Adaptive σ aromaticity in the rhenacyclopropene rings.
Species generally exhibit one-state aromaticity either in the lowest singlet state (S0 ) or the lowest triplet state (T1 ) according to the Hückel's and Baird's rules. Hence, it is rare for species exhibit two-state aromaticity in both the S0 and T1 states (termed as adaptive aromaticity), let alone adaptive σ aromaticity. Here, we report adaptive σ aromaticity in unsaturated rhenacyclopropene rings via density functional theory (DFT) calculations. Various aromaticity indices including NICS, ACID, EDDB together with isodesmic reactions support the adaptive σ aromaticity in these rhenacyclopropene rings. As the T1 state of these species is formed by the ππ* excitation, the σ-aromaticity of these three-membered rings in the S0 state could hold in the T1 state. In addition, the aromaticity effect of the fused rings is also examined. Our findings expand the family of adaptive σ aromaticity, enriching the metallaaromatic chemistry.


Therapeutic targets in triple negative breast cancer.
Outcomes have improved significantly for many women diagnosed with breast cancer. For the heterogeneous group of tumours lacking expression of the oestrogen, progesterone and HER2 receptors, 'triple negative' breast cancers (TNBC), the prognosis overall has remained quite poor. When TNBC recurs, there is often little response to chemotherapy, and there are a few treatment options in this setting. Thus, there is an urgent clinical need to identify new therapeutic targets in order to improve the outlook for these patients. This review highlights the most promising therapeutic targets identified through new sequencing technologies, as well as through studies of apoptosis. We also present mounting evidence that the developmental signalling pathways Wnt/β-catenin, NOTCH and Hedgehog play an important role in the pathogenesis and progression of TNBC with new therapeutic approaches inhibiting these pathways in advanced preclinical studies or early clinical trials.


Magnetic resonance imaging of fetal cerebellar development.
In the last few years fetal magnetic resonance imaging (MRI) has been proposed as a second level technique in the evaluation of fetal brain anomalies. It has been demonstrated that MRI is highly accurate in illustrating the morphologic changes of developing brain and fetal brain abnormalities being a useful procedure when ultrasonography is inconclusive or doubtful. Starting from the 19-20 weeks gestational age (GA), MRI can reliably depict fetal brain anatomy and locating pathology, offering a robust and reliable tool in the assessment of fetal CNS diseases. In this review both in vivo MRI quantitative and qualitative data about fetal cerebellar development are presented and compared with ultrasonography data. Fetal cerebellar development is gradual, steady, and largely comparable to the development of the supratentorial brain. Archicerebellar (flocculo-nodular lobe) and paleocerebellar (vermis) structures develop first, whereas neocerebellum (cerebellar hemispheres) develop slowly and largely after birth.


Characterization of ASK mice, a strain highly sensitive to anaphylactic shock.
A mouse strain named ASK that was originally isolated from El (epilepsy) mice has been shown to be highly sensitive to anaphylactic shock. Here, we characterized the bases of the sensitivity of ASK mice in comparison with the parental strain, El. More than 90% of ASK mice, but not El mice that had been sensitized either actively or passively, died within 1 h following an antigen challenge. The anaphylactic death was effectively blocked by diphenhydramine. Plasma histamine levels increased by 30-50 fold in ASK after the antigen challenge, but only a 2-3-fold increase was observed in El mice. All (El x ASK) F1 mice, either male or female, showed an ASK-like phenotype, suggesting that the impaired plasma histamine response in El mice is due to some recessive mutation(s). Consistent with the plasma histamine responses, cultured mast cells derived from El bone marrow showed impaired potency to degranulate in response to surface IgE engagement, in contrast to ASK mast cells which undergo normal degranulation. Another characteristic feature of ASK mice is their sensitivity to histamine, since 75% of the mice were killed by the subcutaneous administration of 100-200 mg/kg histamine, while C3H and BALB/c mice were resistant to even 600 mg/kg histamine. Taken together, the major bases of the susceptibility to anaphylactic shock in ASK mice are thought to be the enhanced sensitivity to histamine and the recovered degranulation machinery in mast cells that is impaired in El mice.


Total knee arthroplasty in patients with severe obesity provides value for money despite increased complications.
Access to total knee arthroplasty (TKA) is sometimes restricted for patients with severe obesity (BMI ≥ 40 kg/m2). This study compares the cost per quality-adjusted life year (QALY) associated with TKA in patients with a BMI above and below 40 kg/m2 to examine whether this is supported. This single-centre study compared 169 consecutive patients with severe obesity (BMI ≥ 40 kg/m2) (mean age 65.2 years (40 to 87); mean BMI 44.2 kg/m2 (40 to 66); 129/169 female) undergoing unilateral TKA to a propensity score matched (age, sex, preoperative Oxford Knee Score (OKS)) cohort with a BMI < 40 kg/m2 in a 1:1 ratio. Demographic data, comorbidities, and complications to one year were recorded. Preoperative and one-year patient-reported outcome measures (PROMs) were completed: EuroQol five-dimension three-level questionnaire (EQ-5D-3L), OKS, pain, and satisfaction. Using national life expectancy data with obesity correction and the 2020 NHS National Tariff, QALYs (discounted at 3.5%), and direct medical costs accrued over a patient's lifetime, were calculated. Probabilistic sensitivity analysis (PSA) was used to model variation in cost/QALY for each cohort across 1,000 simulations. All PROMs improved significantly (p < 0.05) in both groups without differences between groups. Early complications were higher in BMI ≥ 40 kg/m2: 34/169 versus 52/169 (p = 0.050). A total of 16 (9.5%) patients with a BMI ≥ 40 kg/m2 were readmitted within one year with six reoperations (3.6%) including three (1.2%) revisions for infection. Assuming reduced life expectancy in severe obesity and revision costs, TKA in patients with a BMI ≥ 40 kg/m2 costs a mean of £1,013/QALY (95% confidence interval £678 to 1,409) more over a lifetime than TKA in patients with BMI < 40 kg/m2. In PSA replicates, the maximum cost/QALY was £3,921 in patients with a BMI < 40 kg/m2 and £5,275 in patients with a BMI ≥ 40 kg/m2. Higher complication rates following TKA in severely obese patients result in a lifetime cost/QALY that is £1,013 greater than that for patients with BMI < 40 kg/m2, suggesting that TKA remains a cost-effective use of healthcare resources in severely obese patients where the surgeon considers it appropriate. Cite this article: Bone Joint J 2022;104-B(4):452-463.


Comparison of cimetidine and tripotassium dicitrato bismuthate in healing and relapse of duodenal ulcers.
A comparison between cimetidine and tripotassium dicitrato bismuthate liquid (TDB) in the treatment of endoscopically diagnosed duodenal ulcer by single-blind randomized trial in 48 patients has shown 18 (75%) out of 24 patients receiving TDB and 13 (54%) out of 24 patients receiving cimetidine healed after 4 weeks' therapy. Symptomatic improvement within 1 month was seen in 19 patients on TDB and 18 patients on cimetidine, but did not only occur in patients whose ulcers healed. On follow-up, endoscopically proven relapse occurred within 1 year in 47% of patients whose ulcers had healed during treatment with TDB in comparison with 60% of those healing on cimetidine.


Spatial optimization for radiation therapy of brain tumours.
Glioblastomas are the most common primary brain tumours. They are known for their highly aggressive growth and invasion, leading to short survival times. Treatments for glioblastomas commonly involve a combination of surgical intervention, chemotherapy, and external beam radiation therapy (XRT). Previous works have not only successfully modelled the natural growth of glioblastomas in vivo, but also show potential for the prediction of response to radiation prior to treatment. This suggests that the efficacy of XRT can be optimized before treatment in order to yield longer survival times. However, while current efforts focus on optimal scheduling of radiotherapy treatment, they do not include a similarly sophisticated spatial optimization. In an effort to improve XRT, we present a method for the spatial optimization of radiation profiles. We expand upon previous results in the general problem and examine the more physically reasonable cases of 1-step and 2-step radiation profiles during the first and second XRT fractions. The results show that by including spatial optimization in XRT, while retaining a constant prescribed total dose amount, we are able to increase the total cell kill from the clinically-applied uniform case.


Sodium Diisopropylamide in Tetrahydrofuran: Selectivities, Rates, and Mechanisms of Alkene Isomerizations and Diene Metalations.
Sodium diisopropylamide in tetrahydrofuran is an effective base for the metalation of 1,4-dienes and isomerization of alkenes. Dienes metalate via tetrasolvated sodium amide monomers, whereas 1-pentene is isomerized by trisolvated monomers. Facile, highly Z-selective isomerizations are observed for allyl ethers under conditions that compare favorably to those of existing protocols. The selectivity is independent of the substituents on the allyl ethers; rate and computational data show that the rates, mechanisms, and roles of sodium-oxygen contacts are substituent-dependent. The competing influences of substrate coordination and solvent coordination to sodium are discussed.


Enhancement of HIV-1 marker detection in cell cultures treated with mild heat-shock.
Rapid exposure to supra-optimal temperature (heat-shock) and a variety of other treatments are able to induce changes in cellular translational and transcriptional activity referred to as "the heat-shock response". The effect of heat-shock was investigated in H9 lymphoblastic cells and in peripheral blood lymphocytes infected with human immunodeficiency virus type 1 (HIV-1). The results showed that a mild heat-shock performed either immediately before infection or 7 days after infection consistently increased the recovery of p24 core antigen and reverse transcriptase activity in the supernatants of experimentally infected cell cultures. On the contrary, heat-shock had no effect on the HIV-1 marker recovery from persistently infected H9/HTLV-III cell cultures.


3D visualization of the intratemporal course of the facial canal using computed micro-tomography.
The current study presents high resolution reconstructions showing the course of the facial canal within the temporal bone and visualizes the spatial orientation of the subsequent segments of the facial canal. 3D reconstructions of the facial canal were created from micro-CT data obtained from the right and left human temporal bones of an adult individual of the male sex. For this purpose, volume and surface rendering was applied. 3D models of the facial canal and adjacent osseous structures comprehensively revealed its intricate course and depicted the spatial orientation of its subsequent segments: labyrinthine, tympanic and mastoid. The labyrinthine segment of the facial canal was clearly displayed in the horizontal plane whereas the tympanic and mastoid segments were entirely visible in the sagittal plane, which lines up along the long axis of the petrous part of the temporal bone.


