) are: (1) to introduce a new Patient-Centered Outcomes and Coordinated-Care Management (PCCM) approach for the future practice of sleep medicine, and (2) to test the PCCM approach against a Conventional Diagnostic and Treatment Outpatient Medical Care (CONV) approach in a randomized, two-arm, single-center, long-term, comparative effectiveness trial. The PCCM approach is integrated into a novel outpatient care delivery model for patients with sleep disorders that includes the latest technology, allowing providers to obtain more accurate and rapid diagnoses and to make evidence-based treatment recommendations, while simultaneously enabling patients to have access to personalized medical information and reports regarding their diagnosis and treatment so that they can make more informed health care decisions. Additionally, the PCCM approach facilitates better communication between patients, referring primary care physicians, sleep specialists, and allied health professionals so that providers can better assist patients in achieving their preferred outcomes. A total of 1,506 patients 18 y or older will be randomized to either the PCCM or CONV approach and will be followed for at least 1 y with endpoints of improved health care performance, better health, and cost control. http://www.clinicaltrials.gov, NCT02037438.


The vitamin D receptor agonist EB1089 can exert its antiviral activity independently of the vitamin D receptor.
Vitamin D has been shown to have antiviral activity in a number of different systems. However, few studies have investigated whether the antiviral activity is exerted through the vitamin D receptor (VDR). In this study, we investigated whether the antiviral activity of a vitamin D receptor agonist (EB1089) towards dengue virus (DENV) was modulated by VDR. To undertake this, VDR was successively overexpressed, knocked down and retargeted through mutation of the nuclear localization signal. In no case was an effect seen on the level of the antiviral activity induced by EB1089, strongly indicating that the antiviral activity of EB1089 is not exerted through VDR. To further explore the antiviral activity of EB1089 in a more biologically relevant system, human neural progenitor cells were differentiated from induced pluripotent stem cells, and infected with Zika virus (ZIKV). EB1089 exerted a significant antiviral effect, reducing virus titers by some 2Log10. In support of the results seen with DENV, no expression of VDR at the protein level was observed. Collectively, these results show that the vitamin D receptor agonist EB1089 exerts its antiviral activity independently of VDR.


The possible molecular regulation mechanism of CIK cells inhibiting the proliferation of Human Lung Adenocarcinoma NCL-H157 Cells.
Cytokine-induced killer (CIK) cells were isolated and proliferation from human peripheral blood and cultured in appropriate growth medium. The biological characteristics of CIK cells were further determined by the characterization of surface markers by flow cytometry. CIK cells inhibited the proliferation of human lung adenocarcinoma NCL-H157 cells. Vascular endothelial growth factor (VEGF) expression was down-regulated in CIK cells co-cultured with NCL-H157 cells by western blotting analysis. Furthermore, in comparison with cells untreated by CIK, the NCL-H157 had a lower proliferation capacity. We proposed that the pharmacological mechanisms of NCL-H157 promoted by CIK can be estimated possibly with different biological significance that can be ascribed to down-regulated VEGF expression in vitro. The results suggest that the VEGF pathway guides developmental inhibiting of NCL-H157, and we speculate that the function of VEGF pathways is to guide NCL-H157 to inhibition by abundant CIK.


Second-Order Probability Matching Priors for the Person Parameter in Unidimensional IRT Models.
In applications of item response theory (IRT), it is often of interest to compute confidence intervals (CIs) for person parameters with prescribed frequentist coverage. The ubiquitous use of short tests in social science research and practices calls for a refinement of standard interval estimation procedures based on asymptotic normality, such as the Wald and Bayesian CIs, which only maintain desirable coverage when the test is sufficiently long. In the current paper, we propose a simple construction of second-order probability matching priors for the person parameter in unidimensional IRT models, which in turn yields CIs with accurate coverage even when the test is composed of a few items. The probability matching property is established based on an expansion of the posterior distribution function and a shrinkage argument. CIs based on the proposed prior can be efficiently computed for a variety of unidimensional IRT models. A real data example with a mixed-format test and a simulation study are presented to compare the proposed method against several existing asymptotic CIs.


[Hypertriglyceridemia as a cause of atherosclerosis].
Many observational studies have investigated whether elevated levels of serum triglyceride are associated with increased risk of coronary heart disease. The results of these studies have been inconsistent. Recently, however, evidences are accumulating to suggest that hypertriglyceridemia is an independent risk factor for coronary heart disease. Elevated levels of serum triglyceride are associated with four pathogenic conditions which are considered to accelerate atherosclerosis. These are decreased serum HDL cholesterol levels, increased remnant lipoproteins, increased small dense LDLs, and increased thrombogenic conditions. The results of primary and secondary prevention studies support the concept that some types of hypertriglyceridemia will be the cause of atherosclerosis.


