The role of attention in the programming of saccades.
Accurate saccadic programming in natural visual scenes requires a signal designating which of the many potential targets is to be the goal of the saccade. Is this signal controlled by the allocation of perceptual attention, or do saccades have their own independent selective filter? We found evidence for the involvement of perceptual attention, namely: (1) summoning perceptual attention to a target also facilitated saccades; (2) perceptual identification was better at the saccadic goal than elsewhere; and (3) attempts to dissociate the locus of attention from the saccadic goal were unsuccessful, i.e. it was not possible to prepare to look quickly and accurately at one target while at the same time making highly accurate perceptual judgements about targets elsewhere. We also studied the trade-off between saccadic and perceptual performance by means of a novel application of the "attentional operating characteristic" (AOC) to oculomotor performance. This analysis revealed that some attention could be diverted from the saccadic goal with virtually no cost to either saccadic latency or accuracy, showing that there is a ceiling on the attentional demands of saccades. The links we discovered between saccades and attention can be explained by a model in which perceptual attention determines the endpoint of the saccade, while a separate trigger signal initiates the saccade in response to transient changes in the attentional locus. The model will be discussed in the context of current neurophysiological work on saccadic control.


Pulmonary arteriovenous fistula: detection with magnetic resonance angiography.
Pulmonary arteriovenous fistula are an uncommon disorder, and are most frequently congenital, usually then associated with hereditary hemorrhagic telangectasia (Rendu-Osler-Weber disease). We present, to our knowledge, the first case of a pulmonary arteriovenous fistula detected by gadolinium-enhanced pulmonary magnetic resonance angiography and confirmed by digital subtraction pulmonary angiography in a patient where the CT scan was unremarkable.


Biosynthesis and secretion of enamel proteins during hamster tooth development.
Experiments were designed to detect and determine the biosynthetic behavior of enamel proteins in Syrian Golden hamsters. Enamel matrix proteins were extracted from 3-day-old postnatal first molar tooth organs. Labeling pulse/chase experiments with [35S]-methionine followed by light microscopic autoradiography, or polyacrylamide slab gel electrophoresis and fluorography, showed the synthesis of epithelial-specific gene products. Synthesis and secretion of enamel proteins required approximately 30 min under these in vitro organ culture conditions; both enamelin and amelogenin proteins were synthesized and secreted into the forming extracellular matrix. Amelogenin proteins were secreted initially and rapidly degraded into increasingly smaller polypeptides. In contrast, enamelin proteins were secreted at a slower rate and remained more or less stable over the duration of the experiment. The specific activities of both classes of proteins increased over a 6-hour synthesis period, indicating the accumulation of both proteins into the forming extracellular matrix. Comparisons of the kinetics of formation and posttranslational processing of enamelin and amelogenin are consistent with the presence of possibly two different gene products in hamster secretory ameloblasts.


Systems strategies for developing industrial microbial strains.
Industrial strain development requires system-wide engineering and optimization of cellular metabolism while considering industrially relevant fermentation and recovery processes. It can be conceptualized as several strategies, which may be implemented in an iterative fashion and in different orders. The key challenges have been the time-, cost- and labor-intensive processes of strain development owing to the difficulties in understanding complex interactions among the metabolic, gene regulatory and signaling networks at the cell level, which are collectively represented as overall system performance under industrial fermentation conditions. These challenges can be overcome by taking systems approaches through the use of state-of-the-art tools of systems biology, synthetic biology and evolutionary engineering in the context of industrial bioprocess. Major systems metabolic engineering achievements in recent years include microbial production of amino acids (L-valine, L-threonine, L-lysine and L-arginine), bulk chemicals (1,4-butanediol, 1,4-diaminobutane, 1,5-diaminopentane, 1,3-propanediol, butanol, isobutanol and succinic acid) and drugs (artemisinin).


