Generalized joint hypermobility and voiding dysfunction in children: is there any relationship?
Voiding dysfunction is a common entity in pediatric urology. It is believed to have a multifactorial etiology. The aim of this study was to investigate whether there is an increased prevalence of generalized joint hypermobility (GJH) in children with voiding dysfunction compared to normal children. Moreover, the prevalence of voiding complaints in patients with and without GJH was assessed. A total of 226 children--aged 5 to 14 years--including 113 patients diagnosed with voiding dysfunction and 113 sex/age/body mass index-matched normal children were recruited. GJH was evaluated in both groups using the Beighton score (4 or more= hypermobile). In the patient's group, GJH was significantly more frequent than in controls: 51/113 (45 %) versus 19/113 (17 %) (P=0.001). In addition, in both groups, GJH was more prominent in girls than boys (P<0.05). Urinary tract infection was the most frequent features in children with voiding dysfunction (64 %). In the subgroup of positive GJH, urinary tract infection remained the most common manifestation among the girls (P=0.003), while constipation was the most prevalent manifestation among the boys (P=0.001). Our findings suggest that children with voiding dysfunction have significantly higher prevalence of GJH compared to normal children. Further studies are needed to determine the cause and effect of these two common presentations and will help to develop a multidisciplinary approach in understanding and management of voiding dysfunction in children.


Thio-sugars. IV: Design and synthesis of S-linked fucoside analogs as a new class of alpha-L-fucosidase inhibitors.
alpha-1-Thio-L-fucose derivative 4 and 5 as new alpha-fucosidase inhibitors (K1 = 4.6, and 5.9 microM) have been synthesized in three steps by base catalyzed coupling with bromonitromethane followed by reduction of the nitro group with sodium borohydride/cobalt chloride complex and acetylation.


Describing alcohol consumption. A comparison of three methods and a new approach.
The Absolute Alcohol-Quantity-Pattern index, a new method of measuring alcohol consumption, is described and compared with three other measurement systems.


Communicating with children and parents: recommendations for a child-parent-centred approach for paediatric dentistry.
The European Academy of Paediatric Dentistry has called for a series of evidence-based statements to inform their guidelines on the behavioural management of the child patient. Communication between dentist, parent and child based upon scientifically robust research evidence was felt to be central to this request in order to provide empathetic and child-centred care for children and their parents attending for dental health care. Shekelle and colleagues [1999] devised a series of steps to develop an evidence-based clinical guideline. This framework allows first, the identification and refinement of the subject area and secondly, the identification and assessment of the evidence-base. Four areas of communication were identified as being of central importance. These were identification of the mother-child dyad; affective communication skills; problem solving and negotiation skills. It was recommended that paediatric dentists should become knowledgeable and competent in these skills in order to provide patient-centred care for the children and parents attending their clinics for dental treatment.


Antiproliferative and antiangiogenic effects of ammonium tetrathiomolybdate in a model of endometriosis.
Copper (Cu) is involved in the endometriosis progression. Herein, an experimental endometriosis model was used to evaluate whether its chelation with ammonium tetrathiomolybdate (TM) affects the proliferation and angiogenesis in endometriotic-like lesions and the participation of oxidative stress in these processes. Female C57BL/6 mice were divided into three groups: sham-operated mice, endometriosis-induced mice, and TM-treated endometriosis-induced mice. Each animal in the third group received 0.3 mg of TM/day in their drinking water from the postoperative 15th day. The samples were collected after one month of induced pathology. In peritoneal fluids, Cu and estradiol levels were determined by electrothermal atomic absorption spectrometry and electrochemiluminescence, respectively. Endometriotic-like lesions were processed for the analysis of cell proliferation by PCNA immunohistochemistry, the expression of angiogenic markers by RT-qPCR, the presence of endothelial cells by immunofluorescent staining, and oxidative stress applying spectrophotometric methods. TM treatment decreased Cu and estradiol levels, which were increased by this pathology. In lesions, TM induced: (a) a decrease in tissue weight and volume, (b) a decrease in PCNA-positive cells, (c) antiangiogenic effects by decreasing the number of blood vessels, the mRNA expression of fibroblast growth factor 2 (Fgf2) and platelet-derived growth factor subunit B (Pdgfb), and the presence of endothelial cells, (d) a decrease in antioxidant activity and an increase in lipid peroxidation. TM is a highly effective antiproliferative and antiangiogenic agent, modulating oxidative imbalance in endometriosis. Its anti-endometriotic potential is an attractive feature of TM as a possible non-hormonal treatment.


Trifolium pallidum and Trifolium scabrum extracts in the protection of human plasma components.
Clovers (genus: Trifolium) have been used in traditional medicine by many cultures, but the biological activity of the most of these plants still remains unknown. The aim of our in vitro study was to assess the antioxidative action of phenolic extracts from aerial parts of Trifolium scabrum and Trifolium pallidum in human blood plasma, exposed to oxidative stress. In the present study we also demonstrate, for the first time the effects of the tested extracts on coagulative properties and fibrinolytic activity of blood plasma. The protective properties of the examined extracts (0.5-50 μg/ml) against peroxynitrite-induced oxidative stress were estimated by the measurements of 3-nitrotyrosine, thiol groups and the thiobarbituric acid-reactive substances levels. The extracts considerably prevented the oxidative and nitrative damage to plasma proteins. Even the lowest doses of the Trifolium extracts (0.5 μg/ml) were able to markedly reduce 3-nitrotyrosine formation (by about 50%) and to increase the level of -SH groups (by about 30%), in comparison to the plasma exposed to ONOO(-) in the absence of the extracts. The protective action of all the used concentrations of the Trifolium extracts in the prevention of lipid peroxidation was also found. The tested extracts influenced neither the coagulative properties nor fibrinolytic activity of plasma. Moreover, the extracts were able to significantly reduce the inhibitory effect of ONOO(-) on fibrinolytic activity of plasma (assessed with the use of a chromogenic substrate for plasmin).


Crystal structure of a photobiologically active brominated angular pyran-ocoumarin: bromo-hy-droxy-seselin.
The title compound, C14H13BrO3 [systematic name: rac-(9S,10R)-9-bromo-10-hy-droxy-8,8-dimethyl-9,10-di-hydro-2H,8H-pyrano[2,3-f]chromen-2-one], is a substituted pyran-ocoumarin, obtained by bromination of seselin [8,8-dimethyl-2H,8H-pyrano[2,3-f]chromen-2-one], which was isolated from the Indian herb Trachyspermum stictocarpum (Aajmod). The pyrano ring has a distorted half-chair conformation and its mean plane is inclined to the coumarin mean plane by 1.6 (2)°. In the crystal, mol-ecules are linked by pairs of O-H⋯O hydrogen bonds, forming inversion dimers with an R22(16) ring motif. The dimers stack along the a-axis direction and are linked by offset π-π inter-actions, forming columns [inter-centroid distance = 3.514 (4) Å].


Mutations associated with neutropenia in dogs and humans disrupt intracellular transport of neutrophil elastase.
Cyclic hematopoiesis is a stem cell disease in which the number of neutrophils and other blood cells oscillates in weekly phases. Autosomal dominant mutations of ELA2, encoding the protease neutrophil elastase, found in lysosome-like granules, cause cyclic hematopoiesis and most cases of the pre-leukemic disorder severe congenital neutropenia (SCN; ref. 3) in humans. Over 20 different mutations of neutrophil elastase have been identified, but their consequences are elusive, because they confer no consistent effects on enzymatic activity. The similar autosomal recessive disease of dogs, canine cyclic hematopoiesis, is not caused by mutations in ELA2 (data not shown). Here we show that homozygous mutation of the gene encoding the dog adaptor protein complex 3 (AP3) beta-subunit, directing trans-Golgi export of transmembrane cargo proteins to lysosomes, causes canine cyclic hematopoiesis. C-terminal processing of neutrophil elastase exposes an AP3 interaction signal responsible for redirecting neutrophil elastase trafficking from membranes to granules. Disruption of either neutrophil elastase or AP3 perturbs the intracellular trafficking of neutrophil elastase. Most mutations in ELA2 that cause human cyclic hematopoiesis prevent membrane localization of neutrophil elastase, whereas most mutations in ELA2 that cause SCN lead to exclusive membrane localization.


Messenger RNA binding of a ribosome-associated protein kinase and a ribosomal phosphoprotein(s) in mouse plasmacytoma.
A specific ribosome-associated protein kinase (protein kinase II) and phosphoprotein(s) from the ribosomal KCl wash fraction termed "PPx" have been isolated from plasmacytoma, and tested for their ability to bind to poly(A) and to different plasmacytoma polynucleotides. The nitrocellulose filter binding technique was used to measure RNA-protein interaction. Protein kinase II and PPx preferentially bound mRNA compared to poly(A). They did not bind ribosomal RNA, soluble RNA or DNA. The optimal conditions (temperature, time, protein concentration, ionic strength) for mRNA-protein interaction were determined. Ribosomal protein kinase (protein kinase II) phosphorylated PPx proteins which bound to mRNA represented at least two bands as determined by sodium dodecyl sulphate polyacrylamide gel electrophoresis (Mr = 90 000 and 80 000). The high affinity of protein kinase II and PPx for mRNA suggests that they may function in regulating protein synthesis.


Detecting contrast changes in invisible patterns during binocular rivalry.
When dissimilar images are presented to the two eyes, the human visual system lapses into binocular rivalry, a unique perceptual state characterized by stochastic alternations in dominance of one of the two source images over the other. Probe targets delivered to an eye during suppression phases are more difficult to detect than probes delivered during dominance phases. Nearly all probe studies have involved presenting new stimulation (e.g., a spot of light) either superimposed on or replacing the suppressed stimulus. Here, we ask whether observers can detect a reduction in the contrast of the suppressed stimulus itself. In other words, can observers detect a probe that should make an already invisible stimulus even weaker? Specifically, we compared observers' ability to detect contrast increments and contrast decrements introduced within a rival pattern during dominance and suppression. Contrast increment thresholds were elevated across all pedestal contrasts when the increment was introduced during suppression compared to during dominance, replicating previous results. Contrast decrement thresholds measured during suppression were elevated to an even greater extent, but the fact that they were obtained at all establishes that observers were able to detect probes that should make an already invisible target even more difficult to perceive. In a second experiment, we found a similar pattern of results for contrast change detection in complex images of faces as well. Based on the resulting threshold-vs.-contrast functions, we suggest that, regardless of the complexity of the image, rivalry suppression modulates the neural contrast response function through a mixture of reduced overall response gain and a shift in the contrast gain.


