Effects of exercise on biobehavioral outcomes of fatigue during cancer treatment: results of a feasibility study.
Cancer treatment is associated with decreased hemoglobin (Hb) concentration and aerobic fitness (VO2 max), which may contribute to cancer-related fatigue (CRF) and decreased quality of life (QoL). Endurance exercise may attenuate CRF and improve QoL, but the mechanisms have not been thoroughly investigated. Objectives. To (a) determine the feasibility of conducting an exercise intervention among women receiving treatment for breast cancer; (b) examine the effects of exercise on Hb and VO2 max and determine their association with changes in CRF and QoL; and (c) investigate changes in selected inflammatory markers. Methods. Fourteen women receiving chemotherapy for Stages I-II breast cancer were randomly assigned to exercise (n = 7) or usual care (n = 7). Women in the exercise group performed supervised, individualized treadmill exercise 2-3 times/week for the duration of chemotherapy (9-12 weeks). Data were collected 4 times over 15-16 weeks. Results. Recruitment rate was 45.7%. Sixteen women consented and 14 completed the trial, for a retention rate of 87.5%. Adherence to exercise protocol was 95-97%, and completion of data collection was 87.5-100%. Exercise was well tolerated. VO2 max was maintained at prechemotherapy levels in exercisers but declined in the usual-care group (p < .05). Hb decreased (p < .001) in all participants as they progressed through chemotherapy. Exercise did not have significant effects on CRF or QoL. Changes in inflammatory markers favored the exercise group. Exercise during chemotherapy may protect against chemotherapy-induced decline in VO2 max but not Hb concentration.


Inhibition of ERK activation attenuates endothelin-stimulated airway smooth muscle cell proliferation.
Endothelin is a small peptide that is a potent bronchoconstrictor, mitogen for airway smooth muscle (ASM), and is believed to be involved in the pathogenesis of asthma. To understand how endothelin stimulates the proliferation of ASM cells in culture, we evaluated the relationship between mitogen activated protein (MAP) kinase activation and cell proliferation. Endothelin is a potent stimulator of the extracellular regulated kinase 2 (ERK2) subgroup of MAP kinases, and ERK2 activation was tightly correlated with the proliferation of rat ASM cells. PD98059, a small molecule inhibitor of MEK (MAP or ERK kinase) was used to establish the role of ERK2 activation in the endothelin-stimulated signal transduction pathway leading to cell proliferation. While PD98059 significantly inhibited the ability of endothelin to activate ERK, the drug did not appear to effect the catalytic activity of an activated MEK mutant, or ERK in vitro. The data suggest that the mechanism of PD98059 inhibition of the ERK2 pathway in ASM cells may involve inhibition of MEK activation. The endothelin signal transduction pathway that culminates in ERK2 activation was dependent on protein kinase C (PKC), since depletion of PKC significantly inhibited the ability of endothelin to activate ERK2. Taken together, the data imply that activation of ERK is a critical endpoint in the endothelin signal transduction pathway since inhibition of this kinase inhibits endothelin-induced ASM cell proliferation.


Virus-like particles production in green plants.
Viruses-like particles (VLPs), assembled from capsid structural subunits of several different viruses, have found a number of biomedical applications such as vaccines and novel delivery systems for nucleic acids and small molecules. Production of recombinant proteins in different plant systems has been intensely investigated and improved upon in the last two decades. Plant-derived antibodies, vaccines, and microbicides have received great attention and shown immense promise. In the case of mucosal vaccines, orally delivered plant-produced VLPs require minimal processing of the plant tissue, thus offering an inexpensive and safe alternative to more conventional live attenuated and killed virus vaccines. For other applications which require higher level of purification, recent progress in expression levels using plant viral vectors have shown that plants can compete with traditional fermentation systems. In this review, the different methods used in the production of VLPs in green plants are described. Specific examples of expression, assembly, and immunogenicity of several plant-derived VLPs are presented.


A blood pool contrast aided T1 functional MRI in patients with brain tumors--a preliminary study.
The aim of our study was to determine the possibility of using a new functional technique: a T1-dependent sequence with administration of blood pool contrast agent (BPCA), in patients with brain tumors before and after surgical treatment. We also aimed to compare our results with those obtained using the fMRI technique, based on Blood Oxygenation Level-Dependent (BOLD) contrast. For each of our 14 oncologic patients (four before and ten after neurosurgical intervention), we obtained: a T1-3D GRE sequence (TR = 2.6 ms/TE = 1.1 ms/FA = 10°) after intravenous administration of BPCA (0.03 mmol/kg), as well as a T2*EPI sequence (TR = 3 s/TE = 50 ms/FA = 90°). Movement and/or tactile block type paradigms were carried out during both functional runs. SPM5 software was used for analysis. For both functional techniques, maximum activations were localized in the same areas. There were no significant differences observed in the t values calculated for activations located in the primary motor cortex between groups of pre- and post-intervention patients (in the same functional technique). The mean values for T2* EPI examinations were 10.84 and 9.36, respectively. The mean t values for the T1 technique were lower, especially for the post-intervention patients (5.83 and 3.9, respectively). The T1 technique can be used to detect functional areas in patients with brain tumors, pre-, and post-surgical intervention. This technique enables the evaluation of cortical centers that suffer from susceptibility artifacts when using the T2* BOLD technique. Activations found using both techniques have the same localization, with lower values for the T1 technique.


[Hybrid PET/CT in cancer imaging].
Combination of positron emission tomography (PET) and computed tomography (CT) has revolutionized imaging of cancer. The most often used PET tracer is fluorodeoxyglucose (FDG). FDG-PET/CT shows the extent of the disease more accurately than either CT or MRI alone. With FDG-PET/CT imaging, up to 30% more patients are presented with unexpected distant metastases. This helps to guide patient management.


Four new Cu6S6 cluster-based coordination compounds: synthesis, crystal structures and fluorescence properties.
A hexagonal prismatic Cu6S6 cluster exhibits excellent near-infrared fluorescence properties due to its short Cu-Cu bonds, however, the construction of Cu6S6 cluster-based compounds with extended structures is still a challenge. Here, four new Cu6S6 cluster-based coordination compounds, formulated as Cu3(pymt)3 (1), {(CuCN)2[Cu3(mpymt)3]}n (2), {(CuSCN)[Cu3(mpymt)3]}n (3) and {(CuCN)2[Cu3(dmpymt)3]·CH3CN}n (4) (Hpymt = pyrimidine-2-thiolate, Hmpymt = 4-methyl-pyrimidine-2-thione and Hdmpymt = 4,6-dimethylpyrimidine-2-thione), have been synthesized through the reactions of mercaptopyrimidine derivatives and CuCN or CuSCN under solvo-thermal conditions and characterized by single-crystal X-ray diffraction, powder X-ray diffraction, IR spectroscopy, elemental analysis, and thermal gravimetric analysis. Single-crystal X-ray diffraction analysis reveals that compound 1 is a zero-dimensional Cu6(pymt)6 molecule containing a distorted pseudo-hexagonal prismatic Cu6S6 core. Compounds 2 and 4 with isomorphic frameworks but different organic linkers show a rare three-dimensional framework with nor topology constructed from Cu6(mpymt)6 units and one-dimensional chiral [Cu(CN)]n chains; compared with compound 2, a more hydrophobic one-dimensional channel in compound 4 is observed due to the increase of the methyl groups on the pyrimidine ligand, in which acetonitrile molecules are filled in the channels of compound 4. Compound 3 shows a rare two-dimensional layer constructed from Cu6(mpymt)6 units and one-dimensional puckered (CuSCN)n chains. For the first time, Cu6S6 clusters are connected to one-dimensional inorganic CuCN (or CuSCN) chains through mercaptopyrimidine derivatives to obtain extended arrays in compounds 2-4. The crystals of compounds 1-4 in the solid state all show apparent red light emission. Compound 4 shows sensitive luminescence quenching response to nitrobenzene (NB), and the corresponding quenching constant (Ksv) and detection limit are 2.06 × 103 M-1 and 9.27 ppm, respectively. This study provides a new strategy to construct Cu6S6 cluster-based coordination polymers that have great potential in various applications such as luminescence sensing.


Impact of smoking on marginal bone loss.
To compare marginal implant bone loss (MBL), survival, and radiographic evidence of success of dental implants among smokers and nonsmokers. Consecutive records of 161 patients (aged 23 to 89 years, mean 57 years) treated with a total of 646 implants between the years 1995 and 1998 were examined. Patients were divided into 3 groups: nonsmokers, moderate smokers, and heavy smokers. Tobacco exposure was calculated by cigarettes per day and by pack-years. Follow-up ranged from 1 to 7 years (mean 3.8 years). Postoperative panoramic radiographs obtained before implant exposure and annually thereafter were analyzed for MBL changes. The influence of smoking and other variables on MBL was analyzed at all implant sites. Generally, smokers had more MBL than nonsmokers (0.153 +/- 0.092 mm and 0.047 +/- 0.048 mm, respectively; P < .001). When each jaw was examined separately, smoking had a greater effect on MBL in the maxilla than in the mandible (0.158 +/- 0.171 mm versus 0.146 +/- 0.158 mm, respectively; P < .001). Furthermore, in the maxilla, heavy smokers had the greatest amount of MBL (0.1897 +/- 0.1825 mm), followed by moderate smokers (0.123 +/- 0.156 mm) and nonsmokers (0.0460 +/- 0.070 mm) (P < .001). In the mandible, there was no distinction between heavy and moderate smokers, and both had greater MBL than nonsmokers (P < .001). Only 3 of the 646 implants failed; the cumulative survival rate was 99.5%. Overall radiographic success rate was 93.2%. Nonsmokers had a higher radiographic success rate (97.1%) than smokers (87.8%) (P < .001). This study demonstrated a relationship between MBL and smoking habits. A higher incidence of MBL was found in the smoking group, and this was more pronounced in the maxilla.