Optimizing radiation dose levels in prospectively electrocardiogram-triggered coronary computed tomography angiography using iterative reconstruction techniques: a phantom and patient study.
To investigate the potential of reducing the radiation dose in prospectively electrocardiogram-triggered coronary computed tomography angiography (CCTA) while maintaining diagnostic image quality using an iterative reconstruction technique (IRT). Prospectively-gated CCTA were first performed on a phantom using 256-slice multi-detector CT scanner at 120 kVp, with the tube output gradually reduced from 210 mAs (Group A) to 125, 105, 84, and 63 mAs (Group B-E). All scans were reconstructed using filtered back projection (FBP) algorithm and five IRT levels (L2-6), image quality (IQ) assessment was performed. Based on the IQ assessment, Group D(120 kVp, 84 mAs) reconstructed with L5 was found to provide IQ comparable to that of Group A with FBP. In the patient study, 21 patients underwent CCTA using 120 kV, 210 mAs with FBP reconstruction (Group 1) followed by 36 patients scanned with 120 kV, 84 mAs with IRT L5 (Group 2). Subjective and objective IQ and effective radiation dose were compared between two groups. In the phantom scans, there were no significant differences in image noise, contrast-to-noise ratio (CNR) and modulation transfer function (MTF) curves between Group A and the 84 mAs, 63 mAs groups (Groups D and E). Group D (120 kV, 84 mAs and L5) provided an optimum balance, producing equivalent image quality to Group A, at the lowest possible radiation dose. In the patient study, there were no significant difference in image noise, signal-to-noise ratio (SNR) and CNR between Group 1 and Group 2 (p=0.71, 0.31, 0.5, respectively). The effective radiation dose in Group 2 was 1.21 ± 0.14 mSv compared to 3.20 ± 0.58 mSv (Group 1), reflecting dose savings of 62.5% (p<0.05). iterative reconstruction technique used in prospectively ECG-triggered 256-slice coronary CTA can provide radiation dose reductions of up to 62.5% with acceptable image quality.


Development of a benchmark tool for cancer centers; results from a pilot exercise.
Differences in cancer survival exist between countries in Europe. Benchmarking of good practices can assist cancer centers to improve their services aiming for reduced inequalities. The aim of the BENCH-CAN project was to develop a cancer care benchmark tool, identify performance differences and yield good practice examples, contributing to improving the quality of interdisciplinary care. This paper describes the development of this benchmark tool and its validation in cancer centers throughout Europe. A benchmark tool was developed and executed according to a 13 step benchmarking process. Indicator selection was based on literature, existing accreditation systems, and expert opinions. A final format was tested in eight cancer centers. Center visits by a team of minimally 3 persons, including a patient representative, were performed to verify information, grasp context and check on additional questions (through semi-structured interviews). Based on the visits, the benchmark methodology identified opportunities for improvement. The final tool existed of 61 qualitative and 141 quantitative indicators, which were structured in an evaluative framework. Data from all eight participating centers showed inter-organization variability on many indicators, such as bed utilization and provision of survivorship care. Subsequently, improvement suggestions for centers were made; 85% of which were agreed upon. A benchmarking tool for cancer centers was successfully developed and tested and is available in an open format. The tool allows comparison of inter-organizational performance. Improvement opportunities were successfully identified for every center involved and the tool was positively evaluated.


Length and Charge of Water-Soluble Peptoids Impact Binding to Phospholipid Membranes.
In this study, we provide a quantitative description of the adsorption of water-soluble N-substituted glycine oligomers (peptoids) to supported lipid bilayers that mimic mammalian plasma membranes. We prepared a small array of systematically varied peptoid sequences ranging in length from 3 to 15 residues. Using the nonlinear optical method second harmonic generation (SHG), we directly monitored adsorption of aqueous solutions of 3- and 15-residue peptoids to phospholipid membranes of varying physical phase, cholesterol content, and head group charge in physiologically relevant pH buffer conditions without the use of extrinsic labels. Equilibrium binding constants and relative surface coverages of adsorbed peptoids were determined from fits to the Langmuir model. Three- and 15-residue peptoids did not interact with cholesterol-containing lipids or charged lipids in the same manner, suggesting that a peptoid's adsorption mechanism changes with sequence length. In a comparison of four three-residue peptoids, we observed a correlation between equilibrium binding constants and calculated log D7.4 values. Cationic charge modulated surface coverage. Principles governing how peptoid sequence and membrane composition alter peptoid-lipid interactions may be extended to predict physiological effects of peptoids used as therapeutics or as coatings in medical devices.