Physical plasma: a new treatment option in gynecological oncology.
Non-thermal application of physical plasma is rapidly gaining importance for the future therapy and prevention of chronic inflammatory diseases and tumors. Here, we outline the importance of this innovative and less invasive therapy option, particulary for the treatment and prevention of gynecological cancers.


Relationship of dyspnea vs. typical angina to coronary artery disease severity, burden, composition and location on coronary CT angiography.
Symptom presentations suspicious for coronary artery disease (CAD) vary widely. While dyspnea is associated with worse prognosis than typical angina (TypAng) for patients referred for non-invasive CAD imaging, the relation of dyspnea vs. TypAng to adverse measures of CAD prognosis-including severity, burden, composition, and myocardium at risk-has not been examined. We studied 1443 consecutive individuals without known CAD (mean 61 ± 13 years, 61.6% men) undergoing coronary computed tomographic angiography (CCTA) who presented with dyspnea (n = 170), TypAng (n = 249) or no dyspnea or TypAng (n = 1024). Multivariable logistic regression was performed to evaluate the association of dyspnea or TypAng to obstructive CAD (≥70% stenosis), plaque burden (total segments with plaque), composition (noncalcified, partially calcified) and location (proximal, mid, or distal location in a coronary artery). By multivariable logistic regression, both dyspnea (OR1.9, 95% CI 1.1-3.3, p = 0.02) and TypAng (OR1.9, 95% CI 1.2-3.1, p = 0.01) were associated with obstructive CAD as compared to individuals without dyspnea or TypAng, while dyspnea (OR1.8, 95% CI 1.1-3.1, p = 0.02), but not TypAng (OR1.1, 95% CI 0.7-1.6, p = 0.76) was associated with plaque in the proximal portions of coronary arteries. Neither symptom type was associated with differences in plaque burden nor composition. Both dyspnea and TypAng are associated with higher rates of obstructive CAD compared to those without dyspnea or TypAng, but only dyspnea is associated with coronary plaque in proximal vessel portions.


Renal pelvic carcinoma: morphological correlates of metastatic behavior.
We report a clinicopathological analysis of morphological parameters in relation to subsequent biological behavior in 48 patients with renal pelvic carcinoma. The relationships of subsequent metastasis to tumor stage and grade, as well as the presence of vascular, renal parenchymal or renal hilar invasion were evaluated by parametric and nonparametric statistical tests. Corrected 5-year survival rates for grades 1 to 3 tumors were 100, 67 and 5 per cent, respectively. Grade 3 tumors demonstrated more invasion of the blood vessels, hilus and renal parenchyma compared to grades 1 and 2 tumors (p less than 0.005, 46 patients). Moreover, invasion of renal hilar tissues had greater predictive value for subsequent distant metastatic spread (95 per cent, nonparametric) than either vascular (83 per cent) or renal parenchymal (77 per cent) invasion. Metastases developed in 27 of 48 patients during followup periods of 2 to 39 years. The pattern of metastatic lesions revealed that local spread to hilar soft tissues occurred in 92 per cent of the patients who subsequently had distant metastases. Spread to retroperitoneal lymph nodes and ipsilateral ureteral mucosa occurred in 84 and 44 per cent of the patients, respectively. Our study illustrates the potential value of analysis of individual histological parameters to evaluate the likelihood of subsequent metastasis.


Flower extract of Allium atroviolaceum triggered apoptosis, activated caspase-3 and down-regulated antiapoptotic Bcl-2 gene in HeLa cancer cell line.
Cervical cancer accounts for the second most frequent cancer and also third leading cause of cancer mortality (15%) among women worldwide. The major problems of chemotherapeutic treatment in cervical cancer are non-specific cytotoxicity and drug resistance. Plant-derived products, known as natural therapies, have been used for thousands of years in cancer treatment with a very low number of side effects. Allium atroviolaceum is a species in the genus Allium and Liliaceae family, which could prove to have beneficial effects on cancer treatment, although there is a lack of corresponding attention. The methanolic extract from the A.atroviolaceum flower displayed marked anticancer activity on HeLa human cervix carcinoma cells with much lower cytotoxic effects on normal cells (3T3). The A.atroviolaceum extract induced apoptosis, confirmed by cell cycle arrest at the sub-G0 (apoptosis) phase, characteristic morphological changes, evident DNA fragmentation, observed by fluorescent microscope, and early and late apoptosis detection by Annexin V. Furthermore, down-regulation of Bcl-2 and activation of caspase-9 and -3 strongly indicated that the mitochondrial pathway was involved in the apoptosis signal pathway. Moreover, combination of A.atroviolaceum extract with doxorubicin revealed a significant reduction of IC50 and led to a synergistic effect. In summary, A.atroviolaceum displayed a significant anti-tumour effect through apoptosis induction in HeLa cells, suggesting that the A.atroviolaceum flower might have therapeutic potential against cervix carcinoma.


The resident and fellow relationship in obstetrics and gynecology.
In a nationwide survey, chief administrative residents reported their views on how subspecialty fellowships affect their residency training in obstetrics and gynecology. The residents felt that fellows improve the quality of their training, depending on the degree they consider fellows as junior faculty involved in teaching and modeling patient care. Competition for surgical cases, and the surgical priority fellows have over residents in the new technology and nonroutine cases, potentially detract from the resident-fellow training relationship. These factors varied by subspecialty and the particular content areas of the fellowship. The residents' comments highlight the positive and negative components of each fellowship and identify the features of their relationship with the fellows. The implications of these findings for enhancing this relationship are presented.


A rare case of de novo structural rearrangement of X chromosome diagnosed by amniocentesis.
A dicentric X chromosome was found in a female fetus during cytogenetic studies performed on amniotic cells. Blood samples from the parents showed normal karyotypes and the pregnancy was terminated. The mechanism for the formation of this 'de novo' rearrangement is discussed.


Testing a relational account of search templates in visual foraging.
Search templates guide human visual attention toward relevant targets. Templates are often seen as encoding exact target features, but recent studies suggest that templates rather contain "relational properties" (e.g., they facilitate "redder" stimuli instead of specific hues of red). Such relational guidance seems helpful in naturalistic searches where illumination or perspective renders exact feature values unreliable. So far relational guidance has only been demonstrated in rather artificial single-target search tasks with briefly flashed displays. Here, we investigate whether relational guidance also occurs when humans interact with the search environment for longer durations to collect multiple target elements. In a visual foraging task, participants searched for and collected multiple targets among distractors of different relationships to the target colour. Distractors whose colour differed from the environment in the same direction as the targets reduced foraging efficiency to the same amount as distractors whose colour matched the target colour. Distractors that differed by the same colour distance but in the opposite direction of the target colour did not reduce efficiency. These findings provide evidence that search templates encode relational target features in naturalistic search tasks and suggest that attention guidance based on relational features is a common mode in dynamic, real-world search environments.


[Student assessment of pharmacy practice experiences in France: a national survey].
Pharmacy practice experience (PPE) aims to help trainees to become independent professional practitioners and is a prerequisite for developing skills and competence. In France, it does not exist any study that describes student satisfaction related to preregistration trainings. The aim of this study was to assess student perceptions related to the four PPE types that are planned along the course of study. A questionnaire was sent to each student. Concerning the first and second year introductory PPE, among the 8491 responses, 73% of the students stated that the length was too long regarding their actual knowledge and the objectives were not always achieved. Four thousand and eleven responses regarding third and fourth year PPE were analyzed. Sixty-two percent of the students did not deliver drugs related to the practice's subject and 57% declared doing similar task assigned during the first year PPE especially storage one's. One thousand six hundred and seven questionnaires regarding hospital practices were received. Forty-one percent of the trainees were not asked to perform task that were related to their actual knowledge. Additional comments focused on overmuch shadowing. Among the 853 responses related to the 6th year PPE, 88% of the students considered that they were overall satisfied of the training. Although 30% felt they acquired insufficient skills and professionalism and declared they were not ready to integrate the work world. Those results should prompt decision makers to modify in depth PPE programs in France in order to improve trainees' professionalism and skills acquisition. Promoting and developing researches in the field of PPE is urgently needed.


Pitfalls in counselling of the blepharophimosis, ptosis, epicanthus inversus syndrome (BPES)
Non-penetrance or minimal expression as a genetic counselling problem in the blepharophimosis syndrome is discussed.


The modulation of immune complex aggregation by classical pathway-mediated reactions.
Classical pathway (CP)-triggered reactions of complement-modulated immune complex (IC) aggregation (tetanus toxoid/human anti-tetanus toxoid-IgG; ICs of equivalence) were investigated turbidimetrically during the early stages of reaction. Monospecific Fab'- or Fab-fragments (rabbit) directed against certain complement components were used to block the complement function in normal human serum (NHS). Additionally, parts of the reactions were studied using purified complement components. C1q in serum generated by the addition of EDTA as well as purified C1q were found to increase the IC aggregation. In contrast to C1q, macromolecular C1 is able to inhibit IC aggregation, whereas additional participation of C-1 INH reversed this process. The cooperation of the remaining CP proteins (C4, C2, C4bp, and I) reconstituted the inhibition capacity of the complement. Whereas C3 supported significantly inhibition, a significant influence of other effector pathway (EP) components (C5-C9) was not detectable turbidimetrically.


Stem cell competition: finding balance in the niche.
Adult stem cells reside in local microenvironments (niches) that produce signals regulating the outcome of stem cell divisions and stem cell-niche interactions. Limited space and signals in the niche often force stem cells to compete with one another. Although previous studies have uncovered several examples of genetically distinct stem cells competing for niche access, recent studies demonstrate that genetically equivalent stem cells compete under normal conditions, resulting in dynamic stem cell behavior in the niche. New work in multiple vertebrate and invertebrate tissues shows that stem cell competition occurs continuously and mutations disrupting the balance between competing stem cells can cause diseases and defects in the niche. This review discusses recent insights into stem cell competition in mammals and Drosophila.


Greening coal: breakthroughs and challenges in carbon capture and storage.
Like it or not, coal is here to stay, for the next few decades at least. Continued use of coal in this age of growing greenhouse gas controls will require removing carbon dioxide from the coal waste stream. We already remove toxicants such as sulfur dioxide and mercury, and the removal of CO₂ is the next step in reducing the environmental impacts of using coal as an energy source (i.e., greening coal). This paper outlines some of the complexities encountered in capturing CO₂ from coal, transporting it large distances through pipelines, and storing it safely underground.