[Results of a national program of pediatric heart transplantation: strengths and weakness].
Pediatric heart transplantation is an effective therapy to treat advanced heart failure in children. To analyze the immediate and mid-term results of pediatric patients listed for heart transplantation. Registration of patients admitted to our transplant protocol between October 2001 and July 2016 were reviewed, analyzing demographic data, diagnosis, status at the time of listing, waiting time until transplantation, donor data, use of ventricular assist device, hemodynamic data, complications and global mortality. Thirthy patients where included with a mean age of 9.4 years (1 month to 15 years). The most frequent diagnosis was dilated cardiomyopathy in 24 patients (80%). The status was I (urgency) in 19 cases and II in 11 cases. Ten patients died on the waiting list (33.3%) at an average of 52 days (13-139 days). Fourteen were transplanted (46.7%), with a waiting time of 199.6 days (4-586 days). Nine patients required mechanical support (30%). All patients received triple association of immunosuppression. One patient died 16 days post transplant due to primary graft failure (7.1%). The average follow-up was 43 months (0.5-159 months). Two patients died later on (82 and 55 months), both due to secondary rejection because of voluntary cessation of immunosuppressive therapy. Survival at 1 and 5 years was 93% and 74%, respectively. Our program has successfully transplanted 50% of patients enrolled, with good medium-term survival. A significant proportion of patients were listed as a medical emergency and 34.5% died on the waiting list.


Sarcoidosis with thyroid involvement, polymyalgia rheumatica and breast carcinoma. A case report.
Polymyalgia rheumatica developed in a 71-year-old patient within 2 years of the onset of acute sarcoidosis with biopsy-verified involvement of the thyroid, and concomitant autoimmune thyroiditis with hyperthyroid symptoms. Three years after the onset of muscle symptoms a non-metastasizing breast carcinoma was discovered and treated surgically. Neither the long interval between the onset of polymyalgia rheumatica and the discovery of the breast tumour, nor the good response of muscle symptoms to a one-year maintenance treatment with corticosteroids, was consistent with a paraneoplastic mechanism of the polymyalgia rheumatica syndrome. It was therefore hypothesized that the various disorders suffered by this patient might be related to a partly age-dependent depression of T-lymphocyte function, leading to an altered immunological reactivity to which the various clinical manifestations could be attributed. Such a hypothesis is supported by recent reports showing that in old people and in ageing experimental animals, a decrease in T-lymphocyte function and in the number of circulating T-cells occurs concomitantly with an increase in the incidence of a variety of neoplasms and autoimmune disorders.


Construction of Local Field Potential Microelectrodes for in vivo Recordings from Multiple Brain Structures Simultaneously.
Researchers often need to record local field potentials (LFPs) simultaneously from several brain structures. Recording from multiple desired brain regions requires different microelectrode designs, but commercially available microelectrode arrays often do not offer such flexibility. Here, the present protocol outlines the straightforward design of custom-made microelectrode arrays to record LFPs from multiple brain structures simultaneously at different depths. This work describes the construction of the bilateral cortical, striatal, ventrolateral thalamic, and nigral microelectrodes as an example. The outlined design principle offers flexibility, and the microelectrodes can be modified and customized to record LFPs from any structure by calculating stereotaxic coordinates and quickly changing the construction accordingly to target different brain regions in either freely moving or anesthetized mice. The microelectrode assembly requires standard tools and supplies. These custom microelectrode arrays allow investigators to easily design microelectrode arrays in any configuration to track neuronal activity, providing LFP recordings with millisecond resolution.


Deviation of tracheal pressure from airway opening pressure during high-frequency oscillatory ventilation in a porcine lung model.
Oxygenation during high-frequency oscillatory ventilation is secured by a high level of mean airway pressure. Our objective was to identify a pressure difference between the airway opening of the respiratory circuit and the trachea during application of different oscillatory frequencies. Six female Pietrain pigs (57.1 ± 3.6 kg) were first ventilated in a conventional mechanical ventilation mode. Subsequently, the animals were switched to high-frequency oscillatory ventilation by setting mean airway opening pressure 5 cmH(2)O above the one measured during controlled mechanical ventilation. Measurements at the airway opening and at tracheal levels were performed in healthy lungs and after induction of acute lung injury by surfactant depletion. During high-frequency oscillatory ventilation, the airway opening pressure was set at a constant level. The pressure amplitude was fixed at 90 cmH(2)O. Starting from an oscillatory frequency of 3 Hz, the frequency was increased in steps of 3 Hz to 15 Hz and then decreased accordingly. At each frequency, measurements were performed in the trachea through a side-lumen of the endotracheal tube and the airway opening pressure was recorded. The pressure difference was calculated. At every oscillatory frequency, a pressure loss towards the trachea could be shown. This pressure difference increased with higher oscillatory frequencies (3 Hz 2.2 ± 2.1 cmH(2)O vs. 15 Hz 7.5 ± 1.8 cmH(2)O). The results for healthy and injured lungs were similar. Tracheal pressures decreased with higher oscillatory frequencies. This may lead to pulmonary derecruitment. This has to be taken into consideration when increasing oscillatory frequencies and differentiated pressure settings are mandatory.


Histopathological Evaluation of Orthopedic Medical Devices: The State-of-the-art in Animal Models, Imaging, and Histomorphometry Techniques.
Orthopedic medical devices are continuously evolving for the latest clinical indications in craniomaxillofacial, spine, trauma, joint arthroplasty, sports medicine, and soft tissue regeneration fields, with a variety of materials from new metallic alloys and ceramics to composite polymers, bioresorbables, or surface-treated implants. There is great need for qualified medical device pathologists to evaluate these next generation biomaterials, with improved biocompatibility and bioactivity for orthopedic applications, and a broad range of knowledge is required to stay abreast of this ever-changing field. Orthopedic implants require specialized imaging and processing techniques to fully evaluate the bone-implant interface, and the pathologist plays an important role in determining the proper combination of histologic processing and staining for quality slide production based on research and development trials and validation. Additionally, histomorphometry is an essential part of the analysis to quantify tissue integration and residual biomaterials. In this article, an overview of orthopedic implants and animal models, as well as pertinent insights for tissue collection, imaging, processing, and slide generation will be provided with a special focus on histopathology and histomorphometry evaluation.


Zinc homeostasis and neurodegenerative disorders.
Zinc is an essential trace element, whose importance to the function of the central nervous system (CNS) is increasingly being appreciated. Alterations in zinc dyshomeostasis has been suggested as a key factor in the development of several neuropsychiatric disorders. In the CNS, zinc occurs in two forms: the first being tightly bound to proteins and, secondly, the free, cytoplasmic, or extracellular form found in presynaptic vesicles. Under normal conditions, zinc released from the synaptic vesicles modulates both ionotropic and metabotropic post-synaptic receptors. While under clinical conditions such as traumatic brain injury, stroke or epilepsy, the excess influx of zinc into neurons has been found to result in neurotoxicity and damage to postsynaptic neurons. On the other hand, a growing body of evidence suggests that a deficiency, rather than an excess, of zinc leads to an increased risk for the development of neurological disorders. Indeed, zinc deficiency has been shown to affect neurogenesis and increase neuronal apoptosis, which can lead to learning and memory deficits. Altered zinc homeostasis is also suggested as a risk factor for depression, Alzheimer's disease (AD), aging, and other neurodegenerative disorders. Under normal CNS physiology, homeostatic controls are put in place to avoid the accumulation of excess zinc or its deficiency. This cellular zinc homeostasis results from the actions of a coordinated regulation effected by different proteins involved in the uptake, excretion and intracellular storage/trafficking of zinc. These proteins include membranous transporters (ZnT and Zip) and metallothioneins (MT) which control intracellular zinc levels. Interestingly, alterations in ZnT and MT have been recently reported in both aging and AD. This paper provides an overview of both clinical and experimental evidence that implicates a dysfunction in zinc homeostasis in the pathophysiology of depression, AD, and aging.


Variability in self-esteem, moods, shame, and guilt in women who binge.
Variability in self-esteem, moods, shame, and guilt was explored in a sample of 78 women (37 who binge and 41 who do not binge) attending a large university. Results indicated that women who binge reported significantly greater fluctuations than women who do not binge in state self-esteem, negative affect, shame, and guilt. In addition, contrary to the hypotheses, self-esteem and positive affect increased prior to all eating episodes for women, including binge episodes for women who binge. Women who binge also reported lower levels of state self-esteem and positive affect, and higher levels of shame and guilt prior to binges than controls prior to their eating episodes. Theoretical implications of the differential role of shame and guilt are considered. In addition, results are discussed in terms of support for a self-nurturance explanation of binge eating in nonclinical samples of women.


A spray management valve for hand-compression sprayers.
The commercially available spray management valve provided consistent flow rates when used with hand-compression sprayer systems. The 15-psi spray management valve maintained a constant flow rate of 180, 150, and 155 ml/min in combination with a fine 45 degrees flat fan nozzle and Hudson. B&G, and Chapin hand-compression sprayers, respectively. The 30-psi spray management valve maintained a constant flow rate and adequate spray-on time when combined with the coarse flat fan nozzle for each of the 3 hand-compression sprayers tested.


Rapid social perception is flexible: approach and avoidance motivational states shape P100 responses to other-race faces.
Research on person categorization suggests that people automatically and inflexibly categorize others according to group memberships, such as race. Consistent with this view, research using electroencephalography (EEG) has found that White participants tend to show an early difference in processing Black versus White faces. Yet, new research has shown that these ostensibly automatic biases may not be as inevitable as once thought and that motivational influences may be able to eliminate these biases. It is unclear, however, whether motivational influences shape the initial biases or whether these biases can only be modulated by later, controlled processes. Using EEG to examine the time course of biased processing, we manipulated approach and avoidance motivational states by having participants pull or push a joystick, respectively, while viewing White or Black faces. Consistent with previous work on own-race bias, we observed a greater P100 response to White than Black faces; however, this racial bias was attenuated in the approach condition. These data suggest that rapid social perception may be flexible and can be modulated by motivational states.


