Transcriptional programs of early reproductive stages in Arabidopsis.
The life cycle of flowering plants alternates between a diploid sporophytic and a haploid gametophytic generation. After fertilization of each the egg and central cells by one male gamete, the development of both fertilization products occurs coordinated with the maternally derived seed coat and carpel tissues forming the fruit. The reproduction program is likely to involve the concerted activity of many genes. To identify genes with specific functions during reproduction, we have analyzed the expression profile of more than 22,000 genes present on the Arabidopsis ATH1 microarray during three stages of flower and fruit development. We found 1,886 genes regulated during reproductive development and 1,043 genes that were specifically expressed during reproduction. When compared to cells from an Arabidopsis suspension culture, S-phase genes were underrepresented and G2 and M-phase genes were strongly enriched in the set of specific genes, indicating that important functions during reproduction are exerted in the G2 and M phases of the cell cycle. Many potential signaling components, such as receptor-like protein kinases, phosphatases, and transcription factors, were present in both groups of genes. Members of the YABBY, MADS box, and Myb transcription factor families were significantly overrepresented in the group of specific genes, revealing an important role of these families during reproduction. Furthermore, we found a significant enrichment of predicted secreted proteins smaller than 15 kD that could function directly as signaling molecules or as precursors for peptide hormones. Our study provides a basis for targeted reverse-genetic approaches aimed to identify key genes of reproductive development in plants.


Management of ruptured hepatocellular adenoma.
Hepatocellular adenoma (HA) is an increasingly prevalent benign liver tumor that is strongly associated with use of oral contraceptive medication. The diagnosis is often made after abdominal imaging in female patients with sudden abdominal pain, with or without signs of hemorrhage. Especially larger adenomas are of potential hazard to patients, because of the increased likelihood of rupture or malignant degeneration. Standard treatment of larger adenomas has since long consisted in surgical resection, both for non-ruptured and for ruptured tumors. Although resection is still considered the gold standard, recent reports have advocated initial conservative management. Recently, newer and less invasive methods using selective transarterial embolization have been described that can successfully stop bleeding and even lead to tumor regression. This review addresses different treatment options and recent advances regarding this relatively new condition, focusing mainly on treatment of bleeding and ruptured tumors in an acute setting. A possible algorithm for optimal treatment is presented.


Neurogenesis, learning and associative strength.
Though the role of the hippocampus in processes of learning and memory is well established, the role of new neurons generated there is less understood. Training on some associative learning tasks increases the likelihood that new cells in the subgranular zone of the dentate gyrus will survive. In the rat, an effective training procedure is trace eyeblink conditioning, in which a conditioned stimulus (CS) is paired with an aversive stimulation to the eyelid (unconditioned stimulus; US), but the stimuli are separated by a temporal gap. Here, we manipulated the asymptote or rate of acquisition during trace conditioning, and examined survival of cells generated 1 week before training. Acquisition was disrupted by decreasing associative strength by insertion of unpredicted USs or slowed with latent inhibition. The number of cells was increased in animals that were trained with trace conditioning, irrespective of the decrease in associative strength or slowed acquisition. Disrupting acquisition with unsignaled USs still increased cell numbers, suggesting that the learning effect on cell survival is not dependent on reliable expression of the conditioned response. Further, animals in the latent inhibition conditions that learned but required more trials also retained more of the new cells than animals requiring fewer trials. The number of cells that survived after the effective training procedures was similar to the number of cells that were available for rescue at the beginning of training. Thus, learning can rescue the majority of cells expressed at the beginning of training, and does so most effectively when acquisition requires many trials.


Expression and purification of a neuropeptide nocistatin using two related plant viral vectors.
Both odontoglossum ringspot virus (ORSV) and tobacco mosaic virus (TMV) were investigated as expression viral vectors for the expression of a neuropeptide nocistatin. Chimeras of ORSV and TMV were constructed by fusion of 17 amino acids of mouse nocistatin (mNST) to the C-terminal of the coat protein (CP) gene via a Factor Xa cleavage linker to yield ORSV-mNST and TMV-mNST. Expression of the mNST peptide was demonstrated by immuno-transmission electron microscopy, western blot, mass spectrometry and radioimmunoassay. Serial passaging of the chimeric viruses revealed loss of mNST from TMV-mNST by the fifth passage. The mNST was maintained in ORSV-mNST throughout six passages. The mNST peptide could be effectively cleaved and purified from chimeric ORSV CP. To our knowledge, this is the first successful attempt in obtaining a complete peptide with no additional amino acid sequence after expression and purification through the use of either ORSV or TMV as vectors.


[The current status of organ transplantation: the role of xenotransplantation?].
In the last few years, transplantation was an area of intense research activity. However, there is a worldwide shortage of donor organs for clinical transplantations. Currently, interest in xenotransplantation research is growing not only because of the increased demand for organs but also because of advances in molecular biology techniques that make possible the genetic or immunological manipulations of the animal donor rather than the human recipient. The better definitions of the mechanisms responsible for xenograft rejection should facilitate appropriate therapeutic strategies for long xenograft survival.


[Outcome of non-pharmacologic treatment in a gestational diabetic woman with high insulin resistance HOMA-IR index and allergy to human insulin. Case report].
Gestational diabetes is a syndrome of significant pathophysiological and clinical heterogeneity. This type of diabetes mellitus can be treated with diet, exercise and insulin in cases of unsatisfactory results of nonpharmacologic treatment. It has been reported the case of a 28-year -old female with gestational diabetes treated with high doses of insulin (128 U/per day) on four injections regimens. During the therapy allergic type III reactions to human insulin preparations (Ultratard HM, Actrapid HM Humulin U, Humulin R, Humalog) has been occurred at the injection site. The insulin was omitted. We applied diet modification and 15-30 minutes walking before meals till the afternoon with god metabolic control. High insulin resistance index HOMA-IR, type 2 diabetes history in both parents god metabolic control of nonpharmacologic treatment, and impaired glucose tolerance after post-partum may suggest, the early stage of diabetes type 2 in presented case.


A force-dependent switch reverses type IV pilus retraction.
Type IV pilus dynamics is important for virulence, motility, and DNA transfer in a wide variety of prokaryotes. The type IV pilus system constitutes a very robust and powerful molecular machine that transports pilus polymers as well as DNA through the bacterial cell envelope. In Neisseria gonorrhoeae, pilus retraction is a highly irreversible process that depends on PilT, an AAA ATPase family member. However, when levels of PilT are reduced, the application of high external forces (F = 110 +/- 10 pN) induces processive pilus elongation. At forces of >50 pN, single pili elongate at a rate of v = 350 +/- 50 nm/s. For forces of <50 pN, elongation velocity depends strongly on force and relaxation causes immediate retraction. Both pilus retraction and force-induced elongation can be modeled by chemical kinetics with same step length for the rate-limiting translocation step. The model implies that a force-dependent molecular switch can induce pilus elongation by reversing the retraction mechanism.


Psychotherapy and schizophrenia: an analysis of requirements of individual psychotherapy with persons who experience manifestly barren or empty selves.
Emerging views of schizophrenia emphasize that part of recovery involves persons reclaiming a sense of their own identity, agency and personal worth. While this intuitively seems a matter where psychotherapy might be uniquely useful, it raises the issue of how this should be facilitated particularly among persons who experience themselves as unable to engage in dialogue with others. In this article, we explore how integrative psychotherapy might address issues of self-narrative and recovery from schizophrenia among persons experiencing, in particular profound levels of emptiness or barrenness. Illustrated with two case examples, we explore barriers posed to psychotherapy by clients' minimalist self-presentations and describe three stages for integrative interventions that can revitalize dialogues within the client and between the client and others, ultimately enabling the reconstruction of a client's personal narrative within which a life plan might be articulated, guiding future action.


Neuronal ceroid lipofuscinoses in Scandinavia. Epidemiology and clinical pictures.
The epidemiology of neuronal ceroid lipofuscinoses (NCL) in Scandinavia was studied. For juvenile NCL 40 Swedish living patients were identified. The corresponding number for Finland was 61, for Norway 28, for Denmark 16 and for Iceland three. The prevalence of juvenile NCL was thus 4.6, 12.2, 6.5, 3.1 and 11 per million inhabitants in Sweden, Finland, Norway, Denmark, and Iceland, respectively. For calculating incidence the years 1976-85 were used. The incidence was 2.2 per 100,000 live births in Sweden, 4.8 in Finland, 3.7 in Norway, 2.0 in Denmark, and 7.0 in Iceland. Late infantile NCL was found in five Swedish children, including one variant form, CLN5. This gives a prevalence of about 0.6 per million. In Finland 13 cases gave a prevalence of 2.6 per million with the variant form in 80% of cases. In Norway, three children corresponded to a prevalence of 0.7 per million and one case in Iceland to 3.8 per million. No Danish cases were reported. As for infantile NCL, sixteen Swedish cases have been diagnosed during the 27-year period 1968-95, six are presently alive. This gives an estimated prevalence of 0.7 per million and an incidence of 0.6 per 100,000. The prevalence and incidence of infantile NCL in Finland were 5.4 per million and 5 per 100,000, respectively. The prevalence in Norway was 0.2 per million inhabitants. The variability of onset, clinical course and symptoms in the Swedish cases of juvenile and infantile NCL were analysed.


[Hypophyseal-Leydig function in the diabetic].
Experimental diabetes in animals induces marked alterations of gonadal androgenic functions: reduction in testis weight, morphological alterations of Leydig cells, decrease of plasma testosterone levels and reduction of the ability of the Leydig cells to secrete testosterone in vitro. hCG treatment restores the testicular endocrine function; in addition several morphological and functional changes are observed in the hypothalamic-hypophyseal-gonadal axis which are probably responsible for the testicular lesions found in untreated experimental diabetes mellitus. In diabetic men, the hypothalamic-hypophyseal-gonadal axis seems to be normal (with exception of individual cases); Mean plasma levels of testosterone, LH, FSH and the responses of the gonadal axis to hCG and LHRH are normal.


Recognizing the talent within: preparing clinicians for a role in professional development.
Ongoing professional development is recognized as crucial to the psychiatric and mental health nursing profession; however, implementing effective professional development programs has proved problematic. The Centre for Psychiatric Nursing Research and Practice in Victoria, Australia, developed a clinician-trainer course to overcome some of the identified problems. An evaluation was conducted to measure participant satisfaction with the program. The initial evaluation suggests the course delivery and content were considered useful and relevant to participants, although areas for improvement were identified. The model developed is potentially effective but a longitudinal evaluation is required to determine the impact of the course on the implementation of professional development in the clinical domain.