Association between primary Sjögren's syndrome and pregnancy complications: a systematic review and meta-analysis.
Systemic autoimmune disorders may interfere with normal reproductive function resulting in negative outcome of pregnancy. Primary Sjögren's syndrome (pSS) is a common rheumatic disease that mostly affects females. There are many reports that this condition may increase risk of pregnancy complications and fetal loss. However, data regarding these adverse outcomes are scarce and inconclusive. We performed a systematic review and meta-analysis of available articles that assess the association between pSS and adverse pregnancy outcome. We comprehensively searched the databases of MEDLINE and EMBASE from their dates of inception to March 2016 and reviewed papers with validity criteria. A random-effects model was used to evaluate pregnancy complications in patients with pSS and healthy controls. From 20 full-text articles, 7 studies involving 544 patients and 1586 pregnancies were included in the meta-analysis. Fetal complications included spontaneous abortion, stillbirth, neonatal deaths, and intrauterine growth retardation. Compared with healthy pregnancy, patients with pSS had significantly higher chance of neonatal deaths (pooled odds ratio (OR) = 1.77, 95 % confidence interval (CI) 1.28 to 1.46, p = 0.01). However, there were no significant associations between pSS and premature birth (OR = 2.10, 95 % CI 0.59-7.46, p = 0.25), spontaneous abortion (OR = 1.46, 95 % CI 0.72-2.93, p = 0.29), artificial abortion (OR = 1.12, 95 % CI 0.52-2.61, p = 0.71), or stillbirth (OR = 1.05, 95 % CI 0.38-2.97, p = 0.92). There is an increased risk of fetal loss in pregnant patients with pSS. The presented evidence further supports multidisciplinary care for these patients to prevent complications during pregnancy.


The immunoglobulin kappa locus-or-what has been learned from looking closely at one-tenth of a percent of the human genome.
The immunoglobulin kappa locus and its immediate surroundings, which are described in the present report, comprise 3 Mb of DNA, i.e., 0.1% or one per mill of the 3000 Mb of the human genome. Based on the work of our group during the past 12 years, we can now (1) depict in much detail the structure of the kappa locus with its 76 V kappa genes and pseudo genes, five J kappa elements and one C kappa gene; (2) specify the size of the germ-line repertoire of kappa light chains, which is one of the sources of the practically unlimited antibody diversity; (3) assign the known transcription products (studied as cDNAs) and kappa proteins to certain germ-line V kappa genes and attribute the differences in sequences to hypermutation and, to a lesser extent, to allelic variation; (4) analyze the hypermutation patterns which may contribute to the understanding of this enigmatic process; (5) describe the V kappa-J kappa rearrangements for half of the V kappa genes by a deletion mechanism and for the other half by a mechanism involving inversions of Mb-sized (i.e., 0.5 mm long) DNA fragments; (6) define various regulatory and other conserved sequence elements; (7) get clues as to the variation of the structure of the kappa locus in different individuals and populations, including a haplotype with only half the number of V kappa genes; (8) interpret many aspects of the evolution of the kappa locus in terms of duplications, insertions, deletions and gene conversions; (9) attribute the formation of the 24 V kappa orphons (i.e., genes outside the locus), whose sequences were determined, to pericentric inversions and other transposition processes; (10) answer a series of questions of biomedical interest; and (11) contribute 12.5 Mb of restriction maps, 1.8 Mb of clones and 250 kb of sequences to the elucidation of the human genome.


Prothrombin complex concentrate administration for bleeding associated with non-vitamin K antagonist oral anticoagulants: The SAMURAI-NVAF study.
Antidotes appropriate for non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) are not yet in widespread clinical use. Efficacy of prothrombin complex concentrate (PCC) in NOAC-associated bleeding remains unclarified. Ten NOAC users (4 women, median 74years old) who developed major bleeding and received PCC were prospectively enrolled. Eight single-center NOAC users (0 women, median 74years old) with intracerebral hemorrhage, who over the same period did not receive PCC, were studied for comparison. Of the 10 PCC-treated patients, 8 developed intracerebral hemorrhage, 1 developed subdural hematoma, and another developed gastrointestinal bleeding. The median size of intracerebral hemorrhage was 8mL, relatively lower than the reported size for patients without NOACs. Patients received a median of 1000IU or 16IU/kg of PCC. Before and 1h after PCC administration, the median PT-INR changed from 1.41 to 1.09 (p<0.05) and median aPTT changed from 35.4 to 38.0s (p=0.39). Five patients developed intracranial hematoma expansion and 4 required surgical hematoma evacuation. No symptomatic thrombotic events occurred in either group, no participants died, and 2 participants from each group were independent. Ten NOAC users developed major bleeding and were given relatively low doses of PCC. The effect of PCC on early cessation of bleeding was unclear, while the therapy did not trigger thromboembolic complications.


Morphological and molecular characterization of bacterial pathogens associated with leaf mottle of sunflower in Northern Kazakhstan.
Leaf mottle is a serious disease in the growth and development of sunflowers (Helianthus annuus L.) that can affect their quality and yield. Over the past years, the North Kazakhstan region, a sunflower-producing area in Kazakhstan, has been seriously affected by leaf mottle. Since 2021, symptomatic leaves have been collected from production areas of this base to determine the pathogens of sunflower foliar diseases. One hundred bacterial strains were isolated, and 2 genera and 5 species were identified based on morphological characteristics, molecular genetics and phylogenetic analysis (16S gene region). The genus Bacillus was represented by 4 species-B. subtilis, B. megaterium, B. amyloliquefaciens and B. flexus. The genus Paenibacillus is represented by one species, P. peoriae. Pathogenicity experiments showed that B. subtilis, B. megaterium, B. flexus and P. peoriae could cause disease symptoms. However, B. flexus leaves are highly similar to infected leaves observed under natural conditions in the field. Therefore, these bacterial isolates are considered to be the primary pathogens causing sunflower leaf mottle, and B. flexus was the most common and virulent pathogen in this study. In addition, this is the first study of B. megaterium, B. flexus and P. peoriae as pathogens associated with sunflower leaf mottle in Kazakhstan.


Triggering p53 activation is essential in ziyuglycoside I-induced human retinoblastoma WERI-Rb-1 cell apoptosis.
Ziyuglycoside I (Ziyu I), one of the major components isolated from the root of Sanguisorba officinalis L., has been proved for the antitumor properties on oral cancer, prostate cancer, and colorectal cancer. However, the effect of Ziyu I on retinoblastoma (RB) is not well understood. In this study, we investigated the inhibitory effect and underlying molecular mechanism of Ziyu I on human RB WERI-Rb-1 cells. Our results indicated that Ziyu I could suppress cell viability and induce mitochondrial-dependent cell apoptosis in WERI-Rb-1 cells. Furthermore, Ziyu I treatment increased p53 expression as well as improved p53 stabilization through downregulation of pS166-Mdm2 and upregulation of phosphorylated- and acetylated-p53. Blockade of p53 significantly attenuated Ziyu I-induced mitochondrial dysfunction. Our findings demonstrate that Ziyu I exhibits excellent anticancer effect on human RB WERI-Rb-1 cells by triggering p53 activation, and imply Ziyu I as a potential compound for chemotherapy of human RB.


Facial pressure ulcers in COVID-19 patients undergoing prone positioning: How to prevent an underestimated epidemic?
Prone positioning is an adjuvant therapy used to treat COVID-19 pneumonia complicated by acute respiratory distress syndrome. However, prolonged pressure on facial skin at the level of the bony structures may be responsible for facial pressure ulcers. In the context of severe COVID-19 pneumonia, we hypothesized that hypoxemia, microvascular injury and thrombosis can increase the risk of pressure ulcers. We described two cases in order to emphasize the risk of facial pressure ulcers as a result of prone positioning, so as to discuss their physiopathology and highlight the importance of appropriate preventive measures.


Correction to: Histone demethylase KDM4D promotes gastrointestinal stromal tumor progression through HIF1β/VEGFA signalling.
After the publication of this work [1] an error was noticed in Fig. 7e, in which the incorrect information is shown. The updated figure included in this correction now shows the quantification of tumor microvessel density. This correction does not affect the findings or conclusions of the article. Nevertheless, we apologize for the inconvenience.


Early assessment of bilateral inguinal hernia repair: A comparison between the laparoscopic total extraperitoneal and Stoppa approaches.
The present clinical trial was designed to compare the results of bilateral inguinal hernia repair between patients who underwent the conventional Stoppa technique and laparoscopic total extraperitoneal repair (LTE) with a single mesh and without staple fixation. This controlled, randomised clinical trial was conducted at General Surgery and Trauma of the Clinics Hospital, Medical School, the University of São Paulo between September 2010 and February 2011. Totally, 50 male patients, with a bilateral inguinal hernia, older than 25 years were considered eligible for the study. The following parameters were analysed during the early post-operative period: (1) The intensity of surgical trauma, operation time, C-reactive protein (CRP) levels, white blood cell count, bleeding and pain intensity; (2) quality of life assessment; and (3) post-operative complications. LTE procedure was longer than the Stoppa procedure (134.6 min ± 38.3 vs. 90.6 min ± 41.3; P < 0.05). The levels of CRP were higher in the Stoppa group (P < 0.05) but the number of leucocytes, haematocrit, and haemoglobin were similar between the groups (P > 0.05). There was no difference in pain during the 1st and 7th post-operative, physical functioning, physical limitation, the impact of pain on daily activities, and the Carolinas Comfort Scale during the 7th and 15th post-operative (P > 0.05). Complications occurred in 88% of Stoppa group (22 patients) and 64% in LTE group (16 patients) (P < 0.05). The comparative study between the Stoppa and LTE approaches for the bilateral inguinal hernia repair demonstrated that: (1) The LTE approach showed less surgical trauma despite the longer operation time; (2) Quality of life during the early post-operative period were similar; and (3) Complication rates were higher in the Stoppa group.


Novel technique of left atrial appendage occlusion-a pilot study.
A clot in the left atrial appendage (LAA) is an important cause of cardio-embolic stroke. Concomitant occlusion of the LAA during cardiac surgery is found to have reduced postoperative stroke. A study was designed to observe the results of LAA occlusion in 17 patients undergoing coronary artery bypass graft surgery (CABG) and aortic valve replacement (AVR). The LAA was occluded epicardially with a SIRONIX 60-mm linear noncutting stapler (Healthium Medtech Pvt limited, Peenya, Bengaluru). The effectiveness of occlusion was confirmed by trans-esophageal echocardiography and at 2 years of follow-up with trans-thoracic echocardiography. There was no re-canalization of the LAA, and the patients remained in sinus rhythm. Concomitant LAA occlusion with a linear stapler during cardiac surgery is a safe, feasible, and reproducible option.