Diagnostic accuracy of extended HPV DNA genotyping and its application for risk-based cervical cancer screening strategy.
To evaluate the consistency of 14 high-risk HPVs (hr-HPVs) detection between extended HPV DNA genotyping and a well-validated partial HPV genotyping kit, and to explore the diagnostic accuracy of risk stratification strategy based on extended HPV genotyping for cervical cancer (CC) screening. Baseline data from a clinical trial of recombinant HPV 9-valent vaccine in China was analyzed. All enrolled women aged 20-45 years received cervical cytology, HPV detection by extended and partial HPV genotyping kits. Those who met the indications would further receive colposcopy. The primary endpoints were cervical intraepithelial neoplasia 2/3 or worse (CIN2+/CIN3+). A total of 8,000 women were enrolled between April 2020 and July 2020 and 83/33 cases were diagnosed as CIN2+/CIN3+. The overall agreement between the extended and partial HPV genotyping was 92.66 %. And the agreement further increased with the progression of lesions, which lead to similarly high sensitivity and negative predictive value of these kits. A stratified triage strategy of CC screening was constructed based on the immediate CIN2+/CIN3+ risk of specific HPV. Compared with the conventional HPV primary CC screening strategy, the risk-based strategy had higher specificity for CIN (CIN2+: 94.84 vs. 92.46 %, CIN3+: 96.05 vs. 91.92 %), and needed fewer colposcopies for detecting one cervical disease. Extended HPV genotyping had good agreement with a well-validated partial HPV genotyping CC primary screening kit in hr-HPV detection. Extended HPV genotyping could facilitate risk-based stratified management strategy and improve the diagnostic accuracy of primary CC screening.


Organotypic 3D Models of the Ovarian Cancer Tumor Microenvironment.
Ovarian cancer progression involves multifaceted and variable tumor microenvironments (TMEs), from the in situ carcinoma in the fallopian tube or ovary to dissemination into the peritoneal cavity as single cells or spheroids and attachment to the mesothelial-lined surfaces of the omentum, bowel, and abdominal wall. The TME comprises the tumor vasculature and lymphatics (including endothelial cells and pericytes), in addition to mesothelial cells, fibroblasts, immune cells, adipocytes and extracellular matrix (ECM) proteins. When generating 3D models of the ovarian cancer TME, researchers must incorporate the most relevant stromal components depending on the TME in question (e.g., early or late disease). Such complexity cannot be captured by monolayer 2D culture systems. Moreover, immortalized stromal cell lines, such as mesothelial or fibroblast cell lines, do not always behave the same as primary cells whose response in functional assays may vary from donor to donor; 3D models with primary stromal cells may have more physiological relevance than those using stromal cell lines. In the current review, we discuss the latest developments in organotypic 3D models of the ovarian cancer early metastatic microenvironment. Organotypic culture models comprise two or more interacting cell types from a particular tissue. We focus on organotypic 3D models that include at least one type of primary stromal cell type in an ECM background, such as collagen or fibronectin, plus ovarian cancer cells. We provide an overview of the two most comprehensive current models-a 3D model of the omental mesothelium and a microfluidic model. We describe the cellular and non-cellular components of the models, the incorporation of mechanical forces, and how the models have been adapted and utilized in functional assays. Finally, we review a number of 3D models that do not incorporate primary stromal cells and summarize how integration of current models may be the next essential step in tackling the complexity of the different ovarian cancer TMEs.


Phospholipid:Diacylglycerol Acyltransferase-Mediated Triacylglyerol Synthesis Augments Basal Thermotolerance.
High temperatures rapidly induce a genetically programmed heat-shock response (HSR) that is essential to establish short-term acquired thermotolerance. In addition, an immediate HSR-independent metabolic response is triggered, resulting in an accumulation of unsaturated triacylglycerols (TAGs) in the cytosol. The metabolic processes involved in heat-induced TAG formation in plants and their physiological significance remain to be clarified. Lipidomic analyses of Arabidopsis (Arabidopsis thaliana) seedlings indicated that during heat stress, polyunsaturated fatty acids from thylakoid galactolipids are incorporated into cytosolic TAGs. In addition, rapid conversion of plastidic monogalactosyl diacylglycerols (MGDGs) into oligogalactolipids, acylated MGDGs, and diacylglycerols (DAGs), the direct precursor of TAGs, was observed. For TAG synthesis, DAG requires a fatty acid from the acyl-CoA pool or phosphatidylcholine. Since seedlings deficient in PHOSPHOLIPID:DIACYLGLYCEROL ACYLTRANSFERASE1 (PDAT1) were unable to accumulate TAGs after heat stress, phosphatidylcholine appears to be the major fatty acid donor. Results suggest that rapid plastid lipid metabolism drives TAG accumulation during heat stress. PDAT1-mediated TAG accumulation was found to increase heat resistance, since nonacclimated pdat1 mutant seedlings were more sensitive to severe heat stress, as indicated by a more dramatic decline of the maximum efficiency of PSII and lower seedling survival compared to wild-type seedlings. In contrast, nonacclimated trigalactosyldiacylglycerol1 (tgd1) mutants overaccumulating TAGs and oligogalactolipids were more resistant to heat stress. Hence, thylakoid lipid metabolism and TAG formation increases thermotolerance in addition to the genetically encoded HSR.


Antithrombin III metabolism in patients with liver disease.
Liver diseases are associated with complex haemostasis defects, in which platelets, coagulation, and fibrinolysis may all be affected. The low plasma concentrations of clotting factors often found can be the result of many changes such as impaired synthesis, increased catabolism due to intravascular coagulation, or alternate distribution. In this study, we investigated the metabolism of purified human antithrombin III(AT III) labelled with 125I in 25 patients with histologically established liver disease and in nine control subjects. The results showed that, in general, low plasma concentrations of AT III in liver cirrhosis are not due to consumption in the central compartment but rather to altered transcapillary flux ratio. Such altered transcapillary flux ratios may already exist even with normal plasma AT III concentrations. Altered ratios are not only found for coagulation proteins but also for albumin and thus may be a general phenomenon of liver disease. In micronodular cirrhosis the alpha phase, the transcapillary efflux (k1, 2) and influx (k2, 1) were significantly increased compared with the normal subjects.


Nucleotide substitutions and small-scale insertion produce size and antigenic variation in group A streptococcal M1 protein.
The presence of M protein on the surface of group A streptococci (GAS) confers the ability of the cell to resist phagocytosis in the absence of type-specific antibodies. It undergoes antigenic variation with more than 80 different serotypes having been defined. We have sequenced the M protein gene (emm1.1) from strain CS190 and present evidence that individual nucleotide substitutions are responsible for sequence variation in the N-terminal non-repeat region of emm1.1 and these substitutions have altered antibody recognition of opsonic epitopes. The N-terminal non-repeat domains of two other closely related strains, 71-155 and 76-088, were found to have sequence identical to emm1.1 with the addition of a 21 bp insert. This study provides the first evidence that nucleotide substitutions and small insertions are responsible for size and antigenic variation in the N-terminal non-repeat domain of the M protein of GAS.


An improved trabecular bone model based on Voronoi tessellation.
Accurate numerical and physical models of trabecular bone, correctly representing its complexity and variability, could be highly advantageous in the development of e.g. new bone-anchored implants due to the limited availability of real bone. Several Voronoi tessellation-based porous models have been reported in the literature, attempting to mimic the trabecular bone. However, these models have been limited to lattice rod-like structures, which are only structurally representative of very high-porosity trabecular bone. The objective of this study was to provide an improved model, more representative of trabecular bone of different porosity. Boolean operations were utilized to merge scaled Voronoi cells, thereby introducing different structural patterns, controlling porosity and to some extent anisotropy. The mechanical properties of the structures were evaluated using analytical estimations, numerical simulations, and experimental compression tests of 3D-printed versions of the structures. The capacity of the developed models to represent trabecular bone was assessed by comparing some key geometric features with trabecular bone characterized in previous studies. The models gave the possibility to provide pore interconnectivity at relatively low porosities as well as both plate- and rod-like structures. The mechanical properties of the generated models were predictable with numerical simulations as well as an analytical approach. The permeability was found to be better than Sawbones at the same porosity. The models also showed the capability of matching e.g. some vertebral structures for key geometric features. An improved numerical model for mimicking trabecular bone structures was successfully developed using Voronoi tessellation and Boolean operations. This is expected to benefit both computational and experimental studies by providing a more diverse and representative structure of trabecular bone.


[Benigne multi-recurrent meningitis (Mollaret's disease). A case in a child of 2 years and 8 months].
The authors report a case of meningitis, presenting all characteristics of the disease described in 1944 by P. Mollaret, occurring in a child aged 2 years and 8 months. They stress the rarity of cases on childhood. The cells found in the cerebrospinal fluid, photographs of which are included, are fragile and may undergo early lysis. They are present in association with lymphocytes and polynuclears, giving the slide examined a highly characteristic mottled appearance. The authors raise the question of the morphological similarity of these large cells, with their polygonal contour and small central nucleus, with an epithelium.


Low dopamine function in attention deficit/hyperactivity disorder: should genotyping signify early diagnosis in children?
Attention deficit/hyperactivity disorder (ADHD) is present in 8% to 12% of children, and 4% of adults worldwide. Children with ADHD can have learning impairments, poor selfesteem, social dysfunction, and an increased risk of substance abuse, including cigarette smoking. Overall, the rate of treatment with medication for patients with ADHD has been increasing since 2008, with ≥ 2 million children now being treated with stimulants. The rise of adolescent prescription ADHD medication abuse has occurred along with a concomitant increase of stimulant medication availability. Of adults presenting with a substance use disorder (SUD), 20% to 30% have concurrent ADHD, and 20% to 40% of adults with ADHD have a history of SUD. Following a brief review of the etiology of ADHD, its diagnosis and treatment, we focus on the benefits of early and appropriate testing for a predisposition to ADHD. We suggest that by genotyping patients for a number of known, associated dopaminergic polymorphisms, especially at an early age, misdiagnoses and/or over-diagnosis can be reduced. Ethical and legal issues of early genotyping are considered. As many as 30% of individuals with ADHD are estimated to either have secondary side-effects or are not responsive to stimulant medication. We also consider the benefits of non-stimulant medication and alternative treatment modalities, which include diet, herbal medications, iron supplementation, and neurofeedback. With the goals of improving treatment of patients with ADHD and SUD prevention, we encourage further work in both genetic diagnosis and novel treatment approaches.


Influenza and pneumococcal vaccination coverage in Latin American patients with systemic lupus erythematosus: a cross-sectional and comparative study.
Infections are a major cause of morbidity and mortality in systemic lupus (SLE). Vaccination would be an effective method to reduce infection rate. Coverage for influenza and pneumococcus appears to be low in Latin America. The objective of this study was to evaluate vaccination coverage for influenza and pneumococcus in Latin America, causes of non-vaccination and to compare it with European patients. A survey was conducted through social networks targeting Latin American lupus patients. A self-report was used to assess the demographics, risk factors for pneumonia, vaccination status, and causes of non-vaccination. The same method was used for European patients. We used binary logistic regression to identify factors associated with pneumococcal and influenza vaccination. There were 1130 participants from Latin America. Among them, 97% were women with an average of 37.9 years (SD: 11.3) and 46.5% had more than 7 years of disease duration. Two or more risk factors for pneumonia were found in 64.9%. Coverage for influenza and pneumococcal was 42.7 and 25% respectively, being lower than in Europe. Tetanus coverage was the most important predictor for receiving influenza and pneumococcal vaccination. Lack of prescription was the most common cause of non-application (64.6%). Vaccination coverage for influenza and pneumonia is low in Latin America, especially compared to Europe. It is necessary to make specialists aware of their role in vaccine control and to implement measures to improve coordination between them and general practitioners.


