Nucleation of gold nanoparticle superclusters from solution.
Measurements of the solubility curve of a quasi-monodisperse gold nanoparticle solution are given. Temperature quenches from the one-phase to the two-phase regime yielded superclusters of the nanoparticle solid phase with sizes that depended on the quench depth. Classical nucleation theory was used to describe these sizes using a value of the surface tension for the nanoparticle solid phase of 0.042 erg/cm2. This value is consistent with molecule size scaling of the surface tension. In total these results show that suspensions of nanoparticles act like molecular solutions.


Active establishment of centromeric CENP-A chromatin by RSF complex.
Centromeres are chromosomal structures required for equal DNA segregation to daughter cells, comprising specialized nucleosomes containing centromere protein A (CENP-A) histone, which provide the basis for centromeric chromatin assembly. Discovery of centromere protein components is progressing, but knowledge related to their establishment and maintenance remains limited. Previously, using anti-CENP-A native chromatin immunoprecipitation, we isolated the interphase-centromere complex (ICEN). Among ICEN components, subunits of the remodeling and spacing factor (RSF) complex, Rsf-1 and SNF2h proteins, were found. This paper describes the relationship of the RSF complex to centromere structure and function, demonstrating its requirement for maintenance of CENP-A at the centromeric core chromatin in HeLa cells. The RSF complex interacted with CENP-A chromatin in mid-G1. Rsf-1 depletion induced loss of centromeric CENP-A, and purified RSF complex reconstituted and spaced CENP-A nucleosomes in vitro. From these data, we propose the RSF complex as a new factor actively supporting the assembly of CENP-A chromatin.


Wearable Cardioverter-Defibrillator Used as a Telemonitoring System in a Real-Life Heart Failure Unit Setting.
In patients with reduced left ventricular ejection fraction (LVEF) who are at risk of sudden cardiac death, a wearable cardioverter-defibrillator (WCD) is recommended as a bridge to the recovery of LVEF or as a bridge to the implantation of a device. In addition to its function to detect and treat malignant arrhythmia, WCD can be used via an online platform as a telemonitoring system to supervise patients' physical activity, compliance, and heart rate. We retrospectively analyzed 173 patients with regard to compliance and heart rate after discharge. Mean WCD wearing time was 59.75 ± 35.6 days; the daily wearing time was 21.19 ± 4.65 h. We found significant differences concerning the patients' compliance. Men showed less compliance than women, and younger patients showed less compliance than patients who were older. Furthermore, we analyzed the heart rate from discharge until the end of WCD prescription and found a significant decrease from discharge to 4, 8, or 12 weeks. WCD can be used as a telemonitoring system to help the involved heart failure unit or physicians attend to and adjust the medical therapy. Furthermore, specific patient groups should be educated more intensively with respect to compliance.


A comparative study of the common complaints and secondary complications in patients of osteoarthritis on allopathic, homeopathic and herbal system of medicines.
Osteoarthritis is the most common form of arthritis worldwide and progression of arthritis may lead to secondary complications. Osteoarthritis is the degradation of joint tissues from the effects of injury, grinding sensation and inflammation. There are three main systems of medicine including allopathic, homeopathic and herbal system for the treatment of osteoarthritis. Plants are the basis for traditional medicine which is still widely practiced today. The objective of the present study is to find out the complaints and secondary complications in patients of osteoarthritis on allopathic, homeopathic and herbal system of medicine. This study was conducted in Karachi from January 2019 to January 2020. Allopathic, Homeopathic and Herbal practitioners were consulted in the study (n=600, with= 200 in each study group). Data was analyzed by SPSS 22 version. Finding of the study suggest that after the treatment with allopathic medicines orthopaedician, family physician or rheumatologist / internal medicine specialist, there was no significant difference in complaints (Chi-square =0.598, p=0.742). Moreover, there was no significant difference in complications (Chi-square = 0.039, p=0.981). While treatment with homeopathic medicines either by orthologist or family physician significant difference in complaints were observed (Chi-square =4.86, p=0.027). The patient visiting family physicians have higher number of complications than orthologists. While treatment with herbal medicines either by orthologists or family physician there was significant difference in complaints. (Chi-square =5.404, p=0.020). The study reveals that there is no significant difference of complaints and complications in allopathic systems of medicine when treating osteoarthritis, while it is significant for homeopathic and herbal medicine.


Toward an improved understanding of the dissociation mechanism of gas phase protein complexes.
Understanding the dissociation mechanism of multimeric protein complex ions is important for deciphering gas phase dissociation experiments. The dissociation of cytochrome c' dimer ions in the gas phase was investigated in the present study by constrained molecular dynamics simulations. The center of mass (COM) distance between two monomers was selected as the constrained coordinate. The number of intermolecular hydrogen bonds, smallest distance of intermolecular residuals, value of dipole moments, root-mean-square deviations, and potential energy components of the force field as a function of COM distance were examined for different charge partitionings of the +10 total charge state. These data were rationalized with free energy profiles to produce a qualitative description of the dissociation process. When charges are symmetrically distributed between the monomers in the dimer, dissociation occurs at a well-defined distance with only small structural changes in the monomers. There is an elastic type of stretching that initially resists the separation of the monomers but after dissociation the monomers recoil slightly from this and relax. For asymmetrically distributed charges, the dissociation event is not nearly as well-defined because the more highly charged monomer unfolds before dissociation occurs. It is found in almost all cases, a charged N-terminus tethers this unfolding monomer to its dimer partner by binding in a nonspecific manner. This helps encourage monomer unfolding in the dissociation pathway. It is also shown that while the intermolecular Coulomb repulsion between the monomers is not the largest contribution to the overall potential energy, it dominates the potential energy difference between different charge states.


Chronological Age Prediction: Developmental Evaluation of DNA Methylation-Based Machine Learning Models.
Epigenetic clock, a highly accurate age estimator based on DNA methylation (DNAm) level, is the basis for predicting mortality/morbidity and elucidating the molecular mechanism of aging, which is of great significance in forensics, justice, and social life. Herein, we integrated machine learning (ML) algorithms to construct blood epigenetic clock in Southern Han Chinese (CHS) for chronological age prediction. The correlation coefficient (r) meta-analyses of 7,084 individuals were firstly implemented to select five genes (ELOVL2, C1orf132, TRIM59, FHL2, and KLF14) from a candidate set of nine age-associated DNAm biomarkers. The DNAm-based profiles of the CHS cohort (240 blood samples differing in age from 1 to 81 years) were generated by the bisulfite targeted amplicon pyrosequencing (BTA-pseq) from 34 cytosine-phosphate-guanine sites (CpGs) of five selected genes, revealing that the methylation levels at different CpGs exhibit population specificity. Furthermore, we established and evaluated four chronological age prediction models using distinct ML algorithms: stepwise regression (SR), support vector regression (SVR-eps and SVR-nu), and random forest regression (RFR). The median absolute deviation (MAD) values increased with chronological age, especially in the 61-81 age category. No apparent gender effect was found in different ML models of the CHS cohort (all p > 0.05). The MAD values were 2.97, 2.22, 2.19, and 1.29 years for SR, SVR-eps, SVR-nu, and RFR in the CHS cohort, respectively. Eventually, compared to the MAD range of the meta cohort (2.53-5.07 years), a promising RFR model (ntree = 500 and mtry = 8) was optimized with an MAD of 1.15 years in the 1-60 age categories of the CHS cohort, which could be regarded as a robust epigenetic clock in blood for age-related issues.


Synthesis of potential metabolites of (S)-(-)-bromofosfamide.
(S)-(-)-Bromofosfamide, a newly obtained anticancer agent, recently became a subject of phase I clinical trials in Poland. With the aim to study its metabolism in humans using phosphorus nuclear magnetic resonance a group of potential metabolites of this agent was synthesized.


Growth-inhibiting conditions slow growth plate senescence.
The mammalian growth plate undergoes programmed senescence during juvenile life, causing skeletal growth to slow with age. We previously found that hypothyroidism in rats slowed both growth plate chondrocyte proliferation and growth plate senescence, suggesting that senescence is not dependent on age per se but rather on chondrocyte proliferation. However, one alternative explanation is that the observed slowing of growth plate senescence is a specific consequence of hypothyroidism. We reasoned that, if delayed senescence is a general consequence of growth inhibition, rather than a specific result of hypothyroidism, then senescence would also be slowed by other growth-inhibiting conditions. In this study, we therefore used tryptophan deficiency to temporarily inhibit growth in newborn rats for 4 weeks. We then allowed the animals to recover and studied the effects on growth plate senescence. We found that structural, functional, and molecular markers of growth plate senescence were delayed by prior tryptophan deficiency, indicating that the developmental program of senescence had occurred more slowly during the period of growth inhibition. Taken together with previous studies in hypothyroid rats, our findings support the hypothesis that delayed senescence is a general consequence of growth inhibition and hence that growth plate senescence is not simply a function of time per se but rather depends on growth.


Flexible and Wearable Zinc-Ion Hybrid Supercapacitor Based on Double-Crosslinked Hydrogel for Self-Powered Sensor Application.
The rapidly growing Internet of Things (IoT) has brought about great demand for high-performance sensors as well as power supply devices for those sensors. In this respect, the integration of sensors and energy storage devices, or the development of multifunctional devices having both energy storage and sensing properties, is of great interest in the development of compact sensing systems. As a proof of concept, a zinc-ion hybrid supercapacitor (ZHS) based on a double-crosslinked hydrogel electrolyte is developed in this work, which can be employed not only as an energy storage device, but also as a self-powered sensor for human movement and breathing detection. The ZHS delivers a capacitance of 779 F g-1 and an energy density of 0.32 mWh cm-2 at a power density of 0.34 mW cm-2, as well as sensitive resistance response to strain. Our work provides a useful basis for future designs of self-powered sensing devices and function-integrated systems.


