Milk production and nitrogen excretion of dairy cows fed different amounts of protein and varying proportions of alfalfa and corn silage.
Four trials were conducted to determine the effect of dietary protein amount on lactation performance and N utilization. Each trial used one of the following alfalfa-to-corn-silage ratios for the forage part of the diet: 100:0, 75:25, 50:50, and 25:75. All trials utilized 16 mid-lactation Holstein cows (days in milk averages ranging from 80 to 140 among trials) in a replicated 4 x 4 Latin square design with 3-wk periods, including 2 wk for adaptation and 1 wk for data collection. Diets consisted of 50% forage and 50% concentrate (dry matter basis) and were formulated to contain 15.00, 16.25, 17.50, or 18.75% protein in each trial. The analyzed protein content of the diets was 15.7, 16.9, 18.0, and 19.2% when averaged across trials. Milk yield was similar among dietary protein levels in each trial, ranging from 35.2 to 36.1 kg/d when data were combined across trials. Changes in milk fat and protein due to the protein content of the diet were small and inconsistent. Both milk urea nitrogen and blood urea nitrogen concentrations increased linearly as the protein content of the diet was increased, ranging from 9.9 to 13.1 and from 9.9 to 13.8 mg/dL, respectively, across trials. As dietary protein was increased from the lowest to the highest concentrations when data were combined and analyzed, mean fecal N concentration increased from 2.8 to 3.0%, and urinary N from 5.8 to 7.3 g/L. At the same time, mean total N excretion increased from 484 to 571 g/d, and conversion of intake N to milk N decreased from 0.27 to 0.22, resulting in an average change of 18%. Of the N excreted, urinary N accounted for an increasing proportion, ranging from 41 to 48%, as dietary protein was increased. Overall, based on N utilization as well as milk production, 17% protein in diets utilizing various proportions of alfalfa and corn silage as the forage source appeared sufficient for cows producing 38 kg/d of milk in this study.


Allograft incorporation: a biomechanical evaluation in a rat model.
Allogeneic bone from Sprague-Dawley rat femurs was subjected to levels of freezing and/or irradiation that are known to have produced changes in the associated immune responses to these grafts. This bone was transplanted into an experimentally created gap in the femur of Lewis rats. The subsequent healing of the transplants in the Lewis rats was studied at 2, 4, 8, and 16 weeks after transplantation using torsion testing to failure. There was no clear advantageous biologic response in the union of the grafted material accompanying the alterations in immunologic response as measured by biomechanical testing of the proximal osteosynthesis site in torsion. The torsional strength of all of these groups remained lower than that of intact bone. Furthermore, none of the frozen and/or irradiated allografts exceeded the strength of the fresh allograft at a statistically significant level.


Sensory Profile of Chihuahua Cheese Manufactured from Raw Milk.
Chihuahua cheese is a local artisanal cheese traditionally produced from raw milk. When this cheese is produced with pasteurized milk, cheesemakers complain that there are differences in taste and aroma as compared with traditional manufacturing. This work aimed to obtain a descriptive sensory analysis of Chihuahua cheese manufactured with raw milk under traditional conditions. Samples were collected in five cheese dairies at two different seasons (summer and autumn), and a Quantitative Descriptive Sensorial Analysis was done by a panel of trained judges. For aroma descriptors, cooked descriptor showed differences between dairies, and whey was different among dairies and sampling seasons (P<0.01); diacetyl, fruity (P<0.01), as well as free fatty acids, nutty and sulphur (P<0.05) descriptors varied between seasons. For flavour descriptors, bitter perception was different between dairies and seasons (P<0.01). Salty and creamy cheese was also different among dairies (P<0.01). A Principal Component Analysis for differences among dairies and sampling season demonstrated that the first three components accounted for 90% of the variance; variables were more affected by the sampling seasons than by the geographical location or if the dairy was operated by Mennonites. Chihuahua cheese sensorial profile can be described as a semi-matured cheese with a bitter flavour, slightly salted, and with a cream flavour, with aroma notes associated with whey and sour milk. Principal Component Analysis demonstrated season influence on flavour and aroma characteristics.


Noncontact Infant Apnea Detection for Hypoxia Prevention With a K-Band Biomedical Radar.
Annually, a significant number of premature infants suffer from apnea, which can easily cause a drop in oxygen saturation levels, leading to hypoxia. However, infant cardiopulmonary monitoring using conventional methods often necessitates skin contact, and they are not suitable for long-term monitoring. This paper introduces a non-contact technique for infant cardiopulmonary monitoring and an adjustable apnea detection algorithm. These are developed using a custom-designed K-band continuous-wave biomedical radar sensor system, which features a DC-coupled adaptive digital tuning function. By using radar technology to detect chest motions without physical contact, it is feasible to extract significant biological information regarding an infant's respiration and heartbeat. The proposed algorithm utilizes an adaptively adjusted threshold and personalized apnea warning time to automatically measure the total number of apneic events and their respective durations. Experiments have been conducted in clinical environment, demonstrating that both the accurate cardiopulmonary signals and the apneas of varying durations can be effectively monitored using this method, which suggest that the proposed technique has potential applications both inside and outside of clinical settings.


Previously diagnosed influenza infections and the risk of developing epilepsy.
Several epidemiological studies suggest a possible involvement of viral infection in the development of epilepsy. While recent research from in vitro studies increasingly supports the role of herpes simplex virus type 1 (HSV-1) in the pathogenesis of epilepsy, little is known about the role of other viral infections such as influenza. Using data from the Clinical Practice Research Datalink (CPRD), we conducted a matched case-control analysis to assess the association between GP-diagnosed influenza infections and the risk of developing an incident diagnosis of epilepsy. During the study period 11 244 incident epilepsy cases and 44 976 matched control patients were identified. Prior exposure to influenza was reported in 7·5% of epilepsy cases and 6·7% of controls [adjusted odds ratio (aOR) 1·12, 95% confidence interval (CI) 1·03-1·22]. Prior history of 'complicated influenza', i.e. influenza associated with a possible super-infection, was associated with a slightly increased epilepsy risk (aOR 1·64, 95% CI 1·10-2·46), particularly if recorded within the 2 months preceding the epilepsy diagnosis (aOR 6·03, 95% CI 1·10-33·2). Our findings suggest that prior influenza exposure does not appear to materially alter the risk of developing epilepsy. By contrast, influenza episodes accompanied by complications were associated with a slightly increased epilepsy risk.


Influence of lung volume and electrode position on electromyography of the diaphragm.
In cats anesthetized with Nembutal, electromyograms of the diaphragm (Edi) were recorded from an anchored esophageal electrode, a pair of silver hooks inserted in the paratendinous region, and a pair of silver hooks and a pair of clips of small surface inserted in the costal region of the diaphragm facing the rib cage at FRC but covered with lung tissue at FRC + 80 ml. When single supramaximal electrical stimuli were applied to an isolated phrenic nerve, changes in lung volume from RV to near TLC had a negligible effect on muscle potentials from esophageal or paratendinous hooks, but increased the amplitude of potentials recorded from peripheral hooks and clips. In addition, it was found that small displacements of the esophageal electrode caused substantial changes in the amplitude of the recorded muscle potentials. The integration of the Edi spontaneously generated during occluded inspirations, recorded from paratendinous hooks and the esophageal electrode was linearly related to transdiaphragmatic pressure up to 50 cmH2O at all lung volumes. Above that level, esophageal electrode recordings showed a curvilinear Edi/Pdi relationship, while hook recordings showed a rectilinear relationship.


Osmotic stress signaling and osmoadaptation in yeasts.
The ability to adapt to altered availability of free water is a fundamental property of living cells. The principles underlying osmoadaptation are well conserved. The yeast Saccharomyces cerevisiae is an excellent model system with which to study the molecular biology and physiology of osmoadaptation. Upon a shift to high osmolarity, yeast cells rapidly stimulate a mitogen-activated protein (MAP) kinase cascade, the high-osmolarity glycerol (HOG) pathway, which orchestrates part of the transcriptional response. The dynamic operation of the HOG pathway has been well studied, and similar osmosensing pathways exist in other eukaryotes. Protein kinase A, which seems to mediate a response to diverse stress conditions, is also involved in the transcriptional response program. Expression changes after a shift to high osmolarity aim at adjusting metabolism and the production of cellular protectants. Accumulation of the osmolyte glycerol, which is also controlled by altering transmembrane glycerol transport, is of central importance. Upon a shift from high to low osmolarity, yeast cells stimulate a different MAP kinase cascade, the cell integrity pathway. The transcriptional program upon hypo-osmotic shock seems to aim at adjusting cell surface properties. Rapid export of glycerol is an important event in adaptation to low osmolarity. Osmoadaptation, adjustment of cell surface properties, and the control of cell morphogenesis, growth, and proliferation are highly coordinated processes. The Skn7p response regulator may be involved in coordinating these events. An integrated understanding of osmoadaptation requires not only knowledge of the function of many uncharacterized genes but also further insight into the time line of events, their interdependence, their dynamics, and their spatial organization as well as the importance of subtle effects.


The natural naphthoquinone plumbagin exhibits antiproliferative activity and disrupts the microtubule network through tubulin binding.
Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone), a naphthoquinone isolated from the roots of Plumbaginaceae plants, has potential antiproliferative activity against several tumor types. We have examined the effects of plumbagin on cellular microtubules ex vivo as well as its binding with purified tubulin and microtubules in vitro. Cell viability experiments using human non-small lung epithelium carcinoma cells (A549) indicated that the IC 50 value for plumbagin is 14.6 microM. Immunofluorescence studies using an antitubulin FITC conjugated antibody showed a significant perturbation of the interphase microtubule network in a dose dependent manner. In vitro polymerization of purified tubulin into microtubules is inhibited by plumbagin with an IC 50 value of 38 +/- 0.5 microM. Its binding to tubulin quenches protein tryptophan fluorescence in a time and concentration dependent manner. Binding of plumbagin to tubulin is slow, taking 60 min for equilibration at 25 degrees C. The association reaction kinetics is biphasic in nature, and the association rate constants for fast and slow phases are 235.12 +/- 36 M (-1) s (-1) and 11.63 +/- 11 M (-1) s (-1) at 25 degrees C respectively. The stoichiometry of plumbagin binding to tubulin is 1:1 (mole:mole) with a dissociation constant of 0.936 +/- 0.71 microM at 25 degrees C. Plumbagin competes for the colchicine binding site with a K i of 7.5 microM as determined from a modified Dixon plot. Based on these data we conclude that plumbagin recognizes the colchicine binding site to tubulin. Further study is necessary to locate the pharmacophoric point of attachment of the inhibitor to the colchicine binding site of tubulin.