Endometrial thickness as an orienting factor for the medical treatment of unruptured tubal pregnancy.
To evaluate the efficacy of the endometrial thickness measurement through transvaginal ultrasound as an orienting factor for the medical treatment of unruptured tubal pregnancy with a single dose of methotrexate in order to select the best cases for the medical treatment. A prospective study, in which the largest measurement of endometrial thickness in millimeters was evaluated, along the longitudinal uterine axis, by means of transvaginal ultrasound. A total of 38 patients meeting the inclusion criteria for single-dose methotrexate treatment [50 mg/m2 intramuscularly (i.m.)] were included in the study. We observed whether there was any difference in mean value of endometrial thickness and initial beta-human choriongonadotropin levels, between the cases that evolved successfully with the treatment, and those that failed. The mean value of endometrial thickness and initial beta-human choriongonadotropin (beta-hCG) levels, for patients evolving successfully with medical treatment (28 cases), were 6.39 mm and 1936.2 mUI/ml, respectively, while the mean values for failures were 11.70 mm and 6831.3 mUI/ml. We carried out statistical analysis using the 'Student's t-test', with p < 0.05. The mean value of endometrial thickness, along the longitudinal uterine axis through transvaginal ultrasound, reflects hormonal action and has been demonstrated to be another important parameter in indicating the medical treatment of an unruptured tubal pregnancy.


Role of placental lactogen and prolactin in human pregnancy.
In summary, studies from our and other laboratories strongly suggest that placental lactogen has direct effects on fetal growth and metabolism as well as on maternal metabolism. Prolactin may be important in the regulation of water and ion transport across the amnion, the production of surfactant by the fetal lung, and the immune response during pregnancy. A summary of the postulated effects of placental lactogen on maternal and fetal physiology is depicted in Figure 9 and a summary of the postulated effects of prolactin during pregnancy is shown in Table 6. Undoubtedly, future studies of the physiology of placental lactogen and prolactin will uncover new functions for these hormones during gestation.


Triticeal cartilage: the forgotten cartilage.
The triticeal cartilage (TC) is a small cartilage found within the thyrohyoid membrane. The TC has a variable prevalence between and within individuals. It has been suggested that absence of a TC results from its failure to separate from the superior horn of the thyroid cartilage (SHTC) and that individuals without a TC will have a longer SHTC. This study aims to identify the prevalence of the TC and investigate the relationship between the length of the SHTC and presence of a TC. Eighty seven adult cadavers underwent dissection. Data were collected on presence or absence of a TC and lengths of SHTC. A TC was identified in 28 cadavers (33%). In cadavers with a unilateral TC, there was no significant difference between the lengths of the SHTC on sides with a TC (1.6 mm, ±SEM 0.12 mm) to sides without a TC (1.7 mm, ±SEM 0.10 mm) (P = 0.47). In cadavers with no TCs, the length of the SHTCs (1.8 mm, ±SEM 0.04 mm) was significantly longer than the SHTCs of cadavers with a TC present bilaterally (1.4 mm, ±SEM 0.12 mm) (P = 0.02). A TC was found in 33% of cadavers. This study demonstrates a relationship between the presence of a TC and the length of the SHTC only in cadavers with a TC present or absent bilaterally.


Learning black- and gray-box chemotactic PDEs/closures from agent based Monte Carlo simulation data.
We propose a machine learning framework for the data-driven discovery of macroscopic chemotactic Partial Differential Equations (PDEs)-and the closures that lead to them- from high-fidelity, individual-based stochastic simulations of Escherichia coli bacterial motility. The fine scale, chemomechanical, hybrid (continuum-Monte Carlo) simulation model embodies the underlying biophysics, and its parameters are informed from experimental observations of individual cells. Using a parsimonious set of collective observables, we learn effective, coarse-grained "Keller-Segel class" chemotactic PDEs using machine learning regressors: (a) (shallow) feedforward neural networks and (b) Gaussian Processes. The learned laws can be black-box (when no prior knowledge about the PDE law structure is assumed) or gray-box when parts of the equation (e.g. the pure diffusion part) is known and "hardwired" in the regression process. More importantly, we discuss data-driven corrections (both additive and functional), to analytically known, approximate closures.