Stress-only Tc-99m myocardial perfusion imaging in an emergency department chest pain unit.
Stress-only myocardial perfusion imaging (MPI) saves time by eliminating rest imaging, which is important for emergency department (ED) throughput but has not been studied in an ED population. To determine the prognosis of a normal stress-only MPI study compared to a normal rest-stress MPI and establish its effectiveness in an ED setting. All patients evaluated in the ED over 6.5 years who underwent a stress-only technetium-99m gated MPI were compared to those who had a rest-stress study. All-cause mortality was determined using the Social Security Death Index. Survival was analyzed in patients with normal and abnormal MPI results. A total of 4145 studies (2340 stress-only, 1805 rest-stress) were performed. Patients' average age was 57.9 years, 38.5% were male, and most had an intermediate or low pretest risk of coronary artery disease (87.7%). Average follow-up was 35.9 ± 20.9 months. In patients with normal perfusion, at 1 year of follow-up there were 11 deaths in the stress-only group (0.5% 1-year mortality), and 13 deaths in the rest-stress cohort (1.1% 1-year mortality). At the end of follow-up, the stress-only group had a lower all-cause mortality (p < 0.0001) and similar risk adjusted all-cause mortality (p = 0.10) than the rest-stress cohort. Patients with abnormal perfusion demonstrated the expected differential prognosis based on total perfusion deficits in both groups. A normal stress-only MPI study has a benign 1-year prognosis similar to a rest-stress study when performed in the ED. The ability to triage patients more rapidly and reduce radiation exposure represents an attractive alternative for low-risk patients.


Icariin Attenuates OGD/R-Induced Autophagy via Bcl-2-Dependent Cross Talk between Apoptosis and Autophagy in PC12 Cells.
Icariin (ICA), an active component of Epimedium brevicornum Maxim, exerts a variety of neuroprotective effects such as antiapoptosis. However, the mechanisms underlying antiapoptosis of ICA in neurons exposed to oxygen-glucose deprivation and reperfusion (OGD/R) are unclear. The B-cell lymphoma-2 (Bcl-2) protein family plays an important role in the regulation of apoptosis and autophagy through Bcl-2-dependent cross talk. Bcl-2 suppresses apoptosis by binding to Bax and inhibits autophagy by binding to Beclin-1 which is an autophagy related protein. In the present study, MTT result showed that ICA increased cell viability significantly in OGD/R treated PC12 cells (P < 0.01). Results of western blotting analysis showed that ICA increased Bcl-2 expression significantly and decreased expressions of Bax, cleaved Caspase-3, Beclin-1, and LC3-II significantly in OGD/R treated PC12 cells (P < 0.01). These results suggest that ICA protects PC12 cells from OGD/R induced autophagy via Bcl-2-dependent cross talk between apoptosis and autophagy.


The use of transtelephonic loop recorders for the assessment of symptoms and arrhythmia recurrence after radiofrequency catheter ablation.
Radiofrequency catheter ablation (RFA) is an effective treatment of arrhythmias. However, patients often remain symptomatic after the procedure. We aimed to assess the arrhythmia recurrence after successful RFA in relation to patients' symptoms using transtelephonic loop recorders. Thirty-six consecutive patients (age 50 +/- 14 years, 17 males/19 females) were enrolled after successful RFA for atrioventricular (AV) nodal reentrant tachycardia (n = 21), AV reentrant tachycardia (n = 8), atrial tachycardia (n = 2), atrial fibrillation/flutter (n = 4), and ventricular tachycardia (n = 1). During 23 +/- 6 days of follow-up, 679 events were recorded, 246 of which were true arrhythmic events, mostly (56%) asymptomatic. The vast majority of these true arrhythmic events were due to trivial arrhythmias (extrasystoles or sinus tachycardia), equally distributed among symptomatic and asymptomatic episodes. Arrhythmia relapse was shown in four patients, who had a total of nine episodes, eight of which were symptomatic. No high degree AV block was detected. Overall, symptom recurrence had low sensitivity (44%) and high specificity (95%) for the detection of any arrhythmia, and high sensitivity (89%) but low specificity (58%) for the detection of relapse. In conclusion, transtelephonic monitoring was a useful tool for the assessment of symptoms after RFA and its use may be reserved for the most symptomatic patients to detect a relapse or to reassure them for the benign nature of their symptoms.


Creatine kinase levels after jogging in patients with cardiac disease.
Acute muscle injury is a well-documented complication of strenuous exercise, but milder forms of exertion have not been studied in detail. This report describes a patient undergoing cardiac rehabilitation in whom atypical chest pain developed and who was treated for a myocardial infarction only because of an elevated creatine kinase level. Serum creatine kinase levels were determined before and after exercise in 27 patients undergoing cardiac rehabilitation. In 21 patients who jogged less than three miles, creatine kinase levels were not appreciably changed. In six patients who jogged more than three miles, the mean creatine kinase level rose from 41 to 54 mU/ml, an increase of 31 percent. In four of these six patients, creatine kinase levels rose to abnormal levels, but MB creatine kinase levels remained normal, with no clinical evidence of myocardial ischemia. Serum creatine kinase levels should be interpreted with caution in the setting of even modest exercise.


Natural cytotoxic cells of gilthead seabream: maximum percentage of lysis.
The maximum percentage of lysis of head-kidney non-specific cytotoxic cells (NCC) against mammalian tumour cells (L1210 and K562) in the marine teleost gilthead seabream (Sparus aurata L.) was studied. The present data indicate the short period of time necessary for gilthead seabream NCC to form conjugates and deliver a lethal hit. The maximum percentage of lysis observed demonstrates that seabream NCC activity against L1210 tumour cells is faster than against K562 tumour cells. This kinetic parameter suggests that fish NCC show a less efficient cytotoxic activity than their mammalian counterparts. The possibility of applying theoretical treatments to systems consisting of lower vertebrate non-specific cytotoxic cells and tumour targets, similar to those applied to mammals, is considered, and the phylogenetic implications of our findings are discussed.


The role of roadsides in plant invasions: a demographic approach.
Non-native plant species are common along roadsides, but presence does not necessarily indicate spread along the road axis. Roadsides may serve merely as habitat for a species spreading independently of roads. The potential conduit function of roads depends on the habitat specificity of the spreading species, its dispersal range relative to the spacing of roads in the landscape, and the relative importance of long- and short-range dispersal. We describe a demographic model of the road x species interaction and suggest methods of assessing conduit function in the field based on the model results. A species limited to roadside habitat will be constrained to spread along the road axis unless its long-range dispersal is sufficient to carry it across the intervening unfavorable area to another road. It will propagate along a road corridor at a rate determined by the scale of short-range dispersal. Effective management of an invasion requires distinguishing between the habitat and conduit functions, a distinction difficult to make with only snapshot data. Invasions can be reconstructed by several methods, but none is totally satisfactory. We suggest comparing stem distributions on transects parallel and perpendicular to the road axis, and beside the road, and away from it, with an idealized Gaussian curve. Such comparisons would allow discrimination between pattern determined by habitat suitability and pattern reflecting random and facilitated dispersal.


Determinants of responsiveness in mothers of children with intraventricular hemorrhage.
Explored relationships between maternal responsiveness and parenting stress, family, medical, and demographic factors in mothers of children born prematurely at very low birth weights with intraventricular hemorrhage. Mothers of 82 2-year-olds completed self-report questionnaires and were observed interacting with their children in free play during a yearly assessment. Path analysis (LISREL) revealed that lower maternal responsiveness, measured by the Parent/Caregiver Involvement Scale, was associated with greater demographic disadvantage and with high parent-related stress on selected subscales of the Parenting Stress Index. Child-related parenting stress was not associated with responsiveness, and severity of the child's medical condition at birth was weakly related. Results are discussed in the context of this unique population, and relevant research and measurement issues.


[Painful sacral rachischisis: considerations on the etiopathogenesis and treatment].
The Authors present 13 cases of patients with a painful spina bifida operated between 1965 and 1974. This exiguous number of patients shows that the surgical indication is placed only after a symptoms's severe valuation and the inefficacy of bloodless therapy. The 3 poor results were due to the coexistence of other diseases. The pain is caused by skeletal insufficiency. It would suitable to carry out a close research as Computerized Axial Tomographic Scanning and to join an intervention of arthodesis intersomatic when there are another malformations.


Neonatal screening for metabolic and endocrine disorders.
The impact of metabolic diseases (inborn errors of metabolism) and endocrine disorders in pediatrics has markedly increased during the last few decades. Critical periods in the development of the central nervous system need special attention in children with these disorders. Early diagnosis and treatment are important in order to prevent mental retardation and serious handicaps in some of these patients. Certain patients with metabolic and endocrine disorders lack early clinical symptoms or have so non-specific signs that permanent neurological handicaps are present when the patients are finally diagnosed. One way to identify these patients is by means of mass screening. A blood sample is then collected from every newborn infant and analyzed for abnormal levels of metabolites or hormones. It is possible to detect at least thirty different disorders in this way. In most European countries screening programmes involve phenylketonuria (PKU) and congenital hypothyroidism. The prognosis for these patients has improved dramatically after the introduction of screening. The Swedish neonatal metabolic screening programme was started in 1965 by screening for PKU. Subsequently, screening for galactosemia and congenital hypothyroidism was added. The result of the screening programme 1965-1985 is as follows: (table; see text) The main benefit of early detection and treatment of children with PKU, congenital hypothyroidism and galactosemia is the prevention of mental retardation and other handicaps. Recently nationwide pilot screening for congenital adrenal hyperplasia (adrenogenital syndrome) was started.


Experimental chronic Chagas' disease myocarditis is an autoimmune disease preventable by induction of immunological tolerance to myocardial antigens.
The protozoan Trypanosoma cruzi causes chronic Chagas' disease myocarditis (CCDM) in infected mammals. The pathogenesis of CCDM, however, is still unclear. Indirect evidence for either parasite- or heart-specific immune responses playing a pathogenic role is available. In this work, the participation of autoimmunity in the development of CCDM is demonstrated in mice in which immunological tolerance to heart antigens was induced or strengthened prior to their infection by T. cruzi. Tolerance was induced by heart antigen administration in the presence of complete Freund's adjuvant and anti-CD4 antibodies. Tolerized mice developed less intense CCDM than control non-tolerized animals that had received only anti-CD4 and adjuvant. This result confirms the important notion that tolerance to self, and in particular to heart antigens, may be reinforced/induced in normal animals, and raises the possibility that analogous interventions may prevent the development of CCDM in millions of T. cruzi -infected human beings.