Diagnostics of malformation syndromes using an available computer program.
Increased attention to the malformation syndromatology is motivated by the importance of accurate diagnosis and its necessity in genetic counselling. Given the great number of malformation syndromes, it is logical to make use of computers in their ability perform differential diagnostics. The aim of our present examinations was to assess the benefit that an experienced pediatrician can obtain from an available program. The "Syndrome Program" of R. Winter and M. Baraitser was applied. Using coded symptoms, the computer produces a short list of possible diagnoses, which can then be assessed by the user. References and syndrome features can be recalled and compared with those in undiagnosed cases. The diagnoses of 100 different syndrome features can be recalled and compared with those in undiagnosed cases. The diagnoses of 100 different syndromes were controlled. The method applied yielded very good results. The computer diagnosis of malformation syndromes is a helpful way of supplying information. It may promote the standardization of diagnostic practice, international cooperation and epidemiologic studies in different regions.


[Ultrastructural study of a chordoma].
An ultrastructural study of a case of sacral chordoma is reported. The cell type was monomorphic. The epithelial nature and the secretory function of the tumour cells was obvious in view of their content of desmosomes and the presence of mucopolysaccharide in the ergastoplasm and in the extracellular space. Because of the lack of intracytoplasmic vacuoles in the case reported, the authors doubt the individuality of the so-called "giant physaliphorous cell". The authors consider that the vacuolar appearance of the tumour cells is due to cytoplasmic invaginations caused by the enlarged extracellular space containing acid mucopolysaccharides or by processes of histiocytes containing the same material.


Surface Immobilization of Human Arginase-1 with an Engineered Ice Nucleation Protein Display System in E. coli.
Ice nucleation protein (INP) is frequently used as a surface anchor for protein display in gram-negative bacteria. Here, MalE and TorA signal peptides, and three charged polypeptides, 6×Lys, 6×Glu and 6×Asp, were anchored to the N-terminus of truncated INP (InaK-N) to improve its surface display efficiency for human Arginase1 (ARG1). Our results indicated that the TorA signal peptide increased the surface translocation of non-protein fused InaK-N and human ARG1 fused InaK-N (InaK-N/ARG1) by 80.7% and 122.4%, respectively. Comparably, the MalE signal peptide decreased the display efficiencies of both the non-protein fused InaK-N and InaK-N/ARG1. Our results also suggested that the 6×Lys polypeptide significantly increased the surface display efficiency of K6-InaK-N/ARG1 by almost 2-fold, while also practically abolishing the surface translocation of non-protein fused InaK-N, indicating the interesting roles of charged polypeptides in bacteria surface display systems. Cell surface-immobilized K6-InaK-N/ARG1 presented an arginase activity of 10.7 U/OD600 under the optimized conditions of 40°C, pH 10.0 and 1 mM Mn2+, which could convert more than 95% of L-Arginine (L-Arg) to L-Ornithine (L-Orn) in 16 hours. The engineered InaK-Ns expanded the INP surface display system, which aided in the surface immobilization of human ARG1 in E. coli cells.


Expression, purification, and characterization of C-terminal amidated glucagon in Streptomyces lividans.
Glucagon, a peptide hormone produced by alpha-cells of Langerhans islets, is a physiological antagonist of insulin and stimulator of its secretion. In order to improve its bioactivity, we modified its structure at the C-terminus by amidation catalyzed by a recombinant amidase in bacterial cells. The human gene coding for glucagon-gly was PCR amplified using three overlapping primers and cloned together with a rat alpha-amidase gene in plasmid pMGA. Both genes were expressed under control of the strong constitutive promoter of aph and secretion signal melC1 in Streptomyces lividans. With Phenyl-Sepharose 6 FF, Q-Sepharose FF, SP-Sepharose FF chromatographies and HPLC, the peptide was purified to about 93.4% purity. The molecular mass of the peptide is 3.494 kDa as analyzed by MALDI TOF, which agrees with the theoretical mass value of the C-terminal amidated glucagon. The N-terminal sequence of the peptide was also determined, confirming its identity with human glucagon at the N-terminal part. ELISA showed that the purified peptide amide is bioactive in reacting with glucagon antibodies.


A comparison of Kodak Ultraspeed and Ektaspeed plus dental X-ray films for the detection of dental caries.
Using the fastest dental X-ray film available is an easy way of reducing exposure to ionizing radiation. However, the diagnostic ability of fast films for the detection of proximal surface caries must be demonstrated before these films will become universally accepted. Extracted premolar and molar teeth were arranged to simulate a bitewing examination and radiographed using Ultraspeed and Ektaspeed Plus dental X-ray films. Three different exposure times were used for each film type. Six general dentists were used to determine the presence and depth of the decay in the proximal surfaces of the teeth radiographed. The actual extent of the decay in the teeth was determined by sectioning the teeth and examining them under a microscope. There was no significant difference between the two films for the mean correct diagnosis. However, there was a significant difference between the means for the three exposure times used for Ultraspeed film. The practitioners used were not consistent in their ability to make a correct diagnosis, or for the film for which they got the highest correct diagnosis. Ektaspeed Plus dental X-ray film is just as reliable as Ultraspeed dental X-ray film for the detection of proximal surface decay. The effect of underexposure was significant for Ultraspeed, but not for Ektaspeed Plus. Patient exposure can be reduced significantly with no loss of diagnostic ability by changing from Ultraspeed X-ray film to Ektaspeed Plus X-ray film.


Ligand-promoted dehydrogenation of alcohols catalyzed by Cp*Ir complexes. A new catalytic system for oxidant-free oxidation of alcohols.
[reaction: see text] An efficient catalytic system for oxidant-free oxidation of alcohols has been developed. A new Cp*Ir catalyst bearing a 2-hydroxypyridine ligand has been designed on the concept of "ligand-promoted dehydrogenation". Various secondary alcohols can be dehydrogenatively oxidized to ketones under neutral conditions with high turnover numbers by using the new Cp*Ir catalyst.


Effects of anaesthesia on acute ischaemic arrhythmias and epicardial electrograms in the pig heart in situ.
The aim of the study was to assess the influence of general anaesthesia on electrocardiographic and arrhythmogenic responses to left anterior descending coronary artery occlusion. Pigs weighing 18-20 kg were anaesthetised with alpha chloralose 100 mg.kg-1 (n = 9) or thiopentone 30 mg.kg-1 (n = 9) and the arrhythmogenic effects of coronary artery occlusion were examined by sequential electrocardiographic measurements every 5 min and arrhythmia analysis every minute over a 60 min period. alpha Chloralose predisposed to lower ST segment elevation (analysis of variance for repeated measurements p less than 0.002), less marked epicardial conduction delay (p less than 0.01) with slower progression to monophasic potentials, and in contrast, to a greater number of episodes of ventricular premature beats (p less than 0.005), ventricular tachycardia (51 v 32 episodes), and ventricular fibrillation (6 v 2 pigs) than barbiturate anaesthesia. alpha Chloralose and barbiturates exerted opposite electrocardiographic and arrhythmogenic effects in a porcine model of acute myocardial ischaemia. Due to its proarrhythmic effect chloralose should probably be used in studies dealing with spontaneous and induced ischaemic arrhythmias.


Zinc-Doped Bioactive Glass/Polycaprolactone Hybrid Scaffolds Manufactured by Direct and Indirect 3D Printing Methods for Bone Regeneration.
A novel organic-inorganic hybrid, based on SiO2-CaO-ZnO bioactive glass (BG) and polycaprolactone (PCL), associating the highly bioactive and versatile bioactive glass with clinically established PCL was examined. The BG-PCL hybrid is obtained by acid-catalyzed silica sol-gel process inside PCL solution either by direct or indirect printing. Apatite-formation tests in simulated body fluid (SBF) confirm the ion release along with the hybrid's bone-like apatite forming. Kinetics differ significantly between directly and indirectly printed scaffolds, the former requiring longer periods to degrade, while the latter demonstrates faster calcium phosphate (CaP) formation. Remarkably, Zn diffusion and accumulation are observed at the surface within the newly formed active CaP layer. Zn release is found to be dependent on printing method and immersion medium. Investigation of BG at the atomic scale reveals the ambivalent role of Zn, capable of acting both as a network modifier and as a network former linking the BG silicate network. In addition, hMSCs viability assay proves no cytotoxicity of the Zn hybrid. LIVE/DEAD staining demonstrated excellent cell viability and proliferation for over seven weeks. Overall, this hybrid material either non-doped or doped with a metal trace element is a promising candidate to be translated to clinical applications for bone regeneration.


The computational fluid dynamics study of orientation effects of oar-blade.
The distribution of pressure coefficient formed when the fluid contacts with the kayak oar blade is not been studied extensively. The CFD technique was employed to calculate pressure coefficient distribution on the front and rear faces of oar blade resulting from the numerical resolution equations of the flow around the oar blade in the steady flow conditions (4 m/s) for three angular orientations of the oar (45°, 90°, 135°) with main flow. A three-dimensional (3D) geometric model of oar blade was modeled and the k-ε turbulent model was applied to compute the flow around the oar. The main results reported that, under steady state flow conditions, the drag coefficient (Cd = 2.01 for 4 m/s) at 90° orientation has the similar evolution for the different oar blade orientation to the direction of the flow. This is valid when the orientation of the blade is perpendicular to the direction of the flow. Results indicated that the angle of oar strongly influenced the Cd with maximum values for 90° angle of the oar. Moreover, the distribution of the pressure is different for the internal and external edges depending upon oar angle. Finally, the difference of negative pressure coefficient Cp in the rear side and the positive Cp in the front side, contributes toward propulsive force. The results indicate that CFD can be considered an interesting new approach for pressure coefficient calculation on kayak oar blade. The CFD approach could be a useful tool to evaluate the effects of different blade designs on the oar forces and consequently on the boat propulsion contributing toward the design improvement in future oar models. The dependence of variation of pressure coefficient on the angular position of oar with respect to flow direction gives valuable dynamic information, which can be used during training for kayak competition.


Inflamed molluscum contagiosum in a 6-year-old boy: a case report.
The precise prevalence of molluscum contagiosum (MC) is still unknown. The pediatric studies showed a cumulative incidence of 17% in children less than 15 years, but there are no studies available for Romania. The papular skin lesions are generally less than 5 mm, but the immunocompromised patients may develop large uncommon lesions. The pediatric cases are located mostly on the limbs, trunk or the face. The lab investigations are not usually required because the clinical features are typical. A biopsy followed by a light microscopy may help in some cases. We are presenting the case of a 6-year-old boy suffering from MC since almost a year. When examined in our clinic, the child developed 2 to 4 mm dome-shaped flesh-colored papules with central umbilication on his trunk diagnosed as MC. The microscopic examination revealed bud-like proliferation of the epidermis, molluscum bodies and moderate chronic inflammation of the dermis. In about one month of treatment, all the lesions disappeared without other local or general complications.