A new method to make vascular and bronchial casts of voluminous organs.
Vascular and bronchial endocasts represent a useful instrument to study the ramification pattern of these structures. Casts have been made from different materials, such as waxes in ancient times and, more recently, silicon-like compounds or resins (see e.g. Mercox) to study the finest details. These techniques are valuable for small specimens, whereas they are inadequate for very large organs, where technical difficulties require the development of specific instrumentation. In this study we present a new simple injection technique, based on expanded polyurethane, which allows preparing vascular and bronchial trees for macroscopic and microscopic studies. The new injection technique is very easy to carry out, since the propulsion is provided by compressed air, and it does not require special instrumentation. To this aim, endocasts of the entire tracheal-bronchial tree and casts of vascular kidney from different animals were prepared. The specimens have a very low weight, show the finest ramifications, and are very stable and resistant to mechanical stress. To examine microscopically the details of the casts, specimens from the kidney cast were also analyzed by scanning electron microscopy, revealing good preservation of microcirculatory structures, functional sphincters and endothelial cell impressions. Therefore, the technique may be useful for macroscopic studies of large specimens, retaining sufficiently fine details.


A new classification and regression tree algorithm: Improved diagnostic sensitivity for HCC ≤ 3.0 cm using gadoxetate disodium-enhanced MRI.
To develop and validate an effective algorithm, based on classification and regression tree (CART) analysis and LI-RADS features, for diagnosing HCC ≤ 3.0 cm with gadoxetate disodium‑enhanced MRI (Gd-EOB-MRI). We retrospectively included 299 and 90 high-risk patients with hepatic lesions ≤ 3.0 cm that underwent Gd-EOB-MRI from January 2018 to February 2021 in institution 1 (development cohort) and institution 2 (validation cohort), respectively. Through binary and multivariate regression analyses of LI-RADS features in the development cohort, we developed an algorithm using CART analysis, which comprised the targeted appearance and independently significant imaging features. On per-lesion basis, we compared the diagnostic performances of our algorithm, two previously reported CART algorithms, and LI-RADS LR-5 in development and validation cohorts. Our CART algorithm, presenting as a decision tree, included targetoid appearance, HBP hypointensity, nonrim arterial phase hyperenhancement (APHE), and transitional phase hypointensity plus mild-moderate T2 hyperintensity. For definite HCC diagnosis, the overall sensitivity of our algorithm (development cohort 93.2%, validation cohort 92.5%; P < 0.006) was significantly higher than those of Jiang's algorithm modified LR-5 (defined as targetoid appearance, nonperipheral washout, restricted diffusion, and nonrim APHE) and LI-RADS LR-5, with the comparable specificity (development cohort: 84.3%, validation cohort: 86.7%; P ≥ 0.006). Our algorithm, providing the highest balanced accuracy (development cohort: 91.2%, validation cohort: 91.6%), outperformed other criteria for identifying HCCs from non-HCC lesions. In high-risk patients, our CART algorithm developed with LI-RADS features showed promise for the early diagnosis of HCC ≤ 3.0 cm with Gd-EOB-MRI.


Influence of agents and mechanisms of injury on anatomical burn locations in children <5 years old with a scald.
To demonstrate how the mechanism and agent of injury can influence the anatomical location of a scald. Prospective multicentre cross-sectional study. 20 hospital sites across England and Wales including emergency departments, minor injury units and regional burns units. Children aged 5 years and younger who attended hospital with a scald. Primary outcome: a descriptive analysis of the mechanism, agent and anatomical location of accidental scalds. Secondary outcome: a comparison of these factors between children with and without child protection (CP) referral. Of 1041 cases of accidental scalds, the most common narrative leading to this injury was a cup or mug of hot beverage being pulled down and scalding the head or trunk (132/1041; 32.9% of cases). Accidental scalds in baths/showers were rare (1.4% of cases). Accidental immersion injuries were mainly distributed on hands and feet (76.7%). There were differences in the presentation between children with accidental scalds and the 103 who were referred for CP assessment; children with scalds caused by hot water in baths/showers were more likely to get referred for CP assessment (p<0.0001), as were those with symmetrically distributed (p<0.0001) and unwitnessed (p=0.007) scalds. An understanding of the distributions of scalds and its relationship to different mechanisms of injury and causative agents will help clinicians assess scalds in young children, particularly those new to the emergency department who may be unfamiliar with expected scald patterns or with the importance of using appropriate terminology when describing scalds.


Determination of renal handling of marbofloxacin in Lohi sheep (Ovis aries) following a single intravenous administration.
The objective of present study was to investigate renal clearance, urinary excretion and underlying excretory mechanism of marbofloxacin in Lohi sheep. For this purpose, marbofloxacin was administered intravenously (IV) as single bolus dose (2.5 mg/kg body weight) to eight healthy sheep of Lohi breed. After start of experiment, blood and urine samples were drawn at predetermined time intervals and marbofloxacin concentrations in the samples were measured by reverse phase high performance liquid chromatography (RP-HPLC) using UV/Vis detector. The mean ± SD values of creatinine in plasma and urine were 15.37 ± 0.65 µg/ml and 246.7 ± 48.05 µg/ml, respectively. Glomerular filtration rate was 1.29 ± 0.22 ml/min/kg whereas urinary flow rate was observed to be 0.084 ± 0.016 ml/min/kg. The renal clearance of marbofloxacin in Lohi sheep was 9.45 ± 2.12 ml/min/kg. Cumulative percentage dose excreted was seen to be maximum at 24 h post drug administration. It was concluded that renal handling of marbofloxacin in Lohi sheep involved both glomerular filtration and active tubular secretion.


Thiacalix[4]arene-Protected Titanium-Oxo Clusters: Influence of Ligand Conformation and Ti-S Coordination on the Visible-Light Photocatalytic Hydrogen Production.
p-tert-Butylthiacalix[4]arene (H4TC4A)-decorated tetranuclear (Ti4) and hexanuclear (Ti6) polyoxo-titanium clusters (PTCs) were synthesized in isopropyl alcohol by a low-temperature solvothermal method. The structures were determined by single-crystal X-ray diffraction, in which the ligands adopt 1,2-alternative and cone-shaped conformations, respectively. Both PTCs show UV-vis absorptions up to 600 nm with band gaps at 2.19 eV (Ti4) and 2.24 eV (Ti6), respectively. Visible-light photocatalytic H2 production for Ti4 was measured to be 73.56 μmol/(g h), which is almost 5 times of that of Ti6 (15.16 μmol/(g h)). Results of density functional theory (DFT) calculations suggested that the different Ti-S coordination modes originating from the conformational disparity of the ligands are primarily responsible for the observed different photocatalytic activities. Not only does this work provides a better understanding of the structure-property relationships in using titanium-oxo clusters for photocatalytic H2 production but it also offers a means of tuning the band gap of the catalysts by varying the conformations of the ligands.


Surface Functional Groups Affect Iron (Hydr)oxide Heterogeneous Nucleation: Implications for Membrane Scaling.
Because of its favorable thermodynamics and fast kinetics, heterogeneous solid nucleation on membranes triggers early-stage mineral scaling. Iron (hydr)oxide, a typical membrane scale, initially forms as nanoparticles that interact with surface functional groups on membranes, but these nanoscale phenomena are difficult to observe in real time. In this study, we utilized in situ grazing incidence small angle X-ray scattering and ex situ atomic force microscopy to examine the heterogeneous nucleation of iron (hydr)oxide on surface functional groups commonly used in membranes, including hydroxyl (OH), carboxyl (COOH), and fluoro (F) groups. We found that, compared to nucleation on hydrophilic OH- and COOH-surfaces, the high hydrophobicity of an F-modified surface significantly reduced the extents of both heterogeneously and homogeneously formed iron (hydr)oxide nucleation. Moreover, on the OH-surface, the high functional group density of 0.76 nmol/cm2 caused faster heterogeneous nucleation than that on a COOH-surface, with a density of 0.28 ± 0.04 nmol/cm2. The F-surface also had the highest heterogeneous nucleation energy barrier (26 ± 0.6 kJ/mol), followed by COOH- (23 ± 0.8 kJ/mol) and OH- (20 ± 0.9 kJ/mol) surfaces. The kinetic and thermodynamic information provided here will help us better predict the rates and extents of early-stage scaling of iron (hydr)oxide nanoparticles in membrane processes.


Phonological and semantic priming in American Sign Language: N300 and N400 effects.
This study investigated the electrophysiological signatures of phonological and semantic priming in American Sign Language (ASL). Deaf signers made semantic relatedness judgments to pairs of ASL signs separated by a 1300 ms prime-target SOA. Phonologically related sign pairs shared two of three phonological parameters (handshape, location, and movement). Target signs preceded by phonologically related and semantically related prime signs elicited smaller negativities within the N300 and N400 windows than those preceded by unrelated primes. N300 effects, typically reported in studies of picture processing, are interpreted to reflect the mapping from the visual features of the signs to more abstract linguistic representations. N400 effects, consistent with rhyme priming effects in the spoken language literature, are taken to index lexico-semantic processes that appear to be largely modality independent. Together, these results highlight both the unique visual-manual nature of sign languages and the linguistic processing characteristics they share with spoken languages.


[Laparoscopy in the diagnosis and treatment of pathologic lesions of the genitourinary tract].
The objective of this article is retrospective analysis of laparoscopic surgery that were performed from January 2002 to December 2001 in I Ward of Gynaecology and Obstetrics of Gynaecology and Obstetrics Hospital in Warsaw. 464 laparoscopies that were performed from January 2000 till December 2002 were analysed. Evaluation was made on the basis of: indications for surgery, kind of surgery procedure that was performed, blood loss during surgery, complications and hospitalisation period. The most common indication (39.86%) was non-malignant tumors of cases. Another pathologies of cases: ectopic pregnancy, endometriosis and infertility were respectively 11.21%, 3.02% and 10.34% cases diagnosed before surgery. Many procedures that have been done recently by laparotomy are now performed by laparoscopy, that is: enucleation of a cyst of adnexa, removal of an ectopic pregnancy, hysterectomy. The blood loss during surgery was evaluated on the basis of change of haemoglobin concentration in serum before and after surgery. The average blood loss was 1.2 g%. There were 39 cases of conversion of laparoscopy to laparotomy. The most common reason of conversion (16 cases out of 39) was insufficient hemostasis in the operative area or bleeding in the wound after trocar. We had noted the small amount of infections (4.5%). The average hospitalisation period after laparoscopy was 2.62 days. Laparoscopic procedures can be widely used in gynaecology, have the small number of complications, short hospitalisation period and allow to avoid the big postoperative wound of abdominal segments.