Grape polyphenols reduce gut-localized reactive oxygen species associated with the development of metabolic syndrome in mice.
High-fat diet (HFD)-induced leaky gut syndrome combined with low-grade inflammation increase reactive oxygen species (ROS) in the intestine and may contribute to dysbiosis and metabolic syndrome (MetS). Poorly bioavailable and only partially metabolizable dietary polyphenols, such as proanthocyanidins (PACs), may exert their beneficial effects on metabolic health by scavenging intestinal ROS. To test this hypothesis, we developed and validated a novel, noninvasive, in situ method for visualizing intestinal ROS using orally administered ROS-sensitive indocyanine green (ICG) dye. C57BL/6J mice fed HFD for 10 weeks accumulated high levels of intestinal ROS compared to mice fed low-fat diet (LFD). Oral administration of poorly bioavailable grape polyphenol extract (GPE) and β-carotene decreased HFD-induced ROS in the gut to levels comparable to LFD-fed mice, while administration of more bioavailable dietary antioxidants (α-lipoic acid, vitamin C, vitamin E) did not. Forty percent of administered GPE antioxidant activity was measured in feces collected over 24 h, confirming poor bioavailability and persistence in the gut. The bloom of beneficial anaerobic gut bacteria, such as Akkermansia muciniphila, associated with improved metabolic status in rodents and humans may be directly linked to protective antioxidant activity of some dietary components. These findings suggest a possible mechanistic explanation for the beneficial effects of poorly bioavailable polyphenols on metabolic health.


Incidence rate of symptomatic painless thyroiditis presenting with thyrotoxicosis in Denmark as evaluated by consecutive thyroid scintigraphies.
Painless thyroiditis (PT) is a transient kind of thyrotoxicosis, with lack of uptake on a thyroid scintigraphy in a non-tender thyroid gland, elevated anti-TPO antibodies, no fever, no history of increased iodine intake, and a normal sedimentation rate. The prevalence of PT varies hugely in the literature. To establish the incidence rate of PT in Denmark as well as to describe the phenotype of PT in more detail. Tc-99m pertechnetate scintigraphies were performed over a period of 9.75 years on 6022 consecutive patients (2349 had a thyrotoxic episode), and were divided into high or normal (5528), reduced (300) or lack of uptake (194). Patient records were evaluated: 292 with reduced, and 186 with lack of uptake. As a control measure, 230 consecutive thyrotoxic patients were also analyzed. Based on scintigraphies, 12 patients had PT, 10 with lack of uptake and two with reduced, corresponding to an incidence rate of 0.49/100,000 person years. It was predicted, that only one patient among the newly diagnosed consecutive thyrotoxic cohort had PT. This patient was identified. The prevalence of PT among thyrotoxic patients was 0.51% as evaluated by scintigraphy, and 0.43% among the biochemically thyrotoxic patient cohort. Twenty-five percent had more than one thyrotoxic episode, 75% had at least one subsequent hypothyroid episode, and 33% developed permanent hypothyroidism. PT presenting with symptomatic thyrotoxicosis is an extremely rare disease in Denmark. Symptomatic PT presents most often with no uptake on a Tc-99m pertechnetate scintigraphy. Clinical follow-up is essential.


Jordanian women's postpartum beliefs: an exploratory study.
This study was aimed to determine the beliefs among Jordanian women regarding 10 selected postpartum behaviours. Following Human Subjects approval, a descriptive quantitative questionnaire was administered to 40 postpartum women, 20 from two rural communities and 20 from two urban communities. The majority believed, incorrectly, in prolonged bed rest, that the baby's exhalation on the mother's breast can lead to infection, that kofaleyas (tightly secured wraps around the baby) do not harm newborns, that observation by others while nursing might 'steal' the mother's milk, and that a belt around the mother's abdomen will tighten muscles. The majority correctly believed that dieting affects breast-feeding. Most postpartum women could benefit from increased education about postpartum practices. Educational programmes can help women differentiate between helpful postpartum practices and those which might have adverse effects on the health of a mother and her newborn.


[Evaluation of the accuracy in radiotherapy for carcinomas of the hypopharynx and larynx].
Immobility and reproducibility were investigated to evaluate the accuracy in radiotherapy for carcinomas of the hypopharynx and larynx. Based on our comparative study using a semi-conductor detector, a light-cast shell is sufficient to maintain immobility during radiotherapy. In most cases, the range of reproducibility was within 5 mm throughout the course of radiotherapy.


Forearm and calf tissue oxygenation in term neonates measured with near-infrared spectroscopy.
Peripheral tissue oxygenation has been studied with near-infrared spectroscopy (NIRS) on either the forearm or calf with questionable comparability. The aim was to compare forearm and calf tissue oxygenation in healthy term neonates measured with NIRS. Fractional oxygen extraction, tissue oxygenation index, and mixed venous oxygenation were similar in both extremities, whereas oxygen delivery and oxygen consumption of calf tissue were higher.


Interaction of array of finite electrodes with layered biological tissue: effect of electrode size and configuration.
A hybrid scheme, combining image series and moment method has been utilized for the calculation of the intramuscular three-dimensional (3-D) current density (CD) distribution and potential field transcutaneously excited by an electrode array. The model permits one to study the effect of tissue electrical properties and electrode placement on the CD distribution. The isometric recruitment curve (IRC) of the muscle was used for parameter estimation and model verification, by comparison with experimentally obtained IRCs of functional electrical stimulation (FES)-activated quadriceps muscle of paraplegic subjects. Sensitivity of the calculated IRC to parameters such as tissue conductivity, electrode size, and configuration was verified. The resulting model demonstrated characteristic features that were similar to those of experimentally obtained data. The model IRCs were insensitive to the electrode size; however, the inclusion of the bone-fascia layer significantly increased the intramuscular CD and, consequently, increased the IRC slope. Of the different configurations studied, a four-electrode array proved advantageous because, in this case, the CD between the electrodes was more evenly distributed, providing better resistance to fatigue. However, due to the steeper linear portion of the IRC, this configuration suffered from a somewhat reduced controllability of the muscle.


Imaging large-scale neural activity with cellular resolution in awake, mobile mice.
We report a technique for two-photon fluorescence imaging with cellular resolution in awake, behaving mice with minimal motion artifact. The apparatus combines an upright, table-mounted two-photon microscope with a spherical treadmill consisting of a large, air-supported Styrofoam ball. Mice, with implanted cranial windows, are head restrained under the objective while their limbs rest on the ball's upper surface. Following adaptation to head restraint, mice maneuver on the spherical treadmill as their heads remain motionless. Image sequences demonstrate that running-associated brain motion is limited to approximately 2-5 microm. In addition, motion is predominantly in the focal plane, with little out-of-plane motion, making the application of a custom-designed Hidden-Markov-Model-based motion correction algorithm useful for postprocessing. Behaviorally correlated calcium transients from large neuronal and astrocytic populations were routinely measured, with an estimated motion-induced false positive error rate of <5%.


[Transplantation of human embryonic neural stem cells protects rats against cerebral ischemic injury].
The purpose of this study is to explore the fate and effect of human embryonic neural stem cells (hNSCs) after transplantation into ipsilateral lateral ventricle of stroke rats. Adult rats were exposed to one-hour transient middle cerebral artery occlusion (MCAO), and then hNSCs were transplanted into ipsilateral lateral ventricle 7 days after reperfusion. Infarct volume was calculated by cresyl violet staining. The improvements of neural functions were assessed by behavioral tests. Immunofluorescence staining was performed to observe the migration and differentiation of transplanted hNSCs. The results showed that transplanted hNSCs significantly reduced ischemia-induced infarction in MCAO rats, and improved neural functional restoration when assessed by rotarod, footfault and corner-turn tests. The grafted cells migrated predominantly to several specific brain regions, such as corpus callosum and peri-infarct area. Furthermore, these cells differentiated into oligodendrocytes and astrocytes in corpus callosum, and neurons in peri-infarct parenchyma. These results suggest that transplanted hNSCs through lateral ventricle of the ischemic side may exert effective therapeutic effects on stroke rats via migration and differentiation in specific brain regions.


Outcomes of Geriatric Hip Fractures in a Tertiary Referral Center in Malaysia During the COVID-19 Pandemic.
Introduction With the advancing age of the population, there are an increasing number of patients with geriatric hip fractures. Despite the advancement of surgical knowledge and improvement of implant designs to treat geriatric hip fractures, mortality and morbidity remain high among these frail patients. In conjunction with the COVID-19 pandemic, the collateral damage dealt to these patients remains unknown as scarce resources are funneled to deal with the pandemic. This study is geared to investigate the surgical outcomes of patients with geriatric hip fractures who were admitted during the initial phase of the COVID-19 pandemic. Methods This retrospective study was carried out at Hospital Kuala Lumpur, the largest public hospital in the capital of Malaysia, from March 1, 2020, to March 1, 2021. All patients of age 60 years and above were screened for suitability. Only patients who had undergone surgical intervention during the study period were included in this study. Patients' demographic data, mechanism of injury, waiting time for surgery, type of surgery, complications and ambulatory status were obtained from the medical records. Univariate analysis was performed to determine the factors associated with complications as well as the post-operative ambulatory status of the patients. Results A total of 52 patients were included in this study, with a median age of 72 years. The majority of the patients were Chinese (n=21, 40.4%). This was followed by Malay and Indian (n=14, 26.9% each) and other ethnicity (n=3, 5.8%). More than three-quarters of the patients had a trivial injury such as a fall due to a miss-step (n=16, 30.8%) and slip (n=16, 30.8%) and a fall due to dizziness (n=8, 15.4%). Only 12 patients (23.1%) sustained hip fractures due to trauma. The median time to surgery for these patients was 5 days (interquartile range: 4 days). Most of these patients underwent total hip replacement (n=30, 57.7%). This was followed by unipolar hemiarthroplasty (n=11, 21.2%), bipolar hemiarthroplasty (n=10, 19.2%) and internal fixation (n=1, 1.9%). Among these patients, six of them had documented complications. There were periprosthetic joint infection (n=2, 3.8%), dislocation (n=2, 3.8%), hematoma formation (n=1, 1.9%) and seroma (n=1, 1.9%). Six months after the surgery, most of the patients were able to ambulate, albeit some patients required walking aid such as walking stick and walking frame. Univariate analysis showed that all the factors were not associated with the complications and the post-operative ambulatory status of the patients. Conclusion The incidence of geriatric hip fractures remains high during the COVID-19 pandemic despite the movement control order (MCO) being enforced in Malaysia. With prompt surgical intervention, most of the patients can regain ambulatory status, albeit with a walking aid.