Serum uric acid level in male patients with androgenetic alopecia: A prospective study in China.
The aim of this study was to investigate the serum level of uric acid (UA) in male patients with androgenetic alopecia (AGA) and to compare the level with that of men without AGA. In addition, the comparison of the serum level of uric acid (UA) before and after treatment with finasteride was performed. A total of 120 male patients with AGA and 120 males without AGA were enrolled in this prospective study. Patients with AGA were randomized into two groups: 60 patients were given 1 mg finasteride orally every day for 6 months, and 60 patients were given placebo. Serum UA level was detected at the first visit and after the 6-month treatment by colorimetric analysis. Before treatment, the mean serum UA level in patients with AGA was higher than that in the control group (401.52±83.27 umol/L vs 362.67±60.88 umol/L, P<0.050), and a higher proportion of hyperuricemia was found in patients with AGA (2 9.17% vs 15.00%, P<0.050). After treatment, the mean serum UA level in the finasteride group decreased significantly, from 405.87±87.12 umol/L to 381.84±82.50 umol/L (P<0.050), and from 397.17±79.73 to 394.18±78.09 umol/L in the placebo group (P = 0.370). Patients with AGA with hyperuricemia had a higher BMI (25.38±3.43 kg/m2) when compared to the patients without hyperuricemia (23.88±2.64 kg/m2). For every unit of BMI increase in patients with AGA, the risk of hyperuricemia increased by 30.5% (P = 0.030). Furthermore, the levels of UA were different in the finasteride group before and after treatment (P = 0.049, 95%CI, 0.080, 47.970). We found that AGA has a relationship with hyperuricemia, and the level of serum UA can decrease with the treatment of finasteride.


Analysis and modulation of the immune response of mice to acetylcholine receptor by anti-idiotypes.
Anti-idiotypes were raised in mice against three well-characterized anti-acetylcholine receptor (AChR) monoclonal antibodies (mcAbs), as well as against polyclonal mouse anti-AChR antibodies. In binding experiments, the anti-idiotypic antibodies inhibited the binding of AChR only to the immunizing idiotype. However, a less restricted specificity was found in in vivo experiments. Mice producing anti-idiotypes were challenged with AChR and the idiotypic composition of their anti-AChR response was analysed using specific rabbit anti-idiotypic antibodies. It was found that preimmunization with a certain idiotype leads to the preferential suppression of this particular idiotype in the polyclonal response to AChR. However, preimmunization with either polyclonal or monoclonal anti-AChR antibodies resulted in a reduction of the overall anti-Torpedo AChR and anti-muscle AChR titers. This reduction was greater than would be expected from the representation of each of the respective idiotypes in the polyclonal anti-AChR serum, and may imply that in addition to the immunizing idiotype other anti-AChR idiotypes are also suppressed. Our results suggest that anti-idiotypes may have a potential for the modulation of the autoimmune response directed against AChR in myasthenia.


CT Hounsfield Units as a Predictor for the Worsening of Traumatic Vertebral Compression Fractures.
With vertebral compression fractures (VCF), height loss has been associated with kyphotic deformity and intractable pain, 2 indications for potential surgical intervention. Consequently, assessment of factors associated with continual height loss can provide insights regarding management. Computed tomography (CT) Hounsfield units (HU), a measure of radiodensity, have been implicated for the assessment of bone quality. No studies have assessed the relationship between CT HU and traumatic VCF. Consequently, the objective of this study was to evaluate this relationship. Patients who sustained a traumatic VCF from a motor vehicle accident from 2006 to 2015 were reviewed retrospectively. Inclusion criteria were single VCF from L1 to L4, appropriate imaging, and appropriate follow-up. Clinical data were extracted (age, gender, history of osteoporosis, body mass index [BMI], and length of follow-up). Initial CT imaging was evaluated for averaged HU at the levels above and below the index level of the VCF. Interval percentage change (Δ%) in anterior compression was evaluated between radiographs obtained during initial presentation and at follow-up. Age, BMI, and CT HU significantly correlated with Δ% (P < 0.01), whereas initial height loss, history of osteoporosis, and length of follow-up did not. A multiple linear regression for Δ% that combined age, BMI, and CT HU values elicited a regression model with R(2) 0.648, and adjusted R(2) 0.606; each variable in the model showed P < 0.05. A receiver operating characteristic analysis to predict Δ% < 10% from Δ% ≥10% showed an area under the curve 0.983 (P < 0.01), where CT HU at 171.58 showed a combination of sensitivity at 0.923 and specificity at 0.91. Age, BMI, and CT HU values are independent predictors of worsening VCF. These factors can help determine appropriate clinical follow-up and need for surgical intervention.


A newly established human gestational choriocarcinoma cell line and its characterization.
The cell biological characteristics of a newly established human gestational choriocarcinoma cell line, HM, were examined and compared with four other gestational and two nongestational choriocarcinoma cell lines. Striking heterogeneity in the production and secretion of hCG and its subunits was observed among the cell lines. The HM cell line consisted mainly of cytotrophoblast-like cells, and the hCG and its subunit values in both the cells and culture fluid were extremely low. The syncytiotrophoblast-like multinucleated giant cells which were occasionally seen in other cell lines were scarce in the HM cell line in vitro. On the other hand, deviation of the LDH isozyme pattern to the heart-type (LDH1) was characteristic of the HM cells in contrast to the other cell lines in which LDH3 was dominant. The HM cell line represents useful material for investigating the cell biological heterogeneity of human choriocarcinomas.


ACTN3 R577X variant: could it be a determinant of sports performance in elite athletes in a Turkish population?
ACTN3 gene, which encodes a-actinin-3 and actin-binding protein, has been found to be associated with strong athletic performance, especially among track and field athletes. Therefore, in this study, our aim was to compare the allelic and genotype frequencies of the ACTN3 R577X variant among elite athletes specialized in different branches, and nonathletic controls in Turkey. In the present study, 316 subjects, including 168 athletes and 148 sedentary controls were genotyped for the ACTN3 R577X variant. Genotyping was conducted by polymerase chain reaction (PCR) method. Additionally, we evaluated the groups by dividing them as females and males. There were 48 females and 120 males in the athletes group, and 43 females and 105 males in the control group. Genetic associations were evaluated by chi-squire test or Fisher's exact test. There was a significant difference between the athletes and controls in terms of the ACTN3 R577X variant. ACTN3 RR and XX genotypes increased in the controls compared to the athletes, while RX genotype was higher in the athletes than the controls (P = 0.030). Then we evaluated the groups by separating them as females and males. Genotype distribution of the ACTN3 R577X differed between the male athletes and the male controls (P = 0.046). ACTN3 R577X RX genotype increased in the male athletes compared to the male control (P = 0.046). But ACTN3 R577X genotype and allele distribution was not significant between female athletes and female control group (P>0.05). As far as we know, this study is the largest series examining the ACTN3 R577X variant in Turkish athletes. Our results support that the ACTN3 R577X variant has a heterozygous advantage in athletic performance in the Turkish population. However, epigenetic, gene-gene and gene-environment interactions affects athlete performance should not be forgotten.


Differences in the labeling of axons of passage by wheat germ agglutinin after uptake by cut peripheral nerve versus injections within the central nervous system.
Injections of a radiolabeled derivative of wheat germ agglutinin (WGA) in the subcortical white matter of the cerebral cortex in mice do not give rise to autoradiographic labeling of axon systems coursing through this fiber mass. Exposing the cut-end of mouse tibial nerve to WGA does, however, produce labeling within dorsal root ganglia and the spinal cord. These findings are discussed with consideration for dissimilarity in mode of central versus peripheral administration of the tracer, as well as in the light of potential relative differences in the uptake and transport of WGA and HRP.


Mass and charge transport in highly mesostructured polyelectrolyte/electroactive-surfactant multilayer films.
Dimensionally stable electroactive films displaying spatially addressed redox sites is still a challenging goal due to gel-like structure. Polyelectrolyte and surfactants can yield highly mesostructured films using simple buildup strategies as layer-by-layer. The use of redox modified surfactants is expected to introduce order and an electroactive response in thin films. The assembly of polyacrylic acid and different combinations of redox-modified and unmodified hexadecyltrimethylammonium bromide yields highly structured and electroactive thin films. The growth, viscoelastic properties, mass, and electron transport of these films were studied by combining electrochemical and quartz crystal balance with dissipation experiments. Our results show that the films are highly rigid and poorly hydrated. The mass and charge transport reveal that the ingress (egress) of the counter ions during the electrochemical oxidation (reduction) is accompanied with a small amount of water, which is close to their hydration sphere. Thus, the generated mesostructured films present an efficient charge transport with negligible changes in their structures during the electron transfer process. The control over the meso-organization and its stability represents a promising tool in the construction of devices where the vectorial transfer of electrons, or ions, is required.


Factors influencing the sustainability of volunteer peer support for breast-feeding mothers within a hospital environment: An exploratory qualitative study.
the objectives of this study were to explore breast feeding peer supporters' motivation to volunteer within a hospital environment, to describe their experiences of volunteering within a hospital environment, to examine the relationships between peer supporters and ward staff, and to identify factors contributing to the future sustainability of the service. a qualitative study; peer supporters and clinical ward staff were interviewed using a semi-structured schedule and data were analysed using Thematic Analysis with an inductive approach. six peer supporters and ten ward staff, whose role included giving breast feeding support, working on a maternity ward in one consultant-led unit in England that had been hosting breast feeding peer support volunteers for the previous three years. three main themes were identified: 1. What peer supporters brought to the maternity ward; this included providing breast-feeding mothers with confidence, reassurance and empowerment, and spending 'unhurried time' with mothers; 2. What motivated the peer supporters; this included an interest in midwifery as a future career and a desire to help people; 3. Factors contributing to the sustainability of the service; these included an existing rolling training programme, however recruitment processes were causing long delays and some aspects of operational management needed improvement. individuals with a passion for breast feeding were willing to volunteer as peer supporters and their experience of the activity was positive. Organisational processes did not always provide peer supporters with a positive experience of the organisation and these needed to be improved as they contributed to the future sustainability of the service. the study indicates that a sustainable hospital-based volunteer service for breast feeding peer support requires a rolling training programme for peer supporters, efficient recruitment processes and effective operational management.