Why Does COVID-19 Affect Patients with Spinal Cord Injury Milder? A Case-Control Study: Results from Two Observational Cohorts.
The COVID-19 pandemic represents an unprecedented global challenge in this century. COVID-19 is a viral respiratory infection, yet the clinical characteristics of this infection differ in spinal cord injury patients from those observed in the general population. Cough and asthenia are the most frequent symptoms in this population. Moreover, infected spinal cord injury patients rarely present complications that require admission to an Intensive Care Unit, in contrast to the general population. Thus, there is a clear need to understand how COVID-19 affects spinal cord injury patients from a molecular perspective. Here, we employed an -omics strategy in order to identify variations in protein abundance in spinal cord injury patients with and without COVID-19. After a quantitative differential analysis using isobaric tags and mass spectrometry and a verification phase, we have found differences mainly related to coagulation and platelet activation. Our results suggest a key role of heparin in the response of spinal cord injury patients to COVID-19 infection, showing a significant correlation between these proteins and heparin dose. Although the number of patients is limited, these data may shed light on new therapeutic options to improve the management these patients and, possibly, those of the general population as well.


Injury risk-factor differences between two golf swing styles: a biomechanical analysis of the lumbar spine, hip and knee.
The golf swing has been associated with mechanical injury risk factors at many joints. One swing, the Minimalist Golf Swing, was hypothesised to reduce lumbar spine, lead hip, and lead knee ranges of motion and peak net joint moments, while affecting swing performance, compared to golfers' existing swings. Existing and MGS swings of 15 golfers with handicaps ranging from +2 to -20 were compared. During MGS downswing, golfers had 18.3% less lumbar spine transverse plane ROM, 40.7 and 41.8% less lead hip sagittal and frontal plane ROM, and 39.2% less lead knee sagittal plane ROM. MGS reduced lead hip extensor, abductor, and internal rotator moments by 17.8, 19.7 and 43%, while lead knee extensor, abductor, adductor and external rotator moments were reduced by 24.1, 26.6, 37 and 68.8% respectively. With MGS, club approach was 2° shallower, path 4° more in-to-out and speed 2 m/s slower. MGS reduced certain joint ROM and moments that are linked to injury risk factors, while influencing club impact factors with varying effect. Most golf injuries are from overuse, so reduced loads per cycle with MGS may extend the healthy life of joints, and permit golfers to play injury-free for more years.


Circular dichroism spectra of granal and agranal chloroplasts of maize.
Granum-containing chloroplasts from mesophyll cells of maize (Zea mays L. var. MV 861) leaves exhibited circular dichroism spectra with a large double signal; peaks at 696 nm (+) and 680 nm (-). In the circular dichroism spectra obtained with agranal chloroplasts of bundle sheath cells, this large double signal is absent. Separation of grana lamellae, in a medium of low salt concentration and in KSCN solution, resulted only in a slight decrease of the amplitude, while upon treatment with digitonin the large double signal disappeared. A negative signal of the chlorophyll b peak at 654 nm was observed in the case of both granal and agranal chloroplasts, and it was not affected either by low salt or by digitonin treatment. A positive peak at about 515 nm was higher in granal than in agranal chloroplasts.


Reliability of shoulder internal rotation passive range of motion measurements in the supine versus sidelying position.
Clinical measurement, reliability. To compare intrarater and interrater reliability of shoulder internal rotation (IR) passive range of motion measurements utilizing a standard supine position and a sidelying position. Glenohumeral IR range of motion deficits are often noted in patients with shoulder pathology. Excellent intrarater reliability has been found when measuring this motion. However, interrater reliability has been reported as poor to fair. Some clinicians currently use a sidelying position for IR stretching with patients who have shoulder pathology. However, no objective data exist for IR passive range of motion measured in this sidelying position, either in terms of reliability or normative values. Seventy subjects (mean age, 36.8 years), with (n = 19) and without (n = 51) shoulder pathology, were included in this study. Shoulder IR passive range of motion of the dominant shoulder or involved shoulder was measured by 2 investigators in 2 positions: (1) a standard supine position, with the shoulder at 90 degrees of abduction, and (2) in sidelying on the tested side, with the shoulder flexed to 90 degrees . Intrarater reliability for supine measurements was good to excellent (ICC3,1 = 0.70-0.93) and for sidelying measurements was excellent (ICC3,1 = 0.94-0.98). Interrater reliability was fair to good for the supine measurement (ICC2,2 = 0.74-0.81) and good to excellent for the sidelying measurement (ICC2,2 = 0.88-0.96). The mean (range) value of the dominant shoulder sidelying IR passive range of motion was 40 degrees (11 degrees to 69 degrees ) for healthy subjects and 25 degrees (-16 degrees to 49 degrees) for subjects with shoulder pathology. For subjects with shoulder pathology, measurements of shoulder IR made in the sidelying position had superior intrarater and interrater reliability compared to those in the standard supine position.


Spinach Leaf Intra and Extra Chloroplast Phosphorylase Activities during Growth.
The amino terminal sequence of the spinach (Spinacia oleracea L. cv Bloomsdale Long Standing) leaf cytoplasmic phosphorylase was determined and shown to have little similarity to the known sequence of the potato tuber phosphorylase. The antigenic reaction of spinach chloroplast phosphorylase and rabbit muscle phosphorylase a to antiserum prepared against spinach leaf cytoplasmic phosphorylase was tested. Neither phosphorylase gave a positive reaction when tested by immunodiffusion or neutralization of enzyme activity. The two spinach phosphorylases were assayed throughout the growth of the plant. Activity of cytoplasmic phosphorylase increased 4- to 8-fold at 30 to 35 days from sowing. Enzyme protein levels, as measured by antibody neutralization, increased by a similar amount. There was no corresponding increase in chloroplast phosphorylase activity. The chloroplast phosphorylase varied in parallel with the chloroplast enzyme ADPglucose pyrophosphorylase. Starch levels were high during the earlier stages of growth and then fell to a constant low level just before the increase in cytoplasmic phosphorylase. The results are discussed with respect to the relationship and functions of the two phosphorylases.


Controllable synthesis of graphitic C3N4/ultrathin MoS2 nanosheet hybrid nanostructures with enhanced photocatalytic performance.
Graphitic C3N4/ultrathin MoS2 (MoS2/g-C3N4) hybrids were synthesized via a facile bathing and ultrasound method. In this process, a well-bonded interface structure was formed between ultrathin MoS2 nanosheets and g-C3N4 through adjusting the amount of MoS2 in the MoS2/g-C3N4 hybrids. The MoS2/g-C3N4 hybrids were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), Raman spectroscopy (Raman), transmission electron microscopy (TEM) and UV-vis spectroscopy (UV-vis). The MoS2/g-C3N4 photocatalyst showed excellent photocatalytic activity in the photodegradation of organic pollutants. In this work, methyl orange (MO) was used as the simulative pollutant; the highest photodegradation rate (92.4%) was obtained when the amount of MoS2 was 5 wt% in the MoS2/g-C3N4 hybrids (0.05-MC), with a kinetic constant of 0.0189 min-1 after being irradiated under visible light for 2 h. Besides, 0.05-MC also showed excellent recyclability and chemical stability, and a photodegradation rate of 79.93% was reached after being reused 10 times. For practical pollutants, the photocatalytic degradation rates of ciprofloxacin (CIP) and tetracycline hydrochloride (TC) have been increased dramatically under the visible light irradiation. The excellent photocatalytic properties of MoS2/g-C3N4 hybrids can be ascribed to the enhanced separation rate and accelerated mobility of photogenerated charges through ultrathin MoS2 nanosheets' modification.


The role of nitric oxide in mycobacterial infections.
Although tuberculosis poses a significant health threat to the global population, it is a challenge to develop new and effective therapeutic strategies. Nitric oxide (NO) and inducible NO synthase (iNOS) are important in innate immune responses to various intracellular bacterial infections, including mycobacterial infections. It is generally recognized that reactive nitrogen intermediates play an effective role in host defense mechanisms against tuberculosis. In a murine model of tuberculosis, NO plays a crucial role in antimycobacterial activity; however, it is controversial whether NO is critically involved in host defense against Mycobacterium tuberculosis in humans. Here, we review the roles of NO in host defense against murine and human tuberculosis. We also discuss the specific roles of NO in the central nervous system and lung epithelial cells during mycobacterial infection. A greater understanding of these defense mechanisms in human tuberculosis will aid in the development of new strategies for the treatment of disease.


Discovery of Tolerance to Itraconazole in Japanese Isolates of Aspergillus Section Nigri, Aspergillus tubingensis and Aspergillus welwitschiae, by Microscopic Observation.
Aspergillus section Nigri, a group of black Aspergillus, has several cryptic species that were recently discovered to be intrinsically resistant to azole antifungals. In this study, susceptibility testing of 35 clinical isolates of Aspergillus tubingensis and Aspergillus welwitschiae in Japan was carried out using microdilution method. Strains tolerant to itraconazole in A. tubingensis (14/17 strains) and A. welwitschiae (6/18 strains) were discovered with hyphal growth and conidial germination above the minimal inhibitory concentration by microscopic observation, while no resistant strain was observed macroscopically. In contrast, no strain with reduced susceptibility to voriconazole, posaconazole, and amphotericin-B was found. Further examination may be required to determine the susceptibility of cryptic species in Aspergillus section Nigri to antifungals.


[Correction of pectus excavatum and long-term outcome in adult].
Pectus excavatum is the most common congenital chest malformation characterized by symmetrical or asymmetric depression of the chest with deformation of the sternocostal complex. Pectus excavatum is often associated with other dysplastic diseases of connective tissue. Ravitch thoracoplasty and Nuss minimally invasive correction are the most common today. The authors report surgical correction of PE in a 50-years-old male who underwent Ravitch modified thoracoplasty with implantation of shape memory plate. Long-term treatment outcomes and technical properties of the plate after removing are analyzed.