[A study on the effect of Oncomelania hupensis hupensiss killed with niclosamide in China].
To study the effect of Oncomelania hupensis hupensis of niclosamide, and exploring the main influencing factors. The samples of Oncomelania hupensis hupensis were collected from 37 sampling sites in 33 counties of 10 provinces by means of stratified random sampling methods in accordance with the categories of Oncomelania hupensis hupensis habitats. Samples were randomly located into study group and control group. Oncomelania hupensis hupensis of the study group was marinated in different concentration liquor of niclosamide which was confected with water for 24 hours or 48 hours, then LC50 of niclosamide by which Oncomelania hupensis hupensis was killed and amount calculated. The influencing factors of the mortality of Oncomelania hupensis hupensis in the study group was statistically analyzed by 2 test and by multiple logistic regression using SPSS 13.0 statistical software. The mortality of Oncomelania hupensis hupensis of the two test groups which were marinated in 0.5 mg/L liquor for 48 hours and 1.0 mg/L liquor for 24 hours was 100%. The effect of Oncomelania hupensis hupensis killed by niclosamide was markedly reduced along with the reduction of drug concentration. The average LC50 rates of niclosamide liquor by which Oncomelania hupensis hupensis killed for the 24 hours and 48 hours in the study group, were 0.0939 mg/L and 0.0625 mg/L, respectively. There was significant difference between the two test groups (chi(2) = 5.001, P <0.01) . In determinate range of concentration, the mortality of Oncomelania hupensis hupensis showed significant difference among the geographic types of habitat ( chi(2) = 4.264, P < 0.05). By means of multiple logistic regression using SPSS 13.0 statistical software, the estimate value of coefficient of regression on the influence factors, drug concentration, test time and the geographic types of habitat were 2. 047 ( OR = 5. 573), 0.263 ( OR = 2.924) and 0. 187- 0.210 ( OR = 1.969- 2. 560), respectively. Niclosamide could kill Oncomelania hupensis hupensis effectively. The main influencing factors on the efficacy of niclosamide by which Oncomelania hupensis hupensis was killed, appeared to be drug concentration, time of testing and the geographic types of habitat.


Frequency-modulated continuous-wave microwave generation using stabilized period-one nonlinear dynamics of semiconductor lasers.
Frequency-modulated continuous-wave (FMCW) microwave generation is studied using a semiconductor laser operating at stabilized period-one (P1) nonlinear dynamics when subject to comb-like (CL) optical injection. The phase locking established between the P1 dynamics and the CL optical injection not only improves the P1 oscillation stability considerably but also provides a mechanism to change the P1 oscillation frequency through varying the modulation frequency of the CL optical injection. As a result, a stable FMCW microwave at a central frequency of up to 40 GHz is generated with its frequency varying linearly, triangularly, or step-wisely over a range of 4 GHz during a repeated time period that can be reconfigured at least from 100 ns to 10 ms. This system is capable of operation up to at least 100 GHz.


Event-Based Nonsingular Fixed-Time Tracking Control of an Uncertain Manipulator System Subject to Full-State Static Constraints.
This article centers around investigating the event-triggered nonsingular fixed-time tracking issue for an n -link rigid robot manipulator with full-state constraints, external disturbances, and model uncertainties. We propose the definition of the constrainedly practically fixed-time stability (CPFTS) and provide a sufficient condition for CPFTS. A novel auxiliary function is developed to address the singularity issue caused by repeated differentiation in achieving the fixed-time tracking control. The uncertain parameters are approximated using the radial basis function neural network (RBFNN). This study proposes the model-based and the neutral network-based tracking control approaches, designed using the scaling function technique and the barrier Lyapunov function, respectively, to ensure that the tracking error systems are CPFTS and the full-state constraints comply. Moreover, the communication transmission load is reduced using the relative threshold event-triggered control strategy. Simulation results demonstrate the effectiveness of the proposed tracking control algorithms.


Regulating spleen and stomach can improve bone and joint function of knee osteoarthritis patients complicated with osteoporosis.
This study was designed to determine the influences of spleen and stomach conditioning treatment in Traditional Chinese Medicine (TCM) on patients with both knee osteoarthritis (KOA) and osteoporosis (OP). The medical records of 108 patients with both KOA and OP treated in Wuhan No. 1 Hospital between February 2020 and December 2021 were retrospectively studied. Among them, 58 patients treated with western medicine alone were assigned to a control group, and 50 patients who received spleen and stomach conditioning treatment in TCM based on western medicine treatment were assigned to an observation group. The efficacy on the two groups was compared. The joint function, pain, inflammatory factors and bone turnover markers in the two groups before and after treatment were analyzed, as well as the incidence of adverse reactions after treatment. The prognosis of the patients at 12 months after treatment was counted, and the influencing factors of poor prognosis were analyzed by multivariate analysis. The observation group showed a notably higher total effective rate than the control group (P<0.05). After treatment, the observation group had notably higher Lysholm score, but notably lower Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and visual analogue scale (VAS) scores than the control group (all P<0.05). After treatment, the bone turnover markers (beta collagen degradation products (β-CTx) and procollagen type I amino-terminal propeptide (P1NP)) in both groups decreased notably (P<0.05), with notably lower levels of them in the observation group than those in the control group (both P<0.05). Additionally, after the treatment, the inflammatory indexes (interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α)) in both groups decreased notably (all P<0.05), with notably lower levels of them in the observation group than those in the control group (all P<0.05). Moreover, the observation group presented a notably lower incidence of adverse reactions than the control group (P<0.05). The rate of poor prognosis in the observation group was notably lower than that in the control group. According to multiple logistic regression analysis, older age, higher BMI, higher Kellgren-Lawrence grading based on X-ray and history of bone fracture were independent risk factors for poor prognosis, and spleen and stomach conditioning treatment was an independent protective factor. Additional TCM spleen and stomach conditioning treatment can substantially improve the efficacy in patients with both KOA and OP by adjusting the inflammatory factors and bone turnover markers of patients, improving their joint function, alleviating their pain, and strongly preventing adverse reactions, so it is of great clinical application value.


Intercellular adhesion molecule-1 expression in human kidneys with glomerulonephritis.
Intercellular adhesion molecule-1 (ICAM-1) plays an important role in immune responses. Expression of this molecule was examined on cryostat sections of 15 normal human and 112 glomerulonephritic kidneys using a specific monoclonal antibody and the indirect immunoperoxidase staining technique. The expression of ICAM-1 on renal structures was compared to that of HLA-DQ, -DR, -DR/DP and -DP antigens. On normal kidneys ICAM-1 was observed on some Bowman's capsular cells and on single glomerular cells which probably represent endothelial and mesangial cells. ICAM-1 was present on peritubular capillaries and on vascular endothelium of large vessels as well as on fibroblasts, whereas no expression of ICAM-1 on proximal tubular epithelial cells (PTECs) was detected. In normal renal tissues the distribution of ICAM-1 was similar to that of HLA-DQ and -DP antigens. In kidneys with different forms of glomerulonephritis especially in association with interstitial inflammation, an abnormal expression of ICAM-1 on PTECs was frequently correlated with aberrant expression of HLA-DQ and -DP antigens. These results further support the hypothesis that PTECs may participate in cell-mediated immune reactions in glomerulonephritis.


Endovascular Treatment of Incidentally Found Multiple Aneurysms Originating from a Bronchial Artery: A Case Report.
Bronchial artery aneurysm (BAA) is a rare disease, and multiple aneurysms of a single bronchial artery are rarer. Regardless of the size of the lesion, it is at risk of rupture and can cause massive hemoptysis or severe pain. We report a rare case of bronchial artery embolization (BAE) of multiple aneurysms of a single bronchial artery. During medical examination, a 64-year-old female was diagnosed with multiple BAAs and endobronchial lesions in the right lower lung on CT 10 years prior to presentation to our hospital. Further evaluation of the lesions was recommended; however, the patient was lost to follow-up. The patient complained of dyspnea and visited our hospital, and the size of the BAA had increased on CT. BAE was done successfully using N-butyl-2-cyanoacrylate and detachable coils. Follow up CT after BAE showed significant decrease in extent of inflammatory lesion in the right lung.


Occupational exposure to noise and ototoxic organic solvents.
The objectives of this study were to review the literature on the effects of occupational exposure to organic solvents on the auditory system and to identify work settings in which exposure to these agents and to noise might occur. The criteria for selecting the chemicals were (a) evidence available that indicated that the chemicals may affect the auditory system and enhance noise effects, and (b) the ubiquity of their use. References to ototoxicity were noted for three proven neurotoxicants, i.e., carbon disulfide, toluene, and trichloroethylene, and for two probable human neurotoxicants--styrene and xylene. The percentages of workers (estimated by NIOSH National Occupational Exposure Survey) exposed to these solvents in each economic sector are shown. Work settings are identified where multiple exposures occur to solvents and noise. The need for future research is discussed.


Flavonoid binding to a multi-drug-resistance transporter protein: an STD-NMR study.
Flavonoids are well known to inhibit the function of the multi-drug-resistance (mdr) transporter by interacting with their ATP binding domains. The precise orientation of these molecules inside the ATP binding pocket is still unclear. We applied the saturation transfer difference (STD) NMR technique to investigate the binding of the flavonoid luteolin and its 7-O-beta-D-glycopyranoside to the recombinant nucleotide binding domain (NBD2) of mouse-mdr. First, this NMR technique confirmed binding of both ligands to NBD2, as was determined from tryptophan fluorescence-quenching experiments. Further, the results suggest binding of both luteolin and its 7-O-beta-D-glycopyranoside by their polar groups at positions 4, 5, and 3' to the protein.


