Effect of granulocyte colony-stimulating factor after intensive induction therapy in relapsed or refractory acute leukemia.
Background. Although colony-stimulating factors have been shown to accelerate recovery from severe neutropenia after intensive chemotherapy or bone marrow transplantation, their use in acute leukemia has been controversial because in vitro they stimulate leukemic colonies as well as normal granulocyte colonies. Methods. We conducted a prospective, randomized, controlled study to determine the safety and efficacy of recombinant human granulocyte colony-stimulating factor (CSF) after a standard course of intensive therapy in 108 patients with relapsed or refractory acute leukemia (67 with acute myelogenous leukemia, 30 with acute lymphocytic leukemia, 9 in blast crisis from chronic myelogenous leukemia, and 2 with acute leukemia arising from myelodysplastic syndromes). Treatment with granulocyte CSF (200 micrograms per square meter of body-surface area per day in a 30-minute infusion) was begun two days after the end of the chemotherapy and continued until the neutrophil count rose above 1500 per cubic millimeter. Results. Treatment with granulocyte CSF accelerated the recovery of neutrophils significantly (P less than 0.01), shortening it by about a week, but it had no effect on platelet recovery. Although the incidence of febrile episodes was almost the same, documented infections were significantly less frequent in the group treated with granulocyte CSF (P = 0.028). There was no evidence that granulocyte CSF accelerated the regrowth of leukemic cells. Fifty percent of 48 patients in the CSF group who could be evaluated and 36 percent of 50 controls had complete remission. The rate of relapse was almost the same in the two groups. Conclusions. It appears that recombinant human granulocyte CSF is safe in acute leukemia, accelerating neutrophil recovery and thereby reducing the incidence of documented infection without affecting the regrowth of leukemic cells. It should be used with caution, however, pending further confirmation of these early results.


Corneal perforation associated with silicone oil in the anterior chamber.
To describe the management of three cases of corneal perforation associated with silicone oil in the anterior chamber. Review of 3 case records. Three cases of perforation associated with silicone oil in the anterior chamber are reviewed. One patient required gluing and a bandage contact lens, whereas the second patient required an emergency corneal transplantation. The third patient responded to conservative measures, including the use of topical antibiotic ointment. Corneal perforation associated with silicone oil in the anterior chamber is rare and can be difficult to manage. Potential treatments including the use of cyanoacrylate glue, application of antibiotic ointments, use of aqueous suppressants, and other conservative measures may be effective. In extreme cases, corneal transplantation may be necessary.


Validity of the body mass index as an indicator of adiposity in an ethnically diverse population of youths.
The primary objective was to investigate the influences of ethnicity and pubertal stage on the ability of body mass index (BMI) to rank adiposity in a cohort of 402 Asian, African, Hispanic, and White Americans, aged 9-25 years. BMI was calculated from measured weight and height. Body composition and pubertal stage were determined by dual energy x-ray absorptiometry and self-rating, respectively. Multiple linear regression models with BMI, ethnicity, puberty, and age as explanatory variables were used to determine if ethnicity and pubertal stage modify the ability of BMI to predict percent of body weight that is fat (%BF). Spearman's correlation coefficients of BMI with %BF were also estimated. Both ethnicity and pubertal stage interacted with BMI. The correlation between BMI and %BF (r) was much higher in females (r = 0.72, P < 0.001) than in males (r = 0.15, NS). Among females, correlations did not vary much by pubertal stage, but tended to be higher in Blacks. Among males, correlations tended to be low during mid-puberty. However, a high correlation between BMI and lean body mass (LBM) was consistently observed in mid-pubertal males across all ethnic groups. Stratification by quartile of BMI showed that the correlation was >0 (P < .05) only in the highest quartile. Thus, in an ethnically diverse cohort of 9-25 year olds, the correlation between BMI and %BF is poor in the lower quartiles of BMI. In comparison, LBM correlates better with BMI than %BF in the lower quartiles of BMI. © 1996 Wiley-Liss, Inc.


Bony orbital distances among the Filipino population.
Six hundred and seventy seven radiographs were selected from the logs of films taken in a major hospital in Metro Manila, Philippines over the course of the previous year. Two hundred and eighty-eight female and 389 male, healthy Filipinos between the ages of birth and twenty years were selected based on the availability of a modified Waters' projection and lateral skull film taken at the same time. Measurements for the lateral orbital wall were made at the site of the suture on the medial surface of the zygomatic bone. The medial orbital wall measurement was the distance between the dacrya using a correction factor formula of CF = D-d/D where D is the target film distance and d is the object film distance (1). The actual bony measurements were calculated. The data was gathered and plotted according to sex and in age in years. Graphs were generated using SAS over a graph software. Lines were smooth using cubic spline technique developed by Reinsch with the smoothest value of 75 (2). The mean plus two, four, and six standard deviations were included in each of the curves.


[Construction of an inducible and efficient expression-secretion shuttle vector of B. subtilis].
A new shuttle vector pSB which could replicate in both Escherichia coli and Bacillus subtilis was constructed by fusing the E. coli plasmid pSP72 with the B. subtilis plasmid pUB18. After the sacB promoter and signal peptide sequence of B. subtilis was inserted in the multiple cloning sites (MCS) of pSB, The recombinant plasmid was designated as pSBP. The alpha-amylase gene terminator of Bacillus licheniformis was inserted at the other end of the MCS, resulting in expression-secretion plasmid pSBPT. After a positive control gene degQ of Bacillus pumilus was then cloned into pSBPT, and the inducible and efficient expression-secretion shuttle vector pSBPTQ was thus constructed. To identify the function and the necessary of sacB p. s., alpha-amylase terminator, and degQ in the expression of heterologous gene of pSBPT, the DNA fragment encoding for vasostatin I was cloned downstream of sacB p. s. of pSBP, pSBPT and pSBPTQ, and the resultant plasmid pSV, pSVT and pSVTQ were then transformed into B. subtilis strain DB1342. The transformants were screened on LB plates containing 10 microg/mL kanamycin. The positive transformants were separately grown on kanamycin containing 2 x MSR medium and sucrose was added to 2% final concentration for induction after 2h cultivation. The culture supernatant was used to run SDS-PAGE and Western blot. The results show that after induced by sucrose, very few recombinant Vasostatin I was expressed in DB1342(pSV), and recombinant Vasostatin I expressed in DB1342(pSVTQ) with the positive control gene degQ is more than in DB1342(pSVT) without degQ, suggesting that the Vasostatin I gene expression in pSVTQ was enhanced by degQ. Comparing the recombinant Vasostatin I in DB1342(pSVTQ) cells and its culture supernatant, the SDS-PAGE result show that most of the recombinant Vasostatin I was secreted into the culture supernatant and there is no Vasostatin in inclusion body, the secretion rate is about 90%. The result of plasmid stability test show that pSBPTQ maintains at 83% in B. subtilis after 40 generations.


[Medical and surgical treatment of venous malformations].
Treatment of venous malformations (VM) is difficult as these lesions are ill defined and can infiltrate tissues. Moreover, no specific treatment related to their etiopathogenesis exists. Currently, VM can be treated conservatively or medically and, more aggressively with either sclerotherapy, or surgical resection. A multidisciplinary approach is needed to obtain the best result with minimal complications. Surgical resection, complete or partial, plays an important role in the treatment of symptomatic VM. In case of extensive VM, all techniques of plastic surgery are indicated.


Caloric and rotatory chair test results in patients with Ménière's disease.
To determine whether an association exists between the parameters of the caloric and rotatory chair tests in patients with unilateral Ménière's disease. Patients with unilateral Ménière's disease (n = 100) were subjected to the caloric and the rotatory chair test (sinusoidal harmonic acceleration and impulsive tests) on the same day. Canal paresis and directional preponderance were assessed in the caloric test, and different variables were measured in the rotatory chair test based on the existence of abnormal parameters in the vestibulo-ocular reflex at two or three consecutive frequencies of those tested and on the time constant of the vestibulo-ocular reflex. A prospective study was conducted at a University hospital. An abnormal result in the caloric test was obtained from 73% of the patients. In the rotatory chair test, the most frequent abnormal findings involved increases in the normal phase lead at 2 consecutive frequencies tested (23%). There was a stronger association between an abnormal result in phase, gain, and/or symmetry at three adjacent frequencies and a pathological result in the caloric test. Very few of the criteria used to define the caloric and rotatory chair tests seem to be associated. This confirms previous knowledge that both tests examine vestibulo-ocular reflex by different ways. Only when vestibular dysfunction is severe enough (manifested by the finding of an abnormal result in at least three consecutive frequencies in the rotatory chair test), the caloric test is also found to be abnormal.


A model of the entrance pupil of the human eye.
The aperture stop of the iris is subject to refraction by the cornea, and thus an outside observer sees a virtual image: the "entrance pupil" of the eye. When viewed off-axis, the entrance pupil has an elliptical form. The precise appearance of the entrance pupil is a consequence of the anatomical and optical properties of the eye, and the relative positions of the eye and the observer. This paper presents a ray traced model eye that provides the parameters of the entrance pupil ellipse for an observer at an arbitrary location. The model is able to reproduce empirical measurements of the shape of the entrance pupil with good accuracy. I demonstrate that accurate specification of the entrance pupil of a stationary eye requires modeling of corneal refraction, the misalignment of the visual and optical axes, and the non-circularity of the aperture stop. The model, including a three-dimensional ray tracing function through quadric surfaces, is implemented in open-source MATLAB code.


Ernst Rüdin's, 1911 vision of a Mendelian psychiatric genetics research program: His paper "Methods and goals of family research in psychiatry".
While working under Kraepelin in Munich, Ernst Rüdin, a Swiss-born Psychiatrist, at the age of 26, outlined in a 1911 98-page article, a detailed plan for a future Mendelian-informed family research program for psychiatry. Rüdin would go on to head the Department of Genealogical and Demographic Studies at Kraepelin's Research Institute which became one of the world's leading programs in psychiatric genetics. I here summarize this article, providing a complete translation online. Rüdin's review outlined a paradigm shift in psychiatric genetics research moving from calculations of aggregate hereditary burden, as they applied to the proband, to examining patterns of transmission within family pedigrees which involved careful individual assessments of relatives. He references widely clinical and statistical genetic studies, many focusing on the newly discovered Mendelian laws. However, Rüdin was no genetic reductionist but recognized the contribution of environmental risk factors to psychiatric illness arguing that they should be studied as part of a comprehensive research program. As a committed eugenicist, Rüdin also explored the implications of such a program for "racial hygiene." Rüdin's contributions should be viewed in the context of his extensive collaboration from 1933 to 1945 with the National Socialists and his support for their eugenics program, including involuntary sterilizations.