Histopathological studies of the labial salivary glands in patients with Sjögren's syndrome. Part II: electron microscopic study.
The ultrastructural changes in the labial salivary glands, in which was demonstrated light microscopically the characteristic appearance of Sjögren's syndrome, were investigated in 12 cases. The significance of the following findings in this syndrome was discussed. The infiltrating cells were chiefly composed of small and medium sized lymphocytes and plasma cells. There were also found large lymphocytes with mitosis and morphologically regarded as T-lymphocytes. A small number of histiocytes and other mononuclear cells scattered among them. The remaining secretory cells were degenerated with disturbance of the secretory process. Degeneration, destruction, squamous metaplasia and proliferation of the duct epithelial cells were associated with mononuclear cell infiltration, and these changes were more conspicuous in the intercalated regions. The basal laminae of the acini and ducts were in part markedly thickened with high electron density. The epimyoepithelial islands in varying forms and sizes were composed of morphologically different kinds of cells which were probably derived from the duct cells. Only a few myoepithelial cells were located in the peripheral portion of the epimyoepithelial islands and there was no proliferation of myoepithelial cells. The hyaline-like substance, occasionally appearing in and around the epimyoepithelial islands, was an accumulation of fine fibrillar substance. Virus-like or tubuloreticular structures were found in the endothelial cells in 1 case.


Are High Levels of Microsatellite Instability and Microsatellite Stability Identical in DNA Mismatch Repair-Deficient Colorectal Cancer Patients?
The purpose of the current study was to determine whether there is a difference between high levels of microsatellite instability (MSI-H) and microsatellite stability (MSS) in DNA mismatch repair-deficient (DMMR) colorectal cancer (CRC) patients. A total of 452 CRC patients with DMMR from December, 2014, to April, 2021, in our hospital were selected retrospectively. However, only 105 patients underwent Sanger or next-generation-sequencing (NGS) to confirm their microsatellite status. Ultimately, 55 MSI-H patients and 20 MSS patients with intact medical record information were included in this study. The MSS group was associated with a higher mutation rate in the KRAS gene (P=0.011). Meanwhile, MSI-H was related to colon cancer (P < 0.01). However, no significant differences in other clinical characteristics were observed between the two groups of patients. There was no significant difference between the MSI-H and MSS groups in terms of overall survival (OS) (P=0.398) and disease-free survival (DFS) (P=0.307). The MSI-H status was associated with colon cancer and a lower mutation rate of the KRAS gene in DMMR patients. In CRC-DMMR patients, the MSS group exhibited better OS and DFS than the MSI-H group, although these differences were not statistically significant. Accordingly, in clinical practice, we should not confuse these two types of patients.


Hand Mycetoma: The Mycetoma Research Centre Experience and Literature Review.
Mycetoma is a devastating, neglected tropical disease characterised by extensive tissue involvement resulting in destruction, deformities and disabilities in the affected patients. The hand is commonly affected by mycetoma thus compromises its functionality and hinder the patient's daily activities of living. In this communication, we report on 533 patients with hand mycetoma managed over a period of 24 years at the Mycetoma Research Centre, University of Khartoum, Khartoum, Sudan. Eumycetoma was the commonest type of mycetoma (83.3%) encountered. Males were predominately affected (69.2%) with a sex ratio of 2.2:1. The majority of the patients (84%) were young adult below the age of 40 years old at presentation. The generality of patients (86.4%) were from the Sudan mycetoma belt. Children and adolescents (28.1%), farmers (18.2%) and workers (17.4%) were more frequently affected. The majority of patients (67.4%) had disease duration of less than 5 years at presentation. The study, did not document significant history of local trauma, familial tendency, concomitant medical diseases or other predisposing cause for mycetoma in this population. Pain (23.1%) was not a disease feature in this series and 52% of patients had past surgery for mycetoma and recurrence. The right hand was affected most (60.4%), and 64% of them had small lesion at presentation. Conventional x-ray was only helpful in patients with advanced disease and the MRI accurately determined the disease extension. Cytological smears, surgical biopsies histopathological examination and grains culture were the principal diagnostic tools for causative organisms' identification. In the present series it was difficult to determine the treatment outcome due to high patients follow up dropout.


Stereoselective Synthesis of Quaternary Pyrrolidine-2,3-diones and β-Amino Acids.
A facile, diastereoselective synthesis of highly substituted pyrrolidine-2,3-diones is reported, along with the one-step conversion of these heterocycles to novel β-amino acids and further functionalized derivatives. This method involves an unusually mild, one-pot, three-component cyclization/allylation followed by a Claisen rearrangement to provide unusual pyrrolidinone products that are densely functionalized and contain an all-carbon quaternary stereocenter. The reported reaction sequence is operationally simple, exquisitely diastereoselective, and provides gram-scale access to valuable heterocyclic scaffolds and β-amino acids not readily accessible via existing approaches.


Individual differences in cyber security behaviors: an examination of who is sharing passwords.
In spite of the number of public advice campaigns, researchers have found that individuals still engage in risky password practices. There is a dearth of research available on individual differences in cyber security behaviors. This study focused on the risky practice of sharing passwords. As predicted, we found that individuals who scored high on a lack of perseverance were more likely to share passwords. Contrary to our hypotheses, we found younger [corrected] people and individuals who score high on self-monitoring were more likely to share passwords. We speculate on the reasons behind these findings, and examine how they might be considered in future cyber security educational campaigns.


[Perioperative serious complications in patients undergoing transcatheter aortic valve replacement: a single-center experience].
Objective: To observe the incidence of perioperative severe complications in aortic stenosis (AS) patients undergoing transcatheter aortic valve implantation (TAVR), and to explore the influence of the accumulated experience of the operators on the incidence of complications. Methods: This is a single-center retrospective study. Patients with AS who underwent TAVR from May 2016 to November 2020 in General Hospital of Northern Theater Command were included. The occurrence of severe complications during perioperative period was recorded. Severe complications included all-cause death, surgical transfer to thoracotomy, coronary artery occlusion, peripheral vascular approach complications, severe cerebrovascular events, moderate or above perivalvular leakage, valve displacement (implanted valve middle valve), pacemaker implantation, etc. In order to observe the influence of the accumulated experience of the operators on the occurrence of postoperative complications, the complications in each stage of the patients were counted and the bar chart was drawn with interval of every 30 patients. Results: A total of 119 patients were included, including 64 males and 55 females, the mean age was (73.9±6.9) years. The valve implantation was unsuccessful in 3 out of 119 patients (2.5%). There were 39 cases of severe complications during perioperative period, including 1 death (0.8%), 2 cases of thoracotomy (1.7%), 2 cases of coronary artery occlusion (1.7%), 8 cases of peripheral vascular approach complications (6.7%), and 1 case of new severe cerebrovascular event (0.8%), 3 cases of moderate or higher perivalvular leakage (2.5%), 8 cases of valve displacement leads to midvalvular implantation (6.7%), 14 cases of permanent pacemaker implantation due to new atrioventricular block (11.8%). The bar chart showed that the incidence of permanent pacemaker implantation and in-valve implantation did not significantly decrease with the accumulation of experience, while the incidence of other complications showed a decreasing trend after 30 cases. Conclusions: Most serious complications occurred in the early stage of TAVR in our center. The incidence of all cause death, coronary artery occlusion and peripheral vascular approach complications in the perioperative period post TAVR could be reduced in the TAVR center in the learning stage through the accumulation of procedure-related experience, but the incidence of pacemaker placement and the implanted valve within the valve dose not significantly decrease over time.


Renal involvement in children and adolescents with inflammatory bowel disease.
The incidence of inflammatory bowel disease (IBD) is rapidly increasing, and several reports have described the renal complications of IBD. We sought to evaluate the clinical manifestations of renal complications in children with IBD in order to enable early detection and prompt treatment of the complications. We retrospectively reviewed the medical records of 456 children and adolescents aged <20 years who had been diagnosed with IBD since 2000. We analyzed patient age, sex, medication use, IBD disease activity, and clinical manifestations of renal symptoms. Our study comprising 456 children with IBD included 299 boys (65.6%) and 157 girls (34.4%). The study included 346 children with Crohn disease and 110 children with ulcerative colitis. The incidence of kidney-related symptoms was 14.7%, which was significantly higher than that in normal children. We observed 26 children (38.8%) with isolated hematuria, 30 children (44.8%) with isolated proteinuria, and 11 children (16.4%) with hematuria and concomitant proteinuria. A renal biopsy was performed in 7 children. Histopathological examination revealed immunoglobulin A nephropathy in 5 children (71.4%). All children presented with mild disease and well-controlled disease activity of IBD. Children with IBD are more likely to show kidney-related symptoms than healthy children and adolescents are. Therefore, regular screening of urine and evaluation of renal function in such children are necessary for early detection of renal complications.


A simple aqueous electrochemical method to synthesize TiO₂ nanoparticles.
Here, a simple and rapid electrochemical approach to synthesize TiO2 nanoparticles in aqueous solution is reported. This method consists in the electro-oxidation of titanium foil in a tetrabutylammonium bromide aqueous solution, which acts as both an electrolyte and a surfactant. Amorphous TiO2 particles in the nanoscale (∼5 nm), well dispersed in aqueous solution, were directly formed by applying low current densities in a short reaction time. It was demonstrated that several experimental parameters influence the reaction yield; an increase in the current, temperature and reaction time augments the quantity of the obtained material. Then, the amorphous nanoparticles were completely crystallized into a pure anatase phase by thermal treatment under an air atmosphere as analyzed by X-ray diffraction and Raman spectroscopy. Besides, the size of the nanoparticles increased to approximately 12 nm in the calcination process. The band gap energies of the resulting TiO2 anatase nanoparticles were determined by diffuse reflectance measurements according to the Kubelka Munk theory, revealing low values between 2.95 and 3.10 eV. Therefore, the results indicate the success of this method to create TiO2 nanoparticles in aqueous medium with good optical properties.