Labels matter: Use and non-use of 'anti-vax' framing in Australian media discourse 2008-2018.
Childhood vaccine refusal is a globally contentious topic, with some jurisdictions addressing it with punitive policies. Media discourse influences how solutions are framed by implying blame - a process known as framing. We examined Australian media discourse on vaccine rejection over a period in which mandatory childhood vaccination policies were discussed and introduced, focusing on the common Australian pejorative term 'anti-vaxxer'. We mapped frequency of use from January 2008 to December 2018. We then searched Factiva for print media articles on childhood vaccination and parents published in that period, searching separately for articles using and not using 'anti-vaxxer' and variants. We constructed a set of 85 articles that did, and 85 articles date-matched that did not use the term to make comparisons and conducted a frame analysis of each set. 'Anti-vaxxer' was absent in Australian media discourse 2008-2010, rising to a peak of 247 articles using the term at the height of legislative change in 2017. Parents were framed as: 1) deviant "others"; 2) ignorant and in need of informing; 3) vulnerable and in need of protection from anti-vaccination activists; 4) thoughtful, critical, informed, and in need of agency and respect; 5) entitled, privileged and selfish; and finally, 6) lacking access to vaccination, rather than being unwilling. Articles using 'anti-vax' terms were more likely to negatively characterise non-vaccinating parents, while articles not including this language were more likely to frame them as thoughtful or lacking access. This study clearly demonstrates strategic use of pejoratives in the Australian mass media around a time of pressure for legislative change and conflation of anti-vaccination activists with non-vaccinating parents. We suggest fundamental changes to how non-vaccination is framed and dealt with in the media to curb polarization and fostering more respectful dialogue, and better social and public health outcomes.


Vaginal cuff dehiscence following controlled ovarian stimulation recognized during egg retrieval.
Vaginal cuff dehiscence is a rare complication of hysterectomy. Those who choose to undergo controlled ovarian stimulation (COS) and oocyte cryopreservation following hysterectomy must be aware that elevated abdominal pressure from stimulation as well as transvaginal ultrasound use during monitoring may increase the risk of cuff dehiscence. We present a case of a 25-year-old patient who had undergone a hysterectomy four months prior for endometrial cancer who was found to have vaginal cuff dehiscence which was recognized at the time of egg retrieval after COS. Prompt recognition and appropriate management led to successful treatment. Patients presenting for oocyte cryopreservation following hysterectomy are at risk for cuff dehiscence. Providers should allow ample time for proper cuff healing prior to COS and oocyte cryopreservation.


Metabolic Regulation of Macrophages by SIRT1 Determines Activation During Cholestatic Liver Disease in Mice.
Inflammation is the hallmark of chronic liver disease. Metabolism is a key determinant to regulate the activation of immune cells. Here, we define the role of sirtuin 1 (SIRT1), a main metabolic regulator, in controlling the activation of macrophages during cholestatic liver disease and in response to endotoxin. We have used mice overexpressing SIRT1, which we treated with intraperitoneal lipopolysaccharides or induced cholestasis by bile duct ligation. Bone marrow-derived macrophages were used for mechanistic in vitro studies. Finally, PEPC-Boy mice were used for adoptive transfer experiments to elucidate the impact of SIRT1-overexpressing macrophages in contributing to cholestatic liver disease. We found that SIRT1 overexpression promotes increased liver inflammation and liver injury after lipopolysaccharide/GalN and bile duct ligation; this was associated with an increased activation of the inflammasome in macrophages. Mechanistically, SIRT1 overexpression associated with the activation of the mammalian target of rapamycin (mTOR) pathway that led to increased activation of macrophages, which showed metabolic rewiring with increased glycolysis and broken tricarboxylic acid cycle in response to endotoxin in vitro. Activation of the SIRT1/mTOR axis in macrophages associated with the activation of the inflammasome and the attenuation of autophagy. Ultimately, in an in vivo model of cholestatic disease, the transplantation of SIRT1-overexpressing myeloid cells contributed to liver injury and fibrosis. Our study provides novel mechanistic insights into the regulation of macrophages during cholestatic disease and the response to endotoxin, in which the SIRT1/mTOR crosstalk regulates macrophage activation controlling the inflammasome, autophagy and metabolic rewiring.


Neutrophil Gelatinase-Associated Lipocalin (NGAL) is Associated with Symptomatic Carotid Atherosclerosis and Drives Pro-inflammatory State In Vitro.
Neutrophil gelatinase-associated lipocalin (NGAL), a protein found in activated neutrophils, is expressed in kidney tubule cells in response to noxious stimuli, and is thus recognized as a marker of acute kidney injury. Recent studies have suggested that NGAL could also have pathophysiological importance in cardiovascular diseases. The aim of the present study was to examine NGAL expression in human carotid endarterectomy tissues ex vivo as well as the effects of NGAL in the main cell types involved in atherogenesis, namely in human macrophages, endothelial cells, and smooth muscle cells in vitro. NGAL protein was analyzed in human endarterectomy samples from patients with asymptomatic and symptomatic carotid stenosis by immunofluorescence, and NGAL mRNA expression was detected using RealTime-PCR. Human monocyte derived macrophages (MDM), human coronary artery smooth muscle cells (HCASMC), and human umbilical vein endothelial cells (HUVEC) were treated with recombinant human (rh) NGAL at different concentrations. Interleukin (IL)-6, IL-8, and monocyte chemo-attractant protein-1 (MCP-1) were determined by specific enzyme linked immunosorbent assays (ELISAs) in culture supernatants of such treated cells. Expression of NGAL protein was demonstrated by macrophages, smooth muscle cells, and endothelial cells in human carotid atherosclerotic tissue. NGAL mRNA expression was detected at a higher rate in atherosclerotic tissue of patients with symptomatic carotid stenosis (in 70%; n = 19) compared with asymptomatic patients (in 37%; n = 20, p < .001). Treatment of MDM, HCASMC, and HUVEC with rhNGAL led to a significant (p < 0.05) and concentration dependent increase of pro-inflammatory cytokines IL-6, IL-8, and MCP-1 in all cell types analyzed. By induction of pro-inflammatory mediators in human macrophages, smooth muscle cells and endothelial cells, NGAL, which is predominantly expressed in atherosclerotic plaques of symptomatic patients, could be involved in creating the local and systemic pro-inflammatory environment characteristic for atherosclerosis.


Experimental study of a new tracheal prosthesis: pored Dacron tube.
This study was designed to evaluate how various sizes and densities of pores in Dacron tubing might enhance its utility as a tracheal prosthesis. A vascular prosthesis made of knitted external velour polyester was prepared for pore formation with a laser. The first set compared different pore sizes (300, 500, and 700 microm) and pore densities (25/cm(2) or 100/cm(2)). Grafts were reinforced with an externally heat-sealed silicone ring. The second set tested grafts with a pore density of 64/cm(2) and a pore size of 500 microm internally reinforced with a stainless-steel spiral stent. In all experiments, a canine mediastinal trachea 10 cartilage rings in length was resected, and the prosthesis was then implanted with an omental flap. Lower pore size and density (300 microm, 25 pores/cm(2)) led to essentially no tissue ingrowth. Larger pore size (700 microm) and low density (25 pores/cm(2)) led to rapid and excessive ingrowth of granulation. Midrange pore size (500 microm) and high density (100 pores/cm(2)) invited steady tissue ingrowth, but marked luminal stenosis eventually developed. Stent-reinforced prostheses with 500-microm pores at 64 pores/cm(2), as used in the second set, maintained an average patency rate of 60% or more (range, 20%-100%) at least 12 months after implantation. Our data show that porosity is a key factor for tissue growth through our Dacron tracheal prostheses. This artificial trachea model has led to long-term survivors up to 27 months after the operation and seems promising as a basic model for clinical tracheal repair.


Optimization and prediction of CBN tool life sustainability during AA1100 CNC turning by response surface methodology.
The aluminium alloy (AA1100) was familiar with automotive flexible shaft coupling applications due to its high strength, good machinability, and superior thermal and resistance to corrosion characteristics. Machining tool life drives the prominent role for deciding the product quality (machining) act aims to productivity target with zero interruptions. The novelty of this present investigation is the focus on increasing tool life during the complexity of CNC turning operation for AA1100 alloy by using CBN coated insert tool with varied input parameters of spindle speed (SS), feed rate (f), and depth of cut (DOC). Design of experiment (L16), analysis of variance (ANOVA) statistical system adopted with response surface methodology (RSM) is implemented for experimental analysis. The turning input parameters of SS, f and DOC are considered as factors and its SS (900, 1100, 1300, and 1500 rpm), f (0.1, 0.15, 0.2, and 0.25), and DOC (0.1, 0.2, 0.3, and 0.4 mm) values are treated as levels. The investigational analysis was made with the ANOVA technique and the desirability of high tool life with input turning parameters was optimized by RSM, and sample no 11/16 was predicted as high tool life and performed with extended working hours compared to other samples. The RSM optimized best turning parameter combinations are 0.1 mm DOC, 0.2mm/rev to 0.25mm/rev f, and 1300 rpm-1500 rpm SS, facilitating a higher tool life of more than 20min.


Nutritional and metabolic effects of gonadotropin-releasing hormone agonist treatment for prostate cancer.
Cancer commonly leads to weight loss associated with increased glucose production and protein breakdown. Medical or surgical castration results in decreased muscle mass, increased fat mass, and weight gain. The aim of this study was to evaluate the changes in body composition, protein metabolism, hepatic glucose production, (HGP), and basal energy expenditure in 10 men with advanced stage C and D prostate cancer receiving a gonadotropin-releasing hormone (GnRH) agonist (Buserelin). Metabolic parameters and nutritional status were determined at 0, 2, 6, and 12 months of therapy. Baseline measurements of plasma leucine appearance (76.2 +/- 5.4 microM/kg/h) and HGP rates (80.1 +/- 2.9 mg/m2/min) were greater than previously reported for normal volunteers. GnRH agonist therapy in prostate cancer patients was associated with a significant reduction in serum testosterone, dihydrotestosterone (DHT), luteinizing hormone (LH), and cortisol, and significant increases in triiodothyronine (T3) and free triiodothyronine (free T3). Neither basal energy expenditure nor plasma leucine appearance rates were changed over time, but there were significant linear reductions in HGP rates (80.1 +/- 2.9 mg/m2/min, mean +/- SEM; 79.9 +/- 2.3, 73.7 +/- 3.4, 72.5 +/- 2.3; P less than .01; baseline, 2, 6, and 12 months, respectively, by repeated measures ANOVA). In all patients, significant increases in body weight, triceps skin fold, cholesterol, and fat mass were noted. Total body water content was not significantly increased after the 12-month period; therefore, the weight gain seen in these patients was water-free tissue, ie, fat mass.