CD4+CD8+ human small intestinal T cells are decreased in coeliac patients, with CD8 expression downregulated on intra-epithelial T cells in the active disease.
The intestinal lesion of coeliac disease is thought to be initiated and exacerbated by dysregulation of local T-lymphocyte sub-populations. This study examines changes in intestinal T cells from coeliac patients, with a particular focus on CD4CD8 T cells, immunoregulatory cells normally found in relatively high proportions in the small intestine. Cells were obtained from duodenal biopsies from active and treated coeliac patients using chelating and reducing agents (epithelial layer) followed by collagenase treatment (lamina propria). Cell yield and viability were assessed and flow cytometric analysis was used to examine CD4CD8 T cells and to quantify CD8 expression. Surprisingly, total T-cell yields in the epithelial layer did not increase in active coeliac disease although enterocyte counts decreased significantly, giving an appearance of infiltration. In active coeliac patients, CD4CD8 T cell percentages were significantly decreased in both the epithelial layer and lamina propria. Levels of CD8 expression by CD4CD8 T cells in the epithelial layer were decreased significantly in patients with active coeliac disease. CD4CD8 T cell proportions did not return to normal in treated coeliac patients whose villous architecture had responded to gluten withdrawal. No increase of intra-epithelial lymphocytes in the coeliac lesion may require us to reconsider the definition of coeliac disease as an inflammatory condition. Low CD4CD8 populations in treated as well as untreated coeliac patients indicate that these T cells are inherently absent in individuals genetically predisposed to coeliac disease.


Talonavicular arthrodesis for the acquired flatfoot in the adult.
The acquired painful flatfoot in the adult is a syndrome that commonly is disabling and progressive. Patients should benefit from a surgical technique that can provide correction of the major deformities and lasting stability with limited surgical morbidity. Twenty-nine patients treated with a talonavicular arthrodesis for this disorder were followed up a minimum of 12 months and an average of 26 months. Twenty-five patients (86%) were satisfied with no or minor reservations and achieved good or excellent results. A talonavicular arthrodesis, by addressing the instability at its focal point, appears to achieve these goals with one surgical procedure.


Genetic Ace2 deficiency accentuates vascular inflammation and atherosclerosis in the ApoE knockout mouse.
Angiotensin-converting enzyme (ACE)2 opposes the actions of angiotensin (Ang) II by degrading it to Ang 1-7. Given the important role of Ang II/Ang 1-7 in atherogenesis, we investigated the impact of ACE2 deficiency on the development of atherosclerosis. C57Bl6, Ace2 knockout (KO), apolipoprotein E (ApoE) KO and ApoE/Ace2 double KO mice were followed until 30 weeks of age. Plaque accumulation was increased in ApoE/Ace2 double KO mice when compared to ApoE KO mice. This was associated with increased expression of adhesion molecules and inflammatory cytokines, including interleukin-6, monocyte chemoattractant protein-1, and vascular cell adhesion molecule-1, and an early increase in white cell adhesion across the whole aortae on dynamic flow assay. In the absence of a proatherosclerotic (ApoE KO) genotype, ACE2 deficiency was also associated with increased expression of these markers, suggesting that these differences were not an epiphenomenon. ACE inhibition prevented increases of these markers and atherogenesis in ApoE/ACE2 double KO mice. Bone marrow macrophages isolated from Ace2 KO mice showed increased proinflammatory responsiveness to lipopolysaccharide and Ang II when compared to macrophages isolated from C57Bl6 mice. Endothelial cells isolated from Ace2 KO mice also showed increased basal activation and elevated inflammatory responsiveness to TNF-α. Similarly, selective inhibition of ACE2 with MLN-4760 also resulted in a proinflammatory phenotype with a physiological response similar to that observed with exogenous Ang II (10(-7) mol/L). Genetic Ace2 deficiency is associated with upregulation of putative mediators of atherogenesis and enhances responsiveness to proinflammatory stimuli. In atherosclerosis-prone ApoE KO mice, these changes potentially contribute to increased plaque accumulation. These findings emphasize the potential utility of ACE2 repletion as a strategy to reduce atherosclerosis.


Chitosan modification and pharmaceutical/biomedical applications.
Chitosan has received much attention as a functional biopolymer for diverse applications, especially in pharmaceutics and medicine. Our recent efforts focused on the chemical and biological modification of chitosan in order to increase its solubility in aqueous solutions and absorbability in the in vivo system, thus for a better use of chitosan. This review summarizes chitosan modification and its pharmaceutical/biomedical applications based on our achievements as well as the domestic and overseas developments: (1) enzymatic preparation of low molecular weight chitosans/chitooligosaccharides with their hypocholesterolemic and immuno-modulating effects; (2) the effects of chitin, chitosan and their derivatives on blood hemostasis; and (3) synthesis of a non-toxic ion ligand--D-Glucosaminic acid from oxidation of D-Glucosamine for cancer and diabetes therapy.


Colorectal anastomotic leakage corrected by transanal laparoscopy.
Interest in transanal laparoscopy has increased in the last decade. This approach can allow primary procedures such as polypectomy, total mesorectal excision and the treatment of postoperative complications such as bleeding, leakage and fistula formation. Two patients treated by transanal repair for leakage of a colorectal anastomosis after laparoscopic anterior resection of the rectum are reported. The first developed leakage immediately during the surgery and in the second leakage presented at 4 weeks. A new transanal platform according to DAPRI (Karl Storz-Endoskope, Tuttlingen, Germany), formed by a reusable port and reusable monocurved instruments was developed to permit manipulation of sutures introduced via the anus in a maximally ergonomic manner. Laparoscopic suturing was performed transanally and a protective ileostomy was added as well. The transanal procedures took 60 and 45 min and the patients were discharged after 5 days and 2 days. At 2 months both defects were found to be healed on contrast radiology and endoscopy; therefore the ileostomy was closed. Anal function was satisfactory with a frequency of two and one times per 24 h with no incontinence or evidence of sepsis. Intra-operative or late leakage of colorectal anastomosis can be safely treated by transanal laparoscopy. This new transanal platform offers the surgeon the possibility to work in ergonomic positions, without increasing the cost of the procedure thanks to the reusable nature of the material used.


Multisystem inflammatory syndrome in children associated with novel coronavirus SARS-CoV-2: Presentations to a pediatric emergency department in Michigan.
The SARS-CoV-2 is a respiratory virus of the coronavirus family responsible for a global pandemic since December 2019. More than 35 million people have been affected with the novel coronavirus disease (COVID-19), with more than one million deaths worldwide. Michigan was one of the top three states in the United States that was severely affected by the SAR-CoV-2 pandemic with more than 7000 deaths in adults and greater than 145,000 confirmed infections. However, compared to adults, the majority of children until recently were either asymptomatic or had a mild illness with SARS-CoV-2. Recently, a rare but potentially serious presentation associated with SARS-CoV-2 called multisystem inflammatory syndrome in children (MIS-C) has been recently reported and the Centers for Disease Control (CDC) released a case definition for the same. We report the clinical and laboratory presentations and outcomes of 34 children with MIS-C who were evaluated within a 12 week period at a pediatric emergency department (PED) of single institution in Michigan. These cases presented approximately three weeks after the peak of adult SAR-CoV-2 related deaths occurred in the state. While many children presented with clinical characteristics similar to incomplete Kawasaki disease (KD), they also exhibited certain unique features which differentiated MIS-C from KD. The information presented below will aid clinicians with early recognition, evaluation and management of MIS-C in the emergency department.


Is High IQ Protective Against Cognitive Dysfunction in Narcoleptic Patients?
The aims of this study were to elucidate the cognitive functions of narcoleptics and determine whether intelligence protects against cognitive dysfunction and depressive mood in these patients. Sixty-six subjects (33 narcoleptics, 33 controls) were administered a battery of neuropsychological tests and an individual standardized intelligence test. The cognitive functions of the narcoleptic patients and the healthy controls were compared, as were those of high-IQ and mid-to-low-IQ narcoleptic patients. Narcoleptics exhibited significantly lower scores in the Corsi Block-Tapping Test forward and backward, and the digit symbol tests, and significantly higher Beck Depression Inventory scores than the controls. However, verbal attention, verbal-visual long-term memory, and executive function task scores did not differ significantly between patients and controls. The mid-to-low-IQ patient group had lower mean digit span backward test, phonemic and semantic fluency Controlled Oral Word Association Test and Korean version of the Boston Naming Test scores, and a higher total score and general depressive symptoms subscales Beck Depression Inventory score than the high-IQ patient group. However, controls exhibited no IQ-related differences in cognitive performance or depressive mood. Patients in the high-IQ group exhibited impaired visual attention and working memory as compared with controls. The findings of the present study show that narcolepsy patients have deficits in visual attention and visual working memory, and tend to feel more general depressive symptoms but not somatic symptoms than their control, nonnarcoleptic counterparts. In addition, it appears that higher intelligence protects against cognitive dysfunction and depressive mood.


The pMTL nic- cloning vectors. I. Improved pUC polylinker regions to facilitate the use of sonicated DNA for nucleotide sequencing.
A series of nic- cloning vectors have been constructed analogous to the pUC plasmids but which are smaller in size and carry more extensive polylinker regions within the lacZ' gene. The vectors pMTL20 and pMTL21 carry six additional sites (AatII, MluI, NcoI, BglII, XhoI and StuI) to those present in pUC18 and pUC19, while pMTL22 and -23 possess eleven new cloning sites (ActII, MluI, NcoI, BglII, XhoI, StuI, NaeI, EcoRV, ClaI, NdeI and NruI). More importantly, the relative order of the restriction sites within the polylinker of these latter vectors has been totally rearranged, relative to pUC18 and pUC19, to facilitate the conversion of DNA fragments with incompatible ends to fragments with compatible termini. The availability of such DNA fragments is a crucial requirement when M13 templates are generated for dideoxy sequencing by the sonication procedure. Derivatives of these vectors have also been constructed which demonstrate improved segregational stability by incorporation of the pSC101 par locus. During the construction of these new vectors data were obtained which demonstrated that the pUC and pMTL plasmids contain a previously unreported single base pair difference within the RNA I/RNA II region (compared to pBR322) responsible for a three-fold increase in plasmid copy number. The pUC and pMTL plasmids were also shown to be functionally nic-, thus affording the lowest categorisation in genetic manipulation experiments.