The delay of breast cancer diagnosis and management during the Syrian war.
Early detection of breast cancer (BC) is crucial for better prognosis especially in low-income countries, where advanced cancer stages are common. The Syrian war severely affected the healthcare system restraining the proper timely management of BC cases. We aimed to investigate the prevalence of patient- and system-related delays in BC diagnosis and management in Syria in addition to their predisposing characteristics and impact on the staging. This is a cross-sectional retrospective cohort study on patients followed by the BC unit at Al-Bairouni main cancer center in Syria. The data were collected through personal interviews and retrospective revision of patients' records. A total number of 519 patients were recruited; A quarter of them (n = 126) reported more than three months intervals between symptoms recognition and presentation to a physician. Additionally, 72 (13.9 %) patients received a confirmed diagnosis more than three months after presentation, and 12 (2.3 %) started treatment at least three months after the diagnosis. Patients who suffered from war-related inaccessibility to healthcare were 2.55 [1.58-4.11] times more likely to report significant delays. Additionally, the most common self-reported reasons for patient delay were the lack of awareness, which was more evident for less common symptoms like the change in breasts size, and shyness. Patients who reported significant delays were more likely to receive an advanced-stage diagnosis. War-related inaccessibility to healthcare rendered a significant group of BC patient susceptible to evident delay. This combined with significant system delays because of the overwhelmed hospitals, high costs, and insufficient personnel, equipment, medications, and training. However, personal factors, which might not be directly related to the war, like the inadequate awareness of rare symptoms and shyness still necessitate urgent interventions on the public knowledge and performed screening practices. These delays associated with receiving advanced-stage diagnoses and minimizing them can return better prognoses.


Psychiatric and neurological complications of long COVID.
COVID-19 was primarily considered a pulmonary disease with extrapulmonary manifestations. As the pandemic spread, there has been growing evidence that the disease affects various organs/systems, including the central and peripheral nervous systems. Accumulation of clinical data demonstrates that in a large population of survivors impairments in the function of one or more organs may persist for a long time, a phenomenon commonly known as post COVID or long COVID. Fatigue and cognitive dysfunction, such as concentration problems, short-term memory deficits, general memory loss, a specific decline in attention, language and praxis abilities, encoding and verbal fluency, impairment of executive functions, and psychomotor coordination, are amongst the most common and debilitating features of neuropsychatric symptoms of post COVID syndrome. Several patients also suffer from compromised sleep, depression, anxiety and post-traumatic stress disorder. Patients with long COVID may demonstrate brain hypometabolism, hypoperfusion of the cerebral cortex and changes in the brain structure and functional connectivity. Children and adolescents represent a minority of COVID-19 cases, so not surprisingly data on the long-term sequelae after SARS-CoV-2 infections in these age groups are scarce. Although the pathogenesis, clinical characteristics, epidemiology, and risk factors of the acute phase of COVID-19 have been largely explained, these areas are yet to be explored in long COVID. This review aims to provide an update on what is currently known about long COVID effects on mental health.


Respiratory and cardiovascular responses to hypoxia in the Australian lungfish.
Simultaneous measurements of pulmonary blood flow (qPA), coeliacomesenteric blood flow (qCoA), dorsal aortic blood pressure (PDA), heart rate (fH) and branchial ventilation frequency (fv) were made in the Australian lungfish, Neoceratodus forsteri, during air breathing and aquatic hypoxia. The cholinergic and adrenergic influences on the cardiovascular system were investigated during normoxia using pharmacological agents, and the presence of catecholamines and serotonin in different tissues was investigated using histochemistry. Air breathing rarely occurred during normoxia but when it did, it was always associated with increased pulmonary blood flow. The pulmonary vasculature is influenced by both a cholinergic and adrenergic tonus whereas the coeliacomesenteric vasculature is influenced by a beta-adrenergic vasodilator mechanism. No adrenergic nerve fibers could be demonstrated in Neoceratodus but catecholamine-containing endothelial cells were found in the atrium of the heart. In addition, serotonin-immunoreactive cells were demonstrated in the pulmonary epithelium. The most prominent response to aquatic hypoxia was an increase in gill breathing frequency followed by an increased number of air breaths together with increased pulmonary blood flow. It is clear from the present investigation that Neoceratodus is able to match cardiovascular performance to meet the changes in respiration during hypoxia.


[Separation of ionic currents responsible for action potential generation in isolated neurons of frog spinal ganglia].
The technique was developed for isolating neurons from the frog spinal ganglia. The isolated cells completely preserved electrical excitability and were investigated under intracellular dialysis conditions. Fast and slow inward current components were found. They were separated by TTX and cadmium: the fast inward current component was blocked by TTX, while the slow inward current was blocked by cadmium. Slow inward current diminished in Na-free solution and calcium ions are supposed to participate in its transfer.


Asymptomatic pheochromocytoma in the posterior mediastinum.
A 66-year-old female patient was treated for a posterior mediastinal tumour with unknown histology. During thoracotomy, repetitive hypertensive crises had to be treated. The tumour was completely resected. Pathology revealed an extra-adrenal pheochromocytoma. Diagnosis of pheochromocytoma is usually made on the basis of clinical presentation and elevated catecholamine levels in serum or urine. Imaging is used primarily for localizing tumours prior to surgery. Complete surgical excision is the primary treatment. The only absolute indicator of malignancy is the identification of distant metastases to bone, liver, lung or lymph nodes.