A subpopulation of T cells bearing Fc receptors.
A wide range of cell populations were examined for Fc receptor (FcR)-bearing T cells: thymus, spleen, peritoneal cells, and T cells activated to H-2 antigens in spleen (ATC spleen) and in thoracic duct lymph (T-TDL). In addition, B lymphocytes from thoracic duct lymph of athymic nude mice and a Thy-1-positive, FcR-positive thymoma served as control cell populations. Reagents used were aggregates of human gamma-globulin and of various mouse myeloma proteins (IgG1, IgG2a, IgG2b), radioiodinated antigen-antibody complexes, and sheep erythrocyte antibody rosettes. Labeling techniques involving radioautography and immunofluorescence were used to demonstrate FcR by one of the above reagents and to identify T cells either by staining with anti-Thy-1.2 or by a specific rabbit anti-mouse T cell serum, or by failure to stain with anti-mouse immunoglobulin. In some experiments phagocytic cells were removed whereas in others they were identified by their capacity to engulf latex particles. Approximately 25% of cells with T cell markers were FcR-bearing cells in thymus, normal spleen, and peritoneal cavity, and 17% in ATC spleen. FcR on T cells in peripheral lymphoid tissues were detectable by aggregates of HGG and myeloma proteins and by radioiodinated immune complexes. Those on T cells in thymus were revealed only by aggregates of HGG. Circulating T cells (T.TDL) failed to display FcR: a) despite the use of a wide range of the above labeling techniques, each of which was shown to detect FcR on other T cells, thymoma cells, and B cells, and b) even after removal of Ig associated with their cell membranes. In contrast to B cell FcR which bound IgG1 preferentially, those on T cells bound both IgG1 and IgG2, raising the possibility that the FcR on T cell is distinct from that on B cell. It is concluded that FcR-bearing T cells represent a subpopulation of cells within the thymus and the secondary lymphoid tissues.


The ERF transcription factor TaERF3 promotes tolerance to salt and drought stresses in wheat.
Salinity and drought are major limiting factors of wheat (Triticum aestivum) productivity worldwide. Here, we report the function of a wheat ERF transcription factor TaERF3 in salt and drought responses and the underlying mechanism of TaERF3 function. Upon treatment with 250 mM NaCl or 20% polyethylene glycol (PEG), transcript levels of TaERF3 were rapidly induced in wheat. Using wheat cultivar Yangmai 12 as the transformation recipient, four TaERF3-overexpressing transgenic lines were generated and functionally characterized. The seedlings of the TaERF3-overexpressing transgenic lines exhibited significantly enhanced tolerance to both salt and drought stresses as compared to untransformed wheat. In the leaves of TaERF3-overexpressing lines, accumulation levels of both proline and chlorophyll were significantly increased, whereas H₂O₂ content and stomatal conductance were significantly reduced. Conversely, TaERF3-silencing wheat plants that were generated through virus-induced gene silencing method displayed more sensitivity to salt and drought stresses compared with the control plants. Real-time quantitative RT-PCR analyses showed that transcript levels of ten stress-related genes were increased in TaERF3-overexpressing lines, but compromised in TaERF3-silencing wheat plants. Electrophoretic mobility shift assays showed that the TaERF3 protein could interact with the GCC-box cis-element present in the promoters of seven TaERF3-activated stress-related genes. These results indicate that TaERF3 positively regulates wheat adaptation responses to salt and drought stresses through the activation of stress-related genes and that TaERF3 is an attractive engineering target in applied efforts to improve abiotic stress tolerances in wheat and other cereals.


Chronic calcaneal pain in athletes: entrapment of the calcaneal nerve?
In 11 heels in 10 athletes with chronic heel pain unrelieved by conservative therapy, the symptoms and physical findings caused a suspicion of entrapment of the calcaneal branches of the tibial nerve. The nerves were, therefore, surgically decompressed. No macroscopic signs of compression of the nerves were noted, but an entrapment of the anterior calcaneal branch could occur where the nerve passes between the tight and rigid edge of the deep fascia of the abductor hallucis and the medial edge of the os calcis. Followup of 58 months after surgery revealed that 10 of the 11 heels were asymptomatic and the patients had resumed athlete participation after an average of 5 weeks.


Estimating the Dose-Response Relationship for Ocular Pain after Radiotherapy of Head and Neck Cancers and Skull Base Tumors based on the LKB Radiobiological Model.
Radiotherapy is considered a compromise between the amount of killed tumor cells and the damage caused to the healthy tissue. Regarding this, radiobiological modeling is performed to individualize and optimize treatment strategies. This study aimed to determine the normal tissue complication probability (NTCP) of acute ocular pain following radiotherapy. In this prospective observational study, the clinical data were collected from 45 patients with head and neck cancers and skull-base tumors, and dosimetric data were recorded after contouring the eye globe. Acute ocular pain was prospectively assessed with a three-month follow-up. The Lyman-Kutcher-Berman (LKB) parameters were estimated using the Area Under Curve (AUC) of Receiver Operating Characteristic (ROC) maximization and Maximum Likelihood (MLH) methods, and the NTCP of acute ocular pain was then determined using generalized LKB radiobiological model. The model performance was evaluated with AUC, Brier score, and Hosmer-Lemeshow tests. Six out of 45 (13.33%) patients developed acute ocular pain (grade 1 or more). LKB model showed a weak dose-volume effect (n=0.09), tolerance dose for a 50% complication (TD50) of 27.54 Gy, and slope parameter (m) of 0.38. The LKB model showed high prediction performance. The LKB model predicted that NTCP would be less than 25% if the generalized equivalent uniform dose (gEUD) was kept below 20 Gy. The LKB model showed a high performance in determining the NTCP of ocular pain so that the probability of ocular pain will be less than 25% if the eye globe mean dose is kept below 12 Gy.


Direct spectroscopic detection of a C-H-cleaving high-spin Fe(IV) complex in a prolyl-4-hydroxylase.
The Fe(II)- and alpha-ketoglutarate (alphaKG)-dependent dioxygenases use mononuclear nonheme iron centers to effect hydroxylation of their substrates and decarboxylation of their cosubstrate, alphaKG, to CO(2) and succinate. Our recent dissection of the mechanism of taurine:alphaKG dioxygenase (TauD), a member of this enzyme family, revealed that two transient complexes accumulate during catalysis in the presence of saturating substrates. The first complex contains the long-postulated C-H-cleaving Fe(IV)-oxo intermediate, J, and the second is an enzyme.product(s) complex. Here, we demonstrate the accumulation of two transient complexes in the reaction of a prolyl-4-hydroxylase (P4H), a functional homologue of human alphaKG-dependent dioxygenases with essential roles in collagen biosynthesis and oxygen sensing. The kinetic and spectroscopic properties of these two P4H complexes suggest that they are homologues of the TauD intermediates. Most notably, the first exhibits optical absorption and Mössbauer spectra similar to those of J and, like J, a large substrate deuterium kinetic isotope on its decay. The close correspondence of the accumulating states in the P4H and TauD reactions supports the hypothesis of a conserved mechanism for substrate hydroxylation by enzymes in this family.


Peptidomic analysis of skin secretions from Rana heckscheri and Rana okaloosae provides insight into phylogenetic relationships among frogs of the Aquarana species group.
The members of the Aquarana (or Rana catesbeiana species group) form a monophyletic group comprising seven species: R. catesbeiana, Rana clamitans, Rana grylio, Rana virgatipes, Rana septentrionalis, Rana heckscheri and Rana okaloosae. Previous work has led to structural characterization of the antimicrobial peptides present in electrically-stimulated skin secretions from the first five species listed and this study presents the primary structures of orthologs from the river frog R. heckscheri and the Florida bog frog R. okaloosae. Peptidomic analysis of R. heckscheri and R. okaloosae skin secretions led to the identification of peptides with antimicrobial activity belonging to the ranalexin, ranatuerin-2, and temporin families. In addition, a peptide (GFLDIIKDTGKDFAVKILNNLKCKLAGGCPR) was isolated from R. okaloosae whose primary structure identified it as a member of the palustrin-2 family. Consistent with previous data based upon morphological analysis and comparisons of the nucleotide sequences of mitochondrial and ribosomal genes, cladistic analysis based upon a comparison of the amino acid sequences of antimicrobial peptides indicates a sister-group relationship between R. heckscheri and R. grylio and a close, but less well defined, phylogenetic relationship between R. okaloosae and R. clamitans.


Production and purification of agarase from a marine agarolytic bacterium Agarivorans sp. HZ105.
Isolation and characterization of an agarase-producing bacterium Agarivorans sp. HZ105. An agarase-producing bacterium strain HZ105 had been isolated from marine sediment sample. Based on phylogenetic analysis of the 16S rRNA gene sequence and phenotypic analysis, as well as biochemical analyses, this strain was named Agarivorans sp. HZ105. Effect of pH, NaCl on the growth and agarase production of strain HZ105 was studied. Strain HZ105 produced three extracellular agarases which were purified to homogeneity from bands in the PAGE gel. Two agarases of these three had a molecular mass of 54, 58 kDa, respectively. And the MS and MS/MS spectra were used to identify the agarases. The MS spectra result showed that the agarases of strain HZ105 should be beta-agarase and belong to the family 50 of glycosyl hydrolases. The agarases could keep stable activity at room temperature. The strain HZ105 was useful to produce stable agarases. The solution produced by agar's degradation in the agar plates was first reported to be used for purification of agarase. Agarases were purified to homogeneity directly from the PAGE gel without stained by Coomassie brilliant blue.


Clinical features and therapeutic outcomes of patients with acromegaly: single-center experience.
The aim of this study was to review the outcome of acromegaly treatment, as well as co-morbidity and mortality in a series of patients with acromegaly attending a single center in the last 10 yr. In that period, 53 patients were treated for acromegaly. Transsphenoidal operation was applied as the first-line therapy in 94.3% of patients and it led to disease remission in 59.2% of them. The remission criteria included a nadir GH<1 μg/l after glucose load, and normal age-related IGF-I levels. The remission rate after transsphenoidal surgery was significantly higher in the group of patients with microadenoma (76.9%), than in the group of patients with macroadenoma (52.8%). Patients with invasive tumors had remission rate of 16.7% after transsphenoidal surgery. There were no perioperative deaths. As the second-line treatment somatostatin analogues, radiotherapy, and dopaminergic agonists were used. Hypertension and diabetes were the most frequent co-morbidities in the group of patients. After successful treatment, 30% of patients with diabetes or impaired glucose tolerance had significant improvement of glycemic control. Transsphenoidal surgery is the appropriate firstline therapy in patients with somatotropinoma. Medical and radio-therapy should be reserved as the second-line therapy after surgery failure.