M-mode speckle tracking--a novel echocardiographic approach to assess left ventricular torsional deformation.
Speckle tracking echocardiography (STE) requires special image processing for complex assessment of left ventricular (LV) function, including strain and rotation. To evaluate a novel M-mode STE technique as a readily applicable approach, providing potential insights into LV deformation. Fifty one patients (mean age 52 +/- 14 years, 24 women) with normal or impaired LV function (mean LVEF 51 +/- 16%, range between 14% and 66%) were studied. Left ventricular rotation at mitral valve and apical level was measured using dedicated conventional STE software. Grey-scale short axis digital loops at mitral valve level were also used to obtain M-mode STE images, presenting the movement of LV wall speckles along the cursor, with the LV cavity left out. Then, the distance of peak systolic shift (PSS) was measured for one selected speckle. Mean rotation at mitral valve level was 7.4 +/- 3.1 degrees , apical rotation was 7.6 +/- 6.4 degrees and LV torsion was 14.9 +/- 7.1 degrees . Measurement of PSS with a novel M-mode STE approach was feasible in all patients, producing a mean value of 7 +/- 2 mm. Subsequently, two subsets with PSS of less than 7 mm and PSS equal to or above 7 mm showed a significant difference between mean LV torsion of 10.7 degrees and 17.0 degrees , respectively (p = 0.002). In the ROC analysis, PSS cut-off value of less than or equal to 7 mm yielded a sensitivity of 92% and a specificity of 61% to predict LV torsion < 10.7 degrees (p < 0.0001). M-mode STE appears to be a feasible approach to detect movement of speckles and to measure PSS within the LV inferior and septal wall in short axis view images. PSS cut-off value of less than 7 mm indicates significantly lower LV torsion. Further studies are required to assess the potential role of M-mode STE in cardiac imaging.


Microfluidic testing of flocculants for produced water treatment: Comparison with other methodologies.
Flocculants are often added during produced water treatment to improve the crude oil droplet growth and separation from the water phase. Prior to use in the field, their performance is tested in laboratory conditions, typically with jar tests that require quite large volumes of sample. In this paper we present a microfluidic method as an alternative to study the efficiency of flocculants on enhancing coalescence between oil droplets. Two crude oil emulsions and four flocculants at different concentrations were tested. The new method is also compared to the more traditional techniques. An anionic flocculant showed the biggest improvement in separation for almost all systems. What is more, marked differences were observed between methods with static (bottle and turbidity tests) and dynamic test conditions (light scattering and microfluidics), where stabilization and dispersion effects were observed for the latter. The microfluidic methodology, with added benefits such as visualization, lower sample volumes and shorter measurement times, yielded similar trends as compared to other techniques. Overall, it was shown that microfluidics is a viable alternative to the standard tests.


Hereditary gingival fibromatosis with distinct dental, skeletal and developmental abnormalities.
A case of a 9-year-old child with hereditary gingival fibromatosis, supernumerary tooth, chest deformities, auricular cartilage deformation, joint laxity and undescended testes is described. The exact mode of inheritance is unclear; a new mutation pattern is possible. These features resemble but differ from the previously reported Laband syndrome. The dental treatment consisted of surgical removal of the fibrous tissue and conservative restorative treatment under general anesthesia. The dental practitioner should be alert for developmental abnormalities such as supernumerary teeth and delayed tooth eruption. A comprehensive medical history and physical systemic evaluation is essential to rule out other systemic abnormalities. Genetic consultation is mandatory for future family planing.


Coffee-Ring-Free Quantum Dot Thin Film Using Inkjet Printing from a Mixed-Solvent System on Modified ZnO Transport Layer for Light-Emitting Devices.
Inkjet printing has been considered an available way to achieve large size full-color RGB quantum dots LED display, and the key point is to obtain printed film with uniform and flat surface profile. In this work, mixed solvent of 20 vol % 1,2-dichlorobenzene (oDCB) with cyclohexylbenzene (CHB) was used to dissolve green quantum dots (QDs) with CdSe@ZnS/ZnS core/shell structure. Then, by inkjet printing, a flat dotlike QDs film without the coffee ring was successfully obtained on polyetherimide (PEI)-modified ZnO layer, and the printed dots array exhibited great stability and repeatability. Here, adding oDCB into CHB solutions was used to reduce surface tension, and employing ZnO nanoparticle layer with PEI-modified was used to increase the surface free energy. As a result, a small contact angle is formed, which leads to the enhancement of evaporation rate, and then the coffee ring effect was suppressed. The printed dots with flat surface profile were eventually realized. Moreover, inverted green QD-LEDs with PEI-modified ZnO film as electron transport layer (ETL) and printed green QDs film as emission layer were successfully fabricated. The QD-LEDs exhibited the maximum luminance of 12 000 cd/m2 and the peak current efficiency of 4.5 cd/A at luminance of 1500 cd/m2.


Presence of antibody reactive with synthetic peptide derived from L2 open reading frame of human papillomavirus types 6b and 11 in human sera.
Nine oligopeptides corresponding to segments of different open reading frame (ORF) proteins of human papillomavirus (HPV) 6b and HPV-16 were prepared and tested for reactivity with human sera in enzyme-immunoassay (ELISA). Of these only heptadecapeptide derived from L2 ORF of HPV-6b, and encoded also by L2 ORF of HPV 11, was reactive with some human sera. Over 400 human sera of different origin were tested for the presence of antibody to this antigen. While less than 15% of sera from healthy subjects or cervical carcinoma patients were found antibody positive, sera from the majority of condylomata accuminata (CA) patients were reactive. The antibody titres varied from 1:10 (initial serum dilution) to 1:80; in this respect there was no marked difference between sera from CA patients and the other subjects. The prevalence of antibody was higher among promiscuous than nonpromiscuous women. This is in line with the assumption that sexual intercourse is the most important route of HPV 6 and 11 transmission.


Water molecule adsorption properties on the BiVO4 (100) surface.
The water absorption properties at the surface of BiVO4 are attracting a great deal of attention because the system is a promising candidate as a photocatalyst operating in the visible light range. This has motivated the present investigation via first principles molecular dynamics, which has revealed that a H2O molecule is adsorbed molecularly, instead of dissociatively, at the fivefold Bi site with an adsorption energy of approximately 0.58 eV/molecule. The band gap of the system shrinks slightly (by approximately 0.2 eV) upon water adsorption and it is likely that oxygen atoms belonging to the adsorbed water molecules to the Bi sites are oxidized, as inferred by the small Bi-Owater equilibrium distance (approximately 2.6-2.8 A) very close to the Bi-O bond in the bulk crystal. In the case of water adsorption at a Bi site, the distance between Hwater and V, which is a reduction site, is larger than in the case of adsorption at a V site, indicating that the proton reduction processes may be suppressed.


A Review of the Discriminant Analysis Methods for Food Quality Based on Near-Infrared Spectroscopy and Pattern Recognition.
Near-infrared spectroscopy (NIRS) combined with pattern recognition technique has become an important type of non-destructive discriminant method. This review first introduces the basic structure of the qualitative analysis process based on near-infrared spectroscopy. Then, the main pretreatment methods of NIRS data processing are investigated. Principles and recent developments of traditional pattern recognition methods based on NIRS are introduced, including some shallow learning machines and clustering analysis methods. Moreover, the newly developed deep learning methods and their applications of food quality analysis are surveyed, including convolutional neural network (CNN), one-dimensional CNN, and two-dimensional CNN. Finally, several applications of these pattern recognition techniques based on NIRS are compared. The deficiencies of the existing pattern recognition methods and future research directions are also reviewed.


GABAergic neuron deficit as an idiopathic generalized epilepsy mechanism: the role of BRD2 haploinsufficiency in juvenile myoclonic epilepsy.
Idiopathic generalized epilepsy (IGE) syndromes represent about 30% of all epilepsies. They have strong, but elusive, genetic components and sex-specific seizure expression. Multiple linkage and population association studies have connected the bromodomain-containing gene BRD2 to forms of IGE. In mice, a null mutation at the homologous Brd2 locus results in embryonic lethality while heterozygous Brd2+/- mice are viable and overtly normal. However, using the flurothyl model, we now show, that compared to the Brd2+/+ littermates, Brd2+/- males have a decreased clonic, and females a decreased tonic-clonic, seizure threshold. Additionally, long-term EEG/video recordings captured spontaneous seizures in three out of five recorded Brd2+/- female mice. Anatomical analysis of specific regions of the brain further revealed significant differences in Brd2+/- vs +/+ mice. Specifically, there were decreases in the numbers of GABAergic (parvalbumin- or GAD67-immunopositive) neurons along the basal ganglia pathway, i.e., in the neocortex and striatum of Brd2+/- mice, compared to Brd2+/+ mice. There were also fewer GABAergic neurons in the substantia nigra reticulata (SNR), yet there was a minor, possibly compensatory increase in the GABA producing enzyme GAD67 in these SNR cells. Further, GAD67 expression in the superior colliculus and ventral medial thalamic nucleus, the main SNR outputs, was significantly decreased in Brd2+/- mice, further supporting GABA downregulation. Our data show that the non-channel-encoding, developmentally critical Brd2 gene is associated with i) sex-specific increases in seizure susceptibility, ii) the development of spontaneous seizures, and iii) seizure-related anatomical changes in the GABA system, supporting BRD2's involvement in human IGE.


FGF-2 abolishes the chondrogenic effect of combined BMP-6 and TGF-beta in human adipose derived stem cells.
In this study, we investigated the influence of transforming growth factor beta 3 (TGF-beta3), bone morphogenetic protein 6 (BMP-6) and basic fibroblast growth factor (FGF-2) on chondrogenesis in adipose derived stem cells (ASC). Cells were isolated from liposuction material, expanded and subjected to chondrogenic differentiation. Micromass pellets were cultured in chondrogenic medium containing 10 ng/mL TGF-beta3 which was additionally supplemented with 10 ng/mL BMP-6, 10 ng/mL FGF-2 or a combination of both. We quantitatively evaluated the cartilage specific gene expression after 14 days of culture. The end point measurements on day 35 included glycosaminoglycan (GAG) quantification, histological staining for chondrogenic markers, and transmission electron microscopy (TEM). In comparison to cultures induced with TGF-beta3/FGF-2, the presence of TGF-beta3/BMP-6 demonstrated strong induction of collagen type II, collagen type IX and aggrecan mRNA expression. This was corroborated by quantification and histological staining for GAGs and immunohistological staining for collagen II. However, when a combination of BMP-6 and FGF-2 in addition to TGF-beta3 was added, FGF-2 counteracted BMP-6, as indicated by reduced marker gene expression and weak to absent staining for GAGs. In conclusion, this study demonstrates that BMP-6 combined with TGF-beta3 is a potent inducer of chondrogenesis in human ASC. In contrast, FGF-2 does not contribute to differentiation, but rather suppresses the chondrogenic potential of BMP-6.