Cytochrome P450-derived eicosanoids and inflammation in liver diseases.
Hepatic inflammation is a key pathologic mediator in a wide array of acute and chronic liver diseases. Hepatitis is a crucial driver of liver tissue damage provoking the progression to severe fibrosis, cirrhosis and hepatocellular carcinoma, irrespective of the etiologic cause. Inflammatory liver diseases are collectively considered one of the most critical public health risks. Cytochrome P450 (CYP) enzymes are superfamily of monooxygenases which possess the greater diversity of substrate structures amidst all other enzyme families. Members of omega-3 as well as omega-6 polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid and arachidonic acid, respectively, can be metabolized by CYP isoforms leading to the production of biologically active lipid mediators called eicosanoids. CYP-derived eicosanoids have been shown to play significant roles in the pathophysiology and protection of multiple inflammatory liver diseases. In this review, we elucidate the intricate role of CYP-derived eicosanoids in inflammation in liver diseases paving the way for better therapeutic approaches.


Safety, tolerability, pharmacokinetics, and antitumour activity of oleclumab in Japanese patients with advanced solid malignancies: a phase I, open-label study.
Cluster of differentiation (CD) 73-targeted immunotherapy and CD73 inhibition may reduce adenosine production, which can augment the host and/or immunotherapy response to tumours. We aimed to assess the safety and tolerability, pharmacokinetics, and antitumour activity of oleclumab, an anti-CD73 monoclonal antibody, in adult Japanese patients with advanced solid malignancies resistant to standard therapy. In this phase I, single-centre, open-label study, patients received oleclumab 1500 mg (Cohort 1) or 3000 mg (Cohort 2) intravenously every 2 weeks. In total, six patients were enrolled in the study (three in each cohort), and all six patients received the study treatment. The median patient age was 56.0 years and 4/6 were males. All patients (100%) reported adverse events (AEs) during the study; five (83.3%) patients reported AEs related to the study treatment. One (16.7%) patient reported a Grade 3 AE (neutrophil count decreased) that was not related to the study treatment. No AEs with an outcome of death were reported, and no patients reported AEs or serious AEs leading to oleclumab discontinuation/dose interruption. No dose-limiting toxicities were reported, and no patient discontinued due to an AE related to the study treatment. Oleclumab exposure increased dose proportionally. No patient achieved disease control at 8 weeks, and all six patients developed progressive disease. Oleclumab was well tolerated in adult Japanese patients with advanced solid malignancies and no unexpected safety concerns were raised; oleclumab exposure increased with dose. Future studies on combination therapy with other agents are warranted.


Fitness, growth and transmissibility of SARS-CoV-2 genetic variants.
The massive scale of the global SARS-CoV-2 sequencing effort created new opportunities and challenges for understanding SARS-CoV-2 evolution. Rapid detection and assessment of new variants has become one of the principal objectives of genomic surveillance of SARS-CoV-2. Because of the pace and scale of sequencing, new strategies have been developed for characterizing fitness and transmissibility of emerging variants. In this Review, I discuss a wide range of approaches that have been rapidly developed in response to the public health threat posed by emerging variants, ranging from new applications of classic population genetics models to contemporary synthesis of epidemiological models and phylodynamic analysis. Many of these approaches can be adapted to other pathogens and will have increasing relevance as large-scale pathogen sequencing becomes a regular feature of many public health systems.


Outline of restorative neurology: definition, clinical practice, assessment, intervention.
Rather than focusing on the deficits and lost function caused by upper motor neuron lesions or disorders, it is more advantageous to elucidate, in each individual, the specific neural functions that remain available, and then, to build upon them by designing a treatment protocol to optimize their effectiveness and thus improve recovery. The practice of Restorative Neurology is based on detailed assessment of the individual patient, the use of neurophysiological methods to elucidate and characterize subclinical function and the application of interventions that modify neural activity to improve clinical function.