Interexaminer reliability of infrared thermography for the diagnosis of complex regional pain syndrome.
Infrared thermography (IRT) is a useful tool for assessing skin temperature abnormalities in patients with complex regional pain syndrome (CRPS). Although determining regions of interest (ROIs) is an essential process for interpreting thermographic images, there are no validated and standardized guidelines to determine ROIs. Therefore, ROIs may be determined differently by each observer even for the same IRT images, which can result in an important issue for IRT reliability. The purpose of this study was to investigate the interexaminer reliability of IRT in patients with CRPS. Infrared thermographic images of 28 patients diagnosed with CRPS were reviewed by three independent examiners. The shapes, sizes, and the detailed locations of the ROIs were determined by the investigator's own opinion based on patient history and symptoms. After maximal skin temperature of the ROI was obtained for each patient, the degree of agreement among the three examiners limbs was assessed. The intraclass correlation coefficient among the three independent raters was 0.865 (95% confidence interval, 0.748-0.933), indicating a high degree of reliability (P < 0.001). The reliability of IRT for assessing skin temperature abnormalities in CRPS was high when the ROIs were determined based on patient history and symptoms.


Lipid-protein interactions: Lessons learned from stress.
Biological membranes are essential for normal function and regulation of cells, forming a physical barrier between extracellular and intracellular space and cellular compartments. These physical barriers are subject to mechanical stresses. As a consequence, nature has developed proteins that are able to transpose mechanical stimuli into meaningful intracellular signals. These proteins, termed Mechanosensitive (MS) proteins provide a variety of roles in response to these stimuli. In prokaryotes these proteins form transmembrane spanning channels that function as osmotically activated nanovalves to prevent cell lysis by hypoosmotic shock. In eukaryotes, the function of MS proteins is more diverse and includes physiological processes such as touch, pain and hearing. The transmembrane portion of these channels is influenced by the physical properties such as charge, shape, thickness and stiffness of the lipid bilayer surrounding it, as well as the bilayer pressure profile. In this review we provide an overview of the progress to date on advances in our understanding of the intimate biophysical and chemical interactions between the lipid bilayer and mechanosensitive membrane channels, focusing on current progress in both eukaryotic and prokaryotic systems. These advances are of importance due to the increasing evidence of the role the MS channels play in disease, such as xerocytosis, muscular dystrophy and cardiac hypertrophy. Moreover, insights gained from lipid-protein interactions of MS channels are likely relevant not only to this class of membrane proteins, but other bilayer embedded proteins as well. This article is part of a Special Issue entitled: Lipid-protein interactions.


Improved control effect of pathological oscillations by using delayed feedback stimulation in neural mass model with pedunculopontine nucleus.
The role of delayed feedback stimulation in the discussion of Parkinson's disease (PD) has recently received increasing attention. Stimulation of pedunculopontine nucleus (PPN) is an emerging treatment for PD. However, the effect of PPN in regulating PD is ignored, and the delayed feedback stimulation algorithm is facing some problems in parameter selection. On the basis of a neural mass model, we established a new network for PPN. Four types of delayed feedback stimulation schemes were designed, such as stimulating subthalamic nucleus (STN) with the local field potentials (LFPs) of STN nucleus, globus pallidus (GPe) with the LFPs of Gpe nucleus, PPN with the LFPs of Gpe nucleus, and STN with the LFPs of PPN nucleus. In this study, we found that all four kinds of delayed feedback schemes are effective, suggesting that the algorithm is simple and more effective in experiments. More specifically, the other three control schemes improved the control performance and reduced the stimulation energy expenditure compared with traditional stimulating STN itself only. PPN stimulation can affect the new network and help to suppress pathological oscillations for each neuron. We hope that our results can gain an insight into the future clinical treatment.


Identification and functional validation of HLA-C as a potential gene involved in colorectal cancer in the Korean population.
Colorectal cancer (CRC) is the third most common cancer worldwide and is influenced by environmental and genetic factors. Although numerous genetic loci for CRC have been identified, the overall understanding of the genetic factors is yet to be elucidated. We sought to discover new genes involved in CRC applying genetic association analysis and functional study. We conducted exome array analysis on 194 CRC and 600 control subjects for discovering new candidate CRC genes. Fisher's exact test detected one exome-wide significant functional locus for CRC on SMCO1 (P < 10-6) and two suggestive functional loci on HLA-C and NUTM1 (10-6 ≤ P < 10-4). To evaluate the biological role of three candidate CRC genes, the differential expression of these genes between CRC and non-cancer colorectal cells was analyzed using qRT-PCR and publicly available gene expression data. Of three genes, HLA-C consistently revealed the significant down-regulation in CRC cells. In addition, we detected a reduction in cell viability in the HLA-C overexpression CRC cell line, implying the functional relevance of HLA-C in CRC. To understand the underlying mechanism exerted by HLA-C in CRC development, we conducted RNA sequencing analyses of HLA-C overexpression CRC cells and non-cancer colorectal cells. Pathway analysis detected that significantly down-regulated genes in HLA-C overexpression CRC cells were highly enriched in cancer-related signaling pathways such as JAK/STAT, ErbB, and Hedgehog signaling pathways. Exome array CRC case-control analysis followed by functional validation demonstrated that HLA-C likely exerts its influence on CRC development via cancer-related signaling pathways.


Evaluating the efficacy of chitosan and CMC incorporated with moringa leaf extracts on reducing peteca spot incidence on 'Eureka' lemon.
Lemon (Citrus limon L.) is one of the most cultivated citrus fruit in South Africa. In citrus packhouses, fruit are coated with commercial synthetic waxes to enhance shelflife. However, the use of waxes has been linked to peteca spot (PS) incidence in lemons. This study evaluated the efficacy of chitosan (CH) and carboxymethyl cellulose (CMC) incorporated with moringa leaf extracts (M) on reducing peteca spot incidence on 'Eureka' lemon. A total of 500 'Eureka' lemons were harvested from outside and inside canopy positions from a commercial orchard in KwaZulu-Natal, South Africa. Fruit were assigned to five coating treatments, namely; control, 1% M + CMC, 1% CMC, 1% CH and 1% M + CH. After coating, fruit were transferred into a cold room with delivery air temperature set at 3 °C for 12 weeks to induce the disorder. At each sampling week, peteca spot incidence, fruit physicochemical and phytochemical properties including color, mass, vitamin C, carotenoids, TSS, TA and phenolics were measured. The results showed that coating treatments and canopy position significantly affected PS incidence. Fruit coated with M + CMC, CMC, CH were less susceptible to PS development in both inside and outside canopy compared to the control and M + CH coated fruit. Coating treatments significantly affected phenolic and flavonoid concentration. Moreover, coating treatments significantly reduced mass loss, ascorbic acid loss and delayed color change of fruit. The results found in this study demonstrated the ability of either M + CMC, CMC, or CH as coating treatments for reducing PS in 'Eureka' lemon.


Decreased microRNA-142-3p/5p expression causes CD4+ T cell activation and B cell hyperstimulation in systemic lupus erythematosus.
To examine the role of microRNA-142-3p/5p (miR-142-3p/5p) in the development of autoimmunity in patients with systemic lupus erythematosus (SLE). MicroRNA-142-3p/5p expression levels were determined by real-time quantitative polymerase chain reaction, and potential target genes were verified using luciferase reporter gene assays. The effects of miR-142-3p/5p on T cell function were assessed by transfection with miR-142-3p/5p inhibitors or mimics. Histone modifications and methylation levels within a putative regulatory region of the miR-142 locus were detected by chromatin immunoprecipitation assay and bisulfite sequencing, respectively. We confirmed that miR-142-3p and miR-142-5p were significantly down-regulated in SLE CD4+ T cells compared with healthy controls and observed that miR-142-3p/5p levels were inversely correlated with the putative SLE-related targets signaling lymphocytic activation molecule-associated protein (SAP), CD84, and interleukin-10 (IL-10). We demonstrated that miR-142-3p and miR-142-5p directly inhibit SAP, CD84, and IL-10 translation, and that reduced miR-142-3p/5p expression in CD4+ T cells can significantly increase protein levels of these target genes. Furthermore, inhibiting miR-142-3p/5p in healthy donor CD4+ T cells caused T cell overactivation and B cell hyperstimulation, whereas overexpression of miR-142-3p/5p in SLE CD4+ T cells had the opposite effect. We also observed that the decrease in miR-142 expression in SLE CD4+ T cells correlated with changes to histone modifications and DNA methylation levels upstream of the miR-142 precursor sequence. The results of this study indicate that reduced expression of miR-142-3p/5p in the CD4+ T cells of patients with SLE causes T cell activity and B cell hyperstimulation.


Isolation of the epidermal growth factor from the shrew submaxillary gland.
The epidermal growth factor (EGF) from the submaxillary glands of the Chinese Shrew (Suncus murinus) is purified to apparent homogeneity by using a sequence of four chromatographic steps, viz. gel filtration on Sephacryl S-200, affinity chromatography on immobilized Ni, hydrophobic interaction on phenyl-Sepharose CL-4B and reverse-phase HPLC. An 800-fold increase in specific activity and an overall recovery of 46% were achieved. The most effective step in its purification is the successful use of immobilized metal ion affinity chromatography (IMAC). This method was very selective, reproducible and requires a minimum of sample pre-treatment prior to chromatography.


Emerging Applications for Computer Vision and Artificial Intelligence in Management of the Cardiovascular Patient.
Artificial intelligence and telemedicine promise to reshape patient care to an unprecedented extent, leading to a safer and more sustainable work environment and improved patient care. In this article, we summarize how these emerging technologies can be used in the care of cardiovascular patients in such ways as fall detection and prevention, virtual nursing, remote case support, automation of instrument counts in the operating room, and efficiency optimization in the cardiovascular suite.


Acoustic chiasm V: inhibition and excitation in the ipsilateral and contralateral projections of LSO.
When this series of experiments was begun in 1984, the activity of each lateral superior olive (LSO) in the mammalian hindbrain was known to encode the hemifield of acoustic space containing a sound source. However, the almost random bilaterality of its ascending projections seemed to jumble that identification before reaching the midbrain. At the same time, electrophysiological studies of LSO and its efferent target in the inferior colliculus, along with the strictly contralateral deficits in sound localization resulting from unilateral lesions above the level of the superior olives, indicated that hemifield allegiance was largely maintained (though reversed) at the midbrain. Here we present seven lines of biochemical evidence, some combined with prior ablations, supporting the notion that the anatomical segregation of the ipsilateral and contralateral fibers ascending from the LSO is accompanied by a corresponding segregation of their neurotransmitters: most of the ascending ipsilateral projection is probably glycinergic and, hence, inhibitory in effect, while most of the contralateral projection is probably glutamatergic/aspartergic and, hence, excitatory in effect. Taken together, the inhibitory ipsilateral projections and the excitatory contralateral projections serve to amplify functional contralaterality at the higher levels of the auditory system.