Alternative to the wavelength interpretation of the auditory kappa effect.
We argue that the simple wavelength interpretation of the auditory kappa effect proposed by Yoblick and Salvendy in 1970 is inadequate since only the frequency of an incoming soundwave is preserved at the tympanic membrane. Alternative explanations are proposed in terms of psychological variables. The kappa effect with tonal intervals is explained using an imputed velocity model in which frequency differences are equated to phenomenological "distances." The continuous tone effect is explained in terms of previously observed correlations between frequency and the volume or " bigness " of a tone and between size and perceived duration.


A Comparison of Efficacy of Segmental Epidural Block versus Spinal Anaesthesia for Percutaneous Nephrolithotomy.
Percutaneous nephrolithotomy (PCNL) is done under general anaesthesia in most of the centres. Associated complications and cost are higher for general anaesthesia than for regional anaesthesia. Present study is designed to compare the efficacy of epidural block versus spinal anaesthesia with regards to intraoperative mean arterial pressure, heart rate, postoperative pain intensity, analgesic requirement, Postoperative complications and patient satisfaction in patients undergoing PCNL. After taking Ethical Committee clearance, patients were randomly allocated into 2 groups using table of randomization (n= 40 each) Group E- Epidural block, Group S- Spinal block. Various parameters like intraoperative mean arterial pressure, heart rate, postoperative pain intensity, analgesic requirement, postoperative complications and patient satisfaction were studied in these groups. Quantitative data was analysed using unpaired t-test and qualitative data was analysed using chi-square test. Twenty four times in Epidural as compared to fifteen times in spinal anaesthesia two or more attempts required. Mean time (min) required to achieve the block of anaesthesia in group E and group S was 15.45±2.8 and 8.52±2.62 min respectively. Mean arterial pressure (MAP) at 5 min, 10 min and 15 min were significantly lower in spinal group as compared to epidural group. After 30 minutes, differences were not significant but still MAP was lower in spinal group. After 30 minutes difference in heart rate between two groups was statistically significant and higher rate recorded in spinal group till the end of 3 hours. Postoperative VAS score was significantly higher in spinal group and 4 hours onwards difference was highly significant. Postoperative Nausea Vomiting (PONV) Score was significantly higher in spinal group as compared to epidural group. For PCNL, segmental epidural block is better than spinal anaesthesia in terms of haemodynamic stability, postoperative analgesia, patient satisfaction and reduced incidence of PONV. Epidural anaesthesia is difficult to execute and takes longer time to act as compared to spinal block which limits its use.


Evidence against gene expression after meiosis in the male mouse.
Isozyme patterns in homogenates from various testicular cell types from mice were examined in an effort to ascertain whether the haploid genome is expressed during spermiogenesis. Male mice heterozygous for electrophoretic variants of several glycolytic enzymes were analyzed by starch gel electrophoresis. The enzymes examined were isocitrate dehydrogenase, glucose-6-phosphate dehydrogenase, and glucosephosphate isomerase. The isozyme patterns produced by these dimeric enzymes reflect the relative activity of genes in each cell type. These patterns reveal the presence or absence of the transcription of specific genes during spermiogenesis. We found that the genes encoding these enzymes continue to increase during spermiogenesis. Synthesis of these enzymes most likely continues in spermatids, but this synthesis must depend upon premeiotically produced mRNA. These data provide biochemical evidence for the hypothesis that the phenotype of the haploid mammalian gamete depends upon the preceding diploid genome and that a mechanism must exist for the long term post-transcriptional regulation of gene expression during spermiogenesis.


Internalization of Muscle-Specific Kinase Is Increased by Agrin and Independent of Kinase-Activity, Lrp4 and Dynamin.
Muscle-specific kinase (MuSK) is a receptor tyrosine kinase absolutely required for neuromuscular junction formation. MuSK is activated by binding of motor neuron-derived Agrin to low-density lipoprotein receptor related protein 4 (Lrp4), which forms a complex with MuSK. MuSK activation and downstream signaling are critical events during the development of the neuromuscular junction. Receptor tyrosine kinases are commonly internalized upon ligand binding and crosstalk between endocytosis and signaling has been implicated. To extend our knowledge about endocytosis of synaptic proteins and its role during postsynaptic differentiation at the neuromuscular junction, we studied the stability and internalization of Lrp4, MuSK and acetylcholine receptors (AChRs) in response to Agrin. We provide evidence that MuSK but not Lrp4 internalization is increased by Agrin stimulation. MuSK kinase-activity is not sufficient to induce MuSK internalization and the absence of Lrp4 has no effect on MuSK endocytosis. Moreover, MuSK internalization and signaling are unaffected by the inhibition of Dynamin suggesting that MuSK endocytosis uses a non-conventional pathway and is not required for MuSK-dependent downstream signaling.


[Construction and function of a high-efficient complex microbial system to degrade cellulose and lindane in compost].
A complex microbial system capable of degrading cellulose and lindane with high efficiency was isolated from four compost heaps. It was selected and domesticated through two methods and by combination of different microbial communities. The results show that the complex microbial system can decompose filter paper, absorbent cotton, rice straw powder and sawdust effectively, especially has high degrading activity for the materials with higher native cellulose such as filter paper and absorbent cotton. As for both of them, the CMC saccharification activity is more than 40U and the degradation efficiency is more than 95% on the 5th day of inoculation. The complex microbial system can also keep a higher degrading capability in a wider range of pH. Filter paper and lindane can be degraded effectively by the complex microbial system during pH 7.0 - 9.0, and the degradation rates are more than 90 % and 45% respectively. Under pH 6.0 - 9.0, there is a good consistency between the degradation of Lindane and the decomposition of filter paper.


Specific unresponsiveness to skin allografts in anti-lymphocyte serum-treated, marrow-injected mice: participation of donor marrow-derived suppressor T cells.
Sequential changes of cell-mediated immune reactivities were examined in anti-lymphocyte serum-(ALS) treated, C3H/He (C3H; H-2k) bone marrow-injected (C57BL/6 X A)F1 (B6AF1; H-2b/k.d) mice bearing enhanced C3H skin grafts. Spleen cells of these mice exhibited marked suppression of the proliferative response to phytohemagglutinin and concanavalin A. When the spleen cells were assayed for the direct lymphocyte-mediated cytotoxicity against H-2k targets, their lytic activity remained low until the time of graft rejection, in contrast to the increasingly high cytotoxic activity exhibited by spleen cells of control B6AF1 mice given only ALS and C3H skin grafts. When spleen cells of marrow-injected B6AF1 mice were cultured with mitomycin-C treated C3H spleen cells, the proliferative response was significantly suppressed the throughout the course, despite the early appearance of high "secondary-type" cytotoxic activity. Co-culture experiments demonstrated the presence of C3H antigen-specific suppressor cells in the ALS-treated, marrow-injected mice bearing intact allografts. Treatment of spleen cells with anti-H-2, anti-Thy 1 and anti-I-J sera and C revealed that the suppressor cells present late in the marrow-injected mice were T cells of donor C3H bone marrow cell origin.


Comprehensive analysis of histone methylation modification regulators for predicting prognosis and drug sensitivity in lung adenocarcinoma.
Histone methylation is an epigenetic modification regulated by histone methyltransferases, histone demethylases, and histone methylation reader proteins that play important roles in the pathogenic mechanism of cancers. However, the prognostic value of histone methylation in lung adenocarcinoma (LUAD) remains unknown. Here, we found that LUAD cases could be divided into 2 subtypes by the 144 histone methylation modification regulators (HMMRs), with a significant difference in OS time. Ninety-five of the HMMRs were identified as differentially expressed genes (DEGs) between normal and tumor samples, and 13 of them were further discovered to be survival-related genes (SRGs). By applying the least absolute shrinkage and selector operator (LASSO) Cox regression, we constructed an 8-gene-based risk signature according to the TCGA (training) cohort, and the risk score calculated by the signature was proven to be an independent factor in both the training and validation cohorts. We then discovered that the immune functions were generally impaired in the high-risk groups defined by the HMMR signature (especially for the DCs and immune check-point pathway). Functional analyses showed that the DEGs between the low- and high-risk groups were related to the cell cycle. The drug sensitivity analysis indicated that our risk model could predict the sensitivity of commonly used drugs. Moreover, according to the DEGs between the low- and high-risk groups, we discovered several new compounds that showed potential therapeutic value for high-risk LUAD patients. In conclusion, our study demonstrated that HMMRs were promising predictors for the prognoses and drug therapeutic effects for LUAD patients.


Effectiveness of Community Health Worker-Led Interventions in Enhancing Colorectal Cancer Screening Uptake in Racial and Ethnic Minority Populations: A Systematic Review and Meta-analysis.
The colorectal cancer (CRC) screening uptake rate is substantially lower in ethnic minority populations than in the general population. Racial and ethnic minority individuals experience more barriers in obtaining a screening test for CRC when compared with the non-Hispanic White population. To examine the effectiveness of community health worker-led interventions in improving the CRC screening uptake rate in racial and ethnic minority populations. Five databases, EMBASE, CINAHL, MEDLINE, Scopus, and PubMed, were systematically searched, and reference lists of the identified articles were manually searched for relevant articles in May 2022. Only randomized controlled trials were included. A total of 10 randomized controlled trials conducted in the United States were included in this review. The findings of the meta-analysis showed that CRC screening uptake was enhanced in participants receiving community health worker-led interventions compared with those receiving no intervention (odds ratio, 2.25; 95% confidence interval, 1.48-3.44; P < .001). The subgroup analysis by diverse racial and ethnic groups and number of components (single vs multiple) of the community health worker-led interventions showed that multicomponent interventions were more effective in increasing the CRC uptake rate among all racial and ethnic groups regardless of their background. Multicomponent community health worker-led interventions can improve CRC screening uptake in racial and ethnic minority populations. The findings of the present review show that multicomponent community health worker-led interventions are shown to be effective to improve the CRC screening uptake targeting other racial and ethnic minority groups in other countries.