Further developed device for human sperm freezing by the twenty-minute method.
A further developed, practical device for human sperm freezing is described by which the preparation of sperm and the freezing process are reduced to a simple procedure requiring about 20 minutes. The instrument is based on the principle of evaporation of liquid nitrogen, which acts as a refrigerant for the freezing plate under the control of a thermostat. Rapid-rate freezing can be performed for pellet production and slow-rat freezing for paillettes; a high degree of isolation of samples is maintained by easily interchangeable freezing plates. Typical stages of freezing are accomplished at temperatures of +5 degrees C and--80 degrees C, with storage at--196 degrees C. The recovery index is 50% to 70%. The treatment was applied to 56 patients, resulting in 19 normal deliveries, 3 abortions, and 9 current pregnancies.


Isolation of a sequence encoding human cystatin C. Conservation of exon-intron structure between members of the cysteine proteinase inhibitors superfamily.
The human cystatin C gene was cloned using a synthetic oligonucleotide predicted from a portion of its amino-acid sequence. The nucleotide sequence of the restriction fragment hybridizing with the oligonucleotide confirms the existence of one exon encoding amino acids 56-93 of human cystatin C and its relationship to kininogens. However the deduced amino-acid sequence differs in one position from the sequence of the cystatin C fragment deposited as amyloid fibrils in hereditary cerebral hemorrhage with amyloidosis of icelandic origin.


Intraductal pressure in experimental models of acute and chronic pancreatitis in mice.
Pancreatic intraductal pressure is related to the development of pancreatitis, including post-ERCP (endoscopic retrograde cholangiopancreatography) pancreatitis. In this study, we investigate pancreatic intraductal pressure in various mouse models of acute and chronic pancreatitis. Post-ERCP pancreatitis was induced by retrograde infusion of normal saline or radiocontrast at the constant rate of 10 or 20 μL/min. Obstructive pancreatitis was induced by ligation of the pancreatic duct followed by a single injection of caerulein and the changes of intraductal pressure were recorded in day 3 for obstructive acute pancreatitis and day 14 for obstructive chronic pancreatitis. Non-obstructive pancreatitis was induced by repetitive intraperitoneal injections of caerulein. The changes of intraductal pressure were recorded right after the last caerulein injection for non-obstructive acute pancreatitis and after the completion of 4-week caerulein injections for non-obstructive chronic pancreatitis. Elevated pancreatic intraductal pressure was observed in both normal saline and radiocontrast infusion groups and was furtherly indicated that was positively correlated with the viscosity of solution but not genders. In the models of obstructive pancreatitis, a rise in intraductal pressure was observed in both acute and chronic pancreatitis; whereas in the models of non-obstructive pancreatitis, a rise in intraductal pressure was only observed in chronic, but not acute pancreatitis. During ERCP, the elevations in pancreatic intraductal pressure are induced by increasing rate or viscous solution of infusion. During different forms of experimental acute and chronic pancreatitis, obstructive or non-obstructive etiologies of pancreatitis also induces the elevations in pancreatic intraductal pressure.


Poor iron store recovery in voluntary blood donors in the northern zone of Ghana; a five-month three-centre cohort study.
In Ghana, although iron deficiency is endemic, post blood donation iron supplementation is not routine. We sought to determine whether at five months post-donation of a single unit of whole blood, donors were able to recover iron stores. This three-centre cohort study recruited 164 blood donors at the Lawra, Nandom, and Bimbila communities in the northern zone of Ghana. Venous blood samples were drawn at baseline to estimate full blood count (FBC), haemoglobin variants, qualitative G6PD status, and serum ferritin. Five months post-donation, venous blood samples were drawn for a repeat measurement of FBC and serum ferritin. Data were analysed using SPSS and GraphPad prism to assess recovery of iron stores. Whereas 26.8 % had inherited haemoglobin variants, 18.9 % of the donors had qualitative G6PD deficiency. Overall, mean difference between pre-donation and five months post donation iron stores significantly differed from zero (p < 0.001; one sample t-test). After five months post donation, 76.8 % of the blood donors could not achieve pre-donation iron stores. Whereas 6.1 % and 8.5 % blood donors had depleted iron stores and iron deficient erythropoiesis at baseline, these increased to 9.8 % and 21.3 % respectively at five-month post donation. Moreover, at five months post donation, 11 % of these blood donors would have been disqualified per haemoglobin screening cut off of 12.5 g/dl. Reliance on food intake to replenish iron store lost per blood donation may not adequately assure donor health in the study area; iron supplementation should be considered.