The Use of Artificial Gel Forming Bolalipids as Novel Formulations in Antimicrobial and Antifungal Therapy.
The alarming growth of multi-drug resistant bacteria has led to a quest for alternative antibacterial therapeutics. One strategy to circumvent the already existing resistance is the use of photodynamic therapy. Antimicrobial photodynamic therapy (aPDT) involves the use of non-toxic photosensitizers in combination with light and in situ oxygen to generate toxic radical species within the microbial environment which circumvents the resistance building mechanism of the bacteria. Hydrogels are used ubiquitously in the biological and pharmaceutical fields, e.g., for wound dressing material or as drug delivery systems. Hydrogels formed by water-insoluble low-molecular weight gelators may potentially provide the much-needed benefits for these applications. Bolalipids are a superior example of such gelators. In the present work, two artificial bolalipids were used, namely PC-C32-PC and Me2PE-C32-Me2PE, which self-assemble in water into long and flexible nanofibers leading to a gelation of the surrounding solvent. The aim of the study was to create stable hydrogel formulations of both bolalipids and to investigate their applicability as a novel material for drug delivery systems. Furthermore, methylene blue-a well-known photosensitizer-was incorporated into the hydrogels in order to investigate the aPDT for the treatment of skin and mucosal infections using a custom designed LED device.


Validation of rectal sparing throughout the course of proton therapy treatment in prostate cancer patients treated with SpaceOAR®.
The purpose of this study was to investigate the consistency of rectal sparing using multiple periodic quality assurance computerized tomography imaging scans (QACT) obtained during the course of proton therapy for patients with prostate cancer treated with a hydrogel spacer. Forty-one low- and intermediate-risk prostate cancer patients treated with image-guided proton therapy with rectal spacer hydrogel were analyzed. To assess the reproducibility of rectal sparing with the hydrogel spacer, three to four QACTs were performed for each patient on day 1 and during weeks 1, 3, and 5 of treatment. The treatment plan was calculated on the QACT and the rectum V90%, V75%, V65%, V50%, and V40% were evaluated. For the retrospective analysis, we evaluated each QACT and compared it to the corresponding treatment planning CT (TPCT), to determine the average change in rectum DVH points. We were also interested in how many patients exceeded an upper rectum V90% threshold on a QACT. Finally, we were interested in a correlation between rectum volume and V90%. On each QACT, if the rectum V90% exceeded the upper threshold of 6%, the attending physician was notified and the patient was typically prescribed additional stool softeners or laxatives and reminded of dietary compliance. In all cases of the rectum V90% exceeding the threshold, the patient had increased gas and/or stool, compared to the TPCT. On average, the rectum V90% calculated on the QACT was 0.81% higher than that calculated on the TPCT. The average increase in V75%, V65%, V50%, and V40% on the QACT was 1.38%, 1.59%, 1.87%, and 2.17%, respectively. The rectum V90% was within ± 1% of the treatment planning dose in 71.2% of the QACTs, and within ± 5% in 93.2% of the QACTs. The 6% threshold for rectum V90% was exceeded in 7 out of 144 QACTs (4.8%), identified in 5 of the 41 patients. We evaluated the average rectum V90% across all QACTs for each of these patients, and it was found that the rectum V90% never exceeded 6%. 53% of the QACTs had a rectum volume within 5 cm3 of the TPCT volume, 68% were within 10 cm3. We found that patients who exceeded the threshold on one or more QACTs had a lower TPCT rectal volume than the overall average. By extrapolating patient anatomy from three to four QACT scans, we have shown that the use of hydrogel in conjunction with our patient diet program and use of stool softeners is effective in achieving consistent rectal sparing in patients undergoing proton therapy.


Comprehensive vacuum ultraviolet photoionization study of the CF3(●) trifluoromethyl radical using synchrotron radiation.
The trifluoromethyl radical, CF(3)(●), is studied for the first time by means of threshold photoelectron spectroscopy (TPES). The radical is produced in the gas phase using the flash-pyrolysis technique from hexafluoroethane as a precursor. CF(3)(+) total ion yield and mass-selected TPES of the radical are recorded using a spectrometer based upon velocity map imaging and Wiley-McLaren time-of-flight coupled to the synchrotron radiation. The high resolution of the instrument and of the photons allows the observation of rich vibrational progressions in the TPES of CF(3)(●). By using Franck-Condon factors computed by Bowman and coworkers, we have been able to simulate the TPES. The initial vibrational temperature of the radical beam has been evaluated at 350 ± 70 K. The structures have been identified as transitions between (n(1),n(2)) and (n(1)(+),n(2)(+)) vibrational levels of CF(3) and CF(3)(+) with small excitation of the breathing mode, ν(1)(+) (,) and large excitation (n(2)(+) = 10-26) of the umbrella mode, ν(2)(+), in the cation. From the energy separation between the two resolved peaks of each band, a value of 994 ± 16 cm(-1) has been derived for the ν(1)(+) breathing frequency of CF(3)(+). For the high-lying n(2)(+) levels, the apparent ν(2)(+) umbrella spacing, 820 ± 14 cm(-1), is fairly constant. Taking into account the ν(2)(+) anharmonicity calculated by Bowman and coworkers, we have deduced ν(2)(+) = 809 ± 14 cm(-1), and semi-empirical estimations of the adiabatic ionization energy IE(ad.)(CF(3)(●)) are proposed in good agreement with most of previous works. A value of the vertical ionization potential, IE(vert.)(CF(3)(●)) = 11.02 eV, has been derived from the observation of a photoelectron spectrum recorded at a fixed photon energy of 12 eV.


Small Molecules in the Cone Snail Arsenal.
Cone snails are renowned for producing peptide-based venom, containing conopeptides and conotoxins, to capture their prey. A novel small-molecule guanine derivative with unprecedented features, genuanine, was isolated from the venom of two cone snail species. Genuanine causes paralysis in mice, indicating that small molecules and not just polypeptides may contribute to the activity of cone snail venom.


Radiological cavitation, sputum mycobacterial load and treatment response in pulmonary tuberculosis.
Royal Free Hospital, London. To investigate the relationship between sputum mycobacterial load, assessed by time to positivity (TTP) in liquid culture, radiological cavitation and change in sputum bacterial load in response to anti-tuberculosis treatment. The study was conducted on 95 patients treated for sputum culture-positive pulmonary tuberculosis (TB), with pre-treatment TTP and baseline chest X-ray (CXR). Of these, 31 had chest computed tomography scans assessed for number and volume of cavities. The microbiological treatment response was measured in 56 patients with serial TTP, and related to baseline radiological cavitation. Cavitation was present in 48% of patients, and was associated with a shorter TTP at baseline (P < 0.001). Patients with more cavities and greater total cavitary volume had a shorter TTP (P < 0.001 for both). No difference was demonstrated in the rate of change in TTP on treatment (P = 0.36) between patients with and without cavities. This study confirms that cavitation is associated with higher baseline sputum mycobacterial load. The rate of decline in bacterial load in response to treatment is similar in patients with and without radiologically demonstrable cavities, suggesting that response to, and hence duration of, effective treatment may be predicted by the initial number of organisms present in the sputum.


Investigation of Amino Acids As Herbicides for Control of Orobanche minor Parasitism in Red Clover.
Certain amino acids induce inhibitory effects in plant growth due to feedback inhibition of metabolic pathways. The inhibition patterns depend on plant species and the plant developmental stage. Those amino acids with inhibitory action on specific weeds could be utilized as herbicides, however, their use for weed control has not been put into practice. Orobanche minor is a weed that parasitizes red clover. O. minor germination is stimulated by clover root exudates. The subsequent seedling is an obligated parasite that must attach quickly to the clover root to withdraw its nutrients. Early development of O. minor is vulnerable to amino acid inhibition and therefore, a series of in vitro, rhizotron, and field experiments were conducted to investigate the potential of amino acids to inhibit O. minor parasitism. In in vitro experiments it was found that among a collection of 20 protein amino acids, lysine, methionine and tryptophan strongly interfere with O. minor early development. Field research confirmed their inhibitory effect but revealed that methionine was more effective than lysine and tryptophan, and that two successive methionine applications at 308 and 543 growing degree days inhibited O. minor emergence in red clover up to 67%. We investigated additional effects with potential to influence the practical use of amino acids against broomrape weeds, whether the herbicidal effect may be reversible by other amino acids exuded by host plants or may be amplified by inducing host resistance barriers against O. minor penetration. This paper suggests that amino acids may have the potential to be integrated into biorational programs of broomrape management.


Risk Stratification in People with Diabetes for Fasting During Ramadan: Consensus from Arabic Association for the Study of Diabetes and Metabolism.
Current international guidelines recommend a pre-Ramadan risk assessment for people with diabetes (PwDM) who plan on fasting during the Holy month. However, a comprehensive risk assessment-based recommendation for the management of PwDM intending to fast is still controversial. Therefore, the Arabic Association for the Study of Diabetes and Metabolism (AASD) developed this consensus to provide further insights into risk stratification in PwDM intending to fast during Ramadan. The present consensus was based on the three-step modified Delphi method. The modified Delphi method is based on a series of voting rounds and in-between meetings of the expert panel to reach agreements on the statements that did not reach the consensus level during voting. The panel group comprised professors and consultants in endocrinology (both adult and pediatric). Other members included experts in the fields of cardiovascular medicine, nephrology, ophthalmology, and vascular surgery, affiliated with academic institutions in Egypt. In PwDM who intend to fast during Ramadan, risk stratification is crucial to optimize patient outcomes and prevent serious complications. The present consensus provides risk assessment of those living with diabetes according to several factors, including the type of diabetes, presence, and severity of complications, number of fasting hours, and other socioeconomic factors. According to their risk factors, patients were classified into four categories (very high, high, moderate, and low risk). Future research is warranted due to the controversial literature regarding the impact of fasting on certain comorbidities.


The DAOA gene is associated with schizophrenia in the Taiwanese population.
The gene D-amino acid oxidase activator (DAOA), which has a former name of G72, and the D-amino acid oxidase (DAO) gene have been suggested as candidate genes of schizophrenia. However, association studies have so far yielded equivocal results. We analyzed one single nucleotide polymorphism (SNP) for DAO (rs3741775) and seven SNPs for G72 (rs3916956, rs2391191, rs9558562, rs947267, rs778292, rs3918342, and rs1421292) in this study enrolling 248 schizophrenia cases and 267 controls in the Taiwanese samples. In SNP-based single locus association analyses, the rs778292 in the DAOA gene showed significant association with schizophrenia. The rs3741775 in the DAO gene could not withstand statistically significant after multiple corrections. Additionally, a three-SNP haplotype (rs778292-rs3918342-rs1421292) in the DAOA gene were observed to be significantly associated with schizophrenia. Among them, the TCT haplotype presented higher prevalence in controls than in cases whereas the TTT and CTT haplotype were significantly more frequent in cases than in controls. The study also provides significant evidence for epistatic interactions among DAOA and DAO gene in the development of schizophrenia. These results provide additional evidence and indicate that the DAOA gene and DAOA-DAO gene-gene interactions might play a role for schizophrenia in a Taiwanese sample.