Deep Learning Reconstruction to Improve the Quality of MR Imaging: Evaluating the Best Sequence for T-category Assessment in Non-small Cell Lung Cancer Patients.
Deep learning reconstruction (DLR) has been recommended as useful for improving image quality. Moreover, compressed sensing (CS) or DLR has been proposed as useful for improving temporal resolution and image quality on MR sequences in different body fields. However, there have been no reports regarding the utility of DLR for image quality and T-factor assessment improvements on T2-weighted imaging (T2WI), short inversion time (TI) inversion recovery (STIR) imaging, and unenhanced- and contrast-enhanced (CE) 3D fast spoiled gradient echo (GRE) imaging with and without CS in comparison with thin-section multidetector-row CT (MDCT) for non-small cell lung cancer (NSCLC) patients. The purpose of this study was to determine the utility of DLR for improving image quality and the appropriate sequence for T-category assessment for NSCLC patients. As subjects for this study, 213 pathologically diagnosed NSCLC patients who underwent thin-section MDCT and MR imaging as well as T-factor diagnosis were retrospectively enrolled. SNR of each tumor was calculated and compared by paired t-test for each sequence with and without DLR. T-factor for each patient was assessed with thin-section MDCT and all MR sequences, and the accuracy for T-factor diagnosis was compared among all sequences and thin-section CT by means of McNemar's test. SNRs of T2WI, STIR imaging, unenhanced thin-section Quick 3D imaging, and CE-thin-section Quick 3D imaging with DLR were significantly higher than SNRs of those without DLR (P < 0.05). Diagnostic accuracy of STIR imaging and CE-thick- or thin-section Quick 3D imaging was significantly higher than that of thin-section CT, T2WI, and unenhanced thick- or thin-section Quick 3D imaging (P < 0.05). DLR is thus considered useful for image quality improvement on MR imaging. STIR imaging and CE-Quick 3D imaging with or without CS were validated as appropriate MR sequences for T-factor evaluation in NSCLC patients.


Relative contribution of IL-1α, IL-1β and TNF to the host response to Mycobacterium tuberculosis and attenuated M. bovis BCG.
TNF and IL-1 are major mediators involved in severe inflammatory diseases against which therapeutic neutralizing antibodies are developed. However, both TNF and IL-1 receptor pathways are essential for the control of Mycobacterium tuberculosis infection, and it is critical to assess the respective role of IL-1α, IL-1β, and TNF. Using gene-targeted mice we show that absence of both IL-1α and IL-1β recapitulates the uncontrolled M. tuberculosis infection with increased bacterial burden, exacerbated lung inflammation, high IFNγ, reduced IL-23 p19 and rapid death seen in IL-1R1-deficient mice. However, presence of either IL-1α or IL-1β in single-deficient mice is sufficient to control acute M. tuberculosis infection, with restrained bacterial burden and lung pathology, in conditions where TNF deficient mice succumbed within 4 weeks with overwhelming infection. Systemic infection by attenuated M. bovis BCG was controlled in the absence of functional IL-1 pathway, but not in the absence of TNF. Therefore, although both IL-1α and IL-1β are required for a full host response to virulent M. tuberculosis, the presence of either IL-1α or IL-1β allows some control of acute M. tuberculosis infection, and IL-1 pathway is dispensable for controlling M. bovis BCG acute infection. This is in sharp contrast with TNF, which is essential for host response to both attenuated and virulent mycobacteria and may have implications for anti-inflammatory therapy with IL-1β neutralizing antibodies.


Secreted Frizzled-related protein 4 (sFRP4) chemo-sensitizes cancer stem cells derived from human breast, prostate, and ovary tumor cell lines.
This study investigated molecular signals essential to sustain cancer stem cells (CSCs) and assessed their activity in the presence of secreted frizzled-related protein 4 (sFRP4) alone or in combination with chemotherapeutic drugs. SFRP4 is a known Wnt antagonist, and is also pro-apoptotic and anti-angiogenic. Additionally, sFRP4 has been demonstrated to confer chemo-sensitization and improve chemotherapeutic efficacy. CSCs were isolated from breast, prostate, and ovary tumor cell lines, and characterized using tumor-specific markers such as CD44+/CD24-/CD133+. The post-transcription data from CSCs that have undergone combinatorial treatment with sFRP4 and chemotherapeutic drugs suggest downregulation of stemness genes and upregulation of pro-apoptotic markers. The post-translational modification of CSCs demonstrated a chemo-sensitization effect of sFRP4 when used in combination with tumor-specific drugs. SFRP4 in combination with doxorubicin/cisplatin reduced the proliferative capacity of the CSC population in vitro. Wnt/β-catenin signaling is important for proliferation and self-renewal of CSCs in association with human tumorigenesis. The silencing of this signaling pathway by the application of sFRP4 suggests potential for improved in vivo chemo-responses.


Development of the Systems Thinking Scale for Adolescent Behavior Change.
This report describes the development and psychometric testing of the Systems Thinking Scale for Adolescent Behavior Change (STS-AB). Following item development, initial assessments of understandability and stability of the STS-AB were conducted in a sample of nine adolescents enrolled in a weight management program. Exploratory factor analysis of the 16-item STS-AB and internal consistency assessments were then done with 359 adolescents enrolled in a weight management program. Test-retest reliability of the STS-AB was .71, p = .03; internal consistency reliability was .87. Factor analysis of the 16-item STS-AB indicated a one-factor solution with good factor loadings, ranging from .40 to .67. Evidence of construct validity was supported by significant correlations with established measures of variables associated with health behavior change. We provide beginning evidence of the reliability and validity of the STS-AB to measure systems thinking for health behavior change in young adolescents.


Cellulase EGZ of Erwinia chrysanthemi: structural organization and importance of His98 and Glu133 residues for catalysis.
Biochemical, genetic and primary sequence analyses of the Erwinia chrysanthemi endoglucanase EGZ allowed us to identify two functional domains and to locate their boundaries. The catalytic domain extends from residue 1 to 288, while a domain required for EGZ to bind to microcrystalline cellulose lies from residues 324 to 385. Each domain was found capable of functioning in the absence of the other. A region rich in Pro, Thr, and Ser residues links both domains and appeared to be susceptible to proteolytic attack. Based upon predictions derived from a method developed to compare sequences sharing a low level of similarity, e.g. hydrophobic cluster analysis (HCA), we analysed the importance of either residue His98 or Glu133 in EGZ catalytic activity. Two EGZ-derived proteins were engineered in which either His98 or Glu133 amino acid was converted to an Ala residue. Characterization of the purified proteins showed that no enzymatic activity could be detected, by using carboxymethylcellulose (CMC) or paranitrophenyl-cellobioside (pNPC) as substrates, while both mutated proteins retained the capacity to bind to microcrystalline cellulose. These studies, which to date constitute the first experimental testing of HCA-derived predictions, allowed us to identify two particular amino acids involved in cellulolytic activity. By taking into account data from chemical modification studies of other cellulases, we speculate that the His98 residue is involved in the folding of the catalytic domain while the Glu133 residue intervenes directly in the beta, 1-4 glycosidic bond cleavage.


Stimulation of adrenergic development in neural crest cultures by a reconstituted basement membrane-like matrix is inhibited by agents that elevate cAMP.
Previous work (Maxwell and Forbes: Development 101:767-776, 1987) has shown that an overlay of reconstituted basement membrane-like (RBM) gel dramatically increased the number of catecholamine-positive (CA+) cells which differentiated in neural crest cultures. We report here that this increase was inhibited when cultures were grown for 7 days in the presence of agents that elevate cAMP, such as 8-bromo-cAMP and 3-isobutyl-1-methylxanthine. The action of 8-bromo-cAMP was dose dependent with a half-maximal effect at about 50 microM. The development of CA+ cells was dramatically reduced when 8-bromo-cAMP was present from days 0-4 in vitro, but was relatively unaffected if 8-bromo-cAMP was present from days 4-7 in vitro. The development of tyrosine hydroxylase immunoreactive cells was also inhibited by 8-bromo-cAMP. The addition of 8-bromo-cAMP increased the number of melanocytes and resulted in either no change or only modest reductions in the number of E/C8 and neurofilament immunoreactive cells, indicating that the effect on CA+ cell ontogeny was selective. In contrast to the effect of 8-bromo-cAMP, addition of 8-bromo-cGMP did not inhibit CA+ cell development in the presence of the RBM gel nor did it stimulate CA+ cell development in the absence of the RBM gel overlay. Our results suggest that cAMP may be an important regulator of phenotypic expression in at least some neural crest cell lineages.(ABSTRACT TRUNCATED AT 250 WORDS)


Proatherogenic Lipid Profile in Early Childhood: Association with Weight Status at 4 Years and Parental Obesity.
To determine lipid profiles in early childhood and evaluate their association with weight status at 4 years of age. Additionally, we evaluated whether the risk of overweight or having an altered lipid profile was associated with parental weight status. Five hundred eighty two mothers and their 4-year-old children from 2 Spanish population-based cohorts were studied. Weight status in children at 4 years of age was classified as overweight or obese using the International Obesity Task Force criteria. Plasma total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol were determined in children and lipid ratios were calculated. A proatherogenic lipid profile was defined as having the 3 lipid ratios in the third tertile. A total of 12.9% of children were overweight and 6.4% were obese. Weight status at 4 years of age was related to maternal prepregnancy body mass index, paternal body mass index, gestational diabetes, and birth weight, but not with other sociodemographic characteristics of the mother. We found no association with gestational age, sex of the child, or breastfeeding. The risk of overweight/obesity was increased 4.17-fold if mothers were overweight/obese (95% CI 1.76-9.88) and 5.1-fold (95% CI 2.50-10.40) if both parents were overweight/obese. There were 133 children (22.8%) with a proatherogenic lipid profile. The risk of a proatherogenic lipid profile was increased 2.44-fold (95% CI 1.54-3.86) if they were overweight/obese at 4 years of age and 2-fold if the father was overweight/obese (95% CI 1.22-3.35). Four-year-old overweight/obese children have higher lipid risk profiles. Offspring of overweight/obese parents have an increased risk for obesity and a proatherogenic lipid profile.


Eosinophilic gastroenteritis causing stenosis of bulbo-duodenal junction: medical and endoscopic management.
Eosinophilic gastroenteritis is a rare disease characterised by tissue eosinophilia that can involve any layer or part of the gut from the oesophagus to the rectum. In Saudi Arabia, the disease has not been reported in the literature before. We report the disease entity as an unusual cause of gastric outlet obstruction. A 50-year-old man was admitted through the gastrointestinal clinic with complaints of epigastric pain associated with dyspepsia for 1 month, and weight loss of 4 kg in 2 months. Examination revealed only the epigastric tenderness on deep palpation. Laboratory investigations including full blood count, liver function tests and renal function tests were normal. Gastroscopy disclosed stenosis of the second and third part of the duodenum. Biopsies were taken and the patient underwent endoscopic dilatation of the pylorus and duodenal bulb. Histopathology showed chronic active eosinophilic inflammation. The patient was successfully treated with a tapering course of steroids and had a complete recovery post-endoscopic dilatation.