A Case of Auditory Neuropathy Caused by Pontine Hemorrhage in an Adult.
A pontine hemorrhage can evoke several neurological symptoms because the pons contains various nuclei and nerve fibers. Hearing loss can develop as a result of a pontine hemorrhage because there is an auditory conduction pathway in the cochlear nucleus of the pons. However, very few cases of hearing loss caused by pontine lesions have been reported, and there have been no reports of auditory neuropathy that developed following a pontine hemorrhage. Recently we had a patient who experienced a nontraumatic pontine hemorrhage who was diagnosed with auditory neuropathy. The 34-year-old male patient was admitted to the emergency department with sudden alteration of mental status. His brain computed tomographic imaging revealed a hemorrhage in the central pons. He complained of hearing difficulties after his mental status recovered through conservative treatment, but a pure-tone audiogram showed very mild hearing loss in both ears. Further hearing tests using otoacoustic emissions, which showed normal responses, and auditory brainstem responses, which showed no waveforms at maximum stimulus intensity, revealed that his hearing difficulties were caused by auditory neuropathy. This case implies that the threshold of sound detection can be preserved in patients with pontine hemorrhage who complain of hearing difficulties. Auditory neuropathy should be considered as a possible cause of hearing difficulties in these patients and appropriate hearing tests should be performed.


Binding and biologic characterization of recombinant human serum albumin-eTGFBR2 fusion protein expressed in CHO cells.
Transforming growth factor-β1 (TGF-β1) signaling is involved in cell metabolism, growth, differentiation, carcinoma invasion and fibrosis development, which suggests TGF-β1 can be treated as a therapeutic target extensively. Because TGF-β1 receptor type α(TGFBR2) is the directed and essential mediator for TGF-β1 signals, the extracellular domain of TGFBR2 (eTGFBR2), binding partner for TGF-β1, has been produced in a series of expression systems to inhibit TGF-β1 signaling. However, eTGFBR2 is unstable with a short half-life predominantly because of enzymatic degradation and kidney clearance. In this study, a fusion protein consisting of human eTGFBR2 fused at the C-terminal of human serum albumin (HSA) was stably and highly expressed in Chinese Hamster Ovary (CHO) cells. The high and stable expression sub-clones with Ig kappa signal peptide were selected by Western blot analysis and used for suspension culture. After fed-batch culture over 8 d, the expression level of HSA-eTGFBR2 reached 180 mg/L. The fusion protein was then purified from culture medium using a 2-step chromatographic procedure that resulted in 39% recovery rate. The TGF-β1 binding assay revealed that HSA-eTGFBR2 could bind to TGF-β1 with the affinity constant (KD of 1.42 × 10-8 M) as determined by the ForteBio Octet System. In addition, our data suggested that HSA-eTGFBR2 exhibited a TGF-β1 neutralizing activity and maintained a long-term activity more than eTGFBR2. It concluded that the overexpressing CHO cell line supplied sufficient recombinant human HSA-eTGFBR2 for further research and other applications.


Statistical analysis of unstructured amino acid residues in protein structures.
We have performed a statistical analysis of unstructured amino acid residues in protein structures available in the databank of protein structures. Data on the occurrence of disordered regions at the ends and in the middle part of protein chains have been obtained: in the regions near the ends (at distance less than 30 residues from the N- or C-terminus), there are 66% of unstructured residues (38% are near the N-terminus and 28% are near the C-terminus), although these terminal regions include only 23% of the amino acid residues. The frequencies of occurrence of unstructured residues have been calculated for each of 20 types in different positions in the protein chain. It has been shown that relative frequencies of occurrence of unstructured residues of 20 types at the termini of protein chains differ from the ones in the middle part of the protein chain; amino acid residues of the same type have different probabilities to be unstructured in the terminal regions and in the middle part of the protein chain. The obtained frequencies of occurrence of unstructured residues in the middle part of the protein chain have been used as a scale for predicting disordered regions from amino acid sequence using the method (FoldUnfold) previously developed by us. This scale of frequencies of occurrence of unstructured residues correlates with the contact scale (previously developed by us and used for the same purpose) at a level of 95%. Testing the new scale on a database of 427 unstructured proteins and 559 completely structured proteins has shown that this scale can be successfully used for the prediction of disordered regions in protein chains.


Clinical role of guidance by C-arm CT for 125I brachytherapy on pulmonary tumors.
To evaluate the clinical value of C-arm CT (CACT)-guided interstitial iodine-125 (125I) brachytherapy on pulmonary tumors. 30 patients with 40 solid pulmonary tumors were enrolled to undergo CACT-guided interstitial 125I brachytherapy between November 2011 and November 2014. The needle path was planned on a CACT virtual navigation and real-time fluoroscopy system. Technical success, puncture score, procedure time, local control rate (LCR), radiation exposure, complications and survival were investigated. The technical success of interstitial 125I brachytherapy under CACT guidance was 40/40 (100%). The performance score was 4.7 ± 0.5 with a mean total procedure time of 17.7 ± 5.6 min. LCR in small (≤2.0 cm), intermediate (2.1-4.9 cm) and large (≥5.0 cm) pulmonary tumors was 100, 89.5 and 72.7% at the 4-month follow-up, respectively. The mean effective dose was 10.1 ± 2.8 mSv. Major complications occurred in four patients (13.3%). The mean survival time was 28.4 ± 2.3 months. CACT can provide virtual navigation and real-time fluoroscopy synchronously for interstitial 125I seed implantation on pulmonary tumors.


Current Fragment-to-lead Approaches Starting from the 7-azaindole: The Pharmacological Versatility of a Privileged Molecular Fragment.
Fragment-based drug discovery is one of the most powerful paradigms in the recent context of medicinal chemistry and is being widely practiced by academic and industrial researchers. Currently, azaindoles are among the most exploited molecular fragments in pharmaceutical innovation projects inspired by fragment-to-lead strategies. The 7-azaindole is the most prominent representative within this remarkable family of pyrrolopyridine fragments, as it is present in the chemical structure of several approved antitumor drugs and also of numerous therapeutic candidates. In this paper, a brief overview on existing proofs of concept in the literature will be presented, as well as some recent works that corroborate 7-azaindole as a privileged and pharmacologically versatile molecular fragment.


Iatrogenic benign paroxysmal positional vertigo: review and personal experience in dental and maxillo-facial surgery.
The post-traumatic origin of benign paroxysmal positional vertigo remains the most likely, from a patho-physiologic point of view. Benign paroxysmal positional vertigo due to surgical "traumas" has been described in the medical literature. According to personal experience, these iatrogenic cases represent a rare possibility and may be the consequence of surgical interventions differing according to the anatomical district involved and surgical technique performed. The temporal relationship with the surgical action and clinical features may be involved in some of these cases, even if it is not possible to define any real cause-effect link. Herewith some cases of paroxysmal positional vertigo are described, strongly held to be of iatrogenic origin, focusing on dental and maxillo-facial surgery as risk factors for benign paroxysmal positional vertigo.


Effect of herbo-mineral formulation EHb in experimental anaemia in rodents.
EHb-a herbo-mineral formulations of iron (ferrous form) produced a significantly higher and dose dependent increase in the haemoglobin level, as compared to Fefol (a non-complex-chelated iron preparation). Also, EHb did not produce any overt toxicity or gastric irritation at these dose levels. The results suggest that EHb can be of a better choice in the treatment of anaemia than any other commercially available chelated iron preparations.


The relationship between ipsilateral cochlear gain reduction and speech-in-noise recognition at positive and negative signal-to-noise ratios.
Active mechanisms that regulate cochlear gain are hypothesized to influence speech-in-noise perception. However, evidence of a relationship between the amount of cochlear gain reduction and speech-in-noise recognition is mixed. Findings may conflict across studies because different signal-to-noise ratios (SNRs) were used to evaluate speech-in-noise recognition. Also, there is evidence that ipsilateral elicitation of cochlear gain reduction may be stronger than contralateral elicitation, yet, most studies have investigated the contralateral descending pathway. The hypothesis that the relationship between ipsilateral cochlear gain reduction and speech-in-noise recognition depends on the SNR was tested. A forward masking technique was used to quantify the ipsilateral cochlear gain reduction in 24 young adult listeners with normal hearing. Speech-in-noise recognition was measured with the PRESTO-R sentence test using speech-shaped noise presented at -3, 0, and +3 dB SNR. Interestingly, greater cochlear gain reduction was associated with lower speech-in-noise recognition, and the strength of this correlation increased as the SNR became more adverse. These findings support the hypothesis that the SNR influences the relationship between ipsilateral cochlear gain reduction and speech-in-noise recognition. Future studies investigating the relationship between cochlear gain reduction and speech-in-noise recognition should consider the SNR and both descending pathways.


Sagittal alignment of the first metatarsophalangeal joint after arthrodesis for rheumatoid forefoot deformity.
The present study assessed the midterm results of reconstruction for rheumatoid forefoot deformity with arthrodesis of the first metatarsophalangeal (MTP) joint, scarf osteotomy, resection arthroplasty of the metatarsal head of the lesser toes, and surgical repair of hammertoe deformity (arthrodesis of the proximal interphalangeal joint). Special focus was placed on the sagittal alignment of the first metatarsophalangeal joint after arthrodesis. We retrospectively evaluated the postoperative clinical outcomes and radiographic findings for 16 consecutive female patients (20 feet) with symptomatic rheumatoid forefoot deformities. The mean duration of follow-up was 7.9 (range 4 to 13) years. All first MTP joints and first metatarsal bones were fused successfully. The mean value of the American Orthopaedic Foot and Ankle Society and Japanese Society for Foot Surgery clinical scores significantly improved overall, except for 2 patients (10%), who complained of first toe pain at the final follow-up visit owing to sagittal misalignment of the fused first MTP joint. Sagittal alignment of the first metatarsal varies greatly because of the rheumatoid midfoot and hindfoot deformities. Therefore, inclination of the first metatarsal should be considered when determining the first MTP joint sagittal fusion angle.


Cu removal and response mechanisms of periphytic biofilms in a tubular bioreactor.
This work studied Cu removal and response mechanisms of periphytic biofilms in a tubular bioreactor. Periphytic biofilms immobilized in a tubular bioreactor were used to remove Cu from wastewater with different Cu concentrations. Results showed that periphytic biofilms had a high removal efficiency (max. 99%) at a hydraulic retention time (HRT) of 12h under initial Cu concentrations of 2.0 and 10.0mgL-1. Periphyton quickly adapted to Cu stress by regulating the community composition. Species richness, evenness and carbon metabolic diversity of the periphytic community increased when exposed to Cu. Diatoms, green algae, and bacteria (Gammaproteobacteria and Bacteroidia) were the dominant microorganisms and responsible for Cu removal. This study indicates that periphytic biofilms are promising in Cu removal from wastewater due to their strong adaptation capacity to Cu toxicity and also provides valuable information for understanding the relationships between microbial communities and heavy metal stress.