Influence of estrogens on neurodegenerative processes.
Gonadal steroids are known to be of prime importance in the normal maintenance of brain function. Data from epidemiological studies suggest that the decline in estrogen following menopause may increase the risk of neurodegenerative diseases. There is accumulating epidemiological evidence for neuroprotection by estrogens against neurodegenerative diseases, such as Alzheimer's disease. Although it is unclear whether estrogen may be effective in preventing further cognitive decline in women who already have Alzheimer's disease, several studies indicate that estrogen replacement improves the cognitive performance of postmenopausal women. Despite the somewhat controversial data from human studies, experimental investigations in different animals have shown that estrogen is neuroprotective. Although estrogens are known to exert several direct effects on neurons, the cellular mechanisms involved in the neuroprotective effects of estrogen are still unclear. Estrogen causes most of its neuroprotective effects by means of direct binding to specific nuclear receptors. The anti-oxidant effects of estrogens and activation of different membrane-associated intracellular signaling pathways or neurotrophic cross talk through the signal cascade shared with neurotrophic factors could also contribute to neuroprotection. In this article, we outline the evidence supporting a direct role of estrogen in neuronal survival, and


Knowledge and attitudes toward dental avulsion of public and private elementary schoolteachers.
The purpose of this study was to evaluate and compare the knowledge and attitudes toward dental avulsion of public and private elementary schoolteachers. the study was performed by applying a questionnaire in a sample composed of 95 elementary schoolteachers (46 from public schools and 49 from private schools). The questionnaire comprised 9 questions and was pretested before final implementation. Thirty-nine percent of private schoolteachers and 15% of public schoolteachers witnessed at least 1 case of dental avulsion at the school (P=.009). Ninety-two percent and 62% of private and public schoolteachers, respectively, admitted the possibility of an avulsioned tooth to be reimplanted (P<.001). Both responses were statistically different when school type (public or private) was considered. Only 27% of private schoolteachers and 11% of public schoolteachers knew the procedures to be taken in cases of avulsed teeth, and more than 95% of all teachers did not feel capable of executing tooth reimplantation. The study showed no statistical difference between private and public schoolteachers' knowledge. Teachers and other professionals involved in children's care and supervision must be correctly and well informed about dental avulsion, its consequences and the correct procedures to be performed in such cases.


Feeding, uptake, and utilization of carbohydrates by western subterranean termite (Isoptera: Rhinotermitidae).
Western subterranean termite, Reticulitermes hesperus (Banks), prefers various mono-, di-, and trisaccharides, total feeding being the greatest on paper disks treated with 5% ribose followed by 3% xylose, 2% maltose, 2% fructose, 2% arabinose, and 2% ribose. In multiple choice tests, termites were not able to discriminate between 2% ribose, 2% fructose, 2% xylose, and 2% maltose. Termites readily take up [14C] sucrose in feeding studies. Most of the sucrose is used as an energy source for respiration (89.2%), a very small proportion remains within the termite (9.3%), and an even smaller amount is excreted as solid waste (1.5%). The amount of 14C label transferred to other colony members via trophallaxis, body contact, or grooming is small and directly dependent upon the time and numbers of donors and recipients. At day 15 postmixing, the percentage of transfer was highest, 14.4 and 15.1% for both 1:1 and 2:1 donor to recipient mixing ratios, respectively. The mean amount of labeled 14C received by recipients increased from seven disintegrations per minute (dpm) on day 2 to 30 dpm on day 15 for 1:1. Overall mean radioactivity recovered from recipient termites when mixed with donor termites at 1:1 ratio (20 dpm) was significantly less than (28 dpm) when mixed with donor termites at 2:1 ratio. Sugars act as phagostimulants to the termites at concentrations much higher to those that termites naturally encounter in wood. Termites readily metabolize carbohydrates such as sucrose, and thus their use in bait matrices may increase consumption and retention at bait stations.


The ultrasound appearance of radiation-induced hepatic injury. Correlation with computed tomography and magnetic resonance imaging.
The ultrasound findings in three cases of radiation-induced hepatic injury are described and compared with computed tomography and magnetic resonance imaging findings. Fatty infiltration of the liver was present in two of the cases in which concurrent chemotherapy was being administered. On ultrasound B-scans, the regions of radiation injury were hypoechoic relative to the remainder of the liver. This finding was more obvious in the patients with fatty livers. CT scans on the patients with fatty infiltrated livers showed higher attenuation in the irradiated region than in unexposed liver. In the patient where no fatty infiltration was present, the radiated section of liver had lower attenuation consistent with previous reports. Magnetic resonance imaging showed decreased signal in the exposed areas on T1 weighted images.


TIVA-A Promising Approach to Anaesthetic Management of Montgomery T-tube Insertion.
One of the treatment modalities for tracheal stenosis is tracheal dilatation and stenting using silicone Montgomery T-tube. Various techniques have been reported for this procedure. For safe anaesthetic management, anaesthesiologist must be aware of the surgical procedure, limitations of T-tube, likelihood of compromised airway besides the inherent problems of sharing the airway with surgeons. Total intravenous anaesthesia (TIVA) is a technique which has become very popular and possible now a days for various surgical procedures owing to its advantages. The anaesthetic technique should be based on the provider's experience and severity of tracheal stenosis. We present here the anaesthetic management using TIVA technique with propofol and atracurium for the insertion of Montgomery T-tube in a case of post intubation tracheal stenosis.


Regulation of the trafficking and antiviral activity of IFITM3 by post-translational modifications.
IFITM3 restricts cellular infection by multiple important viral pathogens, and is particularly critical for the innate immune response against influenza virus. Expression of IFITM3 expands acidic endolysosomal compartments and prevents fusion of endocytosed viruses, leading to their degradation. This small, 133 amino acid, antiviral protein is controlled by at least four distinct post-translational modifications. Positive regulation of IFITM3 antiviral activity is provided by S-palmitoylation, while negative regulatory mechanisms include lysine ubiquitination, lysine methylation and tyrosine phosphorylation. Herein, we describe specific insights into IFITM3 trafficking and activity that were provided by studies of IFITM3 post-translational modifications, and discuss evidence suggesting that IFITM3 adopts multiple membrane topologies involving at least one intramembrane domain in its antivirally active conformation.


Systemic therapy in metastatic salivary gland carcinomas: A pathology-driven paradigm?
Salivary gland carcinomas (SGCs) represent one of the most complex tumors from a pathological point of view. According to the World Health Organization (WHO) classification (2005), twenty-four malignant histotypes are recognized, almost all characterized by specific morphological and genetic features as well as by particular clinical behavior. Loco-regional relapse and distant metastases are quite common. Distant metastases are diagnosed in 25-55% of the patients and only 20% of them are alive after 5years. Adenoid cystic carcinoma (ACC) is the most common (60%) malignant histotype observed in patients with metastatic disease, whilst the other histotypes such as mucoepidermoid carcinoma, salivary duct carcinoma, adenocarcinoma, not otherwise specified (NOS), and myoepithelial carcinoma are rarer. The most common therapeutic approach in cases of metastatic disease is systemic chemotherapy, although the results with this type of approach are poor both in terms of response rate and overall outcome. No consensus has yet been reached on what the standard regimen of chemotherapy should be in this setting. New therapies are under investigation e.g. antiangiogenic agents, histone deacetylase inhibitors, and hormonal deprivation treatment. We have focused our review on systemic treatments in ACC and in non-ACC tumors, including in this latter group all SGC histotypes other than ACC.


Treatment of severe peri-implant bone loss using autogenous bone and a resorbable membrane. Case report and literature review.
Clinical case reports and animal studies have demonstrated that the principle of guided bone regeneration can be applied for surgical treatment of moderate to profound peri-implant bone loss (peri-implantitis). However, the degree of bone regeneration within the peri-implant osseous defect was reported to be variable depending on different clinical factors and on the postoperative course. Most papers dealing with surgical treatment of peri-implantitis advocate the use of a non-resorbable ePTFE membrane for secluding the peri-implant bone defect enabling bone regeneration. Additionally some surgeons fill the defects with allografts or alloplasts. The present case report demonstrates another surgical approach by using autogenous cancellous bone for grafting into the peri-implant bone defect and placing a bioresorbable polylactide membrane as a matrix barrier. The successful outcome of this modified surgical approach enabled the patient to maintain the implant for prosthetic reconstruction after early but severe bone loss.


Application of hierarchical MFI zeolite for the catalytic pyrolysis of Japanese larch.
The catalytic pyrolysis of Japanese larch was carried out over a hierarchical MFI zeolite (Meso MFI C16). The zeolite was synthesized using an amphiphilic organosilane as a mesopore-directing agent, and its catalytic activity was compared with that of the conventional HZSM-5 and the mesoporous material from HZSM-5 (MMZ(ZSM-5)). The effect of the hierarchical MFI zeolite on the product distribution and chemical composition of the bio-oil was also examined. The hierarchical MFI zeolite exhibited the highest activity in deoxygenation and aromatization during the catalytic pyrolysis of Japanese larch. In particular, it showed high selectivity for valuable aromatics, such as benzene, toluene, and xylenes (BTX), even though it decreased the organic fraction of bio-oil. Its higher mesoporosity resulted, however, in an increase in the coke amount and in undesirable products, such as polycyclic aromatic hydrocarbons (PAHs).