Cost analyses of community-acquired pneumonia from the hospital perspective.
Community-acquired pneumonia (CAP) is a widespread disease with important implications for health-care systems worldwide. This study investigated direct costs, treatment patterns, and outcomes associated with two patient cohorts hospitalized with CAP. The study design was naturalistic, prospective, and open. The study enrolled 580 patients. Two hundred sixty-one patients were treated initially with IV moxifloxacin (45%, cohort M); the remaining 319 patients received nonstandardized treatment (cohort S). Twenty-two hospitals in Germany. Clinical success rates were similar between treatment groups (cohort M, 242 of 256 patients, 95%; cohort S, 286 of 312 patients, 92%; p = 0.208). Mean +/- SD length of hospital stay was 10.8 +/- 5.2 days, with cohort M having a significantly shorter hospital stay (10.0 +/- 4 days) compared to cohort S (11.5 +/- 6 days; p < 0.001). Median of all direct costs was dollar 1,333 (minimum, dollar 127; maximum, dollar 9,488), with direct costs of dollar 1,250 in cohort M (minimum, dollar 372; maximum, dollar 9,488) and dollar 1,409 in cohort S (minimum, dollar 127; maximum, dollar 9,366) per treated episode of CAP (p = 0.066). Major determinants of costs were length of hospital stay and ICU admission, whereas costs for staff and hotel were major contributors to direct costs. Initial antibiotic therapy with moxifloxacin resulted in similar clinical efficacy and direct costs compared to nonstandardized therapy; however, patients treated with moxifloxacin benefited with an earlier hospital discharge.


Overcoming barriers to lung cancer screening using a systemwide approach with additional focus on the non-screened.
The lung cancer screening program at St Elizabeth Healthcare (Kentucky, USA) began in 2013. Over 33,000 low-dose computed tomography lung cancer screens have been performed. From 2015 through 2021, 2595 lung cancers were diagnosed systemwide. A Screening Program with Impactful Results from Early Detection, reviews that experience; 342 (13.2%) were diagnosed by screening and 2253 (86.8%) were non-screened. As a secondary objective, the non-screened cohort was queried to determine how many additional individuals could have been screened, identifying barriers and failures to meet eligibility. Our QlikSense database extracted the lung cancer patients from the Cancer Patient Data and Management System, and identified and categorized them separately as screened or non-screened populations. Stage distribution was compared in screened and non-screened groups. Those meeting age criteria, with any smoking history, were further queried for screening eligibility, accessing the electronic medical record smoking history and audit trail, and determining if enough information was available to substantiate screening eligibility. The same methodology was applied to CMS 2015 and USPSTF 2021 criteria. The screened and non-screened patients were accounted for in a stage migration chart demonstrating clear shift to early stage among screened lung cancer patients. Additionally, analysis of non-screened individuals is presented. Of the St Elizabeth Healthcare eligible patients attributed to primary care providers, 49.6% were screened in 2021. Despite this level of success, this study highlighted a sizeable pool of additional individuals that could have been screened. We are shifting focus to the non-screened pool of patients that meet eligibility, further enhancing the impact on our community.


[Chronic diarrhea as the main symptom of histiocytosis X].
A chronic diarrhea accompanied by vomiting and weight loss was the major symptom in a one-year-old infant during a fulminant course of histiocytosis X. The diagnosis was suggested by the radiologic evidence of alternating dilated and stenotic segments in the small and large bowel as well by a massive intestinal protein loss and the presence of histiocytes in the mucosa and submucosa of the rectum. The histological picture of enlarged mesenteric lymph nodes, obtained during a diagnostic laparotomy, confirmed the diagnosis.


Improving the therapeutic index in cancer therapy by using antibody-drug conjugates designed with a moderately cytotoxic drug.
The antibody-drug conjugate (ADC), IMMU-130, of the moderately cytotoxic topoisomerase I inhibitor, SN-38, and the CEACAM5-targeted humanized antibody (mAb), labetuzumab, was evaluated in model systems of human colon carcinoma and in phase I clinical trials of heavily pretreated patients with metastatic colorectal cancer. The conjugate, designed with a near-homogeneous drug substitution of 7-8 SN-38/mAb and with a linker that released 50% of the drug in ∼20 h, showed significant antitumor effects compared to a nontargeted ADC in human tumor xenografts, which could be augmented in combination with bevacizumab. The advantage of fractionated dosing was demonstrated, with potential implications for the clinical dosing schedule. Biodistribution comparing IMMU-130 with labetuzumab showed that the conjugate cleared somewhat faster from the blood, but this did not affect tumor uptake and retention. The use of an ultrastable linker in the conjugate design abrogated antitumor effects. A tolerability study in rabbits showed a high safety margin, with no-observed-adverse-effect level (NOAEL) corresponding to a cumulative human-equivalent protein dose of 40-60 mg/kg. The preclinical findings appear to be corroborated in two phase I clinical trials, with high tolerability and evidence of antitumor activity, including objective responses. The impact of the ADC design on the utility of IMMU-130, tailored to a poorly internalizing target, is discussed.