Self-referential method for calculation of the free energy of crystals by Monte Carlo simulation.
We propose a Monte Carlo simulation method for the evaluation of free energies in crystalline systems. In principle, the method involves evaluating the free-energy difference between systems of N molecules and 2N molecules. This difference, coupled with the assumption that the free energy is extensive and thus proportional to N, provides sufficient information to obtain the absolute free energy of the crystal. The approach to doubling the system size does not involve insertion or removal of molecules in the system. Instead, the configurations of the molecules are expressed in terms of the normal-mode coordinates of a harmonic lattice. By decoupling certain of these coordinates from the molecule configurations, we obtain a transformation that in effect yields the system-size doubling. The method is examined via application to a system of hard rods in one dimension. This simple model is considered principally because of the availability of an analytic solution for its free energy, which permits accurate testing of the performance and correctness of the proposed method. In using the hard-rod model we also avoid other complications related to treatment of the temperature, and application of normal-mode coordinate decoupling in higher dimensions. The proposed method is shown to be able to provide good results for the free-energy calculation, but further development will be needed before it can be considered practical for general-purpose use.


Managing Syphilis in the HIV-infected Patient.
Syphilis has re-emerged in the United States and elsewhere, and clinicians caring for HIV-infected patients are challenged with syphilis diagnosis and management decisions. HIV alters the natural history of syphilis to an extent that is poorly understood, and initial presentation may be more varied in coinfected patients. Although commonly available diagnostic assays for syphilis should be interpreted as usual, such tests rely on antibody measurement and may be an imperfect indicator of active infection. Assessment of all available clinical and risk behavior data remains critically important in the diagnosis of syphilis in coinfected patients. Treatment of syphilis in such patients requires stage-appropriate therapy, with careful serologic monitoring to assess response. Clinicians must have heightened appreciation of the role of frequent risk assessment, serologic screening, symptom recognition, and follow-up of treated patients, as well as an understanding of public health functions such as sex partner treatment and communicable disease reporting.


Changes in bacterial denitrifier community abundance over time in an agricultural field and their relationship with denitrification activity.
This study measured total bacterial and denitrifier community abundances over time in an agricultural soil cropped to potatoes (Solanum tuberosum L.) by using quantitative PCR. Samples were collected on 10 dates from spring to autumn and from three spatial locations: in the potato "hill" between plants (H), close to the plant (H(p)), and in the "furrow" (F). The denitrification rates, N(2)O emissions, and environmental parameters were also measured. Changes in denitrifier abundance over time and spatial location were small (1.7- to 2.7-fold for the nirK, nosZ, and cnorB(B) guilds), whereas the cnorB(P) community (Pseudomonas mandelii and closely related spp.) showed an approximately 4.6-fold change. The seasonal patterns of denitrifier gene numbers varied with the specific community: lower nosZ gene numbers in April and May than in June and July, higher cnorB(P) gene numbers in May and June than in March and April and September and November, higher nirK gene numbers in early spring than in late autumn, and no change in cnorB(B) gene numbers. Gene numbers were higher for the H(p) than the H location for the nosZ and nirK communities and for the cnorB(P) community on individual dates, presumably indicating an effect of the plant on denitrifier abundance. Higher cnorB(P) gene numbers for the H location than the F location and for nosZ and cnorB(B) on individual dates reflect the effect of spatial location on abundance. Denitrifier abundance changes were not related to any environmental parameter, although a weak relationship exists between cnorB(P) gene numbers, extractable organic carbon values, and temperature. Denitrification and N(2)O emissions were mostly regulated by inorganic nitrogen availability and water-filled pore space but were uncoupled from denitrifier community abundances measured in this system.


Renoprotective effects of blockade of angiotensin II AT1 receptors in an animal model of type 2 diabetes.
To evaluate the efficacy of angiotensin II receptor blockers (ARBs) for use in the treatment of diabetic nephropathy, we examined the effects of olmesartan medoxomil (olmesartan), an angiotensin II type 1 (AT1) specific ARB, on the progression of nephropathy in Zucker diabetic fatty (ZDF) rats, an animal model of type 2 diabetes. We used 2 doses of olmesartan, a sub-antihypertensive dose and an antihypertensive dose, to specifically examine whether the drug exerts beneficial effects on the kidney without lowering blood pressure. Olmesartan mixed in the diet at a concentration of 0.001% (approximately 0.6 mg/kg/day) or 0.01% (approximately 6 mg/kg/day) was administered for 19 weeks starting from 12 weeks of age, when the animals developed microalbuminuria. Lean non-diabetic rats served as controls. ZDF rats had hyperglycemia, hyperinsulinemia, and moderate hypertension as compared to lean control rats. Plasma glucose and insulin concentrations were not affected by olmesartan, and blood pressure was lowered only by the high dose of olmesartan. Progressive proteinuria in ZDF rats was greatly (about 70%) suppressed by the high dose of olmesartan and moderately (about 30%) suppressed by the low dose that did not significantly lower blood pressure. ZDF rats exhibited hyperlipidemia and hypoalbuminemia, both of which were substantially corrected by treatment with olmesartan. The histological evidence of glomerular and tubular damage in the ZDF rats was also reduced by the drug. These results indicate that AT1 receptor blockade with olmesartan retards the progression of nephropathy associated with type 2 diabetes without affecting glucose metabolism, and that this renal protective effect is at least partly independent of the antihypertensive effect of the drug.


Black people are convicted more for being black than for being poor: The role of social norms and cultural prejudice on biased racial judgments.
Black and poor people are more frequently convicted of committing crimes. However, the specific role played by skin color and social class in convicting a person has yet to be clarified. This article aims to elucidate this issue by proposing that belonging to a lower social class facilitates the conviction of black targets and that this phenomenon is because information about social class dissimulates racial bias. Study 1 (N = 160) demonstrated that information about belonging to the lower classes increases agreement with a criminal suspect being sentenced to prison only when described as being black. Furthermore, Studies 2 (N = 170) and 3 (N = 174) show that the anti-prejudice norm inhibits discrimination against the black target when participants were asked to express individual racial prejudice, but not when they expressed cultural racial prejudice. Finally, Study 4 (N = 134) demonstrated that lower-class black targets were discriminated against to a greater degree when participants expressed either individual or cultural prejudice and showed that this occurs when racial and class anti-prejudice norms are salient. The results suggest that social class negatively affects judgments of black targets because judgment based on lower class mitigates the racist motivation of discrimination.


Methodology for Intraoperative Laser Doppler Vibrometry Measurements of Ossicular Chain Reconstruction.
Despite the increasing number of research concerning the applications of the Laser Doppler Vibrometry (LDV) in medicine, its usefulness is still under discussion. The aim of this study is to present a methodology developed in our Department for the LDV intraoperative assessment of ossicular chain reconstruction. Ten patients who underwent "second look" tympanoplasty were involved in the study. The measurements of the acoustic conductivity of the middle ear were performed using the LDV system. Tone bursts with carrier frequencies of 500, 1,000, 2,000, and 4,000 Hz set in motion the ossicular chain. The study was divided into four experiments that examined the intra- and interindividual reproducibility, the utility of the posterior tympanotomy, the impact of changes in the laser beam angle, and the influence of reflective tape presence on measurements. There were no statistically significant differences between the two measurements performed in the same patient. However, interindividual differences were significant. In all cases, posterior tympanotomy proved to be useful for LDV measurements of the ossicular prosthesis vibrations. In most cases, changing the laser beam angle decreased signal amplitude about 1.5% (not significant change). The reflective tape was necessary to achieve adequate reflection of the laser beam. LDV showed to be a valuable noncontact intraoperative tool for measurements of the middle ear conductive system mobility with a very good intraindividual repeatability. Neither a small change in the angle of the laser beam nor performing the measurements through posterior tympanotomy showed a significant influence on the results. Reflective tape was necessary to obtain good quality responses in LDV measurements.


Aligning the backroom with the boardroom at Blue Cross/Blue Shield.
A recent survey of Blue Cross/Blue Shield organizations reveals fundamental differences in the attitudes and objectives of top management and information executives. Both groups learned valuable lessons for improving I/S effectiveness.


DWI filtering using joint information for DTI and HARDI.
The filtering of the Diffusion Weighted Images (DWI) prior to the estimation of the diffusion tensor or other fiber Orientation Distribution Functions (ODF) has been proved to be of paramount importance in the recent literature. More precisely, it has been evidenced that the estimation of the diffusion tensor without a previous filtering stage induces errors which cannot be recovered by further regularization of the tensor field. A number of approaches have been intended to overcome this problem, most of them based on the restoration of each DWI gradient image separately. In this paper we propose a methodology to take advantage of the joint information in the DWI volumes, i.e., the sum of the information given by all DWI channels plus the correlations between them. This way, all the gradient images are filtered together exploiting the first and second order information they share. We adapt this methodology to two filters, namely the Linear Minimum Mean Squared Error (LMMSE) and the Unbiased Non-Local Means (UNLM). These new filters are tested over a wide variety of synthetic and real data showing the convenience of the new approach, especially for High Angular Resolution Diffusion Imaging (HARDI). Among the techniques presented, the joint LMMSE is proved a very attractive approach, since it shows an accuracy similar to UNLM (or even better in some situations) with a much lighter computational load.