Cancer genomic research at the crossroads: realizing the changing genetic landscape as intratumoral spatial and temporal heterogeneity becomes a confounding factor.
The US National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI) created the Cancer Genome Atlas (TCGA) Project in 2006. The TCGA's goal was to sequence the genomes of 10,000 tumors to identify common genetic changes among different types of tumors for developing genetic-based treatments. TCGA offered great potential for cancer patients, but in reality has little impact on clinical applications. Recent reports place the past TCGA approach of testing a small tumor mass at a single time-point at a crossroads. This crossroads presents us with the conundrum of whether we should sequence more tumors or obtain multiple biopsies from each individual tumor at different time points. Sequencing more tumors with the past TCGA approach of single time-point sampling can neither capture the heterogeneity between different parts of the same tumor nor catch the heterogeneity that occurs as a function of time, error rates, and random drift. Obtaining multiple biopsies from each individual tumor presents multiple logistical and financial challenges. Here, we review current literature and rethink the utility and application of the TCGA approach. We discuss that the TCGA-led catalogue may provide insights into studying the functional significance of oncogenic genes in reference to non-cancer genetic background. Different methods to enhance identifying cancer targets, such as single cell technology, real time imaging of cancer cells with a biological global positioning system, and cross-referencing big data sets, are offered as ways to address sampling discrepancies in the face of tumor heterogeneity. We predict that TCGA landmarks may prove far more useful for cancer prevention than for cancer diagnosis and treatment when considering the effect of non-cancer genes and the normal genetic background on tumor microenvironment. Cancer prevention can be better realized once we understand how therapy affects the genetic makeup of cancer over time in a clinical setting. This may help create novel therapies for gene mutations that arise during a tumor's evolution from the selection pressure of treatment.


Reduced cytocidal efficacy for adriamycin in cultured human carcinoma cells depleted of polyamines by difluoromethylornithine treatment.
We have studied the effect of pretreatment with difluoromethylornithine (DFMO), an ornithine decarboxylase inhibitor, on the cytocidal responses of four human adenocarcinoma cell lines to Adriamycin (ADR). The cell lines utilized included HuTu-80 (duodenum), HT-29 (colon), ME-180 (cervix), and A-427 (lung). A 48-h DFMO pretreatment reduced putrescine and spermidine content to less than 10 and less than 1% of control levels and decreased spermine to between 70 and 30% of controls. Plating efficiency assays were used to generate ADR dose-response survival curves for DFMO-treated and control cultures. The DFMO pretreatment significantly protected human adenocarcinoma cells from the lethal effects of ADR. Addition of exogenous putrescine to the DFMO-treated cultures 24 h before treatment with ADR restored their cytocidal response to ADR to near control levels. Putrescine had no effect on cell survival in cultures that were not pretreated with DFMO. These observations suggest that DFMO-induced protection from ADR may be a specific consequence of DFMO-induced inhibition of polyamine biosynthesis. Alternatively, since ADR efficacy varies directly with cellular growth rates and DFMO inhibits proliferation, the protection may have resulted from DFMO-induced growth inhibition. Comparison of ADR uptake in DFMO-pretreated and control cells showed that the protection did not result from decreased intracellular accumulation of ADR.


Efficacy of Yushen Tongluo Granule Combined with Clomiphene Citrate for Anovulatory Infertility: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial.
To evaluate the efficacy and safety of Yushen Tongluo Granule (YSTLG) combined with clomiphene citrate (CC) in the treatment of anovulatory infertility. This randomized, double-blinded, placebo-controlled clinical trial was carried out in the Department of Obstetrics and Gynecology and the Department of Traditional Chinese Medicine (TCM). During the 3 menstrual cycle intervention periods, all subjects received 50 mg/day CC from day 5 until day 9 of the menstruation. If no ovulation, the amount of CC per cycle increased 50 mg/day until 150 mg/day. Participants in the experimental group received YSTLG, while participants in the control group received YSTLG placebo. The granules were orally taken from the end of menstruation until ovulation. When one leading follicle attained a diameter of 18 mm or more, 5000 U human chorionic gonadotropin (hCG) was given intramuscularly. The primary outcome measure was the ovulation rate, and follicular development was monitored by transvaginal ultrasound on the 10th day of the cycles until ovulation. Secondary outcome measures including the overall curative effect, endometrial thickness, and pregnancy outcomes were also compared between the two groups. The ovulation rate in the experimental group was higher than that in the control group (P < 0.05). Compared with the control group, the overall curative effect of the experimental group was better than that of the control group (P < 0.05), and the endometrial thickness in the ovulation phase was significantly thicker than that in the control group (P < 0.01). There was no significant difference in pregnancy rate and miscarriage rate between the experimental group and control group (P > 0.05). The combined YSTLG and CC used to treat anovulatory infertility can improve the ovulation rate without affecting endometrial thickness, which is efficacious and safe.


Identification of novel GLI1 target genes and regulatory circuits in human cancer cells.
Hedgehog (HH) signaling is involved in many physiological processes, and pathway deregulation can result in a wide range of malignancies. Glioma-associated oncogene 1 (GLI1) is a transcription factor and a terminal effector of the HH cascade. Despite its crucial role in tumorigenesis, our understanding of the GLI1 cellular targets is quite limited. In this study, we identified multiple new GLI1 target genes using a combination of different genomic surveys and then subjected them to in-depth validation in human cancer cell lines. We were able to validate >90% of the new targets, which were enriched in functions involved in neurogenesis and regulation of transcription, in at least one type of follow-up experiment. Strikingly, we found that RNA editing of GLI1 can modulate effects on the targets. Furthermore, one of the top targets, FOXS1, a gene encoding a transcription factor previously implicated in nervous system development, was shown to act in a negative feedback loop limiting the cellular effects of GLI1 in medulloblastoma and rhabdomyosarcoma cells. Moreover, FOXS1 is both highly expressed and positively correlated with GLI1 in medulloblastoma samples of the Sonic HH subgroup, further arguing for the existence of FOXS1/GLI1 interplay in human tumors. Consistently, high FOXS1 expression predicts longer relapse-free survival in breast cancer. Overall, our findings open multiple new avenues in HH signaling pathway research and have potential for translational implications.


Dental anomaly pattern (DAP): agenesis of mandibular second premolar, distal angulation of its antimere and delayed tooth formation.
To test the null hypotheses that children with unilateral agenesis of the mandibular second premolar (MnP2) do not show (1) greater distal angulation of the unerupted antimere and (2) delayed tooth formation compared with children without agenesis. Panoramic radiographs of 38 patients with unilateral aplasia of MnP2 were retrospectively examined and compared to a non-agenesic control group of 82 patients. Ages ranged from 8 to 15 years. Contralateral mandibular deciduous second molars were present for all participants. Each unerupted MnP2 was traced, and its developmental stage and angulation were recorded (measured with the distal angle and the premolar-molar angle). Dental age was evaluated using the Haavikko method. Student's t-test was performed to identify significant differences between the compared groups. The significance level for statistical testing was set at P < .05. The results indicated a 9.5° decrease in the distal angle and a 13.2° increase in the premolar-molar angle for the unerupted MnP2 in the agenesis sample. This was a highly statistically significant difference (P < .001 and P < .0001, respectively) compared with the MnP2 inclinations in the control sample. The delay in dental age was significantly greater in patients with agenesis (2.1 years) compared with the delay in the control group (1.5 years) (P < .001). Both null hypotheses are rejected. The results of this study statistically support the hypothesis that aplasia of MnP2, distally displaced MnP2s, and delayed tooth formation are part of a genetically related pattern of dental anomalies.


Real-time measures of context to improve fall-detection models.
Real-time fall detection has been a challenging area of research and even more challenging as a viable commercial service, given the need for near perfect classification algorithms. True fall events are rare is monitored data sets, whereas confounding events for automated algorithms are quite frequent. In this paper we describe a decision theoretic approach to classification and alerting that incorporates context, such as location and activities, to improve probability and utility estimates for new classes, including near falls and known confounding events. We describe how to use monitored context to provide real-time assessment of true patient state to improve training data sets, as well as the use of context in improving classification, detection and alerting.


An Integrative Process-Based Model for Biomass and Yield Estimation of Hardneck Garlic (Allium sativum).
We introduce an integrative process-based crop model for garlic (Allium sativum). Building on our previous model that simulated key phenological, morphological, and physiological features of a garlic plant, the new garlic model provides comprehensive and integrative estimations of biomass accumulation and yield formation under diverse environmental conditions. This model also showcases an application of Cropbox to develop a comprehensive crop model. Cropbox is a crop modeling framework featuring declarative modeling language and a unified simulation interface for building and improving crop models. Using Cropbox, we first evaluated the model performance against three datasets with an emphasis on biomass and yield measured under different environmental conditions and growing seasons. We then applied the model to simulate optimal planting dates under future climate conditions for assessing climate adaptation strategies between two contrasting locations in South Korea: the current growing region (Gosan, Jeju) and an unfavorable cold winter region (Chuncheon, Gangwon). The model simulated the growth and development of a southern-type cultivar (Namdo, ND) reasonably well. Under Representative Concentration Pathway (RCP) scenarios, an overall delay in optimal planting date from a week to a month, and a slight increase in potential yield were expected in Gosan. Expansion of growing region to northern area including Chuncheon was expected due to mild winter temperatures in the future and may allow ND cultivar production in more regions. The predicted optimal planting date in the new region was similar to the current growing region that favors early fall planting. Our new integrative garlic model provides mechanistic, process-based crop responses to environmental cues and can be useful for assessing climate impacts and identifying crop specific climate adaptation strategies for the future.


Disability-Adjusted Life Years among Drug Users in Khon Kaen: An Evidence-Based Approach.
To examine the Disability Adjusted Life Years (DALYs) among drug users in Khon Kaen. A cross-sectional descriptive study was conducted between January 2014 and February 2015. Patients' medical records, supported by the Khon Kaen Provincial Public Health Office, were used for data regarding the treatment ofthe drug users between October 2013 and September 2014. SPSS version 19.0 for windows was used to analyze descriptive statistics and Pearson's correlations. A review of medical records revealed a total number of drug users were 3,605 males (92.25%) and 303 females (7.75%). A total of 2,195 cases (56.17%) were drug dependence. 20 drug users died due to drug-related causes. A total DALYs were 6,772.26 and a prevalence rate of DALYs was 3.76/1,000 populations. The correlation analyses showed significantly factors related to the DALYs among drug users were age, occupation, pattern of drug use, levels of severity, drug-related death and treatment services. The DALYs were apparently high among male drug users, who completed primay school education, were drug-dependent and being treated in group therapy. The health authorities may use these associated factors in order to develop or improve programs related to prevention, harm reduction and treatment services effectively.