[Evaluation of oxidative stress parameters in diabetes 2 patients in different stage of metabolic compensation].
Etiopathogenesis of vascular complications in diabetes is complex and multifactorial. One of the factors that is connected both with chronic complications of diabetes and intensification of oxidative stress is long-term hyperglicaemia. It has been noted that control improvement of glicaemia delays and/or inhibits the development of further complications. The aim of the study was to evaluate selected parameters of oxidative stress in patients with metabolic compensated or decompensated diabetes by means of marking in red blood cells of the patients in question the activity of antioaxidative enzymes such as: superoxide dysmutase (SOD-1) and catalase (CAT) and concentration of malondialdehyde (MDA). 61 diabetic patients took part in the research, 31 of which met the criteria of metabolic compensation whereas 30 were metabolically decompensated. The reference group (K) consisted of 40 healthy men. The activity of SOD-1 was marked by Misra and Fridovich's method, the activity of CAT by Beers and Sizer's method and the concentration of MDA in red blood cells was indicated by Placer et al. The activity of evaluated antioxidative enzymes SOD-1 and CAT in the erythrocytes of diabetes type 2 patients was statistically lower as compared with the control group. The highest activity of SOD-1 and CAT was noted in metabolic decompensated diabetes type 2 group. The concentration of MDA in diabetes type 2 patients red blood cells was significantly higher as compared with the control group. Significantly higher concentration of MDA was noted in metabolically decompensated diabetic patients comparing to patients with proper metabolically compensated diabetes. The obtained results confirm the toxicity of glucose. Long-term hyperglicaemia through activation of different metabolic paths leads to the intensification of free radical processes and attenuation of antioxidative mechanisms.


Isolation and characterization of a novel human thioredoxin-like gene hTLP19 encoding a secretory protein.
A novel human gene, named as hTLP19, was isolated and characterized as secretory protein by combining bioinformatics tools with experiments. The hTLP19 encodes 172 amino acid residues with signal peptide in its N-terminal and a thioredoxin (Trx) domain that is homologous with some genes in Mus musculus, Xenopus laevis, etc. Moreover, the result from insulin reduction assay indicated that the hTLP19 protein has Trx enzymatic activity. By comparing full-length cDNA with human genomic DNA, the hTLP19 gene might have seven coding exons spanning 35 kb of genomic DNA on the human chromosome 1p32.3. Northern blot analysis showed that human hTLP19 is expressed widely in many tissues with 1.6 kb band and extra 1.2 kb band in placenta. Subcellular localization and immunoblotting assays indicated that hTLP19 might be secreted out of cell through trans-Golgi network (TGN).


The influence of trauma from occlusion on the bacterial repopulation of periodontal pockets in dogs.
Pockets were surgically created in the two upper external incisors of four beagle dogs, and a copper band adapted to prevent reattachment. After 4 weeks the copper bands were removed, the teeth scaled and root-planed and crowns placed on both experimental teeth in such a way that one of them was forced bucally when the teeth occluded. An orthodontic appliance anchored in bands cemented to the cuspid teeth brought the tooth back to its original position when disclusion occurred. Experimental time was 12 weeks. Clinical indices and bacterial samples for darkfield examination were taken at baseline and weekly thereafter. The dogs were fed a diet that favored plaque accumulation and no oral hygiene was performed. Surgically created pockets initially became populated by cocci (65%-75%) and small amounts of motile bacteria (12%-15%) including 3% to 4% spirochetes. In 4 weeks the percentage of cocci declined steadily (42%-45%) and motile bacteria increased to 37% to 43% with spirochetes representing 24% to 27%. After scaling and root planing, the number of cocci increased again and motile bacteria declined although the baseline values were not reached. This decline persisted for 2 weeks after scaling. Repopulation of the pocket in traumatized and nontraumatized teeth followed the same initial pattern, taking again 5 weeks to return to prescaling levels. No difference was found between traumatized and nontraumatized teeth. Clinical measurements, however, revealed a statistically greater loss of attachment in traumatized teeth as compared with nontraumatized teeth.


Achilles Tendon Reconstruction Using a Hamstring Tendon Autograft for Chronic Rupture of the Achilles Tendon in Patients Over 70 Years of Age: A Retrospective Case Series.
Reconstruction techniques using autologous hamstring tendons were generally applied for chronic Achilles tendon rupture with a large defect size. Previous studies have reported good clinical results of this technique for young or middle-aged patients, however, the clinical outcomes in older patients have been unclear. This retrospective case series reviewed four male patients aged >70 years (mean age, 78.5 years) who underwent Achilles tendon reconstruction using the hamstring tendon autograft for chronic rupture of the Achilles tendon with a large tendon defect. The proximal-distal length between the healthy tendon stumps was measured using sagittal T2-weighted magnetic resonance imaging (MRI). The American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and postoperative complications were evaluated. The duration from the traumatic event or appearance of symptoms to surgery was 3.8 (range, 2-6) months. The mean measured gap between the healthy tendon stumps was 67.5 mm on MRI. The AOFAS ankle-hindfoot score improved from 67.3 to 99.5 at the mean follow-up period of 40.3 (range, 23-75) months. No donor site morbidity was observed in all patients. Re-rupture was detected at the five-month follow-up in one patient who had removed a hinged ankle-foot orthosis with adjustable heel wedges without permission. Achilles tendon reconstruction using a hamstring tendon is a viable option for treating selected patients with chronic rupture of the Achilles tendon with a large tendon defect even in older patients. To improve clinical outcomes, a better understanding should be provided to family members as well as older patients regarding the postoperative rehabilitation program.


Stochastic simulations of ErbB homo and heterodimerisation: potential impacts of receptor conformational state and spatial segregation.
ErbB overexpression is linked to carcinogenesis. It is hypothesised that this is due to increased receptor density and receptor clustering, leading to increased receptor dimerisation and activation. Herein, spatial stochastic simulations have been performed to shed light receptor dimerisation processes. First, ligand-independent homodimerisation, is considered, based upon constitutive oligomerisation estimates (14%) in A431 cells that overexpress epidermal growth factor receptor (EGFR). When autocrine stimulation is blocked, ligand-independent EGFR activation is demonstrated by persistent, low levels of phosphorylation. The possibility that ligand-independent signalling is due to the fluctuation of EGFR conformation is considered. The agent-based model predicts the frequency (expressed as a probability) that uniformly distributed receptors would need to flux to the open conformation to reach 14% EGFR dimers at high receptor density. Simulations suggest that ligand-independent EGFR homodimerisation is highly density dependent, since collisions between 'open', dimerisation-competent receptors are a rare event at low receptor levels. Simulations that incorporate receptor clustering lower the threshold for homodimerisation of unoccupied receptors as well as the estimate of the probability for fluxing to the dimer-competent conformation. The impact of ErbB receptor clustering patterns on hetero and homodimerisation rates is also considered, using immunoelectron microscopy data derived from SKBR3 breast cancer cells that express ErbB2>>EGFR>ErbB3. Partial spatial segregation of ErbB receptors has a profound effect on simulated heterodimerisation rates. Despite the general assumption that ErbB2 is a preferred heterodimerising partner for other ErbBs, it is predicted that most ErbB2 will form homodimers. Overall, it is proposed that both receptor density and membrane spatial organisation contribute to the carcinogenesis process.


Females as the Gatekeepers to Seasonal Breeding: What We Can Learn by Studying Reproductive Mechanisms in Both Sexes.
Seasonal reproduction is a widespread adaptation in vertebrates, such that individuals time their reproductive efforts to match peak resource abundance. Individuals rely on environmental cues to regulate hormonal mechanisms governing timing of breeding. Historically, studies on physiological mechanisms of seasonal reproduction, specifically in birds, have disproportionately focused on males compared to females. For this review, I conducted a literature search of the last decade of avian research and found a persistent sex bias in the field of physiological mechanisms of seasonal reproduction. Using work conducted with the dark-eyed junco (Junco hyemalis) as a case study, I present a possible solution to combat the sex bias: natural comparisons of populations that differ in reproductive timing to investigate mechanisms of reproduction in both sexes. Populations of dark-eyed juncos that differ in migratory behavior (i.e., migrant and resident) exhibit overlapping ranges during winter and early spring; residents begin breeding in early spring prior to the departure of migrants. This system, and others like it, provides an opportunity to compare mechanisms of reproduction in populations that differ in reproductive timing despite experiencing the same environmental conditions in early spring. In juncos, migrant and resident females and males exhibit similar patterns of hypothalamic regulation of reproduction in early spring, but sex differences in gonadal sensitivity between the populations could be an important distinction that partially explains sex differences in reproductive development. Comparing mechanisms of reproduction in free-living populations and in captivity can reveal important mechanisms that determine the onset of reproductive development, as well as potential sex differences in these mechanisms. Understanding the mechanisms of reproductive phenology has important implications for understanding how species will survive and reproduce in a changing climate.


Advanced capabilities for future light sources.
Methods to extend the capabilities of light sources beyond those available at the current generation synchrotron radiation sources based on undulators in electron storage rings are discussed. Taking advantage of the radiation-particle interaction and/or the availability of high-power ultrashort optical lasers, it is possible to develop sources with higher brightness, smaller temporal resolution, or higher photon energy. This paper is a summary of some of these schemes, with an emphasis on new ideas rather than on a comprehensive review.


Dielectric screening of excitons in monolayer graphene.
Excitonic transitions in graphene monolayers embedded in different dielectric environments have been investigated using combined absorption and transmission spectroscopy techniques. To vary the dielectric environment, graphene monolayer has been exfoliated in liquid medium. It has been shown that exciton binding energy decreases with increase in the dielectric constant of exfoliating solvents due to the screening of electron-electron and electron-hole interactions in graphene. The typical line shape of the excitonic peak in the absorption spectra is explained by the Fano resonance between the excitonic state and band continuum. Further it has been shown that, there exists a scaling relationship between the dielectric constant of the liquid and the exciton binding energy.