Predictors of 30-day follow-up visit completion after primary bariatric surgery: an analysis of the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program data registry.
Adherence to follow-up visits is often unsatisfactory after bariatric surgery. To identify predictors, including surgery type and preoperative demographics, body mass index (BMI), medical conditions, and smoking status, of 30-day follow-up visit completion. Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program participating centers (2015-2018). Patients who underwent primary Roux-en-Y gastric bypass or sleeve gastrectomy were included in this analysis. Data were analyzed using weighted logistic regression. Subanalyses included stratification of the sample by sex and age (<45, 45-60, and >60 years). Patients (n = 566,774) were predominantly female (79.6%), White (72.4%), non-Hispanic (77.9%), and middle-aged (44.5 ± 11.9 years), with a mean BMI of 45.3 ± 7.8 kg/m2. More than 95% of patients completed the 30-day visits. In the whole-sample analysis, older age (odds ratio [OR], 1.02) and the presence of non-insulin-dependent diabetes (OR, 1.04), hypertension (OR, 1.03), hyperlipidemia (OR, 1.10), obstructive sleep apnea (OR, 1.15), and gastroesophageal reflux disease (OR, 1.16) were positive predictors of the 30-day visit completion (Ps < .01). Conversely, sleeve gastrectomy procedure (OR, .86), Black race (OR, .87), Hispanic ethnicity (OR, .94), and the presence of insulin-dependent diabetes (OR, .96) and smoking (OR, .83) were negative predictors (Ps < .01). Several differences emerged in subanalyses. For example, in sex stratification, Hispanic ethnicity lost its significance in men. In age stratification, BMI and male sex emerged as positive predictors in the age groups of <45 and 45-60 years, respectively. Although challenged by small effect sizes, this analysis identified subgroups at a higher risk of being lost to follow-up after bariatric surgery.


Rational design of sulfidogenic granular sludge reactor with clostridia as dominant bacteria for energy-efficient sulfate-laden wastewater treatment.
The sludge flotation and washout are frequently observed in anaerobic sulfidogenic reactor. This challenge raised the interests of re-thinking/re-designing of a compact and low-flotation bioreactor. The present study investigated to understand the temporal dynamics of microbial community and granular sludge properties in a pneumatic-mixing reactor treating sulfate-laden wastewater. The findings revealed that the reactor performance and sludge properties were dynamically changed and correlated over long-term run. In the bioreactor, a rarer type of sulfate reducing bacteria (genus Clostridium XVIII) was remarkably enriched (~30% abundance). The Clostridium XVIII-mediated COD removal (92.7 ± 3.9%) was further confirmed via mass balance which demonstrated the growth rate of total active biomass and sulfate-reducing active biomass were 19.95 and 6.0 mg-COD/Linfluent respectively. The PICRUSt data suggested that i) high abundance of carbohydrate metabolism and S-reductase enzymes enriched, and ii) energy metabolism enzymes decreased which implies that the new SRB communities are more energy-efficient than conventional ones.


Boron Neutron Capture Therapy Followed by Image-Guided Intensity-Modulated Radiotherapy for Locally Recurrent Head and Neck Cancer: A Prospective Phase I/II Trial.
This trial investigated the efficacy and safety of salvage boron neutron capture therapy (BNCT) combined with image-guided intensity-modulated radiotherapy (IG-IMRT) for recurrent head and neck cancer after prior radiotherapy (RT). BNCT was administered using an intravenous boronophenylalanine-fructose complex (500 mg/kg) in a single fraction; multifractionated IG-IMRT was administered 28 days after BNCT. For BNCT, the mucosa served as the dose-limiting organ. For IG-IMRT, the clinical target volume (CTV) and the planning target volume (PTV) were generated according to the post-BNCT gross tumor volume (GTV) with chosen margins. This trial enrolled 14 patients, and 12 patients received combined treatment. The median BNCT average dose for the GTV was 21.6 Gy-Eq, and the median IG-IMRT dose for the PTV was 46.8 Gy/26 fractions. After a median (range) follow-up period of 11.8 (3.6 to 53.2) months, five patients had a complete response and four had a partial response. One patient had grade 4 laryngeal edema; another patient had a grade 4 hemorrhage. Most tumor progression occurred within or adjacent to the CTV. The 1-year overall survival and local progression-free survival rates were 56% and 21%, respectively. Despite the high response rate (64%) of this trial, there was a high incidence of in-field and marginal failure with this approach. Future studies combining BNCT with modalities other than radiation may be tried.


Vitamin D insufficiency underlies unexpected hypocalcemia following high dose glucocorticoid therapy.
Vitamin D insufficiency is a reemerging and common health problem for skeletal system. Pharmacological application of glucocorticoid inhibits intestinal calcium absorption and stimulates tubular calcium excretion, thus induces severely negative calcium balance. We report a patient presenting symptomatic hypocalcemia following high dose glucocorticoid administration. After a pulse-therapy with methylprednisolone, hypocalcemia with muscle cramp developed in association with hypercalciuria and secondary hyperparathyroidism in the absence of hypomagnesemia. Circulating level of 1,25-dihydroxyvitamin D was in a reference range, while that of 25-hydroxyvitamin D was insufficient. Treatment with alfacalcidol of 1 mug/day promptly improved serum calcium level within a couple of weeks. Vitamin D insufficiency could be a serious problem in patients with high dose glucocorticoid therapy.


Structural insights into the clustering and activation of Tie2 receptor mediated by Tie2 agonistic antibody.
Angiopoietin (Angpt)-Tie receptor 2 (Tie2) plays key roles in vascular development and homeostasis as well as pathological vascular remodeling. Therefore, Tie2-agonistic antibody and engineered Angpt1 variants have been developed as potential therapeutics for ischemic and inflammatory vascular diseases. However, their underlying mechanisms for Tie2 clustering and activation remain elusive and the poor manufacturability and stability of Angpt1 variants limit their clinical application. Here, we develop a human Tie2-agonistic antibody (hTAAB), which targets the membrane proximal fibronectin type III domain of Tie2 distinct from the Angpt-binding site. Our Tie2/hTAAB complex structures reveal that hTAAB tethers the preformed Tie2 homodimers into polygonal assemblies through specific binding to Tie2 Fn3 domain. Notably, the polygonal Tie2 clustering induced by hTAAB is critical for Tie2 activation and are resistant to antagonism by Angpt2. Our results provide insight into the molecular mechanism of Tie2 clustering and activation mediated by hTAAB, and the structure-based humanization of hTAAB creates a potential clinical application.


Close coupling of systolic and diastolic function: combined assessment provides superior prediction of exercise capacity.
Isolated diastolic dysfunction is thought to account for approximately 50% of cases of heart failure. We tested the hypotheses that (1) the use of different methods for assessing systolic and diastolic function may contribute to the apparent frequency with which they are dissociated and (2) that combined assessment of systolic and diastolic function is superior to either one alone. A total of 110 patients underwent echocardiography with tissue Doppler imaging (TDI) of the mitral annulus before maximal exercise testing. The correlation between left ventricular (LV) ejection fraction (EF) and exercise capacity was weak (r = 0.199). Among patients with EF greater than 55%, those with normal exercise capacity (>7 METs) had a higher systolic velocity of the mitral annulus than those achieving less than 7 METs (9.6 +/- 0.3 versus 7.5 +/- 0.4 cm/s, P = .001). The mitral annular systolic (Sa) and early diastolic (Ea) velocities each correlated moderately with exercise tolerance (r = 0.40 and 0.49, respectively). Sa and Ea correlated highly with each other (r = 0.79, P < .001). The sum of isovolumic contraction and relaxation times measured from TDI correlated moderately with exercise duration (r = -0.59). A combined index of systolic and diastolic function that includes isovolumic contraction and relaxation times and ejection time had the best correlation with achieved METs (r = -0.73, P < .001). A TDI index of cardiac performance higher than 0.52 had excellent sensitivity (86%) and specificity (100%) for predicting reduced exercise tolerance lower than 7 METs. When assessed with the same technique, LV systolic and diastolic function are tightly linked. A TDI-derived combined index of myocardial performance is the best predictor of exercise capacity.


The Duration in Treatment With Electroconvulsive Therapy Among Patients Screening Positive or Negative for Borderline Personality Disorder Traits: A Retrospective Cohort Study.
While emerging evidence suggests that electroconvulsive therapy (ECT) is an effective treatment for depressive symptoms in patients with co-occurring borderline personality disorder (BPD) traits, it is unclear whether the presence of BPD traits modulates the tolerability of ECT. This study estimates the association between BPD traits and retention in acute course ECT treatment. This study used a retrospective cohort of patients receiving ECT between 2015 and 2020 and who were assessed using the McLean Screening Instrument for BPD, the Quick Inventory of Depressive Symptomatology Self-Report 16-item scale, and the Montreal Cognitive Assessment before initiating treatment. One thousand five hundred eight patients received ECT during the study period, of whom 277 (18.4%) screened positive for BPD traits. Borderline personality disorder traits were associated with a higher odds of remaining in ECT for at least 10 treatments (adjusted odds ratio, 1.502; 95% confidence interval, 1.11-2.02; P = 0.007). Among individual symptom domains, only endorsing chronically feeling empty was associated with duration in ECT treatment. Among patients receiving ECT, screening positive for BPD traits was associated with a higher odds of receiving at least 10 ECT treatments. These results support the overall tolerability of ECT in patients with BPD traits.