MHC class I down-regulation: tumour escape from immune surveillance? (review).
Malignant conversion and subsequent in vivo selection can give rise to the cell populations that show stable expression of an immune escape phenotype, MHC class I deficient neoplasms. Deficiencies associated with the MHC class I down-regulation are either irreversible, such as beta2 microglobulin and class I heavy chain gene disabling mutations, or reversible. The reversible MHC class I deficiencies involve all levels of the MHC class I-restricted antigen presentation machinery. They can be repaired, at least partially and in vitro, by cytokines (IFNgamma, TNFalpha) or by DNA demethylation/histone hyperacetylation procedures. The reduced levels of MHC class I antigens result in decreased sensitivity to MHC class I-restricted, cytotoxic T lymphocyte-mediated lysis, the major component of the tumour rejection reaction. MHC class I down-regulation helps tumour cells evade the classical T cell-dependent immune responses but simultaneously imposes another, the NK cell-mediated, surveillance stimulated by the 'missing self' signals. The innate and adaptive antitumour immunity may be under some conditions interconnected: primary activation of the MHC class I-unrestricted surveillance mechanisms may lead to the production of IFNgamma by the activated NK/gammadelta T cells; the in situ produced IFNgamma may then up-regulate the MHC class I molecule expression on the tumour cell surface and in this way it may stimulate the more efficient, MHC class I-restricted, adaptive immunity. If we accept that the MHC class I down-regulation can, under some conditions, indeed be a mechanism of the tumour escape from the immune defence, the problem arises how to cope efficiently with this escape. Either therapeutic procedures aiming at up-regulation of MHC class I expression, or enhancement of MHC class I-unrestricted (CD4+, NK, NKT, gammadelta T) tumour defence effector mechanisms by dendritic cell-based therapeutic vaccines, by cytokines (IL-2, IL-12, IFNgamma, GM-CSF), or by the cytokine gene-based, genetically modified tumour vaccines should be considered.


[Histological and histochemical changes in the neck muscles of spontaneously occurring scoliosis in a special strain of Japanese quail, SQOHM].
A strain of Japanese quail, SQOHM, is known as a model of idiopathic scoliosis in humans. It shows hereditary scoliotic deformities occurring in the cervical region. Histological, histochemical and serological studies were performed in 51 scoliotic and 109 non-scoliotic quail. Histological study revealed internal nuclei and tiny groups of small fibers in the neck muscles. The incidence of these, however, was only 19% in the scoliotic and 7% in the non-scoliotic quail. Histochemical observation with adenosine triphosphatase, phosphorylase and succinic dehydrogenase stains was made on the dorsal neck muscles. An increase in the number of beta-fibers, and a decrease in the number and hyperplasia of alpha-fibers were observed on the concave side of the scoliosis. The increase in number of beta-fibers on the concave side can play a role in promoting the deformity was suggested.


Cellulose sulfate suppresses immunoglobulin E production by murine B lymphocytes in vitro.
Immunoglobulin (Ig) E plays an important role in the pathogenesis of allergic diseases such as atopic dermatitis and allergic asthma.We previously reported that a sulfate polysaccharide, fucoidan, suppressed IgE production by murine B cells in vitro. However, the mechanism by which fucoidan suppresses IgE production remains unclear. We incorporated sulfate groups into cellulose and studied their biological characteristics in vitro to explore the possibility of converting biologically neutral polysaccharides to active reagents with antiallergic functions. Cellulose was chemically processed using N,N-dimethylformamide (DMF) and DMF-sulfurtrioxide and recovered as cellulose sulfate with a molecular weight of around 10 kDa. We then studied the effect of cellulose sulfate on IgE production from B cells, IgE class-switching, and populations of IgE-secreting B cells prepared from murine spleen. We also investigated the effects of sulfated cellulose on the production of interleukin (IL) 4 and interferon (IFN) gamma and the expression of T-bet mRNA by splenic T cells. The cytotoxicity of cellulose sulfate was also examined. Cellulose sulfate suppressed IgE production in B cells stimulated with IL-4 and anti-CD40 antibody by inhibiting IgE class-switch recombination and decreasing the number of IgE-secreting B cells in vitro. Moreover, both cellulose sulfate and fucoidan suppressed IL-4 production and enhanced IFN-gamma production by murine T cells stimulated with anti-CD3 and anti-CD28 antibodies, despite the decrease in T-bet mRNA expression. Cellulose gains an antiallergic effect on B cells and T cells with the addition of sulfate groups.


Correlation between duodenogastric reflux and remnant gastritis after distal gastrectomy.
Many patients who undergo distal gastrectomy develop remnant gastritis. This report describes the correlation between remnant gastritis and the amount of duodenogastric reflux and looks at the relationship between Helicobacter pylori infection and duodenogastric reflux in remnant gastritis. Sixty-two patients who underwent curative distal gastrectomy for gastric cancer with radical lymphadenectomy were studied. The period of bile reflux (percent time) into the gastric remnant was measured with the Bilitec 2000 under standardized conditions. Remnant gastritis was semi-quantified using the neutrophil infiltration score based on the updated Sydney System, and the presence of H. pylori infection was determined 12 weeks after the surgery. Overall, the correlation was not significant between the neutrophil infiltration score and the percent time (p=0.08). Similarly, the correlation was not significant in patients with H. pylori infection (p=0.30), but it was significant in patients without H. pylori infection (p=0.03). Duodenogastric reflux after distal gastrectomy can cause remnant gastritis in patients without H. pylori infection. Reconstruction with biliary diversion is protective against the development of remnant gastritis.


[Studies on the detection of Legionella pneumophila by the application of polymerase chain reaction (PCR)].
DNA fragment of Legionella pneumophila, the PCR was performed with a pair of artificial synthesized primer. Results of agarose electrophoresis and EB staining showed that there was a 870 bp band shared by serogroups 1-14 of L.pneumophila. The sensitivity of PCR in detecting Legionella from water was 350cfu/ml, however, the specific DNA probe labeled with 32P was .43cfu/ml by blot hybridization. The positive rate of tissue specimens from infected guinea-pigs with Legionella pneumophila was 83.3% by PCR detection, and only 26.6% by bacteriological culture method. An outbeak caused by Lp10 was verified by PCR. The result showed that the PCR could detect the infection of Legionella rapidly, specifically and sensitively.


Immunoscintigraphy of colorectal carcinomas with radiolabeled monoclonal antibody fragments.
The aim was evaluation of the accuracy and clinical impact of the immunoscintigraphy for the detection of metastases and recurrences of colorectal carcinomas using two different radiolabeled antibody fragments. The study was performed in 5 patients with IMACIS 1 containing the cocktail of 111MBq 131I MoAb 19-9 F(ab')2 and MoAb anti-CEA F(ab')2 and 8 patients with INDIMACIS 19-9 containing 150MBq of 111In-labeled MoAb 19-9 F(ab')2. With IMACIS 1, in all the patients, both tumor marker values were elevated. The number of TN was 3/5 and TP 2/5. From 2 TP, one had recurrence of the diseases with peritoneal carcinosis and one with liver metastases. In one patient, the results influenced the therapeutical management. With INDIMACIS 19-9, there were 2/8 TN, with borderline value of CEA and CA 19-9. TP were 6/8 (all with elevated tumor marker values, five of them many times; 3 with recurrences, 1 with recurrence and liver metastases and two with only liver metastases. In three patients, immunoscintigraphy influenced patient management. With both radiopharmaceuticals, immunoscintigraphy significantly influenced the patient management or it was complementary. It would be performed in the detection of recurrence, assessment of viability and follow-up of the therapy.


Therapeutic potentials of baicalin and its aglycone, baicalein against inflammatory disorders.
The flavonoids, baicalin (5,6-dihydroxy-2-phenyl-4H-1-benzopyran-4-one-7-O-d-β-glucuronic acid) 1 and its aglycone, baicalein 2 are found in edible medicinal plants, Scutellaria baicalensis Georgi and Oroxylum indicum (L.) Kurz in abundant quantities. The antioxidant and anti-inflammatory effects of these flavonoids have been demonstrated in various disease models, including diabetes, cardiovascular diseases, inflammatory bowel diseases, gout and rheumatoid arthritis, asthma, neurodegenerative-, liver- and kidney diseases, encephalomyelitis, and carcinogenesis. These flavonoids have almost no toxicity to human normal epithelial, peripheral and myeloid cells. Their antioxidant and anti-inflammatory activities are largely due to their abilities to scavenge the reactive oxygen species (ROS) and improvement of antioxidant status by attenuating the activity of NF-κB and suppressing the expression of several inflammatory cytokines and chemokines including monocyte chemotactic protein-1 (MCP-1), nitric oxide synthase, cyclooxygenases, lipoxygenases, cellular adhesion molecules, tumor necrosis factor and interleukins. In this review, we summarize the antioxidant and anti-inflammatory effects of baicalin and baicalein with molecular mechanisms for their chemopreventive and chemotherapeutic applications in the treatment of inflammatory-related diseases.


Detection and semi-quantification of Strongylus vulgaris DNA in equine faeces by real-time quantitative PCR.
Strongylus vulgaris is an important strongyle nematode with high pathogenic potential infecting horses world-wide. Several decades of intensive anthelmintic use has virtually eliminated clinical disease caused by S. vulgaris, but has also caused high levels of anthelmintic resistance in equine small strongyle (cyathostomin) nematodes. Recommendations aimed at limiting the development of anthelmintic resistance by reducing treatment intensity raises a simultaneous demand for reliable and accurate diagnostic tools for detecting important parasitic pathogens. Presently, the only means available to differentiate among strongyle species in a faecal sample is by identifying individual L3 larvae following a two week coproculture procedure. The aim of the present study is to overcome this diagnostic obstacle by developing a fluorescence-based quantitative PCR assay capable of identifying S. vulgaris eggs in faecal samples from horses. Species-specific primers and a TaqMan probe were designed by alignment of published ribosomal DNA sequences of the second internal transcribed spacer of cyathostomin and Strongylus spp. nematodes. The assay was tested for specificity and optimized using genomic DNA extracted from identified male worms of Strongylus and cyathostomin species. In addition, eggs were collected from adult female worms and used to evaluate the quantitative potential of the assay. Statistically significant linear relationships were found between egg numbers and cycle of threshold (Ct) values. PCR results were unaffected by the presence of cyathostomin DNA in the sample and there was no indication of PCR inhibition by faecal sources. A field evaluation on faecal samples obtained from four Danish horse farms revealed a good agreement with the traditional larval culture (kappa-value=0.78), but with a significantly higher performance of the PCR assay. An association between Ct values and S. vulgaris larval counts was statistically significant. The present assay can reliably and semi-quantitatively detect minute quantities of S. vulgaris eggs in faecal samples.