Fatal accidental fall from height in infants and children: a study from South Delhi.
One hundred and seventy-four deaths of infants and children due to accidental fall from height received from South Delhi for autopsy were studied during the 10-year period from January 1998 to December 2007 at the All India Institute of Medical Sciences, New Delhi. Data were analysed with regard to age, sex, location of fall, height of fall, pattern of injury, cause of death and seasonal variation. These cases represented approximately 22.56% of all deaths due to a fall from height and 1.31% of all medicolegal autopsies conducted during the period. There were 106 male (60.9%) and 68 female (39.1%) victims. Age-specific rate of fall showed that the highest rate was in toddlers (39.65%), followed by 26.43% each in preschool children and school-going children and the least in infants (7.47%). The head and face was the most frequently injured body region (93.67%) and the skull was the commonest bone fractured (59.19%). The most common cause of death was head injury (84.48%). Major fall sites in decreasing order of frequency were rooftop (38.50%), balcony (24.13%), household furniture (21.26%), staircase (6.89%), window (4.59%), wall (1.72%), rickshaw/bicycle (1.15%) and tree (0.57%). Most fatalities due to a fall from height were reported in the rainy season.


Cholinergic blockade and the mesenteric artery response to head-up tilt-induced central hypovolaemia.
The influence of muscarinic blockade on the superior mesenteric artery (SMA) response to head-up tilt (HUT) was assessed by Doppler ultrasound in eight healthy adults pretreated with i.v. glycopyrron. During supine rest, cholinergic blockade increased heart rate from 58 +/- 3 to 106 +/- 6 beats min-1 (mean +/- SE) and mean arterial pressure from 81 +/- 3 to 97 +/- 4 mmHg (P < 0.01) and it reduced the cardiac stroke volume from 89 +/- 6 to 59 +/- 7 ml (P < 0.01) with no significant effect on the SMA diameter and blood flow velocities. HUT provoked a further increase in heart rate to 134 +/- 5 beats min-1 (P < 0.01) and a reduction in stroke volume to 45 +/- 4 ml (P < 0.01). The early diastolic velocity increased from -51 +/- 4 to 6 +/- 8 cm s-1 during the normotensive stage of HUT and further to 21 +/- 9 cm s-1 during the hypotensive stage with a reduction in mean arterial pressure from 97 +/- 4 to 73 +/- 7 mmHg (P < 0.01) but, in contrast to control HUT (without cholinergic blockade), the end-diastolic velocity did not change significantly. Maintenance of blood velocity and diameter in spite of an increase in arterial pressure at rest indicates increased SMA impedance. Likewise, during hypovolaemia, a glycopyrron-induced inhibition in diastolic velocity supports an increase in SMA impedance. The results indicate cholinergic vasorelaxing influence on the superior mesenteric artery both at rest and during normotensive central hypovolaemia.


Microglial Intracellular Ca2+ Signaling in Synaptic Development and its Alterations in Neurodevelopmental Disorders.
Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by deficits in social interaction, difficulties with language and repetitive/restricted behaviors. Microglia are resident innate immune cells which release many factors including proinflammatory cytokines, nitric oxide (NO) and brain-derived neurotrophic factor (BDNF) when they are activated in response to immunological stimuli. Recent in vivo imaging has shown that microglia sculpt and refine the synaptic circuitry by removing excess and unwanted synapses and be involved in the development of neural circuits or synaptic plasticity thereby maintaining the brain homeostasis. BDNF, one of the neurotrophins, has various important roles in cell survival, neurite outgrowth, neuronal differentiation, synaptic plasticity and the maintenance of neural circuits in the CNS. Intracellular Ca2+ signaling is important for microglial functions including ramification, de-ramification, migration, phagocytosis and release of cytokines, NO and BDNF. BDNF induces a sustained intracellular Ca2+ elevation through the upregulation of the surface expression of canonical transient receptor potential 3 (TRPC3) channels in rodent microglia. BDNF might have an anti-inflammatory effect through the inhibition of microglial activation and TRPC3 could play important roles in not only inflammatory processes but also formation of synapse through the modulation of microglial phagocytic activity in the brain. This review article summarizes recent findings on emerging dual, inflammatory and non-inflammatory, roles of microglia in the brain and reinforces the importance of intracellular Ca2+ signaling for microglial functions in both normal neurodevelopment and their potential contributing to neurodevelopmental disorders such as ASDs.


[Asymmetric posture of the hip-joints in cerebral palsy (author's transl)].
Asymmetric posture of hip-joints is a common disorder in children with cerebral palsy. One hip is found in abduction-outward rotation, the other in adduction-inward rotation. Most of these patients are severely handicapped, with little voluntary control of muscular activity. Possible causes of the disorder are discussed. In treatment long leg plaster casts with diagonal traction are recommended, in milder cases a corrective plaster mould against malrotation can be applied. The technics of both are described.


Uncertainties in bone mineral density T scores.
In the diagnosis and management of osteopenia and osteoporosis, dual photon absorptiometric measurements of lumbar spine and proximal femur bone mineral density are interpreted by calculating a T score, which is the number of standard deviations by which a result deviates from the mean bone density in young adults of the same sex. Threshold values are then used to categorize patients as having osteopenia or osteoporosis. The uncertainty associated with a single bone mineral density measurement, as well as the uncertainties in the assumed values for the bone mineral density in young adults and the population standard deviation, combine to create an uncertainty in the calculated T score. It is estimated that 95% of bone density measurements have a T score uncertainty of less than 0.4. This means that a single measurement of bone mineral density should not be used in isolation to assign a given patient to a specific diagnostic category. Rather, a bone mineral density measurement should be regarded as only one of the variables that determine the risk of fracture in a given patient.


[Therapy and anthelmintic resistance].
Treatment against nematode parasites in sheep and goats is reviewed. The main risk factors for parasitic infection in these hosts are briefly outlined. The mechanism of action of the most important chemical groups (imidazothiazoles and pyrimidines, benzimidazoles/ pro-benzimidazoles and macrocyclic lactones) to which the modern anthelmintic drugs belong are illustrated and discussed with particular emphasis on possible selection of anthelmintic resistance. The need for strategic integrated control based also on the epidemiological patterns of parasitism, the composition and the production of the herd (milk, meat, wool) and the potency of the drugs are discussed. The importance of diet and potential alternative control measures (nematophagus fungi and natural compounds such as tannins) are illustrated.


PREMIX: PRivacy-preserving EstiMation of Individual admiXture.
In this paper we proposed a framework: PRivacy-preserving EstiMation of Individual admiXture (PREMIX) using Intel software guard extensions (SGX). SGX is a suite of software and hardware architectures to enable efficient and secure computation over confidential data. PREMIX enables multiple sites to securely collaborate on estimating individual admixture within a secure enclave inside Intel SGX. We implemented a feature selection module to identify most discriminative Single Nucleotide Polymorphism (SNP) based on informativeness and an Expectation Maximization (EM)-based Maximum Likelihood estimator to identify the individual admixture. Experimental results based on both simulation and 1000 genome data demonstrated the efficiency and accuracy of the proposed framework. PREMIX ensures a high level of security as all operations on sensitive genomic data are conducted within a secure enclave using SGX.


Natural protection against severe Plasmodium falciparum malaria due to impaired rosette formation.
Genes for two lethal diseases, thalassemia and sickle cell anemia, are favored by evolution because, in their heterozygous form, they protect against cerebral malaria. Rosette formation, the binding of uninfected red cells (RBCs) to Plasmodium falciparum-infected RBCs (PRBCs), has previously been found to be associated with cerebral malaria, the most important severe manifestation of P falciparum malaria. We show here that thalassemic RBCs and, under certain conditions, even hemoglobin S (HbS)-containing RBCs possess an impaired ability to bind to PRBCs, forming small and weak erythrocyte rosettes compared with rosettes formed by normal RBCs. This decreased rosetting ability is associated with the small size of the thalassemic RBCs and with distortion of the mechanical properties of HbS-containing RBCs. The impairment of rosette formation may hinder the development of cerebral malaria by abatement of sequestration.


Clinical experimental considerations on the presence of set uterine pacemakers.
The authors studied the physiology of human uterine muscle contraction. Clinical experimental results obtained from elementary electrophysiological, electrohysterographic and pharmacological studies using PGs suggested that uterine muscle contraction does not originate in "pacemaker" areas. These data also showed that the electric phenomenon is not propagated along preferential "rails".


Human relations as a coronary risk factor.
Psychological variables are significant in the evolution of coronary heart disease (CHD). Two types of personality have been identified as constituting coronary risk: Type 1 which is hypercompetitive and anxious, and Type 2 which is overscrupulous and guilt prone. Both these behavioural types are formed during infancy, and are thought to be neurotic. In rehabilitation it is therefore necessary to take into consideration the psychological as well as the physiological aspects, and so the evaluation of the patient's suitability for return to work, should be, at least in part, psychosomatic. The approach used by the Cardiac Rehabilitation Centre of Udine seems to point towards a successful strategy. The aim of the strategy is to improve the chances of secondary prevention, to correct risk factors on a long-term basis, and to arrive at safe and reliable criteria for return to work.


Community ecology of the metazoan parasites of the grey triggerfish, Balistes capriscus Gmelin, 1789 and queen triggerfish B. vetula Linnaeus,1758 (Osteichthyes: Balistidae) from the State of Rio de Janeiro, Brazil.
Sixty-six specimens of grey triggerfish Balistes capriscus Gmelin, 1788 and thirty specimens of queen triggerfish B. vetula Linnaeus, 1758 (Osteichthyes: Balistidae) collected from the coastal zone of the State of Rio de Janeiro (21-23 degrees S, 41-45 degrees W), Brazil, from April 2001 to May 2003, were necropsied to study their metazoan parasites. All fish were parasitized by at least one parasite species. Twenty-seven parasites species were collected: 22 in B. capriscus and 15 in B. vetula. Ten parasite species were common to the two host species. Balistes capriscus and B. vetula were a new host record for 16 and seven parasite species, respectively. Hypocreadium biminensis and Taeniacanthus balistae were recorded for the first time in Brazil. The copepod T. balistae and the nematode Contracaecum sp. were the dominant species with highest parasitic prevalence and abundance in the parasite community of B. capriscus and B. vetula, respectively. The metazoan parasites of B. capriscus and B. vetula showed typical aggregated pattern of distribution. The infracommunities of adult endoparasites showed highest values of mean abundance and parasite species richness. The parasite species richness, the total number of specimens and the mean Berger-Parker's index of the infracommunities of B. capriscus and B. vetula showed significant differences.