Distinct Function of Mediator Subunits in Fungal Development, Stress Response, and Secondary Metabolism in Maize Pathogen Fusarium verticillioides.
Mediator is a nucleus-localized, multisubunit protein complex highly conserved across eukaryotes. It interacts with RNA polymerase II transcription machinery as well as various transcription factors to regulate gene expression. However, systematic characterization of the Mediator complex has not been performed in filamentous fungi. In our study, the goal was to investigate key biological functions of Mediator subunits in a mycotoxigenic plant pathogen Fusarium verticillioides. Although there is some level of divergence in the constituent subunits, the overall structure was conserved between Saccharomyces cerevisiae and F. verticillioides. We generated 11 Mediator subunit deletion mutants and characterized vegetative growth, conidia formation, environmental stress response, carbon and fatty acid use, virulence, and fumonisin B1 (FB1) biosynthesis. Each Mediator subunit deletion mutant showed deficiencies in at least three of the phenotypes tested, suggesting that each subunit has different principal functions in F. verticillioides development, metabolism, and virulence. The deletion of FvMed1 led to increased FB1 production, and we confirmed that FvMed1 is transported from the nucleus to the cytoplasm under fumonisin-producing conditions. Taken together, our study characterized various important functional roles for Mediator subunits in F. verticillioides and suggests that select subunits can perform unique cytoplasmic functions independent of the core Mediator in fungal nucleus.


Salivary cortisol and dehydroepiandrosterone as oral biomarkers to determine stress in patients with recurrent aphthous stomatitis.
Recurrent aphthous stomatitis (RAS) is one of the most common oral ulcerative diseases with a multifactorial etiology. Although psychological stress is an exacerbating factor, the role of salivary stress hormones, cortisol, and dehydroepiandrosterone (DHEA) in this oral disease has not been extensively reported. The study aimed to estimate and compare the salivary cortisol and DHEA levels in RAS patients and healthy control group with the aid of ELISA microplate reader. Sixty patients were enrolled in our study, which included 30 patients with clinically diagnosed RAS and 30 healthy controls. Two mL of unstimulated whole saliva was collected and salivary cortisol and DHEA levels were measured using ELISA kit, and the values were read by microplate ELISA reader and recorded in both groups. The mean salivary cortisol and DHEA levels were elevated in the RAS patients compared to the healthy controls and were statistically significant. Salivary cortisol and DHEA can serve as oral biomarkers to determine stress in patients with RAS. However, the present study necessitates further studies with larger sample size and an improved protocol to ascertain the actual role of these presumed oral biomarkers as well as anxiety and stress as triggers in the pathogenesis of RAS.


Justification of Sentencing Decisions: Development of a Ratio-Based Measure Tested on Child Neglect Cases.
Theoretically, people's justification of a sentencing decision involves a hybrid structure comprising retribution, incapacitation, general deterrence, and rehabilitation. In this study, a new ratio-type measure was developed to assess this structure and was tested to detect changes in the weighting of justification according to the content emphasized in a particular crime. Two child neglect scenarios were presented to participants, where they read either a severe-damage scenario (where a single mother's selfish neglect caused her son's death) or a moderate-damage scenario (where a single mother became apathetic due to economic deprivation and caused her child's debilitation). Participants then indicated the proportion of importance they placed on each justification in determining the defendant's punishment, with an overall proportion of 100%, along with responding to the sentence on an 11-point scale. This study involved a two-factor analysis of variance for justification ratios, a t-test for the sentence, and a multiple regression analysis with three demographic variables, the four justifications as independent variables, and the sentence as the dependent variable. The ratio of retribution to rehabilitation was reversed depending on the scenario: in the severe-damage scenario, retribution was weighted highest at 27.0% and rehabilitation was weighted at only 19.0%. By contrast, in the moderate-damage scenario, rehabilitation had the highest weighting of about 26.2%, while retribution was weighted at 21.5%. The sentence was more severe in the severe-damage scenario. Multiple regression analysis suggested that in the severe-damage scenario, most participants failed to deviate from choosing retribution by default and decided on heavier sentences, while some who considered rehabilitation and incapacitation opted for lighter sentences. The present measure succeeded in detecting changes in the weighting of justification, which can be difficult to detect with common Likert Scales. In addition, it was found that not only retribution but utilitarian justification was considered in the sentencing decisions of serious cases.


Patterns of Medicaid eligibility: a sample of 408 Medi-Cal eligibles in San Francisco, California.
Medicaid expenditures per recipient have increased substantially in the past decade, even after controlling for medical care price inflation. In response to this Medicaid expenditure growth, various policies to encourage Medicaid enrollment in cost-effective health maintenance organizations (HMOs) are being considered, including guaranteed Medicaid eligibility for Medicaid eligibles enrolled in HMOs. This paper addresses several important questions about Medicaid eligibility that are essential to an analysis of guaranteed eligibility--the length of eligibility, turnover rates, and reasons individuals lose their Medicaid eligibility. We selected a stratified random sample of 408 eligibility case files for individuals eligible for Medicaid in San Francisco County during December 1977. Six aid categories are represented in this study: (1) Cash Grant AFDC; (2) Medically Needy Families; (3) Medically Needy Aged; (4) Medically Needy Disabled; (5) Medically indigent Adults; and (6) Medically indigent Children. We found that the majority of individuals remain eligible for Medicaid for long, uninterrupted spells, ranging from a median of 15 months (Medically Indigent Adults) to 40 months (Medically Needy Aged). A much smaller subset of eligible persons had relatively short spells and higher turnover; some of that turnover was due to failure to comply with income reporting requirements. We used data on length of eligibility to estimate the cost impact of 6 months' guaranteed eligibility (for months during which individuals would otherwise not have been eligible for Medicaid benefits). We also estimated the potential benefits (savings of HMOs relative to average fee-for-service expenditures) and the benefits of guaranteed eligibility appear to be greater than the costs.


Readiness for transition to adult care in adolescents and young adults with Turner syndrome.
Objectives Turner syndrome (TS) is a complex and chronic medical condition that requires lifelong subspecialty care. Effective transition preparation is needed for successful transfer from pediatric to adult care in order to avoid lapses in medical care, explore health issues such as fertility, and prepare caregivers as adolescents take over responsibility for their own care. The objective of this study was to evaluate accuracy of knowledge of personal medical history and screening guidelines in adolescents and young adults (AYA) with TS. Methods This was a prospective cross-sectional study of 35 AYA with TS of ages 13-22 years recruited from a tertiary care center. AYA completed questionnaires on personal medical history, knowledge of screening guidelines for TS, and the Transition Readiness Assessment Questionnaire (TRAQ). Results Eighty percent of AYA with TS were 100% accurate in reporting their personal medical history. Only one-third of AYA with TS were accurate about knowing screening guidelines for individuals with TS. Accuracy about knowing screening guidelines was significantly associated with TRAQ sum scores (r = 0.45, p < 0.05). However, there was no association between knowledge of personal medical history and TRAQ sum scores. Conclusions Transition readiness skills, TS-specific knowledge, and accurate awareness of health-care recommendations are related, yet distinct, constructs. Understanding of one's personal medical history is not an adequate surrogate for transition readiness. Validated tools for general transition, like the TRAQ, can be used but need to be complemented by TS-specific assessments and content. Providers are encouraged to identify opportunities for clinical and educational interventions well in advance of starting transfer to adult care.


Stem cell therapy in bladder dysfunction: where are we? And where do we have to go?
To date, stem cell therapy for the bladder has been conducted mainly on an experimental basis in the areas of bladder dysfunction. The therapeutic efficacy of stem cells was originally thought to be derived from their ability to differentiate into various cell types. Studies about stem cell therapy for bladder dysfunction have been limited to an experimental basis and have been less focused than bladder regeneration. Bladder dysfunction was listed in MESH as "urinary bladder neck obstruction", "urinary bladder, overactive", and "urinary bladder, neurogenic". Using those keywords, several articles were searched and studied. The bladder dysfunction model includes bladder outlet obstruction, cryoinjured, diabetes, ischemia, and spinal cord injury. Adipose derived stem cells (ADSCs), bone marrow stem cells (BMSCs), and skeletal muscle derived stem cells (SkMSCs) are used for transplantation to treat bladder dysfunction. The main mechanisms of stem cells to reconstitute or restore bladder dysfunction are migration, differentiation, and paracrine effects. The aim of this study is to review the stem cell therapy for bladder dysfunction and to provide the status of stem cell therapy for bladder dysfunction.


[Imaging of the postsurgical spine].
Some early complications (hematoma, spondylodiscitis, pseudomeningocele) can occur with all types of surgery while late complications vary with the type of surgery. After discectomy, postsurgical changes (osseous and ligamentous defects, scar tissue, granulation tissue) should be distinguished from postsurgical complications or recurrent disease (recurrent disc herniation, arachnoiditis, spondylodiscitis). Following spinal decompression and fusion procedures, standard radiographs and CT can confirm the adequate position of the fusion devices, the presence of fusion, and the development of late osseous complications: pseudarthrosis, instability and recurrent stenosis.


[Integration-based co-expression network analysis to investigate tumor-associated modules across three cancer types].
In case/control gene expression data, differential expression (DE) represents changes in gene expression levels across various biological conditions, whereas differential co-expression (DC) represents an alteration of correlation coefficients between gene pairs. Both DC and DE genes have been studied extensively in human diseases. However, effective approaches for integrating DC-DE analyses are lacking. Here, we report a novel analytical framework named DC&DEmodule for integrating DC and DE analyses and combining information from multiple case/control expression datasets to identify disease-related gene co-expression modules. This includes activated modules (gaining co-expression and up-regulated in disease) and dysfunctional modules (losing co-expression and down-regulated in disease). By applying this framework to microarray data associated with liver, gastric and colon cancer, we identified two, five and two activated modules and five, five and one dysfunctional module(s), respectively. Compared with the other methods, pathway enrichment analysis demonstrated the superior sensitivity of our method in detecting both known cancer-related pathways and those not previously reported. Moreover, we identified 17, 69, and 11 module hub genes that were activated in three cancers, which included 53 known and three novel cancer prognostic markers. Random forest classifiers trained by the hub genes showed an average of 93% accuracy in differentiating tumor and adjacent normal samples in the TCGA and GEO database. Comparison of the three cancers provided new insights into common and tissue-specific cancer mechanisms. A series of evaluations demonstrated the framework is capable of integrating the rapidly accumulated expression data and facilitating the discovery of dysregulated processes.