Prevalence of Endoscopic Findings Before Bariatric Surgery and Their Influence on the Selection of the Surgical Technique.
Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) are the two most popular procedures performed. The decision of which technique is most appropriate depends on the surgeon's preferences and experience. However, several factors strongly influence the decision of the procedure performed, including gastrointestinal disorders or asymptomatic upper gastrointestinal endoscopy (UGE) findings. This study aimed to describe the pathological endoscopic findings in morbidly obese patients undergoing preoperative routine UGE. A retrospective review of a prospectively collected database of all UGEs performed before bariatric surgery was performed. UGE was routinely performed to all the patients as part of the preoperative evaluation protocol. A total of 790 patients were included. Surgical technique included 610 (77.2%) RYGB and 180 (22.8%) SG. Twenty-one asymptomatic patients presented esophagitis at UGE. In only seven patients (0.89%), the endoscopic findings of esophagitis had changed the initial surgical decision. The presence of ulcers or adenomatous or incompletely resected polyps was an indication for SG, to assure future endoscopic access in case it is needed. In 25 patients (3.17%), the initial operation would have been changed based on UGE findings. Preoperative UGE allows the diagnosis of asymptomatic esophagitis related to gastroesophageal reflux disease and the identification of asymptomatic polyps and ulcers, with the potential ability for malignant transformation. In up to 3.17% of the cases, the endoscopic findings changed the operative strategy. As the complication rate associated with the procedure is low, we recommend the routine performance of preoperative UGE before bariatric surgery.


Effects of stair task training on walking ability in stroke patients.
[Purpose] The aim of this study was to determine the effect of stair task training on gait abilities by conducting stair task training. In this training, step training is applied in various directions with hemiplegia patients. [Subjects and Methods] Thirty-six patients with stroke were selected on the basis of inclusion and exclusion criteria, and they were randomly divided into eighteen patients in the experimental group and eighteen patients in the control group via draw. [Results] In this study, the Dartfish program was used to measure gait capabilities. Experiment group showed a statistically significant improvement in the swing phase time of the affected lower extremity compared to control group. [Conclusion] It was found that the stair task training group had effective results in the swing phase time of the affected lower extremity compared with the group that applied weight support on the affected lower extremity and balance training.


Factors associated with internalizing or somatic symptoms in a cross-sectional study of school children in grades 1-10.
School related factors that may contribute to children's subjective health have not been extensively studied. We assessed whether factors assumed to promote health and factors assumed to have adverse effects were associated with self-reported internalizing or somatic symptoms. In a cross-sectional study, 230 boys and 189 girls in grades 1-10 from five schools responded to the same set of questions. Proportional odds logistic regression was used to assess associations of school related factors with the prevalence of sadness, anxiety, stomach ache, and headache. In multivariable analyses, perceived loneliness showed strong and positive associations with sadness (odds ratio, 1.94, 95% CI 1.42 to 2.64), anxiety (odds ratio, 1.78, 95% CI 1.31 to 2.42), and headache (odds ratio, 1.47, 95% CI 1.10 to 1.96), with consistently stronger associations for girls than boys. Among assumed health promoting factors, receiving necessary help from teachers was associated with lower prevalence of stomach ache in girls (odds ratio, 0.51, 95% CI 0.30 to 0.87). These findings suggest that perceived loneliness may be strongly related to both internalizing and somatic symptoms among school children, and for girls, the associations of loneliness appear to be particularly strong.


Transthoracic echocardiographic measurement of coronary blood flow and reserve.
The objectives of this study were to evaluate the use of high-frequency (5 MHz) transthoracic echocardiography for the noninvasive measurement of coronary blood flow and to test its ability to detect small changes in blood flow that may accompany pharmacologic intervention. High-frequency (5 MHz) transthoracic echocardiography was performed on the distal segment of the left anterior descending coronary artery of 32 consecutive patients (23 men and nine women; mean age 60 +/- 10 years) before and after the administration of 0.4 mg sublingual nitroglycerin. The results were compared with those of 10 patients (eight men and two women; mean age 59 +/- 6 years) in whom the ungrafted left internal mammary artery was studied. Doppler velocity profiles of the left anterior descending coronary artery were detected in 18 (56%) of the 32 Study patients. Left anterior descending coronary artery diameter and blood flow were measured in 14 patients (44%). There was no significant difference in blood flow between the left anterior descending artery (74 +/- 35 ml/min) and the internal mammary artery (52 +/- 25 ml/min). After administration of nitroglycerin, there was a 24% decrease in coronary blood flow from 74 +/- 35 ml/min to 56 +/- 30 ml/min (p < 0.05). This study suggests that high frequency transthoracic echocardiography may allow noninvasive identification of the left anterior descending coronary artery and detection of small changes in blood flow that accompany pharmacologic and mechanical intervention.


Otorhinolaryngology nursing research priorities: results of the 1996/1997 SOHN Delphi survey.
This study was initiated by the Society of Otorhinolaryngology and Head-Neck Nurses, Inc. (SOHN) to establish research priorities for the specialty. Otorhinolaryngology (ORL) Nurses were asked to identify, rate, and rank priorities for ORL nursing research. The survey sample was gleaned from attendees at the 20th Annual SOHN Congress and Nursing Symposium plus a follow-up mailing to active SOHN members who did not attend. A decision-making method, the reactive delphi technique, was employed. Four rounds of soliciting opinions by questionnaires were completed. Data from each round were reviewed and analyzed by three ORL nurse investigators. The respondents were largely actively employed, female SOHN members who were seasoned nurses, experienced in ORL nursing. The majority were Registered Nurses (RN) or held Bachelor of Science (BSN) degrees. They were primarily employed as staff nurses in outpatient settings and working with a general otorhinolaryngology patient population of all ages. The fourteen priorities identified fall in the areas of patient outcomes (three), patient education (three), symptom management (two), patient self-care (two), psychosocial issues (two), and nursing care delivery (two), spanning the practice spectra of all ORL nurse generalists and subspecialists. The top five research priorities identified are; care of neck stomas and related equipment, quality of life in head and neck cancer patients, impact of managed care on ORL nursing care delivery, value of ORL specialty nurses/nursing units, and effective techniques to promote cessation of substance abuse in adolescents. This priority identification provides a baseline for the newly forming SOHN Foundation.


Synthesis and Characterisation of Photocrosslinked poly(ethylene glycol) diacrylate Implants for Sustained Ocular Drug Delivery.
To investigate the sustained ocular delivery of small and large drug molecules from photocrosslinked poly(ethylene glycol) diacrylate (PEGDA) implants with varying pore forming agents. Triamcinolone acetonide and ovalbumin loaded photocrosslinked PEGDA implants, with or without pore-forming agents, were fabricated and characterised for chemical, mechanical, swelling, network parameters, as well as drug release and biocompatibility. HPLC-based analytical methods were employed for analysis of two molecules; ELISA was used to demonstrate bioactivity of ovalbumin. Regardless of PEGDA molecular weight or pore former composition all implants loaded with triamcinolone acetonide released significantly faster than those loaded with ovalbumin. Higher molecular weight PEGDA systems (700 Da) resulted in faster drug release of triamcinolone acetonide than their 250 Da counterpart. All ovalbumin released over the 56-day time period was found to be bioactive. Increasing PEGDA molecular weight resulted in increased system swelling, decreased crosslink density (Ve), increased polymer-water interaction parameter (χ), increased average molecular weight between crosslinks (Mc) and increased mesh size (ε). SEM studies showed the porosity of implants increased with increasing PEGDA molecular weight. Biocompatibility showed both PEGDA molecular weight implants were non-toxic when exposed to retinal epithelial cells over a 7-day period. Photocrosslinked PEGDA implant based systems are capable of controlled drug release of both small and large drug molecules through adaptations in the polymer system network. We are currently continuing evaluation of these systems as potential sustained drug delivery devices.


Antimicrobial activity of SK&F 88070, an expanded-spectrum cephalosporin with high and prolonged levels in blood.
SK&F 88070 (7-[[(2-amino-4-thiazolyl)(methoxyimino)acetyl]amino]-3- [[[1-(2-sulfaminoethyl)-1H-tetrazol-5-yl]thio] methyl]-3-cephem-4-carboxylic acid) is a new parenteral cephalosporin with an expanded-spectrum profile of antibacterial activity, including activity against Pseudomonas aeruginosa, and with high and prolonged levels in sera of experimental animals. The activity of SK&F 88070 was compared with those of cefotaxime and other cephalosporins against more than 500 clinical isolates in vitro by microtiter twofold dilution tests in Mueller-Hinton broth. SK&F 88070 was extremely potent against all of the members of the family Enterobacteriaceae that were tested, including beta-lactamase-producing strains. Its activity against P. aeruginosa was comparable to those of cefotaxime, ceftizoxime, and moxalactam. SK&F 88070 was less potent than cefotaxime or ceftizoxime against Staphylococcus species but was comparable to moxalactam. It had in vivo activity against the same Bacteroides strains as did cefotaxime, although it was less potent. Both SK&F 88070 and cefotaxime had less activity when tested with high inoculum levels of most of the rarer gram-negative bacteria. There was a greater decrease in the activity of SK&F 88070 than of cefotaxime in the presence of human serum, reflecting the higher degree of binding of SK&F 88070 to serum proteins. SK&F 88070 had peak levels and half-lives in serum much greater than those of cefotaxime in experimental animals after parenteral administration. In mouse protection studies, SK&F 88070 was more effective than cefotaxime against gram-negative bacteria but less effective than cefotaxime against Staphylococcus aureus.


[The popliteo-femoral block, a rarely used form of regional anesthesia. With special reference to the use of peripheral nerve stimulators].
Blockade of the sciatic nerve in the fossa poplitea is a rarely used form of regional anaesthesia. A new method of identification of the tibial and peroneal nerve and their blockade in combination with blockade of the femoral nerve using a peripheral nerve stimulator, is described. Results in 300 patients during a 12 month period are described and discussed.


The REHAB-LAB model for individualized assistive device co-creation and production.
Assistive devices are designed to enhance individuals with disabilities' functional abilities. The rise of 3D printing technology enabled the production of individualized assistive devices (IADs). A REHAB-LAB is intended for IAD provision involving technical referents and occupational therapists. This study aimed to develop the REHAB-LAB logic model; to explore its fidelity and desirability; and to explore the characteristics of arising initiatives of IAD production. The REHAB-LAB logic model development involved stakeholders throughout the research process. A pragmatic multimethod approach followed two phases 1) logic model development and 2) exploration of its fidelity and desirability. The REHAB-LAB logic model presented the resources (equipment, space, human) required to implement IAD provision in a rehabilitation center, and the expected deliverables (activities and outputs). The REHAB-LAB logic model highlights the interdisciplinarity of IAD provision including occupational therapists, doctors, engineers, managers, and technical referents and places the users at the center of the IAD production. Results confirmed the fidelity and desirability of the REHAB-LAB logic model. The REHAB-LAB logic model can be used as a reference for future healthcare organizations wishing to implement an IAD provision. This research highlighted the interest of IAD provision based on the REHAB-LAB model involving users and transdisciplinary practices.