Expanded polytetrafluoroethylene (Gore-Tex) augmentation of deep nasolabial creases.
To evaluate the safety and efficacy of expanded polytetrafluoroethylene (PTFE) (Gore-Tex; W. L. Gore & Associates, Flagstaff, Ariz) for augmentation of deep nasolabial creases. Retrospective chart review with a minimum of 12 months of follow-up. Private practice ambulatory surgery center. One hundred consecutive patients (average age, 49 years) undergoing expanded PTFE augmentation of the nasolabial crease. A standardized, reproducible rating scale assessed preoperative crease severity. Clinical effectiveness was determined by the numerical degree of improvement in crease severity rating after surgery, and by the number of procedures required to achieve the desired aesthetic results. Patients initially had grade 1 (14.5%), grade 2 (54.0%), grade 3 (20.0%), or grade 4 (11.5%) crease severity ratings. On average, patients with grade 1 creases required 1.17 total augmentation procedures, those with grade 2 required 1.60, those with grade 3 required 1.93, and those with grade 4 required 1.86. On average, with each augmentation, patients with grade 1 improved 0.61 relative severity points; those with grade 2, 0.85; those with grade 3, 1.29; and those with grade 4, 1.28. Nine patients developed late postoperative sequelae. Four creases (2.0%) displayed an unnatural mounded appearance because of superficial expanded PTFE placement. All 4 creases underwent elective removal of a single superficial PTFE strip, with resultant return of aesthetically correct crease augmentation. Five creases (2.5%) developed implant site infections; in all 5 cases, the involved strips were removed and the infection was resolved with a 10-day course of oral antibiotics. Expanded PTFE augmentation presents a safe, effective method for softening deep nasolabial creases. Patients with more severe creases are likely to show more improvement with each augmentation, but are also more likely to require multiple procedures to achieve the desired aesthetic result.


Amino acid sequence and chemical modification of a novel alpha-neurotoxin (Oh-5) from king cobra (Ophiophagus hannah) venom.
A novel alpha-neurotoxin, Oh-5, was isolated from king cobra (Ophiophagus hannah) venom and purified by successive SP-Sephadex C-25 column chromatography and reversed-phase HPLC. The complete sequence of Oh-5 was determined by Edman degradation of peptide fragments generated by endopeptidases, i.e., trypsin, Saccharomyces aureus V8 protease and lysyl endopeptidase. This novel toxin comprises 72 amino acid residues with 10 cysteines. The sequence shows 89% sequence homology with Oh-4, and 60% with Toxins a and b from the same venom. The tyrosine, tryptophan, lysine and arginine residues in Oh-5 were modified with tetranitromethane (TNM), 2-nitrophenylsulfenyl (NPS) chloride, trinitrobenzene sulfonate (TNBS), and p-hydroxyphenylglyoxal (HPG), respectively. Modification of Tyr-4 or Trp-27 did not affect the lethal toxicity at all, while the Tyr-4 and 23 nitrated derivative retained about 50% of the lethality of native toxin. Selective trinitrophenylation of Lys-51 or 69 resulted in a decrease in lethality by 29%, and 50% lethality was retained after modification of Lys-2, 51, and 69. A drastic decrease in lethality to 26% was observed when both Arg-35 and 37 were modified. The neurotoxicity was further decreased when Arg-9 was additionally modified. These results suggest that the aromatic residues, Tyr-4 and Trp-27, are not crucial for the neurotoxicity, whereas the cationic residues are involved in multipoint contact between the toxin molecule and the nicotinic acetylcholine receptor (nAChR). The residues Tyr-23 and Arg-35 and 37 in the central loop of Oh-5 seem to contribute greatly to the neurotoxicity.


HBME-1 is expressed by erythroid precursors in early maturation stage and can be a valuable tool for evaluation of dyserythropoiesis in bone marrow core biopsy specimens.
The reaction of Hector Battifora mesothelial epitope-1 (HBME-1) antibody with scattered pronormoblasts in normal bone marrow core biopsy specimens has been reported. This study evaluated the immunohistochemical profile of HBME-1 in a panel of 52 normal, dyserythropoietic and neoplastic marrow samples. We compared the staining property of HBME-1 with that of the commonly used erythroid marker, glycophorin A (CD235a) and in each case, we semi-quantitatively evaluated the HBME-1/CD235a-positive cells ratio. In normal samples, HBME-1 labelled scattered immature erythroid precursors. In dyserythropoietic specimens, HBME-1 stained nucleated erythroid precursors in varying degrees, from pronormoblast through normoblast stages, with the highest intensity in immature forms. Overall, the cellular background of non-erythroid progenitors, erythrocytes and neoplastic cells did not react with HBME-1, except in leukaemia cases with myelodysplasia-related changes. Our study shows that HBME-1 is a useful marker to identify immature erythroid precursors and that an HBME-1/CD235a-positive cells ratio ≥10% is associated with dyserythropoiesis.


Moral judgment competence of medical students: a transcultural study.
The authors conducted a cross-sectional short-term study using Lind's Moral Judgment Test (MJT) to compare moral judgment competence (C-score) among students from a medical school in the Northeast region of Brazil and a medical school in the Northern region of Portugal. This study compares the C-scores of groups in the first and eighth semesters of study within each medical school and groups from corresponding semesters between the two medical schools. This study also evaluates the influence of such factors as age and gender on moral competence. A regression of moral judgment competence among the students in their eighth semester versus the students in the first semester of Brazilian medical school (p < 0.001) and a stagnation of moral competence among students in their eighth semester versus the first semester students in the Portuguese medical school (p = 0.06) were observed. For both the first semester and eighth semester groups, the students in the Portuguese medical school had higher C-scores than the students in the Brazilian medical school. In the analysis of the students' performances in terms of MJT dilemmas, the phenomenon of "moral segmentation" was observed in all of the groups, and the students performed better on the worker's dilemma than on the doctor's dilemma. Among students in the same semester of study, older students had lower C-scores. There was generally no significant difference between men's and women's C-scores.


The Assessment of Immediate Postoperative Delirium in Neurologically Intact Adult Patients Admitted to the Post-anesthesia Care Unit: A Cross-Sectional Study.
Background Immediate postoperative delirium (IPD) in the post-anesthesia care unit (PACU) can cause significant morbidity affecting everyday activities and length of stay with cost implications. This study was undertaken to find the proportion of IPD in PACU and its association with anesthesia and other perioperative factors. Methods After obtaining ethical approval and informed consent, this cross-sectional study was conducted in the PACU. A total of 600 consecutive adult patients (American Society of Anesthesiologists (ASA) 1-3) posted for surgery were approached between January and March 2019, of which 402 patients without neurological diseases and language and hearing discrepancies were studied. All patients had the intervention of surgery under anesthesia in a usual manner. Delirium was assessed preoperatively, postoperatively at 15 and 30 minutes, and before discharge from the PACU. IPD was assessed using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) score, while sedation/agitation was assessed using the Richmond Agitation-Sedation Scale (RASS). The primary outcomes were the proportion of IPD, association with anesthesia, and perioperative risk factors. The secondary outcomes were the length of stay, delirium treatment, and mortality. Results Overall, the IPD proportion was 14.7%. A significant association was demonstrated with premedication with midazolam (odds ration (OR): 3.2; 95% confidence interval (CI): 1.42-7.35; P=0.003), general anesthesia (GA) (OR: 6.3; 95% CI: 2.23-17.8; P<0.001), duration of anesthesia (126 versus 95 minutes; P=0.001), laparoscopic mode of surgical access (OR: 3.4; 95% CI: 1.8-6.4; P<0.001), and postoperative RASS >/< 0 (OR: 10.6; 95% CI: 4.69-24.11; P<0.001) at 30 minutes and before discharge from the PACU. Multivariate analysis showed the strongest association of RASS at 30 minutes with IPD. Conclusion The proportion of IPD was found to be 14.7% in this study, and the chances of developing IPD are high if the patient is not awake and calm in the PACU, especially if midazolam is administered as premedication, followed by general anesthesia (GA) for a long duration.


Protective effects of tomato extract with elevated beta-carotene levels on oxidative stress in ARPE-19 cells.
Epidemiological studies show that dietary products rich in carotenoids delay the progression of age-related macular degeneration. Experimental evidence from cellular studies on the antioxidant actions of carotenoids in the retinal pigment epithelium is still, however, fragmentary. The present study examined the uptake and protective potential of dietary carotenoids from tomato on the human retinal pigment epithelial cell line ARPE-19. ARPE-19 cells were incubated in medium supplemented with tomato extract containing high levels of beta-carotene, lycopene and traces of lutein. The cellular uptake of carotenoids was analysed by reverse-phase HPLC. Oxidative stress was induced by treatment with 1 mm-H2O2. Nitrotyrosine was detected by immunocytochemistry, and oxidised proteins (protein carbonyls) were measured by a quantitative ELISA method. Lipid peroxidation was assessed by quantifying thiobarbituric acid reactive substances. ARPE-19 cells preferentially accumulated lutein and beta-carotene rather than lycopene. Nitrotyrosine formation was considerably reduced in cells incubated with tomato extract compared with controls after H2O2 treatment. Protein carbonyls were reduced by 30 % (P = 0.015), and the formation of thiobarbituric acid-reactive substances was reduced by 140 % (P = 0.003) in cells incubated with tomato extract. The present study provides the experimental evidence for protective effects of dietary tomatoes rich in carotenoids on oxidative stress in the retinal pigment epithelium.


[The patient with chronic renal failure].
Reduced renal function probably affects more people than is known. While there are "only" 66,000 dialysis patients in germany, there are few data on the prevalence of less severe renal failure. Renal failure is becoming a problem of the elderly. The highest rates in dialysis patients are reported for people above 65. In the elderly, the two most important causes of renal failure (type II diabetes and hypertension) are present in great numbers. Therapy of terminal renal failure consists of hemodialysis, peritoneal dialysis or kidney transplantation. Before reaching dialysis, the therapy concentrates on correction of calcium-phosphate balance, acidosis, anemia and hypertension. Because many drugs are eliminated via the kidney, the knowledge of renal function is of eminent importance for the pharmacist.


Current Status of Testing for Microdeletion Syndromes and Rare Autosomal Trisomies Using Cell-Free DNA Technology.
Noninvasive prenatal testing using cell-free DNA in maternal blood for trisomy 21 was introduced in 2011. This technology has continuously evolved with the addition of screening for trisomy 18 and trisomy 13 followed by the inclusion of sex chromosome aneuploidies. Expanded noninvasive prenatal test panels have recently become available, which enable screening for microdeletion syndromes such as the 22q11.2 deletion (associated with the velocardiofacial syndrome) and others. However, the performance data for these microdeletion syndromes are derived from a small number of samples, mostly generated in vitro. Rigorous performance evaluation, as was done at least for trisomy 21 testing using cell-free DNA analysis, is difficult to perform given the rarity of each condition. In addition, detection rates may vary considerably depending on deletion size. Importantly, positive predictive values (PPVs), strongly influenced by the low prevalence, are expected to be significantly lower than 10% for most conditions. Thus, screening in an average-risk population is likely to have many more false-positives than affected cases detected. Conversely, testing in a high-risk population such as fetuses with cardiac anomalies may have higher PPVs, but a negative result needs to be considered carefully as a result of uncertain information about detection rates and a significant residual risk for other copy number variants and single gene disorders. This article integrates current knowledge on cell-free DNA testing for microdeletions with the aim to assist clinicians and policymakers in designing optimal programs for screening in pregnancy.