[Dentinal hypersensivity after vertical stripping of enamel].
Vertical stripping of enamel in patients with minor or moderate crowding of teeth and Angle's class I is an effective method which supplements orthodontic treatment. Stripping is an alternative to tooth extraction or to extension of alveolar arches which carries the risk of recurrence of crowding and further periodontal difficulties. Stripping also shortens considerably the duration of treatment. Apart from unquestionable advantages, enamel reduction may lead to complications such as caries or hypersensitivity of interproximal surfaces of stripped teeth. The aim of this study was to determine the prevalence of hypersensitivity and to measure the intensity of pain. We performed a verbal and visual assessment of pain in a group of 32 patients who underwent stripping during the recent few years as part of orthodontic treatment. According to verbal assessment, the highest percentage (46.9%) of patients rated their pain as 1 (gentle pain) which corresponded to 1-3 cm on the 10 cm Visual Analog Scale. 37.5% of patients reported no pain. None of the patients described their pain as very strong and discouraging from further treatment. All symptoms subsided without recurrence. The patients found this method to be more effective than alternative ones.


MicroRNA-138 targets SP1 to inhibit the proliferation, migration and invasion of hepatocellular carcinoma cells.
The identification of microRNAs (miRNAs/miRs) has enabled the improved understanding of the carcinogenesis and progression of hepatocellular carcinoma (HCC). miRNAs are small non-coding RNAs comprised of 19-24 nucleotides that regulate the expression of target genes. In the present study, miR-138 was demonstrated to be downregulated in human HCC tissues and cell lines. Restoration of miR-138 expression repressed the proliferation, migration and invasion of HCC cells. Furthermore, specificity protein 1 (SP1) was identified as a target gene of miR-138 in HCC using bioinformatics analysis, luciferase reporter assay, reverse transcription-quantitative polymerase chain reaction and western blot analysis. Knockdown of SP1 produced similar suppressive effects to those induced by miR-138 overexpression in HCC cells. These results indicate that miR-138 targeted SP1 to repress the growth, migration and invasion of HCC cells, and may therefore represent a therapeutic target in human HCC.


The disposition and metabolism of rofecoxib, a potent and selective cyclooxygenase-2 inhibitor, in human subjects.
The disposition and metabolism of rofecoxib, a selective cyclooxygenase-2 inhibitor, were examined in healthy human subjects and in cholecystectomy patients. After oral administration of [(14)C]rofecoxib (125 mg, 100 micro Ci) to healthy subjects, the mean concentrations of total radioactivity and rofecoxib in plasma as a function of time indicated that the t(max) was achieved at 9 h postdose. After t(max), levels of both radioactivity and rofecoxib decreased in a parallel, exponential fashion (effective t(1/2) approximately equal 17 h). A similar result was obtained after oral administration of [(14)C]rofecoxib (142 mg, 100 micro Ci) to cholecystectomy patients equipped with an L-tube. In healthy subjects, radioactivity was recovered predominantly from the urine (71.5% of dose), with a small amount excreted in feces (14.2%). In patients with an L-tube, half the radioactive dose was recovered in feces, with a lesser amount excreted in urine (28.8%) and a negligible fraction in bile (1.8%). Rofecoxib underwent extensive metabolism in humans, and very little parent drug was recovered unchanged in urine (<1%). Products resulting from both oxidative and reductive pathways were identified by a combination of (1)H NMR and liquid chromatography-tandem mass spectrometry analyses, and included rofecoxib-3',4'-trans-dihydrodiol, 4'-hydroxyrofecoxib-O-beta-D-glucuronide, diastereomeric 5-hydroxyrofecoxib-O-beta-D-glucuronide conjugates, 5-hydroxyrofecoxib, rofecoxib-erythro-3,4-dihydrohydroxy acid, and rofecoxib-threo-3,4-dihydrohydroxy acid. Interconversion of rofecoxib and 5-hydroxyrofecoxib appeared not to be a quantitatively important pathway of rofecoxib disposition in human subjects, in contrast to previous findings in rats.


Manganese uptake and accumulation by the hyperaccumulator plant Phytolacca acinosa Roxb. (Phytolaccaceae).
The perennial herb Phytolacca acinosa Roxb. (Phytolaccaceae), which occurs in Southern China, has been found to be a new manganese hyperaccumulator by means of field surveys on Mn-rich soils and by glasshouse experiments. This species not only has remarkable tolerance to Mn but also has extraordinary uptake and accumulation capacity for this element. The maximum Mn concentration in the leaf dry matter was 19,300 microg/g on Xiangtan Mn tailings wastelands, with a mean of 14,480 microg/g. Under nutrient solution culture conditions, P. acinosa could grow normally with Mn supplied at a concentration of 8000 micromol/l, although with less biomass than in control samples supplied with Mn at 5 micromol/l. Manganese concentration in the shoots increased with increasing external Mn levels, but the total mass of Mn accumulated in the shoots first increased and then decreased. At an Mn concentration of 5000 micromol/l in the culture solution, the Mn accumulation in the shoot dry matter was highest (258 mg/plant). However, the Mn concentration in the leaves reached its highest value (36,380 microg/g) at an Mn supply level of 12,000 micromol/l. These results confirm that P. acinosa is an Mn hyperaccumulator which grows rapidly, has substantial biomass, wide distribution and a broad ecological amplitude. This species provides a new plant resource for exploring the mechanism of Mn hyperaccumulation, and has potential for use in the phytoremediation of Mn-contaminated soils.


Blood-Brain Barrier, Blood-Brain Tumor Barrier, and Fluorescence-Guided Neurosurgical Oncology: Delivering Optical Labels to Brain Tumors.
Recent advances in maximum safe glioma resection have included the introduction of a host of visualization techniques to complement intraoperative white-light imaging of tumors. However, barriers to the effective use of these techniques within the central nervous system remain. In the healthy brain, the blood-brain barrier ensures the stability of the sensitive internal environment of the brain by protecting the active functions of the central nervous system and preventing the invasion of microorganisms and toxins. Brain tumors, however, often cause degradation and dysfunction of this barrier, resulting in a heterogeneous increase in vascular permeability throughout the tumor mass and outside it. Thus, the characteristics of both the blood-brain and blood-brain tumor barriers hinder the vascular delivery of a variety of therapeutic substances to brain tumors. Recent developments in fluorescent visualization of brain tumors offer improvements in the extent of maximal safe resection, but many of these fluorescent agents must reach the tumor via the vasculature. As a result, these fluorescence-guided resection techniques are often limited by the extent of vascular permeability in tumor regions and by the failure to stain the full volume of tumor tissue. In this review, we describe the structure and function of both the blood-brain and blood-brain tumor barriers in the context of the current state of fluorescence-guided imaging of brain tumors. We discuss features of currently used techniques for fluorescence-guided brain tumor resection, with an emphasis on their interactions with the blood-brain and blood-tumor barriers. Finally, we discuss a selection of novel preclinical techniques that have the potential to enhance the delivery of therapeutics to brain tumors in spite of the barrier properties of the brain.


Stack, seal, evacuate, draw: a method for drawing hollow-core fiber stacks under positive and negative pressure.
The two-stage stack and draw technique is an established method for fabricating microstructured fibers, including hollow-core fibers. A stack of glass elements of around a meter in length and centimeters in outer diameter forms the first stage preform, which is drawn into millimeter scale canes. The second stage preform is one of the canes, which is drawn, under active pressure, into microscopic fiber. Separately controlled pressure lines are connected to different holes or sets of holes in the cane to control the microstructure of the fiber being drawn, often relying on glues or other sealants to isolate the differently-pressured regions. We show that the selective fusion and collapse of the elements of the stack, before it is drawn to cane or fiber, allows the stack to be drawn directly under differential pressure without introducing a sealant. Three applications illustrate the advantages of this approach. First, we draw antiresonant hollow-core fiber directly from the stack without making a cane, allowing a significantly longer length of fiber to be drawn. Second, we fabricate canes under pressure, such that they are structurally more similar to the final fiber. Finally, we use the method to fabricate new types of microstructured resonators with a non-circular cross-section.


Recurrent Childhood Animal Cruelty and Its Link to Recurrent Adult Interpersonal Violence.
In the early 1960s, researchers began to examine the potential link between childhood animal cruelty and future interpersonal violence. Findings since then have been inconsistent in establishing a relationship between the two. This may be due to researchers failing to measure the recurrency of childhood animal abuse and the recurrency of later violent acts committed in adulthood. The current study, using data from 257 inmates at a medium-security prison in a Southern state, is a replication of research conducted by Tallichet and Hensley, and Hensley, Tallichet, and Dutkiewicz, which examined this recurrency issue. The only statistically significant predictor of recurrent adult interpersonal violence in this study was recurrent childhood animal cruelty. Inmates who engaged in recurrent childhood animal cruelty were more likely to commit recurrent adult interpersonal violence. Respondents' race, education, and childhood residence were not significant predictors of the outcome variable.


Postencephalitic Parkinson's disease, amyotrophic lateral sclerosis on Guam and influenza revisited: focusing on neurofibrillary tangles and the trail of tau.
Circumstantial evidence links neuropathological changes in postencephalitic Parkinson's disease and amyotrophic lateral sclerosis on Guam to the 1918 influenza pandemic. Postencephalitic Parkinson's disease and amyotrophic lateral sclerosis have neuronal neurofibrillary tangles that anatomically correlate with clinical signs and symptoms. Occurrences of the disorders peaked in the early 1950s and are now disappearing. Neurovirulent influenza associated with the lethal 1918 pandemic is suggested as the etiology of both diseases. Permissive tissue antigens are considered an important contributing factor. Neurofibrillary tangles also correlate with signs and symptoms in Alzheimer's disease. Oxidative stress may be the pathological process that induces neurofibrillary tangles. Tangles contain abnormally phosphorylated tau. In Alzheimer's disease, tau is present in cerebrospinal fluid and is deposited in corpora amylacea, demonstrating the direction of cerebrospinal fluid flow.


Neurological Disorders Seen During Second Wave of SARS-CoV-2 Pandemic from Two Tertiary Care Centers in Central and Southern Kerala.
SARS-CoV-2 infections present with predominant respiratory symptoms. Only a few anecdotal reports of neurological involvement have come out from India so far. Adverse neurological events following immunization (AEFI) were also reported. We present the neurological symptoms seen either in association with vaccination or COVID-19 infection during the second wave. This was a retrospective study that included consecutive COVID-19 patients' admissions during the second wave of COVID-19 pandemic in two tertiary health care centres in Kerala. Neurological symptoms two weeks prior or thirty days after a positive status of antigen or RTPCR was termed as COVID-19-Associated Neurological Disorders (CAND) and those with neurological symptoms within one month of COVID-19 vaccination was termed as Post-Vaccinal Neurological Disorders (PVND). During the study period, 1270 COVID-19 admissions were reported. We identified neurological symptoms in 42 patients (3.3%), of which 35 were CAND and 7 were PVND. Stroke was the most common (50%), followed by seizures and peripheral nervous system disorders (14.2% each). Encephalitis/demyelination (11.9%) and COVID-19-associated infections (9.5%) were also seen. During the SARS-CoV-2 pandemic, CAND and PVND have been emerging. Association of some of these may be fortuitous; however it is worth mentioning as pathogenic mechanisms of COVID-19 affecting various organ systems still remain unclear. Moreover, this may be helpful in future studies designing management options.