[Role of redox- and hormonal metabolism in the mechanisms of skin aging].
The aim of the study was to investigate the role of redox balance in the pathogenesis of skin aging in menopausal women. 30 menopausal women aged 40 to 55 years and 30 reproductive women aged 25 to 35 years were studied. Qualitative assessment of the skin (moisture, fat, elasticity) was performed; in the venous blood hormonal metabolism indicators: estradiole - E, testosterone - T, follicle stimulating hormone - FSH and redox parameters - oxygen and lipid free radical content (EPR method), antioxidant enzymes (catalase, superoxide dismutase (SOD) and glutationreducrase (GR)) activity (spectroscopic method) were studied. According results of the study, in menopausal women statistically significant loss of skin elasticity and increase the number of pores was revealed in comparison to the reproductive women. These changes occur against the background of statistically significant increase of the blood testosterone and FSH content; estradiol in women menopausal period has tendency to decrease. Redox indicators of blood did not differ statistically significant in women of reproductive and menopausal period, although there was a tendency to increase the activity of catalase and GR in menopausal women period, indicating on the intensification of oxidative processes in this age group. Statistically significant negative correlation between blood estradiole content and SOD's activity (r=-0.413, p=0.0017) and positive correlation between blood estradiole content and GR activity (r=0.565, p=0.002) was revealed. Decrease in the estradiol concentration and disbalance in redox-system in the women's blood correlats with the rate of pigmented spots growth and decrease of the skin moisture. It is concluded that in mechanisms of skin aging of menopausal women estrogen-depending alterations in redox-balance places important role.


Kinetic transition in model proteins with a denatured native spinodal.
The relaxation kinetics of three-dimensional lattice model proteins with Gō potential is studied. A kinetic transition from an exponential behavior to a nonexponential one with a denatured native spinodal is characterized. The transition temperatures T(k), obtained from simulations and a semiquantitative estimation, are found to be the same. The change in free energy landscape during the transition is discussed microscopically by studying the detailed folding processes of various paths. The connection of T(k) with the foldability is also studied by a Z-score-like quantity T(f)/T(k).


Normative data on the Boston Diagnostic Aphasia Examination in a Spanish-speaking population.
Normative data of the Boston Diagnostic Aphasia Examination (Goodglass & Kaplan, 1972) in a Spanish-speaking population is presented. This test was given to 180 neurologically normal adults grouped according to three variables: sex, age, and educational level. The statistically significant differences found are presented. Few differences appeared between sexes, but there were marked differences among the different age groups and in particular among educational levels. A correction to the scoring is proposed for each of the subtests according the patient's educational level.


A comparative study for the short-term effects of targeted high-intensity UVB and narrow-band UVB in the treatment of vitiligo.
Vitiligo is a common acquired depigmentation disorder for which many treatments have previously been used with varying effects. The aim of the present study was to evaluate the efficacy and safety of targeted high-intensity (TH) and narrow band (NB) ultraviolet B light (UVB) for vitiligo treatment. A total of 33 patients with vitiligo were enrolled in the present study. Patients with a symmetrical or near-symmetrical distribution of lesions on their bodies were selected for the present study. For each patient, half of the body was treated with TH-UVB and the other with NB-UVB twice weekly over a period of 12 weeks (24 times total). The patients were assessed each week for repigmentation of lesions. All data were analyzed using SPSS software, and a total of 30 patients were evaluated. The effective rate was significantly higher in the TH-UVB group (56.7%) compared with the NB-UVB group (20.0%; P<0.05). Additionally, the mean number of radiations necessary for initial repigmentation was significantly lower in the TH-UVB group (7.95±3.43) compared with the NB-UVB group (15.36±3.43; P<0.05). No correlation was found between the clinical features of patients and the efficacy of treatment. In summary, the results of the present study suggest that TH-UVB is a more effective treatment for vitiligo than NB-UVB.


Microtomographic studies of subdivision of modified-release tablets.
The uniformity of dosage units within a certain batch is ensured when each unit contains the active pharmaceutical ingredient (API) within a narrow range around the label claim. For tablets containing a score-line authorised for dose reductions, the European Pharmacopoeia (Ph. Eur.) considers that the uniformity of the tablet parts may be based on weight measurements regardless of the tablet type (immediate or modified release). This is because it is up to the regulatory authorities first to assess whether the tablet may contain a score-line for such use. X-ray microtomography was applied to assess the symmetry of 36 modified release tablets, containing 300mg of theophylline. The sum of the volume and surface area of the pellets in the subdivided tablets were compared. Simulations were carried out to identify the optimal amount of pellets in the tablet mass. The maximum difference in the API content between two subdivided halves was 165.18mg vs 133.83mg. If the amount of pellets in the tablet mass would drop below 13% on the basis of the pellet surface area, then the Ph. Eur. requirements would be exceeded. The amount of pellets in the tablet halves resulting in the greatest variability in API content was 38%. The results of this study indicate that the pellets were not distributed uniformly in the tablet mass. Thus, the uniformity of the dose in both halves of a tablet containing pellets cannot be based on the weight measurements i.e. it is necessary to develop further standards for tablet subdivision. Microtomographic methods are a very interesting alternative to expensive and time-consuming pharmacokinetic studies.


Ovarian cancer. Geographical, host and environmental factors. An overview.
The incidence of ovarian cancer is reviewed among different races and ethnic groups. We present the effect of socio-economic class, age, endocrinological factors, menstrual cycle, reproductive history, familial, and genetic factors, viral infections, chemical carcinogens, and previous exposure to radiation on the incidence of ovarian cancer. There is evidence that environmental factor affects the distribution of various types of ovarian cancer. Migration may also change the susceptibility to this disease and the mean age was varied between countries being lowest where incidence was highest. The disease appeared to have a familial incidence. The protective effect of oral contraceptive steroids and the role of asbestos as a chemical carcinogen are discussed.


[FUNCTIONAL TRAJECTORIES BEFORE, DURING AND AFTER ACUTE HOSPITALIZATION OF OLDER ADULTS IN INTERNAL MEDICINE WARDS].
Hospital-associated functional decline (HAFD) is recognized as a leading cause of adverse hospitalization outcomes, such as prolonged hospitalization, falls, readmission, and mortality. Since most patients hospitalized in internal medicine wards are older-adults, HAFD presents a major challenge to internal medicine. Describe functional trajectories of older-adults (aged ≥70 years) before, during and after acute hospitalization in internal-medicine units. A prospective cohort study was conducted of 741 older-adults, hospitalized in two tertiary hospitals in Israel during the period 2009-2011. Basic functional status two weeks before admission, on-admission, at-discharge and one-month post-discharge was assessed using the modified Barthel Index (BI). Eight trajectories were identified. Two-thirds of the participants were completely or almost independent at the pre-morbid period. About a half of the older-adults were hospitalized with pre-admission functional decline, a quarter deteriorated or died during hospitalization, and one-third improved during hospitalization. Most of the older-adults who were stable in functioning at the pre-admission period (57.1%) remained stable during and post-hospitalization; however, about a third of them did not return to their pre-morbid functioning levels. Approximately half of those with pre-morbid functional decline experienced additional deterioration of at least 5 points on the BI scale. Pre-morbid instrumental functional status, comorbidity and depressive symptoms have been found to distinguish older adults with similar pre-admission and in-hospital functional trends. Eight functional trajectories describe the hospitalization period of older-adults in internal-medicine units. On-admission personal characteristics may be used to identify older-adults who are at risk of unwarranted hospitalization outcomes and thus allow intervention in the hospital-community interface.


The interaction between farming/rural environment and TLR2, TLR4, TLR6 and CD14 genetic polymorphisms in relation to early- and late-onset asthma.
Asthma phenotypes based on age-of-onset may be differently influenced by the interaction between variation in toll-like receptor (TLR)/CD14 genes and environmental microbes. We examined the associations between single-nucleotide polymorphisms (SNP) in the TLR/CD14 genes and asthma, and their interaction with proxies of microbial exposure (childhood farm exposure and childhood rural environment). Ten SNPs in four genes (TLR2, TLR4, TLR6, CD14) were genotyped for 1,116 participants from the Tasmanian Longitudinal Health Study (TAHS). Using prospectively collected information, asthma was classified as never, early- (before 13 years) or late-onset (after 13 years). Information on childhood farm exposure/childhood rural environment was collected at baseline. Those with early-onset asthma were more likely to be males, had a family history of allergy and a personal history of childhood atopy. We found significant interaction between TLR6 SNPs and childhood farm exposure. For those with childhood farm exposure, carriers of the TLR6-rs1039559 T-allele (p-interaction = 0.009) and TLR6-rs5743810 C-allele (p-interaction = 0.02) were associated with lower risk of early-onset asthma. We suggest the findings to be interpreted as hypothesis-generating as the interaction effect did not withstand correction for multiple testing. In this large, population-based longitudinal study, we found that the risk of early- and late-onset asthma is differently influenced by the interaction between childhood farming exposure and genetic variations.


Cloning of hif-1alpha and hif-2alpha and mRNA expression pattern during development in zebrafish.
Hypoxia-inducible factors (HIFs) regulate gene expression in response to hypoxia and in vertebrates they are known to participate in several developmental processes, including angiogenesis, vasculogenesis, heart and central nervous system development. Over the last decade, major progress in unraveling the molecular mechanisms that mediate regulation of HIF proteins by oxygen tension has been reported, but our knowledge on their developmental regulation during embryogenesis in model organisms is limited. Expression of hif-1alpha and hif-2alpha genes has been characterized during normal mouse development and they were found to be expressed from stages E7.5, later in E9.5 and E15.5 in several different tissues such as the brain, heart and blood vessels. However, there is no detailed temporal information on their expression at other embryonic stages, even though orthologous genes have been described in several different vertebrate species. In this study, we describe the cloning and detailed expression pattern of zebrafish hif-1alpha and hif-2alpha genes. Sequence analysis revealed that zebrafish Hif proteins are highly homologous to other vertebrate orthologues. Zebrafish hif-1alpha and hif-2alpha are both expressed throughout development in discrete territories in a dynamic pattern. Interestingly, in the notochord the expression of hif-1alpha is switched off, while hif-2alpha transcription is turned on, signifying that the two genes might have partially overlapping, although non-redundant functions in development. This is the first time that a detailed comparison of the expression of hif-1alpha and hif-2alpha is directly assessed in a vertebrate model system throughout development.