Magnetically Driven Soft Continuum Microrobot for Intravascular Operations in Microscale.
Remotely controlled soft continuum robots with active steering capability have broad prospects in medical applications. However, conventional continuum robots have the miniaturization challenge. This paper presents a microscale soft continuum microrobot with steering and locomotion capabilities based on magnetic field actuation. The magnetically driven soft continuum microrobot is made of NdFeB particles and polydimethylsiloxane (PDMS), and it can be as small as 200 μm in diameter. Moreover, a hydrogel layer is covered on the surface of the microrobot, which not only overcomes the adhesion force between the microobjects and the soft tip but also reduces the friction between the microrobot and substrate. The performance test indicates the soft continuum microrobot featured excellent control and steering capabilities. The experimental results demonstrate that the soft continuum microrobot can travel through the microfluidic channel by its own vibration and flexibly steer in a bifurcation environment. Moreover, the micromanipulation of microbeads in the microfluidic channels proves that the proposed microscale soft continuum microrobot has a great potential for intravascular manipulation.


Comparison of explicit values clarification method (VCM), implicit VCM and no VCM decision aids for men considering prostate cancer screening: protocol of a randomized trial.
Screening with prostate-specific antigen (PSA) test for prostate cancer is considered a preference sensitive decision; meaning it does not only depend on what is best from a medical point of view, but also from a patient value standpoint. Decision aids are evidence-based tools which are shown to help people feel clearer about their values; therefore it has been advocated that decision aids should contain a specific values clarification method (VCM). VCMs may be either implicit or explicit, but the evidence concerning the best method is scarce. We aim to compare the perceived clarity of personal values in men considering PSA screening using decision aids with no VCM versus an implicit VCM versus an explicit VCM. Male factory employees from an industrial facility in the Northern region of Portugal aged 50 to 69 years old will be randomly assigned to one of three decision aid groups used to support prostate cancer screening decisions: (i) decision aid with information only (control), (ii) decision aid with information plus an implicit VCM, (iii) decision aid with information plus an explicit VCM. Men will be allowed release time from work to attend a session at their workplace. After a brief oral presentation, those willing to participate in the study will fill the baseline questionnaire, plus a 5 point-Likert scale question about intentions to undergo screening, and will then receive the intervention materials to complete. We estimated a total sample size of 276 participants; with 92 in each group. The primary outcome will be the perceived clarity of personal values assessed by the Portuguese validated translation of the three subscales of the Decisional Conflict Scale. Secondary outcomes will be intention to be screened (before and after the intervention), the total score from the Decisional Conflict Scale and the self-report of having or not undergone screening at 6 months. This study will add to the body of evidence on the role of decision aids to support health preference-sensitive choices and provide further insight on the impact of different methods for eliciting people's values embedded within a decision aid. NCT03988673 - clinicalTrials.gov (2019/06/17).


Combination COX-2 inhibitor and metformin attenuate rate of joint replacement in osteoarthritis with diabetes: A nationwide, retrospective, matched-cohort study in Taiwan.
Osteoarthritis (OA) is the most common form of arthritis associated with an increased prevalence of type 2 diabetes mellitus (T2DM), however their impact on decreasing joint replacement surgery has yet to be elucidated. This study aimed to investigate if the combination of COX-2 inhibitor and metformin therapy in OA with T2DM were associated with lower the rate of joint replacement surgery than COX-2 inhibitor alone. In total, 968 subjects with OA and T2DM under COX-2 inhibitor and metformin therapy (case group) between 1 January to 31 December 2000 were selected from the National Health Insurance Research Database of Taiwan, along with 1936 patients were the 1:2 gender-, age-, and index year-controls matched without metformin therapy (control group) in this study. Cox proportional hazards analysis was used to compare the rate of receiving joint replacement surgery during 10 years of follow-up. At the end of follow-up, 438 of all enrolled subjects (15.08%) had received the joint replacement surgery, including 124 in the case group (12.81%) and 314 in the control group (16.22%). The case group tended to be associated with lower rate of receiving the joint replacement surgery at the end of follow-up than the control group (p = 0.003). Cox proportional hazards regression (HR) analysis revealed that study subjects under combination therapy with metformin had lower rate of joint replacement surgery (adjusted HR 0.742 (95% CI = 0.601-0.915, p = 0.005)). In the subgroups, study subjects in the combination metformin therapy who were female, good adherence (>80%), lived in the highest urbanization levels of residence, treatment in the hospital center and lower monthly insurance premiums were associated with a lower risk of joint replacement surgery than those without. Patients who have OA and T2DM receiving combination COX-2 inhibitors and metformin therapy associated with lower joint replacement surgery rates than those without and this may be attributable to combination therapy much more decrease pro-inflammatory factors associated than those without metformin therapy.


Spectrum of diagnostic errors in radiology.
Diagnostic errors are important in all branches of medicine because they are an indication of poor patient care. Since the early 1970s, physicians have been subjected to an increasing number of medical malpractice claims. Radiology is one of the specialties most liable to claims of medical negligence. Most often, a plaintiff's complaint against a radiologist will focus on a failure to diagnose. The etiology of radiological error is multi-factorial. Errors fall into recurrent patterns. Errors arise from poor technique, failures of perception, lack of knowledge and misjudgments. The work of diagnostic radiology consists of the complete detection of all abnormalities in an imaging examination and their accurate diagnosis. Every radiologist should understand the sources of error in diagnostic radiology as well as the elements of negligence that form the basis of malpractice litigation. Error traps need to be uncovered and highlighted, in order to prevent repetition of the same mistakes. This article focuses on the spectrum of diagnostic errors in radiology, including a classification of the errors, and stresses the malpractice issues in mammography, chest radiology and obstetric sonography. Missed fractures in emergency and communication issues between radiologists and physicians are also discussed.


Effects of chronic treatment with clofibric acid on response of rat hepatocytes to mitogenic stimuli.
Mitoinhibitory effects of clofibric acid (CA) were investigated in rat hepatocytes in vitro and in vivo. Female Sprague-Dawley rats, 11 weeks of age, were dietetically treated with CA at 9000 ppm for up to 13 weeks. In the in vitro study, hepatocytes were isolated from rats on day 4 and in weeks 1, 2, 5, 9 and 13, and cultured for 48 h in a medium containing epidermal growth factor. Over the last 24 h, bromodeoxyuridine (BrdU) was added to the medium to determine number of hepatocytes in S-phase. The labeling index (LI) of CA-treated hepatocytes in culture was below control values as early as day 4, and progressively declined with increasing treatment period. In the in vivo study, rats were 2/3 partially hepatectomized at week 13 and maintained for 24 h. BrdU was injected intraperitoneally 1 h prior to necropsy. The LI in the CA-treated liver was also decreased. These data indicated that continuous treatment of CA resulted in decreases in hepatocyte response to growth stimuli, and suggested a possible relation between the chronic growth inhibitory effect on cell multiplication and tumor promotion in rat hepatocarcinogenesis.


Exact computation and large angular momentum asymptotics of 3nj symbols: Semiclassical disentangling of spin networks.
Spin networks, namely, the 3nj symbols of quantum angular momentum theory and their generalizations to groups other than SU(2) and to quantum groups, permeate many areas of pure and applied science. The issues of their computation and characterization for large values of their entries are a challenge for diverse fields, such as spectroscopy and quantum chemistry, molecular and condensed matter physics, quantum computing, and the geometry of space time. Here we record progress both in their efficient calculation and in the study of the large j asymptotics. For the 9j symbol, a prototypical entangled network, we present and extensively check numerically formulas that illustrate the passage to the semiclassical limit, manifesting both the occurrence of disentangling and the discrete-continuum transition.


Developing the next generation of leaders.
Linking the elements of management development to organizational culture and business goals is essential for a successful leadership program. Establishing such a program in your practice is not enough, however--an organization must also evaluate its effect on performance. For organizations that embrace and institute training and leadership development, the financial payoffs can be substantial.


Magnetic resonance imaging of gadolinium-labeled pancreatic islets for experimental transplantation.
New imaging techniques that couple anatomical resolution to sensitivity may greatly contribute to improving islet transplantation. In the present work, a report is given of the direct detection of islets by magnetic resonance imaging (MRI) after ex vivo cell labeling with the MRI T(1) contrast agent GdHPDO3A. Experiments on mouse and human islets demonstrated well-tolerated uptake of GdHPDO3A, based on morphology, viability, glucose-dependent insulin response and apoptosis/toxicity gene array profile. GdHPDO3A loading was sufficient for in vitro MRI cell detection. In vivo isotransplanted mouse islets into the kidney capsule and xenotransplanted human islets within the mouse liver were detected. Imaging specificity was supported by the absence of signal in unlabeled islet transplants, its persistence upon using fat-suppression MRI protocols and the colocalization with the transplanted islets. In conclusion, direct islet imaging with high spatial and contrast resolution after labeling with GdHPDO3A is demonstrated, allowing visualization of kidney subcapsular mouse islet grafts and intrahepatic human islet xenografts.


Application of Machine Learning and Internet of Things Techniques in Evaluation of English Teaching Effect in Colleges.
College English classroom teaching evaluation is one of the key issues discussed by all schools at present. First of all, teachers and students are highly concerned about English learning in the compulsory course of English examination, but there are also many problems. The distance network teaching with computer technology as the main body develops rapidly, a large number of video and audio teaching resources network through the network transmission to present in front of learners, through the network transmission of video and audio aided, expand the audience of network teaching, is conducive to the realization of digitalization, information, lifelong, new education goals. Firstly, this article summarizes the problems of poor effect, uneven performance, and mismatch between evaluation and teaching in college English at present. Then, based on the previous works, the author designed a machine learning-based Internet of things technology and verifies its feasibility. The data of teaching experiments show that the writing performance of the students in the lower section of the experimental class is better than that of the students in the middle and high sections. Among them, significant progresses have been made in grammar, length, expression, and structure, which has optimized students' preclass preview efficiency, autonomous learning motivation, quality of homework completion, and afterclass reflection behavior. Finally, the author summarized the shortcomings of this research and puts forward the prospect of relevant research, in order to provide reference value for the national college English blended teaching and promotes the efficient implementation and vigorous development of college English teaching. In the future, the evaluation index system under the pressure of performance can be further studied.