Feasibility to use whole-genome sequencing as a sole diagnostic method to detect genomic aberrations in pediatric B-cell acute lymphoblastic leukemia.
The suitability of whole-genome sequencing (WGS) as the sole method to detect clinically relevant genomic aberrations in B-cell acute lymphoblastic leukemia (ALL) was investigated with the aim of replacing current diagnostic methods. For this purpose, we assessed the analytical performance of 150 bp paired-end WGS (90x leukemia/30x germline). A set of 88 retrospective B-cell ALL samples were selected to represent established ALL subgroups as well as ALL lacking stratifying markers by standard-of-care (SoC), so-called B-other ALL. Both the analysis of paired leukemia/germline (L/N)(n=64) as well as leukemia-only (L-only)(n=88) detected all types of aberrations mandatory in the current ALLTogether trial protocol, i.e., aneuploidies, structural variants, and focal copy-number aberrations. Moreover, comparison to SoC revealed 100% concordance and that all patients had been assigned to the correct genetic subgroup using both approaches. Notably, WGS could allocate 35 out of 39 B-other ALL samples to one of the emerging genetic subgroups considered in the most recent classifications of ALL. We further investigated the impact of high (90x; n=58) vs low (30x; n=30) coverage on the diagnostic yield and observed an equally perfect concordance with SoC; low coverage detected all relevant lesions. The filtration of the WGS findings with a short list of genes recurrently rearranged in ALL was instrumental to extract the clinically relevant information efficiently. Nonetheless, the detection of DUX4 rearrangements required an additional customized analysis, due to multiple copies of this gene embedded in the highly repetitive D4Z4 region. We conclude that the diagnostic performance of WGS as the standalone method was remarkable and allowed detection of all clinically relevant genomic events in the diagnostic setting of B-cell ALL.


miR167 limits anther growth to potentiate anther dehiscence.
In flowering plants, anther dehiscence and pollen release are essential for sexual reproduction. Anthers dehisce after cell wall degradation weakens stomium cell junctions in each anther locule, and desiccation creates mechanical forces that open the locules. Either effect or both together may break stomium cell junctions. The microRNA miR167 negatively regulates ARF6 and ARF8, which encode auxin response transcription factors. Arabidopsis mARF6 or mARF8 plants with mutated miR167 target sites have defective anther dehiscence and ovule development. Null mir167a mutations recapitulated mARF6 and mARF8 anther and ovule phenotypes, indicating that MIR167a is the main miR167 precursor gene that delimits ARF6 and ARF8 expression in these organs. Anthers of mir167a or mARF6/8 plants overexpressed genes encoding cell wall loosening functions associated with cell expansion, and grew larger than wild-type anthers did starting at flower stage 11. Experimental desiccation enabled dehiscence of miR167-deficient anthers, indicating competence to dehisce. Conversely, high humidity conditions delayed anther dehiscence in wild-type flowers. These results support a model in which miR167-mediated anther growth arrest permits anther dehiscence. Without miR167 regulation, excess anther growth delays dehiscence by prolonging desiccation.


[Turner's phenotype and diagnosis of Noonan's syndrome].
The Authors describe two cases of Noonan's Syndrome (Turner phenotype and normal Karyotype), underlining the necessity of a differential diagnosis with the "True" Syndrome of Turner, for the presence, in the latter, of a non development of the height, weight and phenotype, which moves away from the standard much. While on the contrary in the Noonan's syndrome both the sexual development and the evolution of the height and weight may be normal and in the latter syndrome, so, the attention of the Doctors has to be turned prevalently to the congenital cardiopathy (almost always stenosis of the pulmonary artery), which can also impair the life of the patient.


Electronic structure of crystalline copper phthalocyanine.
The electronic structure of copper-phthalocyanine (CuPc) has been studied both experimentally and theoretically. Experiments have been performed on alpha and beta crystalline phases, using photoemission spectroscopy to probe core levels and valence band spectra. Different photon energies have been used, in order to probe different sample depths. Only minor differences have been observed in the experimental data on the two different phases, except for a small charge effect on the beta phase crystal. First-principles calculations have been performed using the density functional for molecular and three-dimensional periodic solids (Dmol(3)) code on both the single CuPc molecule and the beta phase, allowing the identification of the different atomic and angular contributions to the experimental density of states. In particular, the highest occupied molecular level is mainly due to Cu and N states. The comparison between theoretical data obtained for the CuPc in the beta phase and in the single molecule shows that the interchain interaction between the molecules is negligible, whereas slightly stronger intrachain interactions occur.


Lack of pharmacokinetic interaction of meloxicam with methotrexate in patients with rheumatoid arthritis.
To investigate the pharmacokinetic interaction of oral meloxicam with intravenous (i.v.) methotrexate (MTX) in patients with rheumatoid arthritis (RA). Thirteen patients with RA received MTX 15 mg i.v. in the absence of nonsteroidal antiinflammatory drugs (NSAID) and after one week in the presence of steady state levels of meloxicam. Plasma concentrations of MTX and meloxicam were determined using validated high performance liquid chromatography methods. One patient did not complete the study. The interaction of meloxicam and MTX was examined by equivalence testing. The endpoints AUCMTX, VssMTX, CltotMTX, and CmaxMTX were analyzed parametrically, whereas endpoints MRTMTX, CltotMTX, t1/2MTX, and tmaxMTX were analyzed nonparametrically. The MTX plasma concentrations over time, with and without meloxicam, did not differ significantly. The point estimator for the ratio of log transformed data of the primary endpoint AUCMTX was 108%; the lower 95% confidence limit was 100% and the upper 95% confidence limit was 117%. Clinical laboratory values and adverse events revealed no increased MTX toxicity during concomitant treatment with meloxicam. In this short term interaction study there was no statistically significantly effect of meloxicam on the pharmacokinetics of MTX. The combination of MTX and meloxicam did not lead to increased MTX toxicity.


The coactivator function of Arabidopsis NPR1 requires the core of its BTB/POZ domain and the oxidation of C-terminal cysteines.
NONEXPRESSOR OF PATHOGENESIS-RELATED GENES1 (NPR1) regulates systemic acquired resistance (SAR) in Arabidopsis thaliana, and current models propose that after treatment with salicylic acid (SA), Cys-82 and Cys-216 of NPR1 are reduced, leading to nuclear import. The interaction of nucleus-localized NPR1 with TGA transcription factors results in the activation of defense genes, including the SAR marker PATHOGENESIS-RELATED-1 (PR-1), and the deployment of SAR. Little is known about how TGA factors or NPR1 regulate transcription or whether a TGA-NPR1 complex forms on DNA. We show that TGA2 and NPR1 are recruited to PR-1 independently of each other and of SA treatment. Consistent with the result that a triple knockout in TGA2/5/6 derepresses PR-1, in vivo plant transcription assays revealed that TGA2 is not an autonomous transcription activator but is a transcriptional repressor in both untreated and SA-treated cells. However, after stimulation with SA, TGA2 is incorporated into a transactivating complex with NPR1, forming an enhanceosome that requires the core of the NPR1 BTB/POZ domain (residues 80 to 91) and the oxidation of NPR1 Cys-521 and Cys-529. These Cys residues are found in a new type of transactivation domain that we term Cys-oxidized. These data further our understanding of the mechanism by which TGA2 and NPR1 activate Arabidopsis PR-1.


Correlation between cell migration and reactive oxygen species under electric field stimulation.
Cell migration is an essential process involved in the development and maintenance of multicellular organisms. Electric fields (EFs) are one of the many physical and chemical factors known to affect cell migration, a phenomenon termed electrotaxis or galvanotaxis. In this paper, a microfluidics chip was developed to study the migration of cells under different electrical and chemical stimuli. This chip is capable of providing four different strengths of EFs in combination with two different chemicals via one simple set of agar salt bridges and Ag/AgCl electrodes. NIH 3T3 fibroblasts were seeded inside this chip to study their migration and reactive oxygen species (ROS) production in response to different EF strengths and the presence of β-lapachone. We found that both the EF and β-lapachone level increased the cell migration rate and the production of ROS in an EF-strength-dependent manner. A strong linear correlation between the cell migration rate and the amount of intracellular ROS suggests that ROS are an intermediate product by which EF and β-lapachone enhance cell migration. Moreover, an anti-oxidant, α-tocopherol, was found to quench the production of ROS, resulting in a decrease in the migration rate.


Anesthetic management of a newborn with occipital meningocele for magnetic resonance imaging.
Cranial Meningocoele is a term which represents herniation of meninges and cerebrospinal fluid through the congenital defect in the cranium. Anaesthetic challenges in the management of neonates with occipital meningocoele include airway management and proper positioning of the neonate without pressure on the meningocoele sac so as to preventthe rupture of the membranes. Associated congenital anomalies also can cause anaesthesia and procedure related complications. Other difficulties include performing a difficult airway case in an unfamiliar environment outside operation theatre. We report a case of 6 day old neonate with occipital meningocoele posted for MRI brain and the successful anaesthetic management.


Early inadequate venous flow volume after technically successful balloon angioplasty of radiocephalic arteriovenous fistula: causes and follow-up results.
The objective of this study was to investigate the causes of inadequate venous flow volume, which may lead to re-dysfunction in the early period after technically successful percutaneous transluminal angioplasty (PTA), and the results after one-week follow-up with or without medical treatment. This prospective case-control study included dysfunctional radiocephalic arteriovenous fistula (AVF) cases treated with PTA between December 2021-2022. After PTA, a residual stenosis of less than 30% was considered technically successful. Based on venous flow volume measured 1-2 hours after angioplasty, post-procedural doppler ultrasound (DUS) classified patients as cases (≤400 mL/min) or controls (>400 mL/min). Between groups, pre-post and control DUS parameters were compared. The correlation between fistulography lesion measurements and DUS values was investigated. The pre-procedural DUS resistive index (RI) cut-off value was determined to discriminate groups. A total of 42 patients, 21 cases and 21 controls, were included in the study. Before PTA, 67% of cases had total venous thrombosis, and 71% of controls had stenosis. Lesion measurements and residual stenosis were similar between groups (p>0.05). After PTA, 48% of cases had a free-floating thrombus in the vein, and 10% had a peri-vein hematoma. In pre-procedural DUS, flow volume was the only spectral analysis parameter paired between groups (p=0.057). In post-procedural and control DUS, controls had higher peak systolic velocity (PSV), end-diastolic velocity (EDV), and flow volume, whereas cases had a higher RI (p<0.05). Lesion length and degree of stenosis correlated positively with pre-procedural RI in both groups (p<0.05). The pre-procedural RI cut-off of 0.76 discriminated groups with 76% sensitivity, 67% specificity, 70% positive predictive value (PPV), and 74% negative predictive value (NPV). Low venous flow after PTA has been primarily associated with free-floating thrombi. Routine post-procedural DUS detects low venous flow, high RI, and small thrombi, providing evidence to initiate medical treatment that may prevent early AVF re-dysfunction.