Residential care centers for persons with intellectual disability in Israel. Trends in the number of nursing care patients during 1998-2007.
Nursing care has changed over time and the focus has differed according to the need or the culture involved. One of the first descriptions of nursing of people with intellectual disability (ID) is from the United States at the New York Hospital around 1808. Over the next 200 years, ID nursing developed into a subspecialty in both the United States and England with a curriculum and certification. This process has yet to take place in Israel, but it is a change we would like to see in the coming years. The purpose of this paper was to look at the trend in the number of nursing patients in residential care centers for people with ID in Israel. Data were extracted from the 1998-2007 national annual surveys of all residential care centers in Israel. Over this 10-year period, we found that the number of nursing patients was fairly constant, ranging from 23.9% of the total population in 1998 to 26.5% in 2007. Whereas the percent of nursing patients has remained steady, the burden of nursing has increased. Specifically, due to the aging of this population, residential care centers are now dealing with an increased quantity and complexity of medical problems. As a result, we have experienced a need to establish, on a regional basis, long-term nursing care facilities within our residential care centers.


[The effect of geomagnetic disturbances in capillary blood flow in ischemic heart disease patients].
A total of 80 patients with ischemic heart diseases (men-47, women-33) were followed up daily during 2-3 weeks. We studied capillary flow in the cuticle above the nail (eponichium) with TV-capillaroscope, allowed to conduct prolonged studies. We evaluated capillary indices for perivascular edema, erythrocytes aggregation, blood velocity. Microcirculations data were compared daily values of geomagnetic activity (A-index), three-hour-range indices (K) and atmospheric pressure. In the first day magnetic storms pathological changes of capillary flow were detected in 71.5% patients with acute myocardial infarction (men-73.7%, women-69.2%). We could see appearance of perivascular edema, red blood cell aggregation, delay and slowing down capillary flow. Similar changes were detected in patient with angina pectoris in 64.8% (men-73.3%, women-56.3%). Number patients with ischemic heart diseases reacted upon geomagnetic disturbances exceed more then 2.5 times quantity patients, who react upon change of atmospheric pressure.


Effect of particles on sheep lung hemodynamics parallels depletion and recovery of intravascular macrophages.
We previously showed in newborn lambs that the pulmonary hemodynamic responses to foreign particulate matter (liposomes; Monastral blue) developed in parallel with the maturation of the pulmonary intravascular macrophage system. We now report our use of the liposome-encapsulated heavy-metal-chelating agent dichloromethylene diphosphonate to deplete the intravascular macrophages of small lambs. Functionally and by quantitative histology, we depleted the vast majority of the intravascular macrophages (71% by Monastral blue particle retention, n = 22; 77% by histology; n = 2). Depletion success increased to > 90% as we optimized the liposome-depletion regime. Recovery of the lung hemodynamic response began within 3 days. By 2 wk, the functional responses had fully recovered (n = 8), and, according to quantitative histology, the macrophage population (n = 2) had recovered 65%. Macrophage depletion in lambs is relatively inexpensive and easy to achieve. It is a safe procedure and is followed by full recovery in approximately 2 wk, provided that an aseptic technique is used to prevent bacteremia.


iPSC-derived functional human neuromuscular junctions model the pathophysiology of neuromuscular diseases.
The control of voluntary skeletal muscle contraction relies on action potentials, which send signals from the motor neuron through the neuromuscular junction (NMJ). Although dysfunction of the NMJ causes various neuromuscular diseases, a reliable in vitro system for disease modeling is currently unavailable. Here, we present a potentially novel 2-step, self-organizing approach for generating in vitro human NMJs from human induced pluripotent stem cells. Our simple and robust approach results in a complex NMJ structure that includes functional connectivity, recapitulating in vivo synapse formation. We used these in vitro NMJs to model the pathological features of spinal muscular atrophy, revealing the developmental and functional defects of NMJ formation and NMJ-dependent muscular contraction. Our differentiation system is therefore useful for investigating and understanding the physiology and pathology of human NMJs.


Evolutionary cancer-favoring engineered vaccinia virus for metastatic hepatocellular carcinoma.
Engineered vaccinia virus-based therapy shows promising results in patients with advanced hepatocellular carcinoma, although a strategic virus design for the metastatic liver and the study of its efficacy in treating the cancer has not been well assessed. In this paper, we proposed a simple and strategic virus design for targeting metastatic hepatocellular carcinoma. We developed an evolutionary cancer-favoring engineered vaccinia virus (CVV, which is produced by repeated selective replication in cancerous tissues and then deleting viral thymidine kinase genes) and investigated its therapeutic effects on metastatic liver cancer. The expression of the cell surface marker, CD44, which is associated with cancer stem cells, seems to be correlated with the cells' metastatic characteristics; cellular migration, epithelial-mesenchymal transition (EMT) expression and liver tumorigenicity. The highly metastatic and tumorigenic Sk-Hep-1 cell line was selected and injected directly onto the liver tissue to develop a liver-to-colon metastasis model. In an animal study, the subjects were treated with sorafenib, CVV, or sorafenib with CVV. Metastatic regions were interestingly rare in the CVV-treated groups (i.e., CVV or sorafenib with CVV) whereas metastatic regions existed in the sorafenib-treated group. From results, we concluded that our simple strategy of developing a cancer-favoring virus can successfully eradicate metastatic liver cancer cells, provided that our CVV can be a promising therapeutic virus that targets metastatic liver cancer.


Evaluation of the effectiveness of treatment with prednisone and azathioprine of autoimmune hepatitis in children.
Autoimmune hepatitis is rarely diagnosed in children, but the course of the disease is often aggresive. Combination therapy with prednisone and azathioprine improves the prognosis of patients. To evaluate the effectiveness of combination therapy with prednisone and azathioprine of autoimmune hepatitis (AIH) in children. There was a retrospective analysis of the medical records of 15 patients with AIH, diagnosed before18 years of age, treated in the Provincial Infectious Diseases Hospital in Bydgoszcz in the years 2002 to 2013. We analysed the results of laboratory tests, ultrasound examination, endoscopy, and morphological liver pictures, as well as periods of exacerbation of inflammation and side effects of therapy. Biochemical remission of the disease was achieved on average after 36 days of treatment. Histopathological regression in the control liver biopsy was found in 7/15 patients and progression in 2/15 patients. In the study group 10/15 patients experienced exacerbation of the disease from 1 to 3 times during observation, with an increase of ALT activity to greater than 3 norm, and the remaining 5/15 patients had no increase of ALT activity. In total, 10 patients in the study group experienced 17 exacerbations. In 13/17 cases of exacerbations they were associated with a reduction in the dose of immunosuppressive drugs. There was no correlation between the biochemical exacerbation and changes in the histopathological image. Steroidside effects occurred in 14/15 patients. The treatment allows for biochemical remission of the disease and significantly improves the prognosis of most patients. However, significant side effects of treatment indicate the need for further exploration of effective and safe therapy, especially in the paediatric population.


The molecular and functional phenotype of glomerular podocytes reveals key features of contractile smooth muscle cells.
The glomerular podocyte is a highly specialized cell, with the ability to ultrafilter blood and support glomerular capillary pressures. However, little is known about either the genetic programs leading to this functionality or the final phenotype. We approached this question utilizing a human conditionally immortalized cell line, which differentiates from a proliferating epithelial phenotype to a differentiated form. We profiled gene expression during several time points during differentiation and grouped the regulated genes into major functional categories. A novel category of genes that was upregulated during differentiation was of smooth muscle-related molecules. We further examined the smooth muscle phenotype and showed that podocytes consistently express the differentiated smooth muscle markers smoothelin and calponin and the specific transcription factor myocardin, both in vitro and in vivo. The contractile contribution of the podocyte to the glomerular capillary is controversial. We demonstrated using two novel techniques that podocytes contract vigorously in vitro when differentiated and in real time were able to demonstrate that angiotensin II treatment decreases monolayer resistance, morphologically correlating with enhanced contractility. We conclude that the mature podocyte in vitro possesses functional apparatus of contractile smooth muscle cells, with potential implications for its in vivo ability to regulate glomerular dynamic and permeability characteristics.


Esthetic Restoration of Multiple Congenitally Missing Anterior Teeth with Oral Implants: A Clinical Case Report.
Having multiple congenitally missing anterior teeth heavily influences the patient's countenance and pronunciation. There are few reports on the esthetic restoration of such situations with oral implants. This clinical case history report presents a multidisciplinary approach to treat a young woman with multiple congenitally missing anterior teeth using implant-supported prostheses. The treatment steps and clinical implications are discussed.


CMTM6 knockdown prevents glioma progression by inactivating the mTOR pathway.
Gliomas in the adult brain are complicated and aggressive with a poor prognosis. Gene therapy is a recent alternative glioma treatment. We sought to explore the mechanism of chemokine-like factor (CKLF) MARVEL transmembrane domain-containing 6 (CMTM6) in glioma. The Cancer Genome Atlas database reports that CMTM6 is expressed in tumors and glioma tissue. CMTM6 expression in glioma tissues and cells was detected and its relationship with clinical pathology was analyzed. Short hairpin ribonucleic acid-CMTM6 lentivirus was transfected into U87 and U251 cells to evaluate malignant glioma cells. Using the biological website (https://string-db.org/cgi/input.pl?Sessionid) and reference retrieval, the pathway that interacted with CMTM6 and related to glioma was identified. The level of the mammalian target of rapamycin pathway-related proteins was detected. Functional rescue experiments were performed using the combination of mTOR activator MHY1485 and the knockdown CMTM6. The growth of xenograft tumors was observed and Ki67-positive expression was determined. CMTM6 upregulation in gliomas was associated with a poor prognosis. CMTM6 expression was notably higher in gliomas. After the knockdown of CMTM6, the proliferation, invasion, and migration of U87 and U251 cells were inhibited, and the apoptosis rate was increased. Knocking down CMTM6 inactivated the mTOR pathway. The activation of mTOR pathway reversed the inhibitory effects of CMTM6 knockdown on glioma cell behaviors. CMTM6 knockdown reduced tumor volume, body mass, and Ki67-positive expression. The knockdown of CMTM6 inhibited the activation of mTOR pathway and prevented the malignant episodes of glioma cells.