[Results of vacuum sealing therapy in joint infections].
At present the vacuum sealing technique is acknowledged as a therapy for acute and chronic wounds. An acceleration of the healing process, due to the vacuum suction with occlusive wound dressing, leads to the shortening of a cost-effective medical treatment. This can be applied to wound treatment and infections of soft tissues, but even today there is only sparse information in this context about joint infections. The results of therapy with the vacuum sealing technique in 68 patients with infections of the joints of an extremity or the trunk were analysed in a retrospective study without a control group. The importance of several patient-related factors for the medical treatment have been analysed. An adequate treatment of joint infections can be achieved even in the presence of endoprostheses or osteosynthetic material. The following factors have been found to be of significance for a prolonged medical treatment: diabetes mellitus (p=0.0052), obesity (BMI>25) (p=0.0458) and a preceding trauma (p=0.0457). The results confirm the value of the vacuum sealing technique following surgical debridement in combination with resistance tested antibiotic treatment, as a sufficient therapy for joint infections, even in patients with an endoprosthesis. This procedure leads to a safe treatment of the joint infection, combined with a good function of the treated joint, good patient comfort and a short duration of the therapy.


[Assessment of outcome in treatment of cardiac shock after myocardial infarction with intravenous streptokinase].
In 1986 a prospective randomized study coordinated by the Institute of Cardiology in Warsaw was started in 10 teaching cardiology hospitals in Poland for assessment of the results of treatment with intravenous streptokinase infusion in acute myocardial infarction. The studied population comprised 927 patients admitted to intensive treatment units within 6 hours after the onset of infarction pain. For the groups treated with streptokinase or heparin 752 patients were selected at random. In 175 cases the administration of streptokinase was contraindicated. These patients received conventional treatment and served as controls. The age of the patients was from 38 to 70 years, mean age 57.6 +/- 9.3 years. In 105 out of 927 cases cardiac shock was diagnosed. In the groups of early shock during hospitalization the death rate was 82%. No statistically significant difference was found in the death rates between patients with cardiac shock treated with heparin or with streptokinase.


In vitro mineralization of a glass-ceramic of the MgO-3CaO x P2O5-SiO2 system: wettability studies.
The calcium phosphate deposition on the surface of a bioactive glass-ceramic of the MgO-3CaO. P(2)O(5)-SiO(2) system during a 1-week immersion in biological model fluids, was investigated through wettability studies. Two model fluids with chemical composition similar to the human blood plasma were tested: Hanks' balanced salt solution (HBSS) and a simulated body fluid (SBF) with a higher calcium content. The effect of the presence of albumin, both in solution or previously adsorbed to the surface, was assessed. The behavior observed using two SBF solutions prepared with and without TRIS buffer was compared. The surface free energy of the glass-ceramic samples was determined, before and after immersion, and dynamic contact angle analysis was performed using the biological model fluids as scanning liquids. Scanning electron microscope observations and x-ray photoelectron spectroscopy (XPS) analysis were performed to complement the wettability studies. The experimental results led to the conclusion that the precipitation of a calcium phosphate film in HBSS occurred mainly when the immersion solution was renewed daily or in the presence of adsorbed albumin. In SBF, the addition of TRIS buffer seemed to inhibit the formation of the calcium phosphate film.


Thai perspectives on pain.
This qualitative research aimed to study the meaning, the characteristics, and the dimensions of pain from a Thai point of view. It was conducted under the research project on the development of the quality of pain management for people in the hospital. The subjects were 62 patients, experiencing pain and receiving treatment in 4 hospitals in northeast Thailand. Data were analyzed through content analysis. The findings included: 1) concept from experience of pain, perceived pain as suffering physically and psychologically, 2) different characteristics between acute and chronic pain, 3) four levels of pain intensity: mild, moderate, high and severe, 4) pain effects on four dimensions: physical, psychological, behavioral and societal (family-social-economy), 5) two factors related to pain: alleviating factor and predisposing factor, and 6) pain management relies on beliefs, culture and religion i.e. good deeds in Buddhism affected six dimensions: physical, psychological, social, spiritual, treatment seeking and asking health personnel for help. The results of the present study revealed the influence of culture beliefs on the meaning of pain, pain characteristics, and the effects of pain as well as pain management in terms of cultural contexts. The findings may be implemented for the development of pain assessment and the model development of pain management more appropriately according to cultural contexts.


Noninvasive evaluation of ischemic stroke with SPECT.
Technetium Tc 99m DTPA single photon emission computerized tomography (SPECT) brain scans of 20 patients with acute ischemic stroke were reviewed retrospectively and compared with clinical and radiologic (CT) data. Fourteen of the patients had abnormal SPECT studies. The abnormal findings were demonstrated by static views in eight patients, by the flow study in one patient, and by both sets of images in the other five patients. All abnormalities correlated with the clinical syndrome of presentation, and only two of the patients had no corresponding lesions on CT. Of the six patients with normal SPECT scans, two had abnormal CT studies, and in the other four, no lesions were shown at all. The ability of 99mTc DTPA SPECT to display cerebral infarctions appears to be, at best, comparable to that of CT. SPECT also provides qualitative information regarding flow dynamics in the affected hemisphere of some patients (6/20 in our review). This, we believe, represents the objective demonstration of the preexisting insufficient collateral flow in the hemisphere at risk for ischemic stroke.


The transcription factor sterile alpha motif (SAM) pointed domain-containing ETS transcription factor (SPDEF) is required for E-cadherin expression in prostate cancer cells.
Loss of E-cadherin is one of the key steps in tumor progression. Our previous studies demonstrate that SAM pointed domain-containing ETS transcription factor (SPDEF) inhibited prostate cancer metastasis in vitro and in vivo. In the present study, we evaluated the relationship between SPDEF and E-cadherin expression in an effort to better understand the mechanism of action of SPDEF in prostate tumor cell invasion and metastasis. The results presented here demonstrate a direct correlation between expression of E-cadherin and SPDEF in prostate cancer cells. Additional data demonstrate that modulation of E-cadherin and SPDEF had similar effects on cell migration/invasion. In addition, siRNA-mediated knockdown of E-cadherin was sufficient to block the effects of SPDEF on cell migration and invasion. We also show that stable forced expression of SPDEF results in increased expression of E-cadherin, whereas down-regulation of SPDEF decreased E-cadherin expression. In addition, we demonstrate that SPDEF expression is not regulated by E-cadherin. Moreover, our chromatin immunoprecipitation and luciferase reporter assay revealed that SPDEF occupies E-cadherin promoter site and acts as a direct transcriptional inducer of E-cadherin in prostate cancer cells. Taken together, to the best of our knowledge, these studies are the first demonstrating requirement of SPDEF for expression of E-cadherin, an essential epithelial cell junction protein. Given that loss of E-cadherin is a central tenant in tumor metastasis, the results of our studies, by providing a new mechanism for regulation of E-cadherin expression, could have far reaching impact.


An Overview of Various Rifampicin Analogs against Mycobacterium tuberculosis and their Drug Interactions.
The success of the TB control program is hampered by the major issue of drug-resistant tuberculosis (DR-TB). The situation has undoubtedly been made more difficult by the widespread and multidrug-resistant (XDR) strains of TB. The modification of existing anti-TB medications to produce derivatives that can function on resistant TB bacilli is one of the potential techniques to overcome drug resistance affordably and straightforwardly. In comparison to novel pharmaceuticals for drug research and progress, these may have a better half-life and greater bioavailability, be more efficient, and serve as inexpensive alternatives. Mycobacterium tuberculosis, which is drugsusceptible or drug-resistant, is effectively treated by several already prescribed medications and their derivatives. Due to this, the current review attempts to give a brief overview of the rifampicin derivatives that can overcome the parent drug's resistance and could, hence, act as useful substitutes. It has been found that one-third of the global population is affected by M. tuberculosis. The most common cause of infection-related death can range from latent TB to TB illness. Antibiotics in the rifamycin class, including rifampicin or rifampin (RIF), rifapentine (RPT), and others, have a special sterilizing effect on M. tuberculosis. We examine research focused on evaluating the safety, effectiveness, pharmacokinetics, pharmacodynamics, risk of medication interactions, and other characteristics of RIF analogs. Drug interactions are especially difficult with RIF because it must be taken every day for four months to treat latent TB infection. RIF continues to be the gold standard of treatment for drug-sensitive TB illness. RIF's safety profile is well known, and the two medicines' adverse reactions have varying degrees of frequency. The authorized once-weekly RPT regimen is insufficient, but greater dosages of either medication may reduce the amount of time needed to treat TB effectively.


Rickettsia parkeri in Argentina.
Clinical reports of an eschar-associated rickettsiosis in the Paraná River Delta of Argentina prompted an evaluation of Amblyomma triste ticks in this region. When evaluated by PCR, 17 (7.6%) of 223 questing adult A. triste ticks, collected from 2 sites in the lower Paraná River Delta, contained DNA of Rickettsia parkeri.


Mucoid cyst of the penis: Case report and literature review.
Penile cysts are uncommon lesions. In general, they are asymptomatic and do not interfere with sexual function. Most of them are present since birth, but usually they are only detectable in adolescence or adulthood. We report a rare case of a young adult man with a 5 × 5-cm nodule on the prepuce (ventral face), which appeared 2 years ago and interfered with his sexual function. The nodule was excised by circumcision and a histopathologic study was performed. Histopathologic examination revealed a mucoid cyst of penis with epidermoid metaplasia. No recurrence was observed at a 6 months follow-up and the patient's sexual function returned to normal.


Severe Asthma in Children.
Severe asthma in children is associated with significant morbidity and is a highly heterogeneous disorder with multiple clinical phenotypes. Cluster analyses have been performed in several groups to explain some of the heterogeneity of pediatric severe asthma, which is reviewed in this article. The evaluation of a child with severe asthma includes a detailed diagnostic assessment and excluding other possible diagnoses and addressing poor control due to comorbidities, lack of adherence to asthma controller medications, poor technique, and other psychological and environmental factors. Children with severe asthma require significant resources including regular follow-up appointments with asthma education, written asthma action plan, and care by a multidisciplinary team. Management of pediatric severe asthma now includes emerging phenotypic-directed therapies; however, continued research is still needed to further study the long-term outcomes of pediatric severe asthma and its treatment.