Acetyl-macrocalin B, an ent-kaurane diterpenoid, initiates apoptosis through the ROS-p38-caspase 9-dependent pathway and induces G2/M phase arrest via the Chk1/2-Cdc25C-Cdc2/cyclin B axis in non-small cell lung cancer.
Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide, and novel effective drugs against NSCLC are urgently needed. Isodon species are rich in ent-kaurane diterpenoids that have been reported to have antitumor bioactivity. Acetyl-macrocalin B (A-macB) is a novel ent-kaurane diterpenoid isolated from Isodon silvatica, and its antitumor efficacy against NSCLC and the underlying mechanisms were scrutinized in depth. The viability of cells treated with A-macB was detected by CCK-8 and colony formation assays. Apoptosis and cell cycle distribution were analyzed by flow cytometry. The mechanisms were investigated by detecting ROS and performing western blotting and verification experiments with specific inhibitors. The in vivo effect of A-macB was explored in a nude mouse xenograft model. A-macB effectively inhibited H1299 and A549 cell viability, triggered apoptosis and delayed cells in the G2/M phase. A-macB induced cellular ROS production and then activated the p38 MAPK-mediated, caspase 9-dependent apoptotic pathway. Both the ROS scavenger NAC and the specific p38 inhibitor SB203580 inactivated the function of p38 induced by A-macB, thus preventing cells from apoptosis. A-macB activated the Chk1/2-Cdc25C-Cdc2/cyclin B1 axis to induce G2/M phase arrest. AZD7762 abrogated the function of Chk1/2, abolished the G2/M delay and enhanced the cytotoxicity of A-macB. Moreover, A-macB efficiently suppressed tumor growth in a mouse xenograft model without noticeable toxicity to normal tissues. Having both efficacy and relative safety, A-macB is a potential lead compound that is worthy of further exploration for development as an anticancer agent.


Laser detection of spin-polarized hydrogen from HCl and HBr photodissociation: comparison of H- and halogen-atom polarizations.
Thermal HCl and HBr molecules were photodissociated using circularly polarized 193 nm light, and the speed-dependent spin polarization of the H-atom photofragments was measured using polarized fluorescence at 121.6 nm. Both polarization components, described by the a(0)(1)(perpendicular) and Re[a(1)(1)(parallel, perpendicular)] parameters which arise from incoherent and coherent dissociation mechanisms, are measured. The values of the a(0)(1)(perpendicular) parameter, for both HCl and HBr photodissociation, are within experimental error of the predictions of both ab initio calculations and of previous measurements of the polarization of the halide cofragments. The experimental and ab initio theoretical values of the Re[a(1)(1)(parallel, perpendicular)] parameter show some disagreement, suggesting that further theoretical investigations are required. Overall, good agreement occurs despite the fact that the current experiments photodissociate molecules at 295 K, whereas previous measurements were conducted at rotational temperatures of about 15 K.


Tripfordines A-C, sesquiterpene pyridine alkaloids from Tripterygium wilfordii, and structure anti-HIV activity relationships of Tripterygium alkaloids.
Three new sesquiterpene pyridine alkaloids, tripfordines A-C (1-3), were isolated from an ethanolic extract of the roots of Tripterygium wilfordii, along with eight known pyridine alkaloids, and tested for in vitro cytotoxic and anti-HIV activity. The structures of the new compounds were established on the basis of spectroscopic data interpretation. Anti-HIV structure-activity relationships (SAR) for this compound type are proposed on the basis of the screening results from the newly isolated compounds and prior data of known sesquiterpene pyridine alkaloids. The position of a carboxyalkyl chain on the pyridine moiety was not critical since both 2'- and 4'-substituted compounds exhibited high anti-HIV activity (EC(50) 0.1 microg/mL). In contrast, a hydroxy group at C-8' (carboxypropyl side chain) or C-9' (carboxybutyl side chain) was found to affect anti-HIV activity.


Alfons Maria Jakob (1884-1931), neuropathologist par excellence. Scientific endeavors in Europe and the Americas.
The study briefly reviews the life and work of Alfons Maria Jakob (1884-1931), a notable representative of pre-war German neuropathology. Today Jakob is mainly remembered by neurologists for the spongiform encephalopathy with progressive dementia and spasticity that he, and Kiel neuropathologist Hans Gerhard Creutzfeldt (1885-1964), described independently. However, Jakob has left additional contributions to neuroanatomy, neuropathology and neuropsychiatry in the form of original articles and valuable monographs.


TiO2-based nanopowders and thin films for photocatalytical applications.
TiO2-based nanopowders are elaborated by flame spray synthesis, FSS from organic precursors of titanium and chromium with the Cr content changing from 0 to 15 at.%. Well-crystallized nanopowders with high specific surface area SSA reaching 107 m2/g for undoped TiO2 and 177 m2/g for TiO2 + 15 at.% Cr are obtained. Thin films are deposited by rf reactive sputtering from metallic Ti and Ti-Cr targets in Ar + O2 flow controlled atmosphere. The adjustable area of Cr/Ti allows to obtain up to 16 at.% Cr in TiO2 thin films. X-ray diffraction, transmission electron spectroscopy, TEM, atomic force microscopy, AFM and optical spectrophotometry over the ultraviolet UV and visible VIS range of the light spectrum have been performed in order to characterize the nanomaterials. The particle size of nanopowders is within the range of 5-42 nm. Anatase is the predominating polymorphic form while the amount of rutile increases with Cr content to reach of about 25 wt.% at 15 at.% Cr. The post-deposition annealing of thin films in air at temperatures from 770 K to 1280 K modifies the phase composition, leads to irreversible transformation from anatase to rutile and affects the surface roughness. Structural and optical properties of TiO2-based nanopowders and thin films are compared. The effect of grain size and the level of chromium doping on the band gap E(g) is discussed. Photocatalytic activity of the nanopowders is tested for degradation of methylene blue, MB.


The size and mix of government spending on illicit drug policy in Australia.
To estimate how much governments in Australia spend on reducing and dealing with illicit drug problems. Government documents and supplementary information sources were used to estimate drug-related expenditure for the financial year 2002-03, in Australian dollars. Public sector expenditure on reducing drug problems ('proactive expenditure') was classified into four policy functions: prevention, treatment, harm reduction and enforcement. Expenditure related to the consequences of drug use ('reactive expenditure') was included as a separate category. Spending by Australian governments in financial year 2002-03 on all drug-related activities was estimated to be $3.2 billion. Proactive expenditure was estimated to be $1.3 billion, comprising 55% on enforcement, 23% on prevention, 17% on treatment, 3% on harm reduction and 1% on activities that span several of these functions. Expenditure on dealing with the consequences of drug use was estimated to be $1.9 billion, with the majority the result of crime-related consequences. Several insights result from estimating these expenditures. First, law enforcement is the largest drug policy component, with Australian governments also spending significant amounts on treatment and prevention programmes. Secondly, apart from the prevention component, Australia's drug policy mix is strikingly similar to recent international estimates. Finally, expenditures associated with dealing with the consequences of illicit drugs are large and important for assessing drug-related public sector expenditure.


Dynamic Prevalence of and Factors Associated With Fatigue Following Traumatic Brain Injury: A Systematic Review and Meta-analysis of Observational Studies.
To implement a systematic review and meta-analysis to comprehensively synthesize the prevalence of and factors associated with fatigue following traumatic brain injury (TBI). We systematically searched the PubMed, EMBASE, Cochrane Library, Cumulated Index to Nursing and Allied Health Literature, PsycINFO, and ProQuest Dissertations and Theses A&I databases in all fields from their inception to March 31, 2021. We included observational studies investigating fatigue at specific time points following TBI or factors associated with post-TBI fatigue. All data were analyzed using a random-effects model. This meta-analysis included 29 studies that involved 12 662 patients with TBI and estimated the prevalence of post-TBI fatigue (mean age = 41.09 years); the meta-analysis also included 23 studies that involved 6681 patients (mean age = 39.95 years) and investigated factors associated with post-TBI fatigue. In patients with mild-to-severe TBI, the fatigue prevalence rates at 2 weeks or less, 1 to 3 months, 6 months, 1 year, and 2 years or more after TBI were 52.2%, 34.6%, 36.0%, 36.1%, and 48.8%, respectively. Depression (r = 0.48), anxiety (r = 0.49), sleep disturbance (r = 0.57), and pain (r = 0.46) were significantly associated with post-TBI fatigue. No publication bias was identified among the studies, except for those assessing fatigue prevalence at 6 months after TBI. The pooled prevalence rates of post-TBI fatigue exhibited a U-shaped pattern, with the lowest prevalence rates occurring at 1 to 3 months after TBI. Depression, anxiety, sleep disturbance, and pain were associated with post-TBI fatigue. Younger patients and male patients were more likely to experience post-TBI fatigue. Our findings can assist healthcare providers with identifying appropriate and effective interventions targeting post-TBI fatigue at specific periods.


Behavior of Ultrasensitive C-Reactive Protein in Myocardial Revascularization with and without Cardiopulmonary Bypass.
To analyze the inflammation resulting from myocardial revascularization techniques with and without cardiopulmonary bypass, based on ultrasensitive C-reactive protein (US-CRP) behavior. A prospective non-randomized clinical study with 136 patients was performed. Sixty-nine patients were enrolled for Group 1 (on-pump coronary artery bypass - ONCAB) and 67 patients were assigned to Group 2 (off-pump coronary artery bypass - OPCAB). All study participants had blood samples collected for analysis of glucose, triglycerides, creatinine, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and creatinephosphokinase (CPK) in the preoperative period. The samples of creatinephosphokinase MB (CKMB), troponin I (TnI) and US-CRP were collected in the preoperative period and at 6, 12, 24, 36, 48 and 72 hours after surgery. We also analyzed the preoperative biological variables of each patient (age, smoking, diabetes mellitus, left coronary trunk lesion, body mass index, previous myocardial infarction, myocardial fibrosis). All angiographically documented patients with >70% proximal multiarterial stenosis and ischemia, documented by stress test or classification of stable angina (class II or III), according to the Canadian Cardiovascular Society, were included. Reoperations, combined surgeries, recent acute myocardial infarction, recent inflammatory disease, deep venous thrombosis or recent pulmonary thromboembolism, acute kidney injury or chronic kidney injury were not included. Correlation values between the US-CRP curve and the ONCAB group, the treatment effect and the analyzed biological variables did not present expressive results. Laboratory variables were evaluated and did not correlate with the applied treatment (P>0.05). The changes in the US-CRP at each moment evaluated from the postoperative period did not show any significance in relation to the surgical technique applied.