[What are the needs of caregivers caring for people living in chronic conditions? Qualitative research].
The population ageing generates new challenges related to the treatment of chronic diseases. The course of the disease makes patients and caregivers (CGs) vulnerable and their ability to self-care is threatened. CGs can be supported by the Advanced Practice Nurse (APN). The aim is to deepen the CGs' needs of people with chronic conditions in Insubrica region. It's a qualitative descriptive survey, conducted between September 2019 and February 2020. The CGs' convenience sample of people with chronic illness was differentiated by age, gender, profession, chronic diseases and included 20 participants. Data were collected through short motivational interviews and the compilation of a socio-family genogram. The thematic analysis of the interviews' Verbatim transcription was carried out by 4 researchers. The thematic analysis has shown 26 themes collected in 6 macrothemes and in addition highlighted that the chronic condition and vulnerability are linked together; therapeutic adherence and self-care depend on disease awareness, and CGs make little use of the social support network; CONCLUSION: Based on the results, it can be said that the APN can meet the GCs' needs through the skills gained in training (CanMEDS and Hamric model); encourage inter-professional and integrated care, and promote the formal and informal network.


Milk precipitins, circulating immune complexes, and IgA deficiency.
Twenty-two patients with selective IgA deficiency were studied for the presence of serum precipitins to bovine milk, bovine and fetal calf serum, and circulating immune complexes. Fifty-nine percent had circulating immune complexes, 50% had milk precipitins, 23% had precipitins to bovine serum, and 13% had precipitins to fetal calf serum. All patients with precipitating antibodies against milk or against bovine or fetal calf serum had circulating immune complexes and the precipitin titers correlated with the amount of circulating immune complexes. After one IgA-deficient patient had drunk 100 ml of milk, studies of sequential serum samples showed the presence of casein in the circulation at 60 min and the appearance of increasing amounts of immune complexes for 120 min. These findings are interpreted to indicated that in human beings the IgA system may provide a major barrier to absorption of immunogens from the gastrointestinal tract.


Imaging motor recovery after stroke.
Most patients show improvement in the weeks or months after a stroke. Recovery is incomplete, however, leaving most with significant impairment and disability. Because the brain does not grow back to an appreciable extent, this recovery occurs on the basis of change in function of surviving tissues. Brain mapping studies have characterized a number of processes and principles relevant to recovery from stroke in humans. The findings have potential application to improving therapeutics that aim to restore function after stroke.


Distribution of copper-64 in control mice and in mice bearing ascitic Krebs tumor cells.
Three to 20 hr after an i.p. injection of 64Cu (half-life, 12.8 hr) into mice bearing Krebs ascites cells, a high amount of the radioisotope was recovered in the ascites cells themselves. In the control group, the radioisotope was mainly present in the liver. Similar amounts of 64Cu were recovered in regenerating as well as in normal liver, whereas in the liver of mice bearing ascites cells, this amount was lower by 40 to 50% regardless of the ascitic volume. Thus, the copper metabolism seems to be disturbed at the hepatic level in mice bearing ascites cells. The distribution of 64Cu was 'analyzed in DNA, RNA, and proteins from cellular lysates fractionated by CsCl gradient. There was a uniform pattern of distribution in the macromolecules from ascites cells, while 64Cu' was preferentially associated with the protein fraction from liver. Further experiments indicated that, in vivo, 64Cu was bound to the DNA of ascites cells.


Reanalysis of the Aqueous Spectrum of the Neptunyl(V) [NpO2(+)] Ion.
The actinyl ions, consisting of the dioxoactinde(VI) and dioxoactinide(V) ions, are unique in the periodic table. However, very few quantitative studies of the spectra of these ions have been performed. In this paper the analysis of the optical spectrum of the aqueous neptunyl(V) [NpO2(+)] ion in 1 M HClO4 is reexamined. The species in solution is assumed to be the linear NpO2(+) ion surrounded in the equatorial plane by five oxygen atoms from five H2O molecules. The neptunyl(V) ion has the 5f(2) open-shell configuration, and the low-lying optical transitions (up to ∼20 000 cm(-1)) observed are primarily from the two 5f electrons occupying the 5fφ and 5fδ orbitals. The conventional parametric theory used for f(n) systems is applied to these low-lying transitions utilizing the intensity calculations that Matiska et al.1 have performed for this ion and the data reported by Eisenstein and Pryce.2 Possible ratios for the Slater electrostatic repulsion parameters are obtained from the data for the isoelectronic ion U(4+) (5f(2)) in various host crystals. The results are consistent with earlier crystal field analyses of the 5f(1) neptunyl(VI) [NpO2(2+)] ion.


A method for adjusting gender bias in neonatal tetanus reports in Egypt 1991.
Reports of neonatal tetanus (NT) disease, common in developing countries, often suffers from gender bias because male infants are brought to health facilities while females are attended at home. Using existing health data we applied reasonable assumptions to estimate the true incidence of NT economically. To adjust for gender disparities in national reporting, we ignored the number of female NT cases and doubled the number for males. Governorates with similar demographic risk profiles for NT were assigned to one of six groups. The highest incidence rate within the group was determined and applied to the number of live births represented by the group. Other internal data comparisons were done to support our estimate that the male:female ratio of NT incidence was far less than the reported 412:1. In 1991, the male: female ratio of NT cases was 4.12:1. Decreasing the male: female ratio to 1:1 decreased sensitivity to a 62% estimate. Further adjusting for assumed under-reporting by governorates based on population profiles yielded a reporting sensitivity of 40%. Estimated male and female age-specific NT mortality rates from available data supported the assumption that NT mortality ratios are less than 4.12:1. This report, therefore, describes a unique, economical method to estimate the incidence of a disease assumed to be affected by gender biases in the reporting system. The method relies on two assumptions: that the true NT male:female ratio is close to 1:1 and that populations with similar demographics within a country should have similar incidence rates of NT.


Self-Assembly of Ferritin Nanoparticles into an Enzyme Nanocomposite with Tunable Size for Ultrasensitive Immunoassay.
The self-assembly of nanoparticles into larger superstructures is a powerful strategy to develop novel functional nanomaterials, as these superstructures display collective properties that are different to those displayed by individual nanoparticles or bulk samples. However, there are increasing bottlenecks in terms of size control and multifunctionalization of nanoparticle assemblies. In this study, we developed a self-assembly strategy for construction of multifunctional nanoparticle assemblies of tunable size, through rational regulation of the number of self-assembling interaction sites on each nanoparticle. As proof-of-principle, a size-controlled enzyme nanocomposite (ENC) was constructed by self-assembly of streptavidin-labeled horseradish peroxidase (SA-HRP) and autobiotinylated ferritin nanoparticles (bFNP). Our ENC integrates a large number of enzyme molecules, together with a streptavidin-coated surface, allowing for a drastic increase in enzymatic signal when the SA is bound to a biotinylated target molecule. As result, a 10 000-fold increase in sensitivity over conventional enzyme-linked immunosorbent assays (ELISA) methods was achieved in a cardiac troponin immunoassay. Our method presented here should provide a feasible approach for constructing elaborate multifunctional superstructures of tunable size useful for a broad range of biomedical applications.


New trends in the interventional treatment of ischaemic heart disease.
Direct revascularization of an ischaemic vascular bed represents an attractive treatment option for patients with coronary artery disease. Coronary artery bypass surgery has been demonstrated to provide both symptomatic improvement and, in certain circumstances, to improve prognosis, while catheter-based techniques offer substantial improvement in symptomatology, with reduced morbidity compared with bypass surgery. Although balloon angioplasty has been associated with lesion success rates approximating to 89%, a number of anatomical substrates have proved refractory to this approach and restenosis remains a significant problem. Newer interventional modalities, such as directional atherectomy, rotablation, transluminal extraction catheterization, laser coronary angioplasty and coronary stenting, all have the potential to offer improved rates of restenosis under specific circumstances. With the exception of stents, most have not been shown to provide an overall improvement in rates of restenosis. Numerous pharmacological agents have also been investigated in an attempt to reduce levels of restenosis. Calcium channel blockers have been assessed in five trials, none of which has demonstrated a conclusive benefit, although meta-analysis of the data generated in these trials has shown a 30% reduction in the likelihood of restenosis associated with their use. More recently, monoclonal antibodies to glycoprotein IIb/IIIa have been linked to a reduction in restenosis.


Dioscin protects against diabetic nephropathy by inhibiting renal inflammation through TLR4/NF-κB pathway in mice.
Diabetic nephropathy (DN) is a chronic kidney disease caused by the long-term loss of renal function, which occurs in 20% - 40% of all diabetes and is also the primary cause of end-stage renal diseases. DN is related with other lethal diseases, particularly cardiovascular diseases, leading to an increased risk of death. Therefore, an effective treatment for DN is required. Here we tested the protective effect of dioscin in a mouse model of streptozocin (STZ)-induced DN. First, STZ was intraperitoneally injected into C57BL/6 J mice and TLR4-/- mice respectively, on a daily basis for 5 days to induce diabetes. Dioscin was then orally administered into diabetic mice daily for 8 weeks. Our results show that STZ injection effectively induced diabetes in mice as indicated by the increased blood glucose levels in C57BL/6 J mice, whereas it did not cause diabetes in TLR4-/- mice. Dioscin significantly ameliorated STZ-induced renal damage via reducing inflammatory responses in diabetic mice and antagonizing the activation of TLR4/NF-κB pathway and the production of inflammatory cytokines. In conclusion, our study highlights the potential of dioscin as a novel approach to treat DN in diabetic patients.


[Other treatments for depressive patients].
Electroconvulsive therapy(ECT) is one of the most important methods in treating depressive patients especially who can not be improved with medication. Meta analysis shows that ECT is superior to pharmacotherapy as acute treatment for depression. ECT was invented in 1938, and it took some improvement afterwards such as development of modified ECT and introduction of brief-pulse stimulation for the purpose of reducing adverse effects. However, adverse effects such as cognitive impairment are not completely solved, and some patients do not respond to ECT. Transcranial magnetic stimulation (TMS), vagus nerve stimulation (VNS) and deep brain stimulation (DBS) are under investigation to get over the shortcomings of ECT.