Reduction in paracrine Wnt3 factors during aging causes impaired adult neurogenesis.
The mammalian brain contains neural stem cells (NSCs) that enable continued neurogenesis throughout adulthood. However, NSC function and/or numbers decline with increasing age. Adult hippocampal neurogenesis is unique in that astrocytes secreting Wnt3 promote NSC differentiation in a paracrine manner. Here, we show that both the levels of Wnt3 protein and the number of Wnt3-secreting astrocytes influence the impairment of adult neurogenesis during aging. The age-associated reduction in Wnt3 levels affects the regulation of target genes, such as NeuroD1 and retrotransposon L1, as well as the expression of Dcx, which is located adjacent to the L1 loci. Interestingly, the decline in the extrinsic Wnt3 levels and in the intracellular expression of the target genes with aging was reversible. Exercise was found to significantly increase de novo expression of Wnt3 and thereby rescue impaired neurogenesis in aged animals. Furthermore, the chromatin state of NeuroD1, L1, and the L1 loci near Dcx changed relative to Wnt3 levels in an age- or stimulus-associated manner. These results suggest that the regulation of paracrine factors plays a critical role in hippocampal aging and neurogenesis.


Home hemodialysis treatment and outcomes: retrospective analysis of the Knowledge to Improve Home Dialysis Network in Europe (KIHDNEy) cohort.
Utilization of home hemodialysis (HHD) is low in Europe. The Knowledge to Improve Home Dialysis Network in Europe (KIHDNEy) is a multi-center study of HHD patients who have used a transportable hemodialysis machine that employs a low volume of lactate-buffered, ultrapure dialysate per session. In this retrospective cohort analysis, we describe patient factors, HHD prescription factors, and biochemistry and medication use during the first 6 months of HHD and rates of clinical outcomes thereafter. Using a standardized digital form, we recorded data from 7 centers in 4 Western European countries. We retained patients who completed ≥6 months of HHD. We summarized patient and HHD prescription factors with descriptive statistics and used mixed modeling to assess trends in biochemistry and medication use. We also estimated long-term rates of kidney transplant and death. We identified 129 HHD patients; 104 (81%) were followed for ≥6 months. Mean age was 49 years and 66% were male. Over 70% of patients were prescribed 6 sessions per week, and the mean treatment duration was 15.0 h per week. Median HHD training duration was 2.5 weeks. Mean standard Kt/Vurea was nearly 2.7 at months 3 and 6. Pre-dialysis biochemistry was generally stable. Between baseline and month 6, mean serum bicarbonate increased from 23.1 to 24.1 mmol/L (P = 0.01), mean serum albumin increased from 36.8 to 37.8 g/L (P = 0.03), mean serum C-reactive protein increased from 7.3 to 12.4 mg/L (P = 0.05), and mean serum potassium decreased from 4.80 to 4.59 mmol/L (P = 0.01). Regarding medication use, the mean number of antihypertensive medications fell from 1.46 agents per day at HHD initiation to 1.01 agents per day at 6 months (P < 0.001), but phosphate binder use and erythropoiesis-stimulating agent dose were stable. Long-term rates of kidney transplant and death were 15.3 and 5.4 events per 100 patient-years, respectively. Intensive HHD with low-flow dialysate delivers adequate urea clearance and good biochemical outcomes in Western European patients. Intensive HHD coincided with a large decrease in antihypertensive medication use. With relatively rapid training, HHD should be considered in more patients.


α-Tocopherol as functional excipient for resveratrol and coenzyme Q10-loaded SNEDDS for improved bioavailability and prophylaxis of breast cancer.
The present study evaluates the prophylactic efficacy of α-tocopherol (α-TOH), resveratrol (RES), and coenzyme Q10 (CoQ10) co-loaded self-nanoemulsifying drug delivery system (α-TOH-RES-CoQ10 SNEDDS) in 7,12-Dimethylbenz[a]anthracene (DMBA) induced breast cancer model. SNEDDS formulation components were rationally selected and optimized for maximum drug loading by applying the design of experiments and further evaluated for stability in simulated gastrointestinal fluids, functional stability of antioxidants, in vitro release, Caco-2 cell uptake, oral bioavailability and prophylactic anticancer activity. The SNEDDS demonstrated excellent stability in stimulated gastrointestinal fluids. The functional activity of antioxidants was confirmed by 2,2-diphenylpicrylhydrazyl (DPPH) scavenging assay wherein significantly (p > .05) higher antioxidant activity was observed in case of SNEDDS as compared with free antioxidants. Coumarin 6 (C-6)-loaded SNEDDS formulation demonstrated remarkably higher Caco-2 cell uptake in comparison with free C-6, indicative of efficient internalization of sub-micron SNEDDS droplets by Caco-2 cells. In line with Caco-2 cell uptake observations, α-TOH-RES-CoQ10-SNEDDS showed ∼2.30- and ∼3.64-fold increase in the AUC0-∞ values of RES and CoQ10 in comparison with free antioxidants. Significantly lower (p < .001) tumor volume (∼327 mm3) was found in case of animals treated with α-TOH-RES-CoQ10-SNEDDS in comparison with free antioxidant combination (∼1070 mm3) and DMBA control (∼1540 mm3) groups. Conclusively, the proposed strategy posed great potential in improving the prophylactic activity of antioxidants and hold promise for further exploration.


Effect of iron on lipid peroxidation, and enzymatic and non-enzymatic antioxidants and bacoside-A content in medicinal plant Bacopa monnieri L.
The effect of Fe was investigated in medicinally important plant, Bacopa monnieri L. and the response on malondialdehyde (MDA) content, superoxide dismutase (SOD), peroxidase (POD) and ascorbate peroxidase (APX) was found different in roots and leaves of the metal treated plants. Iron induced stress was observed as indicated by high level of lipid peroxidation, being more steep increase in leaves than roots. In roots, SOD activity was found to increase in metal treated plants except 80 and 160 microM at 72 h, whereas, it decreased in leaves except 10 and 40 microM after 48 h as compared to their respective controls. Among H2O2 eliminating enzymes, POD activity increased in roots, however, it decreased in leaves except at 10 and 40 microM Fe after 48 h as compared to control. At 24 and 48 h, APX activity and ascorbic acid content followed the similar trend and were found to increase in both parts of the metal treated plants as compared to their respective controls. The level of cysteine content in the roots increased at initial period of exposure; however, no marked change in its content was noticed in leaves. In both roots and leaves, non-protein thiol content was found to increase except at higher metal concentrations at 72 h. The data of proline content have shown significant (p<0.01) increase at 40 microM onwards in both part of the plants after 48 and 72 h. Correlation coefficient was evaluated between metal accumulations with various parameters and also between different antioxidant parameters with MDA. Since the level of bacoside-A (active constituent) content in metal treated plants increases, therefore, it is advisable to assess the biological activity of the plants before using for medicinal purposes, particularly in developing countries.


An automatic electronic device (Rite Time) to detect the onset of the infertile period by basal body temperature measurements.
Two trials of an electronic thermometer (Rite Time), designed to record and interpret basal body temperature (BBT) patterns in normal ovulating women, are described. A total of 140 menstrual cycles from 34 women, who used the thermal or symptothermal methods of natural family planning, were studied. Rite Time gave a signal for the start of the infertile period in 117 cycles, of which 114 (97%) appeared to have occurred at appropriate times. Further studies using hormonal and ultrasound reference points for ovulation were carried out in 21 cycles. Rite Time generally produced BBT patterns of quality acceptable for interpretation of the periovulatory BBT shift. About one-half of the volunteers said that they would be willing to replace their conventional charting methods with Rite Time.


Enantioselective CuH-Catalyzed Hydroacylation Employing Unsaturated Carboxylic Acids as Aldehyde Surrogates.
The direct asymmetric copper hydride (CuH)-catalyzed coupling of α,β-unsaturated carboxylic acids to aryl alkenes to access chiral α-aryl dialkyl ketones is reported. A variety of substrate substitution patterns, sensitive functional groups, and heterocycles are tolerated in this reaction, which significantly expands the range of accessible products compared with existing hydroacylation methodology. Although mechanistic studies are ongoing, we propose that CuH-catalyzed silylation of unsaturated acids occurs to access a uniquely effective acyl electrophilic coupling partner.


Synthesis and Biological Evaluation of Pyrazolo[3,4-b]pyridin-4-ones as a New Class of Topoisomerase II Inhibitors.
A series of 1,3,6-triphenylpyrazolo[3,4-b]pyridin-4-one derivatives was designed, synthesized and evaluated for cytotoxic activity in A375 human melanoma and human erythroleukemia (HEL) cells. The new pyrazolopyridones displayed comparable activities to the antitumor compound etoposide. The inhibitory effect of compounds 17, 18, 27 and 32 against topoisomerase II-mediated cleavage activities was measured finding good correlation with the results obtained from MTS assay. Docking studies into bacterial topoisomerase II (DNA Gyrase), topoisomerase IIα and topoisomerase IIβ binding sites in the DNA binding interface were performed.


[Announcement of an Austrian study group for the treatment of leukemia in children (author's transl)].
The formation of an Austrian study group for the treatment of leukemia in children with international cooperation is reported. An essential aim is the centralisation of treatment at the 3 Austrian University clinics, the St. Anna children's hospital in Vienna and other children's hospitals particularly interested in the treatment of leukemia. Secondly the group undertakes randomised therapeutic studies, at present on two new variants of the Pinkel treatment scheme. Within the first 9 months 33 cases were included in this study in cooperation with the Zagreb University children's clinic (Doz. TIEFENBACH).


Color Doppler flow imaging of pediatric soft tissue masses.
The blood flow pattern within and around soft tissue tumors was analyzed to determine if color Doppler images could aid in the differential diagnosis. The study comprised 49 children with 50 masses: 24 inflammatory lesions, eight malformations, six neoplasms, five cysts, and seven traumatic lesions. A peripheral pattern (flow around the mass) was noted in eight of 50 lesions (16%). A mixed pattern (flow within and around the lesion) was noted in eight of 50 lesions (16%), and a central pattern (flow in the central region of the mass) was noted in 10 of 50 lesions (20%). Flow was absent in 24 lesions (48%). The peripheral pattern was observed only in abscesses. The other patterns were seen most frequently in lymphadenitis but were not specific for that diagnosis. Our experience suggests that color Doppler imaging is useful only in the diagnosis of abscess. In other lesions, color Doppler imaging alone is insufficient for diagnosis.