Lamin dynamics.
Nuclear lamins form a highly insoluble structure, the nuclear lamina, which is associated with the nuclear envelope. Recent results suggest, however, that the lamins are more dynamic than originally thought. They accumulate in nucleoplasmic foci in the G1 stage of the cell cycle and later appear mainly in the peripheral lamina. Some of the lamin foci are closely associated with heterochromatin. Furthermore, the various lamin types assemble into the lamina polymer independently of each other. Both the assembly and disassembly of the lamins, as well as the interaction of the lamins with other nuclear structures such as the nuclear membrane, may be mediated by phosphorylation and dephosphorylation.


Innovative energy interaction with a waste incineration plant leads to advanced biological P- and COD-removal and costs reduction of the extension of Nijmegen wastewater treatment plant.
The extension of the Nijmegen wastewater treatment plant for full nitrogen and phosphorus removal is enormously reduced by introducing an innovative energy interaction with an incineration plant. A reduction of the investment costs of 30-40% has been reached. Heating up a part of the primary sedimentation overflow leads to a constant process temperature of 20-25 degrees C and an advanced biological phosphorus and COD removal.


What Are Complex eHealth Innovations and How Do You Measure Them? Position Paper.
eHealth and innovation are often regarded as synonyms - not least because eHealth technologies and applications are new to their users. This position paper challenges this view and aims at exploring the nature of eHealth innovation against the background of common definitions of innovation and facts from the biomedical and health informatics literature. A good understanding of what constitutes innovative eHealth developments allows the degree of innovation to be measured and interpreted. To this end, relevant biomedical and health informatics literature was searched mainly in Medline and ACM digital library. This paper presents seven facts about implementing and applying new eHealth developments hereby drawing on the experience published in the literature. The facts are: 1. eHealth innovation is relative. 2. Advanced clinical practice is the yardstick. 3. Only used and usable eHealth technology can give birth to eHealth innovatio. 4. One new single eHealth function does not make a complex eHealth innovation. 5. eHealth innovation is more evolution than revolution. 6. eHealth innovation is often triggered behind the scenes; and 7. There is no eHealth innovation without sociocultural change. The main conclusion of the seven facts is that eHealth innovations have many ingredients: newness, availability, advanced clinical practice with proven outcomes, use and usability, the supporting environment, other context factors and the stakeholder perspectives. Measuring eHealth innovation is thus a complex matter. To this end we propose the development of a composite score that expresses comprehensively the nature of eHealth innovation and that breaks down its complexity into the three dimensions: i) eHealth adoption, ii) partnership with advanced clinical practice, and iii) use and usability of eHealth. In order to better understand the momentum and mechanisms behind eHealth innovation the fourth dimension, iv) eHealth supporting services and means, needs to be studied. Conceptualising appropriate measurement instruments also requires eHealth innovation to be distinguished from eHealth sophistication, performance and quality, although innovation is intertwined with these concepts. The demanding effort for defining eHealth innovation and measuring it properly seem worthwhile and promise advances in creating better systems. This paper thus intends to stimulate the necessary discussion.


Jeans instability in partially ionized self-gravitating dusty plasmas.
By employing the Boltzmann distributions for electrons and ions and by retaining the full dynamics of charged dust and neutral fluids, we derive a dispersion law for coupled dust-acoustic and neutral sound waves in partially ionized self-gravitating dusty plasmas. This dispersion law exhibits new classes of Jeans instability in both collisionless and highly collisional regimes. The result should help understand the origin of molecular cloud collapse in interstellar space.


Effects of amphetamine and cocaine on the development of acute experimental allergic encephalomyelitis in Lewis rats.
The present experiment deals with the effects of amphetamine and cocaine on the development and course of experimental allergic encephalomyelitis (EAE) induced in Lewis rats. Rats were immunized at the age of eight weeks with purified myelin basic protein isolated from guinea pig brain in complete Freund's adjuvant. Drug administration and recording of EAE clinical signs was performed daily since day 1 post-immunization (PI). On day 14 and 28 PI, six rats per group were bled and sacrificed. Spinal cord was examined histologically for EAE lesions. In vivo administration of 0.5 and 1 mg/Kg of amphetamine or cocaine resulted in a dose-related enhancement of neurological and histological signs of acute EAE in comparison with control rats. Both drugs caused a reduction of latent period together with a delayed regression of neurological signs along with an increase in inflammation in the central nervous system in comparison with placebo. Human & Experimental Toxicology (2007) 26, 637-643.


Annulative π-Extension (APEX) of Heteroarenes with Dibenzosiloles and Dibenzogermoles by Palladium/o-Chloranil Catalysis.
Annulative π-extension (APEX) reactions of heteroarenes are described herein. A catalytic system comprising a cationic palladium species and o-chloranil using dimethyldibenzosiloles as π-extending agents enabled the extension of the π-system of benzo[b]thiophenes. π-Extended dibenzofurans and carbazoles could also be obtained from benzofuran and N-tosylindole, respectively, with dimethyldibenzogermole as a germanium-based π-extending agent. Mechanistic investigations indicated two possible reaction pathways involving carbopalladation-based double C-H arylation of benzothiophene or formal cycloaddition/oxidation cascades.


American Brachytherapy Society-Groupe Européen de Curiethérapie-European Society of Therapeutic Radiation Oncology (ABS-GEC-ESTRO) consensus statement for penile brachytherapy.
To develop a consensus statement between the American Brachytherapy Society (ABS) and Groupe Européen de Curiethérapie/European Society for Therapeutic Radiation and Oncology (GEC-ESTRO) for the use of brachytherapy in the primary management of carcinoma of the penis. The American Brachytherapy Society and Groupe Européen de Curiethérapie/European Society for Therapeutic Radiation and Oncology convened a group of expert practitioners and physicists to develop a statement for the use of (192)Ir in low-dose-rate (LDR), pulse-dose-rate, and high-dose-rate (HDR) brachytherapy for penile cancer. Decades of brachytherapy experience with LDR (192)Ir wire and pulse-dose-rate (192)Ir sources for this rare malignancy indicate a penile preservation rate of 70% at 10 years postimplant. Chief morbidities remain stenosis of the urethral meatus and soft tissue ulceration at the primary site. Nonhealing ulceration can be successfully managed with various measures including hyperbaric oxygen treatment. HDR brachytherapy implant procedures are technically similar to LDR. The optimal HDR dose and fractionation schemes are being developed. The good tumor control rates, acceptable morbidity, and functional organ preservation warrant recommendation of brachytherapy as the initial treatment for invasive T1, T2, and selected T3 penile cancers.


Milieu-specific differences in symptom severity and treatment outcome in psychosomatic rehabilitation in Germany.
Previous studies that focused on socioeconomic differences did not comprehensively explain existing inequalities in psychosomatic rehabilitation in Germany. We applied a social milieu approach, which additionally includes sociocultural factors such as lifestyles, attitudes and values, to investigate differences among patients in symptom severity, psychosocial impairment and improvement over the course of the intervention. As a model for social milieus, the empirical Sinus milieus were used. 2,000 patients of two psychosomatic rehabilitation clinics in Germany were included and their milieu was assessed with the Sinus milieu indicator for Germany 10/2018 questionnaire. BDI-II (N = 1,832) and HEALTH-49 (N = 1,829) questionnaires were used to measure depressiveness and psychosocial impairment at admission (T0) and discharge after 5 weeks of treatment (T1). Milieu differences in severity and improvement were analyzed by mixed-model ANOVAs. Milieu distribution was not representative of the overall population of Germany. We found significant differences between patients from different milieus in both BDI-II and HEALTH-49 (p < 0.001). Patients from the Precarious Milieu had the highest burden of depressive symptoms in BDI-II and the highest impairment on all HEALTH-49 scales at T0 and T1. Over the course of rehabilitation, patients from all milieus improved significantly in all domains (p < 0.001). Significant interaction effects showed milieu-dependent differences in improvement for depressiveness on the BDI-II [F(9, 1822) = 2.50, p = 0.008] and for three HEALTH-49 scales, namely Psychological well-being [F(9, 1819) = 3.30, padj = 0.005], Interactional difficulties [F(9, 1819) = 2.74, padj = 0.036] and Activity and Participation [F(9, 1819) = 4.94, padj < 0.001], while post-hoc tests only revealed two significant group differences for the last scale. In all domains, patients from the Precarious Milieu retained higher symptoms and impairment at T1 than patients from better-off milieus had at T0. Social milieu was associated with symptom severity, treatment access and outcome of psychosomatic rehabilitation patients. Milieu-specific sociocultural habits, psychosocial needs and therapeutic demands may help describe differences and should be considered in therapy planning and implementation, to improve equal access, quality and effectiveness of rehabilitation. Therefore, further research on milieu-specific differences and needs is necessary.


Aerobic gram-positive pleomorphic rods isolated from dental plaque and gingival crevice.
A typical gram-positive pleomorphic aerobe is Rothia dentocariosa. However, there exist many organisms having similar characteristics (Rothia-like organisms). The purpose of this study is to isolate Rothia dentocariosa and Rothia-like organisms from the healthy and diseased sites of the oral cavity and to clarify the characteristics of those organisms. A total of 342 strains were isolated in this study, and 188 strains were identified as gram-positive pleomorphic rods. Seventy-seven typical strains of 188 isolates were examined physiologically and biochemically, and they were classified as follows: 1) 20 strains of A. viscosus; 2) 3 strains of A. naeslundii; 3) 26 strains of Rothia dentocariosa; 4) 2 strains of Bacterionema matruchotii; 5) 15 strains of Corynebacterium; 6) 7 strains of Nocardia; and 4 unknown strains. The strains of Rothia dentocariosa were mainly isolated from the dental plaque (24 of 26 isolates), and they had the ability to adhere on to the glass surface, and 5 of 26 strains of Rothia dentocariosa showed the ability of gelatin liquefaction.