Inhalation therapy in the next decade: Determinants of adherence to treatment in asthma and COPD.
Proceedings of the European Seminars in Respiratory Medicine course, Inhalation therapy in the next decade: Determinants of adherence to treatment in asthma and COPD, held in Taormina, Italy, on 3-4 March, 2017.


Epigenetic regulation of insulin action and secretion - role in the pathogenesis of type 2 diabetes.
The prevalence of type 2 diabetes (T2D) is rapidly increasing worldwide. Obesity, physical inactivity and ageing increase the risk of T2D. Epigenetic modifications can change due to environmental exposures and may thereby predispose to disease. This review aims at summarizing recent advances in epigenetics related to T2D, with a special focus on impaired insulin action and secretion in humans. There will be an emphasis on analyses in human tissues; both from T2D case-control cohorts and intervention studies. Current data support an important role for epigenetics in the pathogenesis of T2D. Numerous studies have found differential DNA methylation and gene expression in skeletal muscle, adipose tissue, the liver and pancreatic islets from subjects with T2D compared with nondiabetic controls. For example, PDX1 has increased DNA methylation and decreased expression in pancreatic islets from patients with T2D compared with nondiabetic controls. Nongenetic risk factors for T2D such as ageing, unhealthy diets and physical activity do also impact the epigenome in human tissues. Interestingly, physical activity altered DNA methylation of candidate genes for T2D such as THADA in muscle and FTO, KCNQ1 and TCF7L2 in adipose tissue. There is also a strong interaction between genetic and epigenetic factors that together seem to affect T2D. mQTL studies in human adipose tissue and pancreatic islets showed that SNPs associated with DNA methylation levels in numerous sites. Several of these SNPs are also associated with T2D. Recent data also support that DNA methylation of some sites in blood may be developed into biomarkers that predict T2D since methylation of, for example TXNIP, ABCG1 and SREBF1 associated with future T2D. Future studies should use this information for development of new therapies and biomarkers and thereby improve prediction, prevention and treatment of T2D and its complications.


Cytomegalovirus antiviral resistance associated with treatment induced UL97 (protein kinase) and UL54 (DNA polymerase) mutations.
HCMV-related illness due to infections with antiviral resistant virus was verified by phenotypic and genotypic assays in 17% (8/47) of high-risk immunocompromised Australian patients. Selective PCR-sequencing of UL97 (protein kinase; PK) and UL54 (DNA polymerase; DNApol) regions important for antiviral sensitivity, identified the majority (6/8) of resistant strains through detection of mutations known to confer antiviral resistance. Additionally, eight UL54 (DNApol) mutations (N408K, T691S, A692V, S695T, L737M, A834P, V955I, and A972V) of unknown phenotype were identified in six specimens from patients with clinical evidence of antiviral resistant infections. One isolate was resistant to ganciclovir (GCV) and another resistant to PFA on phenotypic testing where mutations in UL97 (PK) or UL54 (DNApol) were not detected, suggesting a loss of correlation between phenotype and genotype. Selective PCR-sequencing of UL97 (PK) and UL54 (DNApol) provided rapid and comprehensive results, but missed some resistance detected by phenotypic assays. A combination of phenotypic and genotypic assays is recommended for complete analysis of CMV antiviral resistance, as well as further definition of the clinical relationship between novel UL54 (DNApol) mutations and antiviral resistance.


MEDLARS utilization profile in New England.
The Northeastern Consortium for Health Information's Ad Hoc Committee on Online Statistics conducted a three-month MEDLARS utilization study in New England. Mailing lists from the New England Regional Medical Library Service and the New England Online Users Group were used to solicit participants. Seventy-four libraries submitted data on 8,899 MEDLARS searches. Each search was described by (1) type of institution; (2) occupation of requester; (3) purpose of search; (4) whether requester was a new or repeat user; (5) if the requester was from inside or outside the online center's institution; (6) fees-for-service; and (7) choice of vendor or vendors for accessing MEDLARS. Overall, patient care and research were the most frequently stated purposes of search; 44% of the searches were initiated by physicians.


cisMEP: an integrated repository of genomic epigenetic profiles and cis-regulatory modules in Drosophila.
Cis-regulatory modules (CRMs), or the DNA sequences required for regulating gene expression, play the central role in biological researches on transcriptional regulation in metazoan species. Nowadays, the systematic understanding of CRMs still mainly resorts to computational methods due to the time-consuming and small-scale nature of experimental methods. But the accuracy and reliability of different CRM prediction tools are still unclear. Without comparative cross-analysis of the results and combinatorial consideration with extra experimental information, there is no easy way to assess the confidence of the predicted CRMs. This limits the genome-wide understanding of CRMs. It is known that transcription factor binding and epigenetic profiles tend to determine functions of CRMs in gene transcriptional regulation. Thus integration of the genome-wide epigenetic profiles with systematically predicted CRMs can greatly help researchers evaluate and decipher the prediction confidence and possible transcriptional regulatory functions of these potential CRMs. However, these data are still fragmentary in the literatures. Here we performed the computational genome-wide screening for potential CRMs using different prediction tools and constructed the pioneer database, cisMEP (cis-regulatory module epigenetic profile database), to integrate these computationally identified CRMs with genomic epigenetic profile data. cisMEP collects the literature-curated TFBS location data and nine genres of epigenetic data for assessing the confidence of these potential CRMs and deciphering the possible CRM functionality. cisMEP aims to provide a user-friendly interface for researchers to assess the confidence of different potential CRMs and to understand the functions of CRMs through experimentally-identified epigenetic profiles. The deposited potential CRMs and experimental epigenetic profiles for confidence assessment provide experimentally testable hypotheses for the molecular mechanisms of metazoan gene regulation. We believe that the information deposited in cisMEP will greatly facilitate the comparative usage of different CRM prediction tools and will help biologists to study the modular regulatory mechanisms between different TFs and their target genes.


New 3-deoxyanthocyanidins from leaves of Arrabidaea chica.
Two new 3-deoxyanthocyanidins, 6,7,3',4'-tetrahydroxy-5-methoxyflavylium and 6,7,4'-trihydroxy-5-methoxyflavylium, and the pigment carajurin, which has been previously identified, were isolated from dried leaves of Arrabidaea chica, a creeper native to the American tropics. The structures of the components were elucidated by 1H- and 13C-NMR spectroscopy and HPLC-MS, including X-ray crystallographic analysis for carajurin.


A RCT of psychotherapy in women with nausea and vomiting of pregnancy.
Does adding psychological intervention to medical therapy improve nausea/vomiting, psychological symptoms, and pregnancy distress in women with moderate nausea and vomiting of pregnancy (NVP)? Three weeks of medical therapy plus psychotherapy yielded statistically and clinically significant improvements in NVP-specific symptoms, anxiety/depression symptoms, and pregnancy distress, compared with medical therapy alone. Pregnancy with nausea/vomiting is associated with psychiatric morbidity. Evidence supports the exploration of psychosocial reactions in addition to biochemical markers related to NVP. This prospective, open-label, randomized, controlled, parallel-group study was performed at two obstetrics clinics in Iran. A total of 86 women, aged 18-40 years, between 6 and 12 weeks pregnant with moderate NVP, more than 5 years of education, and not currently practicing any relaxation techniques or undergoing any psychotherapy, were enrolled from June 2013 to November 2014. A total of 86 moderate NVP women were randomly allocated to either a control (medical therapy alone) or experimental (medical therapy plus psychotherapy) group. Block randomization was achieved using a paper list prepared by an investigator with no clinical involvement in the trial. The experimental group was given pyridoxine hydrochloride (40 mg daily) for 3 weeks, and also received intensive mindfulness-based cognitive therapy (MBCT) in eight individual sessions (50 min each) over 3 weeks. The control group was given pyridoxine hydrochloride (40 mg daily tablet) for 3 weeks alone. All participants completed the Rhodes index of nausea, vomiting and retching (RINVR), the hospital anxiety and depression scale (HADS), and the prenatal distress questionnaire (PDQ) at baseline, 3 weeks after baseline at the end of the study, and at a 1 month post-treatment follow-up. Linear mixed-effects models were used, in an intention-to-treat analysis. In the psychotherapy plus medical therapy group, the mean relative difference between baseline and post-treatment decreased for RINVR; nausea 8.2 (95% confidence interval (CI) 4.1, 10.2), vomiting 3.5 (95% CI 1.5, 5.8), and total RINVR 11.7 (95% CI 6.5, 16.5), for HADS; anxiety 5.1 (95% CI 3.2, 9.2), depression 3.5 (95% CI 2.4, 7.3), total HADS 7.2 (95% CI 4.4, 12.1), for PDQ; birth concerns 3.3 (95% CI 1.3, 9.1), body concerns 1.5 (95% CI 0.9, 5.1), relationship concerns 2.1 (95% CI 1.2, 5.9), and total PDQ 5.9 (95% CI 3.5, 10.6). At 1 month after treatment, the statistically significant improvement in RINVR, HADS and PDQ, as well as clinical improvement in severity of symptoms, persisted. Medical therapy plus psychotherapy also improved nausea/vomiting symptoms, psychological symptoms, and reduced pregnancy distress more than medical therapy alone, with an effect size of 0.42-0.72 over the trial period. The conclusions were limited to a small number of women with moderate NVP. It is unclear whether the difference between the outcomes in the different groups was related to MBCT alone, or to the extra time and attention paid to patients in the medical therapy plus psychotherapy. The participants in the study did not remain blind to the treatment and the outcome may only be representative of women with moderate NVP who have been referred to obstetrics clinics. These findings show that adding 3 weeks of psychological intervention to medical therapy may appear to produce positive therapeutic outcomes upon conclusion of treatment, and 1 month after treatment. This suggests that psychotherapy should be considered as an adjunctive treatment option for women with moderate NVP. In future studies, however, a group of patients who are receiving placebo psychotherapy along with medical treatment should be included. Furthermore, an economic evaluation of the addition of psychological intervention to standard medical therapy would be useful.