A study of the action of anticonvulsant drugs on an experimental model of epilepsy.
Repeated electrical low intensity stimulation of various regions of the brain has been shown to induce epileptic seizure activity. This experimental model of epilepsy has been used in our laboratory in rats. Male rats, anaesthetized with nembutal (20 mg/kg, i.p.) and ketalar (60 mg/kg, i.p.) were implanted stereotaxically with electrodes in the dorsal hippocampus and neocortex and received 2 hours stimulation sessions via the hippocampal electrodes (1 sec, 60 Hz, 200-800 microA) one stimulus per minute, during which electrographical and behavioral seizures were induced. The effect of anticonvulsant drugs was tested on this model: phenobarbital (40 mg/kg) reduced the quantity of epileptic electrographic activity and abolished the behavioral aspects of the seizures; diphenylhydantoin (20 mg/kg) reduced the quantity of epileptic electrographic activity, but had no effect on the behavioral component of the seizures; diazepam (6 mg/kg) only blocked the behavioral component of the seizures leaving the animal stuporous and immobile, but the electrographical component was unaffected; carbamazepine (10 mg/kg) had no effect on the electrographical epileptic seizures and reduced the behavioral aspects, but to a lesser extent than diazepam.


Children-robot interaction: a pilot study in autism therapy.
We present here a pilot study of child-robot interactions, in which we discuss developmental origins of human interpersonal communication. For the past few years, we have been observing 2- to 4-year-old children with autism interacting with Keepon, a creature-like robot that is only capable of expressing its attention (directing its gaze) and emotions (pleasure and excitement). While controlled by a remote experimenter, Keepon interacted with the children with its simple appearance and actions. With a sense of curiosity and security, the children spontaneously approached Keepon and engaged in dyadic interaction with it, which then extended to triadic interactions where they exchanged with adult caregivers pleasure and surprise they found in Keepon. Qualitative and quantitative analysis of these unfolding interactions suggests that autistic children possess the motivation to share mental states with others, which is contrary to the commonly held position that this motivation is impaired in autism. We assume Keepon's minimal expressiveness helped the children understand socially meaningful information, which then activated their intact motivation to share interests and feelings with others. We conclude that simple robots like Keepon would facilitate social interaction and its development in autistic children.


Hypertension and Pathogenic hAPP Independently Induce White Matter Astrocytosis and Cognitive Impairment in the Rat.
Hypertension is recognized as a risk factor for Alzheimer disease, but the causal link remains undetermined. Although astrocytes and microglia play an important role in maintaining the neurovascular unit, astrocytes and microglia have been understudied in comorbid models of hypertension and Alzheimer disease. In this study, male transgenic Fischer 344 rats (TgAPP21) overexpressing a pathogenic human amyloid precursor protein received 8 weeks of Angiotensin II infusion to increase blood pressure, and the rats were evaluated for astrocytosis, microgliosis, and cognitive function. A linear relationship between astrocytosis and blood pressure was observed in the corpus callosum and cingulum of wildtype rats, with hypertensive wildtype rats matching the elevated baseline astrocytosis seen in normotensive transgenic rats. In contrast, hypertensive transgenic rats did not demonstrate a further increase of astrocytosis, suggesting a deficient response. Angiotensin II infusion did not affect activation of microglia, which were elevated in the white matter and hippocampus of transgenic rats. Angiotensin II infusion did impair both wildtype and transgenic rats' executive functions in the Morris Water Maze. These results present important implications for the interaction between hypertension and pathogenic human amyloid precursor protein expression, as Angiotensin II infusion produced cognitive impairments in both genotypes, but transgenic rats were additionally impaired in developing a normal astrocytic response to elevated blood pressure.


Functional role of fatty acyl-coenzyme A synthetase in the transmembrane movement and activation of exogenous long-chain fatty acids. Amino acid residues within the ATP/AMP signature motif of Escherichia coli FadD are required for enzyme activity and fatty acid transport.
Fatty acyl-CoA synthetase (FACS, fatty acid:CoA ligase, AMP forming; EC ) plays a central role in intermediary metabolism by catalyzing the formation of fatty acyl-CoA. In Escherichia coli this enzyme, encoded by the fadD gene, is required for the coupled import and activation of exogenous long-chain fatty acids. The E. coli FACS (FadD) contains two sequence elements, which comprise the ATP/AMP signature motif ((213)YTGGTTGVAKGA(224) and (356)GYGLTE(361)) placing it in the superfamily of adenylate-forming enzymes. A series of site-directed mutations were generated in the fadD gene within the ATP/AMP signature motif site to evaluate the role of this conserved region to enzyme function and to fatty acid transport. This approach revealed two major classes of fadD mutants with depressed enzyme activity: 1) those with 25-45% wild type activity (fadD(G216A), fadD(T217A), fadD(G219A), and fadD(K222A)) and 2) those with 10% or less wild-type activity (fadD(Y213A), fadD(T214A), and fadD(E361A)). Using anti-FadD sera, Western blots demonstrated the different mutant forms of FadD that were present and had localization patterns equivalent to the wild type. The defect in the first class was attributed to a reduced catalytic efficiency although several mutant forms also had a reduced affinity for ATP. The mutations resulting in these biochemical phenotypes reduced or essentially eliminated the transport of exogenous long-chain fatty acids. These data support the hypothesis that the FACS FadD functions in the vectorial movement of exogenous fatty acids across the plasma membrane by acting as a metabolic trap, which results in the formation of acyl-CoA esters.


Multidisciplinary collaboration: conceptual development as a foundation for patient-focused care.
A participatory action research design using a combination of qualitative methods was used to induce a conceptual definition of multidisciplinary collaboration and to develop a measure of the concept among health care workers. Conclusions from the study include strategies to foster multidisciplinary collaboration among health care workers when health care delivery systems are being reengineered.


Cold acclimation induces desensitization to adenosine in brown fat cells without changing receptor binding.
The ability of brown fat cells isolated from control and cold-acclimated hamsters to respond to adenosine was investigated. In measurements of the rate of oxygen consumption, it was observed that cells from control hamsters responded as expected to addition of adenosine deaminase, 3-isobutyl-1-methylxanthine (IBMX), or 2-chloroadenosine (i.e., norepinephrine dose-response curves were shifted to left in presence of adenosine deaminase or IBMX and to right with 2-chloroadenosine). However, brown fat cells isolated from cold-acclimated hamsters, under identical conditions, showed almost complete absence of adenosine control. Thus acclimation to cold induced a desensitization to adenosine by physiological means. To evaluate the molecular mechanism underlying desensitization to adenosine, [3H]phenylisopropyladenosine ([3H]PIA) binding to brown fat membranes from control and cold-acclimated hamsters was investigated. [3H]PIA bound with similar high affinity (KD approximately 5 nM) and saturability (Bmax approximately 15 fmol/mg protein) in both membrane preparations, demonstrating that desensitization to adenosine was not due to changes in adenosine receptor number or receptor affinity for adenosine. Furthermore, GTP induced a reduction in [3H]PIA affinity in brown fat membranes from both control and cold-acclimated hamsters, indicating that desensitization was probably not due to an uncoupling between the receptor and Gi protein. It was therefore concluded that the adenosine desensitization process may be located at the Gi protein-adenylate cyclase interaction.


Beneficial Effects of Plant-Based Diets on Skin Health and Inflammatory Skin Diseases.
The human skin is a crucial organ that protects the organism from the outer environment. Skin integrity and health depend on both extrinsic and intrinsic factors. Intrinsic factors such as aging and genetic background contribute to weakened skin and disease susceptibility. Meanwhile, extrinsic factors including UV radiation, pollution, smoking, humidity, and poor diet also affect skin health and disease. On the other hand, healthy dietary patterns such as plant-based diets have gained popularity as a complementary therapy for skin health. A plant-based diet is defined as all diets based on plant foods, including an abundance of vegetables, fruits, beans, lentils, legumes, nuts, seeds, fungi, and whole grains, with limited or no animal products or processed foods. However, some authors also exclude or limit processed foods in the definition. Recent research has shown that these diets have beneficial effects on inflammatory skin diseases. This review explored the beneficial effects of plant-based diets on inflammatory skin diseases and plant-based functional foods on healthy skin. In conclusion, plant-based diets and plant-based functional foods may have beneficial effects on skin health through the gut microbiome.


Placental vascular development and neonatal outcome.
The juxtaposition of the maternal and fetal circulations allows optimal physiological exchange between mother and fetus. Extravillous trophoblast infiltrating into the placental bed transforms the small calibre spiral arteries into large calibre uteroplacental arteries. The absence of these physiological changes, coupled with other lesions such as acute atherosis, results in a reduced uteroplacental blood flow, as seen in pre-eclampsia, intrauterine growth restriction and preterm delivery. A failure to elaborate the placental vascular tree can result in impaired flow through the fetal placental circulation. Placental vascular malformations, such as placental mesenchymal dysplasia and the commoner chorangioma, can lead to neonatal complications. Fetal thrombotic vasculopathy, commonly associated with thrombophilia, may be a cause of neurological deficit in childhood.


Evidence and consequences of spectrum bias in studies of criteria for liver transplant in paracetamol hepatotoxicity.
In severe paracetamol hepatotoxicity, orthotopic liver transplant (OLT) is a standard treatment in patients judged to have a hopeless prognosis. The most commonly used criteria to make this decision are the King's College Criteria (KCC). We aimed to compare the expected survival for patients who meet the KCC and do not receive transplant and those who receive OLT. A systematic review of studies of survival in patients who met the KCC according to whether they were transplanted. Data from these studies was extrapolated to compare long-term survival with and without adjustment for Quality of Life. The survival of patients meeting KCC and undergoing transplant has not been specifically studied. UK data on transplants for acute liver failure indicate 1 and 10 year survival rates of 65 and 44%, respectively. Survival in those without transplant was documented in 15 studies. The average long-term survival rate was 24.9%. Survival was worse in studies originating in the King's unit (13.8 vs. 30.0%). It was apparent that this may be due to spectrum bias occurring in this much larger unit. There was clear evidence that those with the best prognosis were preferentially transplanted at the Kings liver unit, indicating the criteria may perform significantly worse at predicting death without transplant than previously estimated. Even so, for a 20-year-old meeting KCC, the best estimate of life expectancy with transplant (13.5 years) is no better than without (13.4 years). Adjustment for quality of life made OLT clearly a worse option. Criteria for OLT that have a much higher positive predictive value (for death without transplant) are required. Such studies must be conducted only on those who would be considered suitable for transplant. Non-orthotopic liver transplant may be a preferred option in such circumstances, although much more data on survival after this procedure are required.