Multinational prospective cohort study over 18 years of the risk factors for ventilator-associated pneumonia in 9 Asian countries: INICC findings.
Ventilator associated pneumonia (VAP) rates in Asia are several times above those of US. The objective of this study is to identify VAP risk factors. We conducted a prospective cohort study, between March 27, 2004 and November 2, 2022, in 279 ICUs of 95 hospitals in 44 cities in 9 Asian countries (China, India, Malaysia, Mongolia, Nepal, Pakistan, Philippines, Sri Lanka, Thailand, Vietnam). 153,717 patients, followed during 892,996 patient-days, acquired 3,369 VAPs. We analyzed 10 independent variables. Using multiple logistic regression we identified following independent VAP RFs= Age, rising VAP risk 1% per year (aOR=1.01; 95%CI=1.00-1.01, P<.0001); male gender (OR=1.17; 95%CI=1.08-1.26, P<.0001); length of stay, rising VAP risk 7% daily (aOR=1.07; 95%CI=1.06-1.07, P<.0001); mechanical ventilation (MV) device utilization (DU) ratio (OR=1.43; 95%CI=1.36-1.51; p<.0001); tracheostomy connected to a MV (OR=11.17; 95%CI=9.55-14.27; p<.0001); public (OR=1.84; 95%CI=1.49-2.26, P<.0001), and private (OR=1.57; 95%CI=1.29-1.91, P<.0001) compared with teaching hospitals; upper-middle income country (OR=1.86; 95%CI=1.63-2.14, P<.0001). Regarding ICUs, Medical-Surgical (OR=4.61; 95%CI=3.43-6.17; P<.0001), Neurologic (OR=3.76; 95%CI=2.43-5.82; P<.0001), Medical (OR=2.78; 95%CI=2.04-3.79; P<.0001), and Neuro-Surgical (OR=2.33; 95%CI=1.61-3.92; P<.0001) showed the highest risk. Some identified VAP RFs are unlikely to change= age, gender, ICU type, facility ownership, country income level. Based on our results, we recommend limit use of tracheostomy, reducing LOS, reducing the MV/DU ratio, and implementing an evidence-based set of VAP prevention recommendations.


Low Concordance between NYHA Classification and Cardiopulmonary Exercise Test Variables in Patients with Heart Failure and Reduced Ejection Fraction.
The New York Heart Association (NYHA) functional classification is the most commonly used classification system for heart failure (HF), whereas cardiopulmonary exercise testing (CPET) is the gold standard for functional status evaluation in HF. This study aimed to analyze correlation and concordance between NYHA classes and CPET variables. HF patients with clinical indication for CPET and ejection fraction (EF) < 50% were selected. Correlation (Spearman coefficient) and concordance (kappa) between NYHA classification and CPET-based classifications were analyzed. A p < 0.05 was accepted as significant. In total, 244 patients were included. Mean age was 56 ± 14 years, and mean EF was 35.5% ± 10%. Distribution of patients according to NYHA classification was 31.2%% class I, 48.3% class II, 19.2% class III, and 1.3% class IV. Correlation (r) between NYHA and Weber classes was 0.489 (p < 0.001), and concordance was 0.231 (p < 0.001). Correlation (r) between NYHA and ventilatory classes (minute ventilation/carbon dioxide production [VE/VCO2] slope) was 0.218 (p < 0.001), and concordance was 0.002 (p = 0.959). Spearman correlation between NYHA and CPET score classes was 0.223 (p = 0.004), and kappa concordance was 0.027 (p = 0.606). There was a moderate association between NYHA and Weber classes, although concordance was low. Ventilatory (VE/VCO2slope) and CPET score classes had a weak association and a low concordance with NYHA classes.


Sugar modified oligonucleotides: synthesis, nuclease resistance and base pairing of oligodeoxynucleotides containing 1-(4'-thio-beta-D-ribofuranosyl)-thymine.
XdT12 and dT5XdT6, where X is 1-(4'-thio-beta-d-ribofuranosyl)-thymine, were synthesized. The first oligonucleotide presents a better stability against calf spleen phosphodiesterase than natural dT12. The second one hybridizes with complementary sequence. However the X:A base pairing stability is lower than natural T:A one.


Aspirin and gastrointestinal haemorrhage: a methodologic assessment.
The literature on the association between Aspirin (ASA) use and gastrointestinal haemorrhage (GIH) has been reviewed. Thirteen control-studies were selected and examined for (i) the type of design (ii) the choice of outcome measures, and (iii) the adequacy of satisfying defined causation criteria and the influence of sampling strategies on one of these criteria--strength of association. Of the 13 studies seven were large scale randomized control trials (RCTs) and six were case-control studies. Among the outcome measures utilized in these studies and currently available for the assessment of GIH, we found none were uniquely satisfactory for use as a "gold standard". Furthermore, in none of these studies was the particular chosen outcome measure sufficiently satisfactory to allow firm conclusions on the issue of causation. None of the studies adequately met all the defined causation criteria or adequately eliminated the potential biases in the chosen sampling strategies. Thus the evidence that aspirin causes GIH fails to stand up to critical evaluation. This, of course, does not mean that ASA does not cause GIH. However, it is common practice for physicians to advise their patients with a prior history of GIH and or gastrointestinal symptoms to refrain from ASA use. This is probably sound advice in the setting where ASA is being used as a casual or short term analgesic or anti-inflammatory agent. But in the context of severe inflammatory joint disease when the use of ASA is clinically indicated, it should not be withheld on the basis of the risk of GIH. There is a widespread belief in medicine that by implication aspirin and other nonsteroidal anti inflammatory drugs are a common cause of bleeding from the gastrointestinal tract, yet it has been pointed out frequently [1-3] that the evidence to support the belief is weak and circumstantial. Despite this the perceived association of aspirin with gastrointestinal bleeding influences both pharmaceutical and clinical practice and often hinders or prevents the prescription of anti-inflammatory medication to patients with severe inflammatory joint disease. It was felt that a proper critical appraisal of the evidence was essential. It is unfortunate that the evidence most frequently cited implicating ASA as a cause of GIH is almost entirely related to the casual use of the drug. Thus our conclusions must be viewed with some caution in the patient group where this knowledge would be of most importance, that is in patients with inflammatory joint disease.


An EPR investigation of spin-labelled erythrocytes as a diagnostic technique for malignant hyperthermia.
Spin labelled (7-, 12- and 16- doxylsteric (DS) acid) erythrocyte (red blood cell) membranes isolated from six malignant hyperthermia susceptible (MHS) and six malignant hyperthermia normal (MHN) volunteer donors were characterized using the order parameter (S) and rotational correlation time (tau r) determined from 37 degrees C, 9 GHz electron paramagnetic resonance spectra. These parameters were found to decrease due to the increasing fluidization of the membrane as the halothane and benzyl alcohol sample concentration is increased and that significant differences exist in the values of S and tau r between the MHS and MHN sample groups, but that the differences in these parameters between the presence and absence of an external fluidizing agent are not significant for both sample groups. In the absence of these fluidizing agents, the mean values and standard errors of S at 37 degrees C for MHS and MHN are 0.643(2) and 0.652(3) for 7-DS, 0.554(2) and 0.563(3) for 12-DS, respectively, and of tau r are 2.139(12) and 2.223(13) ns for 16-DS, respectively. The values of S and tau r are significantly smaller for the MHS group than for the MHN group contrary to some previous reports. These observations revise and extend previous reports and show that the observed values of S and tau r in the absence of a fluidizing agent depend on the erythrocyte membrane structure in MHS and MHN subjects. They also suggest that the potential to use spin-labelled red blood cells as a screening protocol for MH deserves further investigation.


Successful implementation of a nurse-led teaching programme to independently administer subcutaneous methotrexate in the community setting to children with Crohn's disease.
Methotrexate is increasingly used as a third line immunosuppression agent in children with Crohn's disease (CD). Methotrexate is traditionally administered in the hospital setting. To set up a nurse-led education programme to teach children/their parents to administer subcutaneous methotrexate in the community. All patients were given methotrexate over a 16-month period. Patient demographics including previous treatments were collected. A competency based teaching package was implemented by the inflammatory bowel disease nurse. Distances and travel times together with costings were calculated. Thirty two patients (19 male; 13 female) with a median treatment age of 11.96 years (IQR 10.67-13.92) were studied. Thirty of 32 (17 children, 13 parents) were independently administering methotrexate. The median return journey distance to hospital was 23 miles (IQR 14.4-42.4) taking a median time of 52 min (IQR 41.0-73.5) for each injection. The total patient travel saving was £10,537 (average £730 per patient) and nursing time saving was £12,808 with home administration (total saving £23,345). This paediatric study demonstrates that methotrexate injections can be given successfully in the majority (94%) of patients with CD independently in the community, resulting in significant time and money savings for patients and health professionals alike.


Influence of lysophosphatidylcholine on the gelation of diluted wheat starch suspensions.
Starch is an omnipresent constituent which is used for its nutritional and structuring properties. Recently concerns have been raised since starch is a source of readily available glucose which is tightly correlated with diabetes type II and obesity. For this reason, the possibilities for modulating the digestibility of starch while preserving its functional properties were investigated; therefore the focus of this paper is on starch gelatinization and the effect of lysophosphatidylcholine (LPC) on the structuring properties of wheat starch. The effect of LPC on thermal properties and viscosity behavior of starch suspensions was studied using DSC and RVA, respectively. The influence on granular structure was observed by light microscopy. The RVA profile demonstrated no viscosity increase at high LPC concentrations which proves intact granular structure after gelatinization. LPC in intermediate concentrations resulted in a notable delay of pasting; however the peak and end viscosities were influenced as well. Lower LPC concentrations demonstrated a higher peak viscosity as compared with pure starch suspensions. DSC results imply that inclusion complexes of amylose-LPC might be formed during pasting time. Since the viscosity profiles are changed by LPC addition, swelling power and solubility of starch granules are influenced as well. LPC hinders swelling power and solubility of starch granules which are stimulated by heating.


Prednisolone-3,20-bisguanylhydrazone: the mode of interaction with rat brain sodium and potassium-activated adenosine triphosphatase.
The mechanism of interaction between prednisolone-3,20-bisguanylhydrazone (PBGH) and Na+,K+-ATPase (ATP phosphohydrolase, EC 22.214.171.124) was studied using partially purified rat brain enzyme preparations. PBGH inhibited Na+,K+-ATPase rapidly and reversibly. The enzyme-inhibiting action of PBGH was competitively antagonized by potassium. PBGH inhibited Na+,Mg2+ and ATP-supported binding of (3H)-ouabain to the enzyme. When PBGH was added to the incubation mixture at the time when the (3H)-ouabain binding was close to its equilibrium state, the concentration of (3H)-ouabain complex was rapidly reduced and shifted to a lower equilibrium state. A double reciprocal plot analysis of the (3H)-ouabain binding data indicates that the inhibition of ouabain binding by PBGH is apparently competitive. Binding of (3H)-ouabain in the presence of Tris-phosphate and Mg2+ was also inhibited by unlabeled PBGH. Thus, it appears that the binding of PBGH precludes the binding of ouabain to Na+,K+-ATPase.


Achalasia-like esophagus from amyloidosis. Successful treatment with pneumatic bag dilatation.
A 78-year-old man with amyloidosis involving the esophagus is described. The clinical and radiographic features resembled classic achalasia, while esophageal manometrics demonstrated aperistalsis, incomplete LES relaxation, but a normal LES resting pressure. A review of the literature suggests that esophageal amyloid may have variable presentations. This patient was successfully managed with forceful pneumatic bag dilatation.