Systematic review of 2008-2012 literature and update of recommendations for the use of methotrexate in rheumatic diseases, with a focus on rheumatoid arthritis.
The objective of this review is to update the recommendations of the 2010 Italian Consensus on the use of methotrexate (MTX) in rheumatoid arthritis (RA) and other rheumatic diseases. The literature published between 2008 and 2012 was systematically reviewed and updated recommendations on MTX use in rheumatic diseases, particularly RA, were formulated. These recommendations were approved by a panel of expert Italian Rheumatologists. A total of 10,238 references were identified, among which 70 studies were selected for critical evaluation. Sufficient evidence had accumulated to warrant changes to several of the recommendations in the new version. A new recommendation for patients with RA who are in MTX-induced clinical remission was also proposed and approved by the panel. Updated recommendations for the use of MTX in patients with RA or other rheumatologic disease are proposed.


Experimental GABA A Receptor Agonists and Allosteric Modulators for the Treatment of Focal Epilepsy.
GABA A receptors are ubiquitous in the central nervous system and there is a huge diversity of receptor subtypes in almost all regions of the brain. However, the expression of GABA A receptor subtypes is altered in both the gray and white matter of patients with focal epilepsy. Although there is a number of anticonvulsants with marketing authorization for the treatment of focal epilepsy which act through GABA A receptors, potentiating the inhibitory effects of GABA, it is necessary to develop more potent and more specific GABAergic anticonvulsants that are effective in drug-resistant patients with focal epilepsy. There are three orthosteric and at least seven allosteric agonist binding sites at the GABA A receptor. In experimental and clinical studies, full agonists of GABA A receptors showed a tendency to cause desensitization of the receptors, tolerance, and physical dependence; therefore, partial orthosteric agonists and positive allosteric modulators of GABA A receptors were further developed. Preclinical studies demonstrated the anticonvulsant efficacy of positive allosteric modulators with selective action on GABA A receptors with α2/α3 subunits, but only a handful of them were further tested in clinical trials. The best results were obtained for clobazam (already marketed), ganaxolone (in phase III trials), CVL-865 (in phase II trials), and padsevonil (in phase III trials). Several compounds with more selective action on GABA A receptors, perhaps only in certain brain regions, have the potential to become effective drugs against specific subtypes of focal-onset epilepsy. However, their development needs time, and in the near future we can expect only one or two new GABA A agonists to obtain marketing authorization for focal epilepsy, an advance that would be of use for just a fraction of patients with drug-resistant epilepsy.


Sex and gender differences in hypertensive kidney injury.
Hypertension is a complex, multifaceted disorder, affecting ~1 in 3 adults in the United States. Although hypertension occurs in both men and women, there are distinct sex differences in the way in which they develop hypertension, with women having a lower incidence of hypertension until the sixth decade of life. Despite observed sex differences in hypertension, little is known about the molecular mechanisms underlying the development of hypertension in females, primarily because of their underrepresentation in both clinical and experimental animal studies. The first goal of this review is to provide a concise overview of the participation of women in clinical trials, including a discussion of the importance of including females in basic science research, as recently mandated by the National Institutes of Health. The remaining portion of the review is dedicated to identifying clinical and experimental animal studies that concentrate on gender and sex differences in hypertensive kidney disease, ending with a proposed role for T cells in mediating sex differences in blood pressure.


Application of hydrologic forecast model.
In order to overcome the shortcoming of the solution may be trapped into the local minimization in the traditional TSK (Takagi-Sugeno-Kang) fuzzy inference training, this paper attempts to consider the TSK fuzzy system modeling approach based on the visual system principle and the Weber law. This approach not only utilizes the strong capability of identifying objects of human eyes, but also considers the distribution structure of the training data set in parameter regulation. In order to overcome the shortcoming of it adopting the gradient learning algorithm with slow convergence rate, a novel visual TSK fuzzy system model based on evolutional learning is proposed by introducing the particle swarm optimization algorithm. The main advantage of this method lies in its very good optimization, very strong noise immunity and very good interpretability. The new method is applied to long-term hydrological forecasting examples. The simulation results show that the method is feasible and effective, the new method not only inherits the advantages of traditional visual TSK fuzzy models but also has the better global convergence and accuracy than the traditional model.


A Novel Antifibrotic Mechanism of Nintedanib and Pirfenidone. Inhibition of Collagen Fibril Assembly.
Idiopathic pulmonary fibrosis (IPF) is characterized by excessive deposition of extracellular matrix, in particular, collagens. Two IPF therapeutics, nintedanib and pirfenidone, decelerate lung function decline, but their underlying mechanisms of action are poorly understood. In this study, we sought to analyze their effects on collagen synthesis and maturation at important regulatory levels. Primary human fibroblasts from patients with IPF and healthy donors were treated with nintedanib (0.01-1.0 μM) or pirfenidone (100-1,000 μM) in the absence or presence of transforming growth factor-β1. Effects on collagen, fibronectin, FKBP10, and HSP47 expression, and collagen I and III secretion, were analyzed by quantitative polymerase chain reaction and Western blot. The appearance of collagen fibrils was monitored by scanning electron microscopy, and the kinetics of collagen fibril assembly was assessed using a light-scattering approach. In IPF fibroblasts, nintedanib reduced the expression of collagen I and V, fibronectin, and FKBP10 and attenuated the secretion of collagen I and III. Pirfenidone also down-regulated collagen V but otherwise showed fewer and less pronounced effects. By and large, the effects were similar in donor fibroblasts. For both drugs, electron microscopy of IPF fibroblast cultures revealed fewer and thinner collagen fibrils compared with untreated controls. Finally, both drugs dose-dependently delayed fibril formation of purified collagen I. In summary, both drugs act on important regulatory levels in collagen synthesis and processing. Nintedanib was more effective in down-regulating profibrotic gene expression and collagen secretion. Importantly, both drugs inhibited collagen I fibril formation and caused a reduction in and an altered appearance of collagen fibril bundles, representing a completely novel mechanism of action for both drugs.


Iliac crest bone grafting for mandibular reconstruction: 10-year experience outcomes.
To evaluate 10-year patient data related to mandibular reconstruction with NVBG at a tertiary academic center. Sixty patients with mandibular mandibular reconstruction were included. Patients were divided to continuity defect and non-continuity defect. Pathology lesion, immediate reconstruction, smoking habit, medical comorbidities, site and size of the defect, surgical approach, intraoperative perforation, cadaveric bone use, and maxilla-mandibular fixation use were analyzed as factors of influence on success. Success was defined as maintenance of more than 50% of graft for non-continuity defects (NCD) and bone continuity and stability for continuity defect (CD), and absence of infection on last follow up upon clinical and radiographic examination. Complications were classified as minor or major. The reconstruction was successful in 28 (87%) of CD patients and 23 (82.1%) of NCD patients. Analyses showed that the size of defect was significantly associated with failure. All 4 failed cases of CD had defects more than 9 cm. Four patients had major complications and 43 minor complication. Nonvascularized iliac crest bone grafts are highly successful in mandibular continuity reconstruction for non-Cancer patients and should be considered as first choice for defects less than 9 cm. They are less predictable for defects larger than 9 cm but can be considered in these cases with osteoconductive cribs. Symphysis involvement may or may not be associated with lower success rate if our protocol is followed.


Web-based software tool for constraint-based design specification of synthetic biological systems.
miniEugene provides computational support for solving combinatorial design problems, enabling users to specify and enumerate designs for novel biological systems based on sets of biological constraints. This technical note presents a brief tutorial for biologists and software engineers in the field of synthetic biology on how to use miniEugene. After reading this technical note, users should know which biological constraints are available in miniEugene, understand the syntax and semantics of these constraints, and be able to follow a step-by-step guide to specify the design of a classical synthetic biological system-the genetic toggle switch.1 We also provide links and references to more information on the miniEugene web application and the integration of the miniEugene software library into sophisticated Computer-Aided Design (CAD) tools for synthetic biology ( www.eugenecad.org ).


Dedifferentiated endometrioid adenocarcinoma; clinicopathologic and immunohistochemical features of five cases
Dedifferentiated endometrioid adenocarcinoma is a recently defined uterine tumor composed of low-grade endometrioid adenocarcinoma and undifferentiated carcinoma. Herein, we present clinicopathologic, morphologic, and immunohistochemical features of 5 cases of dedifferentiated endometrioid adenocarcinoma. All cases which were diagnosed as mixed endometrial adenocarcinoma (endometrioid+undifferentiated carcinoma) or dedifferentiated endometrioid adenocarcinoma between January 2008 and December 2014 were retrieved from the archives of our institution's pathology department. The median age of the patients was 58 years. Polypoid growth pattern was seen in 3 patients and 2 were diagnosed at advanced stage. All patients received either external radiotherapy, brachytherapy, chemotherapy or an appropriate combination according to the stage. Only one patient died of the disease. Microscopically, there was a sharp demarcation between the two tumor components. The undifferentiated carcinoma component was composed of diffuse sheets of monomorphic cells lacking any differentiation. Focal pleomorphism and rhabdoid features were also noted. The undifferentiated carcinoma component was variably positive for PAX-8, cytokeratin, EMA, estrogen receptor, and neuroendocrine markers. Misdiagnosis of undifferentiated carcinoma in dedifferentiated endometrioid adenocarcinoma as grade 3 endometrioid adenocarcinoma is not uncommon. The recognition of morphologic and immunohistochemical features of this newly described entity is crucial because it alters treatment and prognosis.


Assessment of the Clinical Performance of Platelet Concentrates Treated by Pathogen Reduction Technology in Santiago de Compostela.
This study assessed the feasibility, performance, and safety of Mirasol®-treated platelet concentrates (M-PC) stored for up to 7 days. This prospective observational study was approved by the ethical committee of the University Clinic of Santiago de Compostela. Informed consent was asked from patients receiving M-PC. M-PCs were treated with the Mirasol system according to the manufacturer's instructions. Thrombocytopenic patients were transfused according to the Spanish transfusion guidelines. Post-transfusion platelet counts were measured at 1 h and/or 24 h after transfusion. Post-transfusion surveillance of patients was maintained during the study. Data from 54 evaluable patients and 135 transfusions were analyzed. The mean age of patients was 58 years. The mean age of M-PC at transfusion was 3.6 days. The mean platelet dose was 3.7 × 1011. The transfusion responses measured as mean corrected count increment 1 h after transfusion (CCI1h) and CCI24h were 9,659 and 4,751, respectively. 65% of transfusions resulted in CCI1h values ≥ 7,500. 51% of transfusions resulted in CCI24h values ≥ 4,500. The use of M-PC in the supportive treatment proved to be safe and effective for this cohort of thrombocytopenic patients.