Six BALB-c IgA myeloma proteins that bind beta-(1-6)-D-galactan. Partial amino acid sequences and idiotypes.
Six IgA myeloma proteins of BALB/c origin which bind antigens containing beta-(1 --> 6)-D-galactan side chains have been isolated by affinity chromatography on galactoside-BSA-Sepharose columns. Partial amino acid sequences of of the light chains to residue Cys23 and the heavy chains to reside 30 were determined on the automated sequencer. No differences were found among the six V(K) sequences. Among some 50 partial V(K) sequences that have thus far been determined these six chains are the only ones thus far identified in this subgroup; at least 25 V(K) subgroups in the mouse have been identified so far. The heavy chain partial sequences were also very closely related but two differences were found. One protein differed from the other five by having isoleucine instead of leucine at position 5, a second protein differed from the others by having an unidentified amino acid at position 19. Using the highly sensitive inhibition of hemagglutination method it was found that each of the proteins possessed a unique inidividual antigenic determinant.


Comparison of arch width, alveolar width and buccolingual inclination of teeth between Class II division 1 malocclusion and Class I occlusion.
To compare the arch width, alveolar width, and buccolingual inclination of maxillary and mandibular posterior teeth between Class II division 1 malocclusion and Class I occlusion. Forty-five subjects with Class I occlusion and 45 subjects with Class II division 1 malocclusion were selected to measure the maxillary and mandibular arch width and alveolar width of premolars and first molars with digital caliper. Buccolingual inclination of maxillary and mandibular premolars and first molars were measured with a modified universal bevel protractor. All of the posterior teeth in both groups were lingually tilted. The maxillary premolars and first molars were significantly more lingually tilted (P < .05) in Class II division 1 malocclusion than in Class I occlusion. Mandibular first premolars were significantly less lingually tilted in Class II division 1 malocclusion than in Class I occlusion. No significant difference of buccolingual inclination was found in mandibular second premolars and first molars between the two groups. No significant difference in maxillary and mandibular arch width and alveolar width was found between the two groups. Buccolingual inclination rather than arch width and alveolar width plays an important role in transverse discrepancy of Class II division 1 malocclusion.


SPARC affects glioma cell growth differently when grown on brain ECM proteins in vitro under standard versus reduced-serum stress conditions.
Secreted protein acidic and rich in cysteine (SPARC) has a suppressive effect on U87 glioma cell proliferation when assessed in vitro and in vivo using parental U87T2 and U87T2-derived SPARC-transfected clones. Since SPARCinteracts with extracellular matrix (ECM) proteins, we examined the effect of SPARC secretion on proliferation, morphology, and cell density of glioma cells grown in vitro, in the absence and presence of ECM proteins under standard (10% fetal bovine serum [FBSI) and reduced (0.1% FBS) serum stress conditions. Under standard conditions, MTT (3-(4,5-cimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide) growth curves, morphology, and Western blot analyses demonstrated that SPARC had a suppressive and biphasic effect on growth that was not grossly modulated by the ECMs. The SPARC-induced changes in morphology observed at 24 h were not altered by the presence of ECMs. Under reduced-serum stress conditions, Western blot, morphological, and flow cytometric analyses indicated that the SPARC-induced suppressive growth effects were eliminated when the cells were grown on plastic. However, ECM-specific changes in growth were observed, some of which correlated with secreted SPARC levels. These results indicate that the differential effects of SPARC and ECMs on proliferation are dependent on culture conditions. Since the results obtained under standard conditions agree with our in vivo observations, we conclude that the ability of SPARC to suppress proliferation is regulated to a greater degree by the level of SPARC and that this suppressive effect is not influenced by the presence of any of the ECMs examined.


A randomized, placebo-controlled, single-blinded, split-faced clinical trial evaluating the efficacy and safety of KLOX-001 gel formulation with KLOX light-emitting diode light on facial rejuvenation.
Many treatment modalities exist to counteract the effects of cutaneous aging. Ablative methods have been the mainstay for nonsurgical facial rejuvenation. In recent years, nonablative techniques have been developed with the aim of achieving facial rejuvenation without epidermal damage. Light-emitting diode (LED) photorejuvenation is a novel nonablative technique that induces collagen synthesis through biophotomodulatory pathways. A single-center, randomized, single-blinded, placebo-controlled, split-faced clinical trial was designed. Thirty-two patients were enrolled for a 12-week study. Patients were randomized into one of four groups: Group A, treatment with KLOX-001 gel formulation and white LED (placebo) light; Group B, treatment with a placebo/base gel (no active chromophore) formulation and KLOX LED light; Group C, treatment with KLOX-001 gel formulation and KLOX LED light; and Group D, treatment with the standard skin rejuvenating treatment (0.1% retinol-based cream). Patients received treatment at weeks 0, 1, 2, and 3, and returned to the clinic at weeks 4, 8, and 12 for clinical assessments performed by an independent, blinded committee of physicians using subjective clinician assessment scales. Tolerability, adverse outcomes, and patient satisfaction were also assessed. Analysis demonstrated that the KLOX LED light with KLOX placebo/base gel and the KLOX LED light + KLOX-001 gel formulation groups were superior to standard of care and KLOX-001 gel formulation with placebo light on subjective clinical assessment and multiple wrinkle scales, with statistically significant results obtained for brow positioning, perioral wrinkling, and total wrinkle score. The study results show that KLOX LED light with KLOX-001 gel formulation and KLOX LED light with KLOX placebo/base gel are effective, safe, well-tolerated, and painless treatment modalities for skin rejuvenation.


Near-Infrared Autofluorescence (NIRAF) in Atherosclerotic Plaque Dissociates from Intraplaque Hemorrhage and Bilirubin.
Near-infrared autofluorescence (NIRAF) in unstable atherosclerotic plaque has been suggested as a novel imaging technology for high-risk atherosclerosis. Intraplaque hemorrhage (IPH) and bilirubin, derived from the subsequent degradation of heme, have been proposed as the source of NIRAF, although their roles and the underlying mechanism responsible for NIRAF remain unclear. To test the proposed role of bilirubin as the source of NIRAF in high-risk atherosclerosis, Biliverdin reductase a gene and apolipoprotein E gene double-knockout (Bvra-/-Apoe-/-) mice were subjected to the Western diet and tandem stenosis (TS) surgery, as a model of both bilirubin deficiency and plaque instability. Human coronary arteries containing atherosclerotic plaques were obtained from heart transplant recipients. The NIRAF was determined by in vivo fluorescence emission computed tomography, and ex vivo infrared imaging. The cholesterol content was quantified by HPLC with UV detection. In Bvra+/+Apoe-/- TS mice, the NIRAF intensity was significantly higher in unstable plaque than in stable plaque, yet the NIRAF in unstable plaque was undistinguishable in Bvra+/+Apoe-/- and littermate Bvra-/-Apoe-/- TS mice. Moreover, the unstable plaque in TS mice exhibited a lower NIRAF compared with highly cellular plaque that lacked most of the features of unstable plaque. In human coronary arteries, the NIRAF associated with cholesterol-rich, calcified lesions, rather than just cholesterol-rich lesions. The NIRAF in atherosclerotic plaque can be dissociated from IPH and bilirubin, such that the compositional meaning of an elevated NIRAF remains obscure.


Morbidly obese individuals with impaired fasting glucose have a specific pattern of insulin secretion and sensitivity: effect of weight loss after bariatric surgery.
Obesity is often associated with hyper-secrection of insulin. Impaired fasting glucose (IFG) has recently been redefined as a fasting plasma glucose of 5.6-6.9 mmol/L. The aim of this study was to determine whether changes in insulin secretion in morbidly obese persons also commence with normal serum glucose levels. 32 morbidly obese subjects were studied before and after bariatric surgery. Measurements were made of glucose tolerance (K(G)), insulin sensitivity (SI), first-phase insulin release and the disposition index (DI) from a frequently sampled intravenous glucose tolerance test. In morbidly obese subjects, the SI (P<0.01), DI (P<0.01) and first-phase insulin release (P<0.02) started changing with serum glucose levels considered to be normal (5.00-5.28 mmol/L). K(G) showed a clear slope according to the baseline glycemia status (P<0.05), and it was significantly related with the DI, both before (r=0.76, P<0.001) and after (r=0.57, P=0.002) surgery. Following surgery, all the variables significantly associated with insulin secretion and insulin sensitivity recovered significantly. The most significant changes occurred in morbidly obese individuals with IFG. Morbidly obese subjects show slopes of insulin sensitivity and insulin secretion in accordance with their baseline serum glucose levels. The fall in first-phase insulin release begins when serum glucose values are considered normal. Morbidly obese persons with the IFG phenotype have a specific pattern of insulin sensitivity and insulin secretion. K(G) clearly discriminates the clinical phenotypes, depending on baseline serum glucose levels.


Depression Among University Students With Attention-Deficit Hyperactivity Disorder Symptoms: A Study of Interpersonal Counseling.
University students with symptoms of attention-deficit hyperactivity disorder (ADHD) often experience depression. This study examined whether interpersonal counseling (IPC) could be an effective treatment for depression among students with ADHD symptoms. Participants were assigned to either an IPC (N=5) or control (N=7) group. Depression was assessed by using the Self-Rating Depression Scale (SDS) at baseline, postintervention, and at 4-, 8-, and 12-week follow-ups. No significant changes in the SDS total score were observed for either group at each postintervention point. However, the IPC group showed a large effect size at the 4- and 12-week follow-ups. A significant intergroup difference was observed after 4 weeks. No significant intergroup difference was observed after 12 weeks, but there was a large effect size. IPC appeared to have effects at 4 weeks postintervention. Because this was an exploratory study, further research is necessary.


Cholesterol synthesis in germfree and conventional rats.
The synthesis of cholesterol from labeled acetate and mevalonate by the liver and intestinal tract was investigated in germfree and conventional rats. When a low cholesterol diet was fed, the rates of in vitro synthesis from acetate by the liver, ileum and cecum of germfree rats were 13%, 11% and 25% of those of conventional rats, respectively. Cholesterol feeding markedly inhibited hepatic cholesterol synthesis from acetate in both germfree and conventional rats. Such inhibitions were released by additional cholestyramine feeding. The rate of hepatic cholesterol synthesis was greater and the liver cholesterol level was less after cholestyramine feeding in germfree rats than in conventional rats, suggesting an importance of bile acids in the regulation of cholesterol metabolism in the germfree rat. There was an inverse proportionality between the logarithmic rate of hepatic cholesterol synthesis and the liver cholesterol level in the germfree rat. Data indicate that endogenous cholesterol synthesis in the germfree rat may not be responsible for the high cholesterol level in plasma or liver and that the liver cholesterol level may play a major role in the regulation of hepatic cholesterogenesis in the germfree rat by a mechanism similar to that in the conventional rat.