[Geographic differences in iodine supply in the Silesia terrain in relation to thyroid cancer risk].
Risk factors associated with differentiated thyroid carcinoma depend on its histotype. Follicular carcinoma is described as a predominant type in the areas with iodine deficiency, in opposite to papillary thyroid cancer. The incidence of thyroid cancer and its histotypes varies considerably throughout Silesia (data obtained from the Institute of Oncology Cancer Register, Gliwice). The factors responsible for these differences are unknown. The aim of our study was to evaluate the present iodine supply in Silesia region and to relate it to the incidence of the various histotypes of thyroid carcinoma. Urinary iodine excretion observed in 7-11 year-old-children was used as a parameter of iodine supply and measured in the group of 1037 school children in sixteen localities, equally dispersed throughout Silesia. Urine samples were obtained to measure iodine concentration by the modified Sandell-Kolthoff's catalytic method. Mean incidence rates of papillary and follicular thyroid carcinoma were calculated for regions of Silesia by averaging the rates of the communities in each region. Despite the intensive iodine prophylaxis the persistent symptoms of iodine deficiency were observed. There were significant differences in children's ioduria among investigated regions. The percentage of low ioduria (lower then 100 micrograms/l) varied from 35.7% to 87.7%. We observed no correlation between age-adjusted rates for histotypes of thyroid carcinoma and the percentage of urine iodine below 100 micrograms/l, which served as an estimation of iodine deficiency. Our study indicates that Silesia is still an area of moderate iodine deficiency. We were unable to explain the factors responsible for the observed differences in the incidence rates of papillary and follicular thyroid carcinoma.


Express-saccades of the monkey: reaction times versus intensity, size, duration, and eccentricity of their targets.
Monkeys were trained to fixate a small spot of light (fixation spot) and to saccade to a peripheral target if and only if the fixation spot was turned off. If the offset of the fixation spot preceded the onset of the peripheral target by a temporal gap of more than 140 ms the animals could change their direction of gaze after saccadic reaction times of no more than 70-80 ms (express-saccades). The reaction times of the express-saccades depend on the luminance and the size of the target and decrease from about 120 ms for near threshold targets by about 50 ms in a range of 2,5 log units above threshold (gap duration 200 ms). The minimum reaction time and the target size for which the minimum is reached are functions of the retinal eccentricity of the target. Comparison with response latencies of afferent visual neurons suggests that the dependence of the reaction times of express- as well as regular-saccades on the physical parameters of the target is mostly determined by retinal factors. The short reaction times of the express-saccades are discussed in relation to the reaction times of other visually-guided goal-directed movements.


Physical Medicine Devices; Reclassification of Shortwave Diathermy for All Other Uses, Henceforth To Be Known as Nonthermal Shortwave Therapy. Final order; technical correction.
The Food and Drug Administration (FDA) is issuing a final order to reclassify shortwave diathermy (SWD) for all other uses, a preamendments class III device, into class II (special controls), and to rename the device "nonthermal shortwave therapy'' (SWT). FDA is also making a technical correction in the regulation for the carrier frequency for SWD and SWT devices.


The role of endothelin and endothelin receptor subtypes in regulation of fetal pulmonary vascular tone.
The physiologic role of endothelin-1 (ET-1) and its receptors in regulating fetal pulmonary vascular tone is unknown. We therefore investigated the role of ET-1 and its receptors in the regulation of fetal pulmonary vascular tone using BQ 123 (an ETa receptor antagonist) and 4 Ala ET-1 (an ETb receptor agonist). In six fetal sheep in utero, we found that injections of ET-1 (250 ng/kg fetal weight) into the left pulmonary artery increased left pulmonary blood flow (21.0 +/- 17.5 to 74.7 +/- 32.9 mL/kg/min, p < 0.05) and decreased left pulmonary vascular resistance (6.02 +/- 7.00 to 0.84 +/- 0.48 mm Hg/kg/min/mL, p < 0.05). BQ 123 (5 mg) increased pulmonary blood flow (24.6 +/- 28.7 to 47.7 +/- 27.4 mL/kg/min, p < 0.05) and decreased pulmonary vascular resistance (8.84 +/- 10.32 to 1.43 +/- 0.80 mm Hg/kg/min/mL, p < 0.05); 4 Ala ET-1 (1725 ng/kg) markedly increased pulmonary blood flow (8.6 +/- 6.8 to 69.4 +/- 23.1 mL/kg/min, p < 0.05) and decreased pulmonary vascular resistance (12.02 +/- 10.2 to 0.78 +/- 0.44 mm Hg/kg/min/mL, p < 0.05). The absolute increase in pulmonary blood flow produced by ET-1 was attenuated by glibenclamide (an ATP-dependent potassium channel blocker) (flow increase of 73.4 +/- 34.1 versus 49.3 +/- 16.8 mL/kg/min, p < 0.05). This study demonstrates that ETa receptor activation has a small role in maintaining basal fetal pulmonary vascular tone, and that specific ETb receptor activation produces marked pulmonary vasodilation. The increase in pulmonary flow produced by ET-1 in fetuses is partly mediated by ATP-dependent potassium channels.


A Spawn Mobile Agent Itinerary Planning Approach for Energy-Efficient Data Gathering in Wireless Sensor Networks.
Mobile agent (MA), a part of the mobile computing paradigm, was recently proposed for data gathering in Wireless Sensor Networks (WSNs). The MA-based approach employs two algorithms: Single-agent Itinerary Planning (SIP) and Multi-mobile agent Itinerary Planning (MIP) for energy-efficient data gathering. The MIP was proposed to outperform the weakness of SIP by introducing distributed multi MAs to perform the data gathering task. Despite the advantages of MIP, finding the optimal number of distributed MAs and their itineraries are still regarded as critical issues. The existing MIP algorithms assume that the itinerary of the MA has to start and return back to the sink node. Moreover, each distributed MA has to carry the processing code (data aggregation code) to collect the sensory data and return back to the sink with the accumulated data. However, these assumptions have resulted in an increase in the number of MA's migration hops, which subsequently leads to an increase in energy and time consumption. In this paper, a spawn multi-mobile agent itinerary planning (SMIP) approach is proposed to mitigate the substantial increase in cost of energy and time used in the data gathering processes. The proposed approach is based on the agent spawning such that the main MA is able to spawn other MAs with different tasks assigned from the main MA. Extensive simulation experiments have been conducted to test the performance of the proposed approach against some selected MIP algorithms. The results show that the proposed SMIP outperforms the counterpart algorithms in terms of energy consumption and task delay (time), and improves the integrated energy-delay performance.


Toughening Poly(l-lactide) Blends: Effectiveness of Sequence-Controlled Six-Arm Star-Branched Block Copolymers of Poly(l-lactide) and Poly(ε-caprolactone).
Well-defined six-arm star-branched bio-degradable block copolymers of l-lactide and ε-caprolactone were prepared using controlled ring-opening polymerization and a sequential monomer addition method using dipentaerythritol as the initiator core and organocatalysts at low temperatures in solution. Sequence of enchainment was changed by reversing the order of monomer addition giving, either, a crystalline PLA block or an amorphous PCL block as the outer segment. Well-defined six-arm poly(ε-caprolactone-b-l-lactide, 6s-PCL-b-PLA) block copolymers were obtained with a range of segment molecular weights. However, in the case of six-arm poly(l-lactide-b-ε-caprolactone, 6s-PLA-b-PCL), disruption of the block structure was observed on account of competing transesterification reactions accompanying a chain-growth reaction. Such sequence-controlled block copolymers showed interesting phase morphologies, as evidenced by differential scanning calorimetry (DSC) studies. 6s-PCL-b-PLA showed two glass-transition temperatures and two melting temperatures characteristic of the amorphous and crystalline blocks. 6s-PCL-b-PLA and 6s-PLA-b-PCL with different segment chain lengths were solution blended (10 wt %) with a commercially sourced PLA. All the blends were highly transparent. The structure and properties of the blend were examined by DSC, measurement of mechanical properties, and scanning electron microscopy. The results show that a phase-separated 6s-PCL-b-PLA copolymer results in two- to three-fold improvement in tensile toughness without the loss of modulus. A possible hypothesis for the mechanism of tensile toughness in the blend has been proposed.


[Experience of 157 vesikoscopic operations in children].
Recent advances in the field of minimally invasive surgical technologies in children and adolescents have led to the development of vesicoscopic (transvesical, pneumoscopic) access (VA). Current limitations in using VA emphasize the need for further studies investigating surgical options for the management of various pathological conditions of the bladder and ureterovesical junction, the features of surgical techniques and the course of the early postoperative period when used in pediatric urological practice. From 2013 to 2017, 157 patients (79 girls and 78 boys) aged between 2 months and 18 years (mean age 4.9-8.7 years) underwent surgery using VD. Unilateral and bilateral vesicoscopic ureterocystoneoimplantation was performed in 110 (70%) and 44 (28%) patients, respectively. A total of 198 ureters was implanted. Three (1.9%) children underwent vesicoscopic excision of the bladder diverticulum. Transvesicoscopic Cohen ureteric reimplantation, pneumovesical Glenn-Anderson procedure, and Chumakov ureterocystoneoimplantation were performed in 151 (96.1%), 2 (1.3%) and 1 (0.6%) patients, respectively. The mean operative time when using VA was 126.8+/-46.7 min. In patients younger than one year, 1-3 years, 4-17 years, it was 136.0+/-43.8 min, 130.1+/-43.5 min and 122.4+/-65.8 min, respectively. The mean length of postoperative hospital stay was 6.2+/-2.3 days. In 3 (1.9%) cases we had to convert to open surgery. Gas migration into the abdominal cavity occurred in 6 (3.8%) patients. Fourteen (9%) patients had early postoperative complications. Transient obstruction of ureterovesical junction occurred in 6 (3.8%) patients. Acute complete obstruction of the distal ureter developed in 3 (1.9%) patients aged three months who did not undergo drainage of the upper urinary tract intraoperatively. A paravesical urine leak occurred in 1 (0.6%) patient. In one (0.6%) of the boys, the distal end of the urinary drainage inserted through the trocar into the ureter migrated in the bladder. The urine leakage from the trocar puncture occurred once (0.6%) and was stopped by indwelling urethral catheterization for seven days. In 2 (1.3%) patients, exacerbation of pyelonephritis required a modification in antibacterial therapy. Despite the accumulated experience, vesicoscopic surgery remains a laborious and complicated surgical intervention, requiring long learning curves even for surgeons who have good manual skills in laparoscopic surgery. In our opinion, vesicoscopic access allows the entire range of surgical interventions on the vesicoureteral junction and bladder in children to be performed. It is effective, significantly less traumatic than traditional open cystotomy access, and associated with an excellent cosmetic result.