Strongly enhancing photostimulated luminescence by doping Tm3+ in Sr3SiO5: Eu2+.
We report a large enhancement of yellow photostimulated luminescence (PSL) by codoping Tm3+ in Sr3SiO5:Eu2+ upon infrared stimulation at 980 nm after pre-exposure in Ultraviolet light. The initial PSL intensity and light storage capacity are enhanced by a factor of 33 and 2, respectively, for Tm3+ concentration at 0.0004. The thermoluminescence spectra indicate that codoping Tm3+ generates a trap peaking at 385 K. The trap is much more sensitive to infrared light than the original one, so that the light storage period of the material is beyond tens of days with the minimum detectable infrared power density only 54 μW/cm2.


Aging, climate change, and legacy thinking.
Climate change is a complex, long-term public health challenge. Older people are especially susceptible to certain climate change impacts, such as heat waves. We suggest that older people may be a resource for addressing climate change because of their concern for legacy--for leaving behind values, attitudes, and an intact world to their children and grandchildren. We review the theoretical basis for "legacy thinking" among older people. We offer suggestions for research on this phenomenon, and for action to strengthen the sense of legacy. At a time when older populations are growing, understanding and promoting legacy thinking may offer an important strategy for addressing climate change.


Saccadic visual suppression and down-beat nystagmus: a case of Arnold-Chiari malformation.
A case is reported in which visual disturbances associated with the sole physical finding of downbeat nystagmus led to investigation of a patient for a foramen magnum lesion. The Arnold-Chiari malformation was suggested by air study and confirmed at surgery. It is suggested that the phenomenon of saccadic suppression was responsible for the patient's visual disability. This was unaccompanied by any of the other neurological manifestations of the Arnold-Chiari malformation. Cases presenting in this manner, with only visual disturbances, may run the risk of being unrecognized for some time as a result.


[Risk factors for cutaneous wart onset in transplant recipients].
Transplant recipients are at increased risk for cutaneous warts. We have investigated the delay of their onset warts and some possible risk factors for their occurrence. Clinical data were summarized on a standard question and examination sheet. Warts were diagnosed on clinical grounds and course duration assessed on patients' report. Immunosuppressive therapy and HLA group were collected from clinical transplantation records. An actuarial curve was used to evaluate the delay of onset of warts. To compare associated risk factors among the two groups (patients with warts and patients without warts) at 1 year and 3 years following transplant, single variate analysis was performed. At the time of transplant, the prevalence of warts was 16 p. 100. It was increased with the duration of immunosuppression: 23 p. 100 at 1 year, 35 p. 100 at 3 years, 45 p. 100 at 5 years and 54 p. 100 at 7 years. Warts were multiple and principally localized on the hands. Transplant recipients without cutaneous warts 3 years after transplant had less intensive immunosuppressive therapy than the group with cutaneous warts. No association was found between age, sex, HLA markers, actinic keratosis and wart onset. The prevalence of warts increases with the duration of transplantation. Cutaneous warts are generally multiple and have a chronical course without spontaneous remission. More intensive immunosuppressive therapy increases their occurrence. This trial cannot evaluate the association between carcinoma and warts. On the basis of our study, there is no relationship between actinic keratosis and warts, nor HLA markers and warts.


Randomized controlled trial comparing the McGrath videolaryngoscope with the C-MAC videolaryngoscope in intubating adult patients with potential difficult airways.
Difficult and failed intubations, although rarely encountered, are major causes of morbidity and mortality in the current anaesthetic practice. To reduce the incidence of difficult and failed intubations, several devices including the recently developed videolaryngoscopes are available. This randomized controlled study aims to compare the use of the McGrath videolaryngoscope with the C-MAC videolaryngoscope in adult patients with potential difficult airways. A total of 130 patients with the Mallampati grade of ≥3, requiring orotracheal intubation, were randomized to either having intubation with the McGrath videolaryngoscope or the C-MAC videolaryngoscope. The primary outcome was time to intubation. The laryngoscopic view, the number of intubation attempts, the proportion of intubation success, the ease of intubation, the haemodynamic responses to intubation, and the incidence of any complications were also recorded. Time to successful intubation with the C-MAC videolaryngoscope was shorter when compared with the McGrath videolaryngoscope {50 s [inter-quartile range (IQR) 38-70] vs 67 s (IQR 49-108), P<0.001}, despite the McGrath videolaryngoscope providing significantly more grade 1 laryngoscopic views. The C-MAC videolaryngoscope also resulted in significantly fewer intubation attempts and greater ease of intubation when compared with the McGrath videolaryngoscope. There were no statistically significant differences in the proportion of intubation success, the number of complications, and the changes in haemodynamic responses between the two videolaryngoscopes. The C-MAC videolaryngoscope allowed a quicker intubation time, fewer intubation attempts, and greater ease of intubation compared with the McGrath videolaryngoscope when used in patients with the Mallampati grade of ≥3.


Left Atrial Appendage Closure Device With Delivery System: A Health Technology Assessment.
Atrial fibrillation is a common cardiac arrhythmia, and 15% to 20% of those who have experienced stroke have atrial fibrillation. Treatment options to prevent stroke in people with atrial fibrillation include pharmacological agents such as novel oral anticoagulants or nonpharmacological devices such as the left atrial appendage closure device with delivery system (LAAC device). The objectives of this health technology assessment were to assess the clinical effectiveness and cost-effectiveness of the LAAC device versus novel oral anticoagulants in patients without contraindications to oral anticoagulants and versus antiplatelet agents in patients with contraindications to oral anticoagulants. We performed a systematic review and network meta-analysis. We also conducted an economic literature review, economic evaluation, and budget impact analysis to assess the cost-effectiveness and budget impact of the LAAC device compared with novel oral anticoagulants and oral antiplatelet agents (e.g., aspirin). We also spoke with patients to better understand their preferences, perspectives, and values. Seven randomized controlled studies met the inclusion criteria for indirect comparison. Five studies assessed the effectiveness of novel oral anticoagulants versus warfarin, and two studies compared the LAAC device with warfarin. No studies were identified that compared the LAAC device with aspirin in patients in whom oral anticoagulants were contraindicated. Using the random effects model, we found that the LAAC device was comparable to novel oral anticoagulants in reducing stroke (odds ratio [OR] 0.85; credible interval [Cr.I] 0.63-1.05). Similarly, the reduction in the risk of all-cause mortality was comparable between the LAAC device and novel oral anticoagulants (OR 0.71; Cr.I 0.49-1.22). The LAAC device was found to be superior to novel oral anticoagulants in preventing hemorrhagic stroke (OR 0.45; Cr.I 0.29-0.79), whereas novel oral anticoagulants were found to be superior to the LAAC device in preventing ischemic stroke (OR 0.67; Cr.I 0.24-1.64). The body of clinical evidence was found to be of moderate quality as assed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. Results from the economic evaluation indicate that the LAAC device is cost-effective compared with aspirin in patients with contraindications to oral anticoagulants. In patients without contraindications to oral anticoagulants, we found that the LAAC device is not cost-effective compared with novel oral anticoagulants. Publicly funding the LAAC device in patients with nonvalvular atrial fibrillation with contraindications to oral anticoagulants could result in additional funding of $1.1 million to $7.7 million over the first five years. Patients interviewed reported on the impact of living with nonvalvular atrial fibrillation and were supportive of the LAAC device as a treatment option. Moderate-quality evidence suggests that the LAAC device is as effective as novel oral anticoagulants in preventing stroke in people with nonvalvular atrial fibrillation. However, our results indicate that the LAAC device is cost-effective only in patients with contraindications to oral anticoagulants. People with nonvalvular atrial fibrillation with whom we spoke reported positive support for the LAAC device.


Experimental Investigation of Wave Propagation Characteristics in Entangled Metallic Wire Materials by Acoustic Emission.
In this paper, the response characteristics of wave propagation in entangled metallic wire materials (EMWMs) are investigated by acoustic emission. The frequency, amplitude of wave emission, and the pre-compression force of the specimen can be adjusted in the experimental setup. EMWM specimens fabricated from stainless steel wires and with different design parameters are tested in this work. The results show that waves of different amplitudes propagate in EMWMs with approximate linear characteristics and the fluctuation coefficient of wave passing ratios is calculated below 15%. The response spectrum of passing waves shows a distinct single-peak characteristic, with the peak response at approximately 14 kHz. The parameters of pre-compression force, porosity, wire diameter, helix diameter, specimen height, and the layered structure of specimens have no significant effect on the frequency characteristics but moderately affect the wave passing ratios. Notably, EMWMs exhibit a lower wave passing ratio (ranging from 0.01 to 0.18) compared to aluminum alloy and natural rubber. The characteristics of response spectrums can be successfully reproduced by the finite element simulation. This work demonstrates EMWMs' potential as an acoustic frequency vibration isolation material, offering excellent performance and engineering design convenience.


Posttraumatic movement disorders after moderate or mild head injury.
We examined the occurrence of posttraumatic movement disorders after moderate or mild head injury with a three-level follow-up study including questionnaires, telephone interviews, and personal examinations 4-6 years after the trauma (mean 5.2 years). Sixteen of 158 patients (10.1%) for whom a detailed follow-up was available had developed movement disorders most probably related to craniocerebral trauma. The most frequent finding was a low-amplitude postural/intention tremor that appeared to resemble enhanced physiological or essential tremor. Twelve patients reported transient tremor, two patients had persistent tremor, one patient had transient tremor and persistent hyperekplexia, and another patient had mild persistent cervical myoclonic twitches. Overall, the movement disorder was transient in 12 patients (7.6%) and persisted in only 4 patients (2.6%). These movement disorders were not disabling and did not require medical therapy. Taking into account possible bias by selection of the sample group, the frequency of movement disorders secondary to moderate or mild head trauma might be lower than 10.1%. Posttraumatic movement disorders occurred significantly more often in the group of patients with Glasgow Coma Scores between 9 and 14 than in those with a score of 15. Severe movement disorders such as low-frequency kinetic tremor or hemidystonia were not identified in this survey.