Cascaded Raman lasing in packaged high quality As₂S₃ microspheres.
We report the observation of cascaded Raman lasing in high-Q As₂S₃microspheres. Cascaded stimulated Raman scattering emission is obtained up to the 5th order for a pump wavelength of 1557 nm and up to the 3rd order for a pump wavelength of 1880 nm. High-Q As₂S₃microspheres are used in a self-frequency locking laser setup without an external laser source. Threshold curves measurements are presented and follow the expected coupled mode theory behavior with a sub-mW threshold pump power.


Ultrathin 2D Metal-Organic Framework Nanosheets.
A facile surfactant-assisted bottom-up synthetic method to prepare a series of freestanding ultrathin 2D M-TCPP (M = Zn, Cu, Cd or Co, TCPP = tetrakis(4-carboxyphenyl)porphyrin) nanosheets with a thickness of sub-10 nm is developed. As a proof-of-concept application, some of them are successfully used as new platforms for DNA detection. The Cu-TCPP nanosheet-based sensor shows excellent fluorescent sensing performance and is used for the simultaneous detection of multiple DNA targets.


Transcriptomics, NF-κB Pathway, and Their Potential Spaceflight-Related Health Consequences.
In space, living organisms are exposed to multiple stress factors including microgravity and space radiation. For humans, these harmful environmental factors have been known to cause negative health impacts such as bone loss and immune dysfunction. Understanding the mechanisms by which spaceflight impacts human health at the molecular level is critical not only for accurately assessing the risks associated with spaceflight, but also for developing effective countermeasures. Over the years, a number of studies have been conducted under real or simulated space conditions. RNA and protein levels in cellular and animal models have been targeted in order to identify pathways affected by spaceflight. Of the many pathways responsive to the space environment, the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) network appears to commonly be affected across many different cell types under the true or simulated spaceflight conditions. NF-κB is of particular interest, as it is associated with many of the spaceflight-related health consequences. This review intends to summarize the transcriptomics studies that identified NF-κB as a responsive pathway to ground-based simulated microgravity or the true spaceflight condition. These studies were carried out using either human cell or animal models. In addition, the review summarizes the studies that focused specifically on NF-κB pathway in specific cell types or organ tissues as related to the known spaceflight-related health risks including immune dysfunction, bone loss, muscle atrophy, central nerve system (CNS) dysfunction, and risks associated with space radiation. Whether the NF-κB pathway is activated or inhibited in space is dependent on the cell type, but the potential health impact appeared to be always negative. It is argued that more studies on NF-κB should be conducted to fully understand this particular pathway for the benefit of crew health in space.


Feather mites (Acari, Astigmata) associated with birds in an Atlantic Forest fragment in Northeastern Brazil.
The present study reports associations between feather mites (Astigmata) and birds in an Atlantic Forest fragment in Rio Grande do Norte state, in Brazil. In the laboratory, mites were collected through visual examination of freshly killed birds. Overall, 172 individuals from 38 bird species were examined, between October 2011 and July 2012. The prevalence of feather mites was 80.8%, corresponding to 139 infested individuals distributed into 30 species and 15 families of hosts. Fifteen feather mite taxa could be identified to the species level, sixteen to the genus level and three to the subfamily level, distributed into the families Analgidae, Proctophyllodidae, Psoroptoididae, Pteronyssidae, Xolalgidae, Trouessartiidae, Falculiferidae and Gabuciniidae. Hitherto unknown associations between feather mites and birds were recorded for eleven taxa identified to the species level, and nine taxa were recorded for the first time in Brazil. The number of new geographic records, as well as the hitherto unknown mite-host associations, supports the high estimates of diversity for feather mites of Brazil and show the need for research to increase knowledge of plumicole mites in the Neotropical region.


[Risk factors related to HIV new infections among men who have sex with men in a cohort study].
Objectives: To analyze and understand the risk factors related to HIV new infections among men who have sex with men (MSM). Methods: A longitudinal observational study among MSM was conducted to collect information on HIV related behaviors and sero-conversion. Univariate and multivariate generalized estimating equations (GEE) were used to discuss the risk factors for HIV new infection. Results: A total number of 4 305 MSM were followed during 2013-2015. Among those self-reported MSM who are seeking partners on the Interner tended to have higher proportion on receptive anal intercourse and consistent condom use during anal intercourse than the subgroups seeking their partners in gay bars or bathrooms. HIV incidence among followed MSM during the study period appeared as 4.3/100 person years, with adjusted RR (aRR) of HIV infection for receptive anal intercourse as group 2.20 (95% CI: 1.49-3.24) times than that of insertion anal intercourse group. Those who used rush-poppers (aRR=1.55, 95% CI: 1.10-2.17), unprotected anal intercourse (aRR=2.24, 95%CI: 1.62-3.08), and those with syphilis infection (aRR=2.95, 95%CI: 2.00-4.35) were also risk factors for HIV new infections. After controlling other factors, the relationship between the ways of seeking partners and HIV new infection was not statistical significant. Conclusion: Risk factors for HIV new infection among MSM appeared complex and interactive, suggesting that further studies are needed to generate tailored strategies for the prevention of HIV epidemic among MSM population.


Conjunctival microbial florae in patients with seriously sulfur mustard induced eye injuries.
Ocular surface disorders and infections in sulfur mustard (SM) exposed patients are of particular clinical importance. The aim of the present study is to detect the conjunctival bacterial florae in patients with seriously SM induced eye injuries. Conjunctival bacterial florae of 143 seriously eye injured subjects as the study group was detected. The results were compared with 26 normal participants. Both groups were matched in age and sex. The samples were taken by sterile swab from interior fornixes of conjunctiva in both groups and were transported to microbiology laboratory by Stuart's Transport Medium. All samples were inoculated onto Blood agar, Mac Conkey agar and Chocolate agar and isolated microorganisms were identified by biochemical tests. The data were analyzed by SPSS and Man Whitney tests. Nineteen cases (13.39%) and none of the controls (0%) had positive culture results (p = .043). Isolated microorganisms from patients included coagulase-negative staphylococci 10 cases (52.6%), Staphylococcus aureus 5 cases (26.3%), non enterobacteriaceae gram negative bacilli 2 cases (10.5%), Penicillium spp. 2 cases (10.5%), Citrobacter sp. 1 case (5.2%), non-spore forming Gram positive bacillus 1 case (5.2%) and α hemolytic streptococcus 1 case (5.2%). Two patients had mixed microorganisms and other patients had just one microorganism. Most of the S. aureus isolates were sensitive to usual antibiotics. The results of this study showed that the prevalence rate of conjunctival bacterial isolates in patients with seriously SM induced ocular injuries are higher and potentially more dangerous than normal controls.


Absent right superior vena cava and persistent left superior vena cava: An incidental finding.
A patient with Marfan syndrome undergoing Bentall operation was found to have an absent right superior vena cava and persistent left superior vena cava. The dilation of coronary sinus raised the suspicion of persistent left superior vena cava. The diagnosis was confirmed by agitated saline contrast echocardiography and computed tomography of the chest.


Interplay between elevated cellular fibronectin and plasma fibrin clot properties in type 2 diabetes.
Type 2 diabetes is associated with faster formation of poorly lysable, denser fibrin clots and elevated cellular fibronectin (cFn), a marker of vascular injury. We investigated whether cFn affects clot properties in type 2 diabetes. In 200 consecutive patients with type 2 diabetes and 100 control subjects matched for age and sex, we determined plasma cFn along with clot formation and degradation using turbidimetric and permeability assays. Diabetic patients had elevated cFn (median, 3.99 [interquartile range, 2.87-4.81] µg/ml]), increased clot density (MaxAbsC) and prolonged lysis time (LysT) compared with those without type 2 diabetes (all p<0.01). Diabetic patients with documented cardiovascular disease (CVD, n=127, 63.5 %) had increased cFn (4.53 [3.68-4.95] µg/ml), decreased clot permeability (Ks) and increased MaxAbsC compared with those without CVD (all p<0.001). Diabetic patients with cFn in the top quartile (>4.81 µg/ml) were two times more likely to have CVD compared with those in the lowest quartile (odds ratio 1.80, 95 % confidence interval 1.41-2.46, p<0.001). No differences in cFn were observed in relation to microvascular complications. After adjustment for potential confounders, cFn accounted for 10.2 % of variance in Ks, 18.2 % of variance in clot density and 10.2 % of variance in AUC in diabetic patients. This study shows that elevated cFn is associated with unfavourably modified clot properties in type 2 diabetes, especially with concomitant CVD, which indicates novel links between vascular injury and prothrombotic alterations in diabetes. Coagulation, cellular fibronectin, type 2 diabetes, cardiovascular disease.


Roscovitine is an effective inducer of apoptosis of Ewing's sarcoma family tumor cells in vitro and in vivo.
The Ewing's sarcoma family of tumors (ESFT) comprises several well-characterized malignant neoplasms with particularly aggressive behavior. Despite recent progress in the use of multimodal therapeutic approaches and aggressive local control measures, a substantial proportion of patients die because of disease progression. Furthermore, this outcome has not changed significantly over the last 15 to 20 years. Consequently, new, more effective therapeutic options are sorely needed for the treatment of ESFT. Because ESFT cells overexpress several cyclin-dependent kinases (CDK), we explored the efficacy against ESFT of roscovitine, a CDK inhibitor shown to be surprisingly safe for humans in clinical trials of their anticancer activity. Results showed that ESFT cell lines are uniformly sensitive to roscovitine. In addition to exerting comparatively minor cell cycle effects, roscovitine treatment concomitantly caused the up-regulation of the expression of the proapoptotic protein BAX and the down-regulation of both survivin and XIAP, thus resulting in caspase-dependent apoptosis. Furthermore, in vivo experiments showed that s.c. growth of ESFT xenografts was also significantly slowed by i.p. injection of roscovitine. These results strongly suggest that roscovitine may be an effective therapeutic agent against ESFT and recommend its evaluation against ESFT in clinical trials and its inclusion in future treatment protocols.


Response of supraoptic magnocellular neurons to stimulation of forebrain alpha-adrenoceptors.
Effects of alpha-adrenoceptor agents on electrophysiologically and immunohistochemically identified supraoptic nucleus (SON) vasopressin (VP) units were investigated by intracarotid infusion. Clonidine, an alpha 2-adrenoceptor agonist always excited SON units and alpha 2-adrenoceptor antagonists consistently inhibited them. alpha 1-Adrenoceptor agents produced inconsistent responses. The results implicate forebrain alpha 2-adrenergic receptors in the excitation of SON VP neurons.