TLK2 enhances aggressive phenotypes of glioblastoma cells through the activation of SRC signaling pathway.
Glioblastoma are among the most common forms of cancer affecting the central nervous system, and yet there is currently no effective means of treating them. In the current study, we reported that tousled-like kinase 2 (TLK2) is a key factor in glioblastoma that modulates SRC signaling, thereby driving tumor malignancy. TLK2 is commonly upregulated in glioblastoma, and such upregulation was associated with poor patient outcomes. TLK2 overexpression induced cell growth, migration, invasion, and epithelial-mesenchymal transition, and cell cycle arrest, while TLK2 knockdown had the opposite effect. SRC pathway inhibition by Saracatinib resulted in reduced TLK2-mediated glioblastoma migration, invasion, confirming a key role for SRC signaling in regulating the functions of TLK2. Together, our findings demonstrate that glioblastoma TLK2 overexpression acts as a key driver of tumor malignancy via SRC signaling pathway.


Hydronephrosis: a new method to visualize vas afferens, efferens, and glomerular network.
We have developed a new preparation for in vivo visualization of the glomerular microcirculation, the vas afferens and the vas efferens. This preparation utilizes postischemic hydronephrosis (PIH) to destroy the renal tubular system while preserving a portion of the cortex. In this preparation, glomeruli and associated vasculature remained intact. Observations can be made with either incident light or transillumination. The inner diameter of the vas afferens, measured within 50 microns of the glomerular vascular pole, was 7.9 +/- 0.5 microns (N = 12; SEM) while that of the vas efferens was 7.7 +/- 0.5 microns (N = 12). Both vessels were narrower adjacent to the glomerulus; minimal diameters in this region were 4.5 +/- 0.5 microns (N = 10) and 4.3 +/- 0.5 microns (N = 11), respectively. A specialized round cell, which may act as a sphincter, was seen in the vas efferens. In a second series of experiments, blood velocity was measured in the vas afferens and efferens about 100 microns from the vascular pole. Mean control velocities at these sites were 5.9 +/- 0.9 (N = 14) and 4.6 +/- 1.3 (N = 9) mm X sec-1, respectively; diameters at these same sites were 10.3 +/- 0.6 microns and 11.2 +/- 0.7. During angiotensin II infusion (first series, 0.2 to 0.4 micrograms X min-1 X kg-1, i.v.) the vas efferens in the vicinity of the glomerulus constricted by 22% whereas the corresponding vas afferens showed no consistent response. During angiotensin II infusion, the filtration fraction (GFR/RPF) may, therefore, be elevated by an increased resistance in the vas efferens, particularly at the outflow point of the glomerulus. In the second series of experiments higher dosages of angiotensin II caused vasoconstriction of both vessels, especially at sites more distant from the glomerulus. Furthermore, the new approach is suitable for observing the flow direction within single capillaries of one third to one half of the glomerulus. Therefore, for the first time it is possible to determine the real flow direction in a three-dimensional way.


Bioaccumulation and effects of PCBs and heavy metals in sea stars (Asterias rubens, L.) from the North Sea: a small scale perspective.
Sea stars (Asterias rubens L.) were collected in different stations distributed in the Southern Bight of the North Sea. Concentrations of four heavy metals and six PCB congeners were measured in two body compartments (body wall and pyloric caeca). In order to assess the potential harm of these contaminants, two biochemical parameters were measured in sea stars, viz. reactive oxygen species (ROS) production by amoebocytes and cytochrome P450 immunopositive protein (CYP1A IPP) induction in pyloric caeca. Sea stars from stations located in the plume of the Scheldt river showed the highest contamination levels. Other stations, similarly located, displayed lower levels. No simple relationship could be established between ROS production by sea star amoebocytes and contaminant levels measured in sea star tissues. CYP1A IPP induction displayed more contrasted responses, and highly significant regressions were found between PCB concentrations measured in pyloric caeca and CYP1A IPP. Both biological parameters were found to vary significantly over the study area. On the whole, data indicated that contamination levels and subsequent effects in sea stars were comparable to those described in previous large-scale studies, but that working at a smaller scale highlighted the existence of patterns of contamination which can blur general trends due to major contamination sources like contaminated rivers.


Effect of Feed Restriction during Pregnancy on Performance and Productivity of New Zealand White Rabbit Does.
This study aimed to evaluate effect of stage of feed restriction on performance and productivity of pregnant does. New Zealand white female rabbits were randomly divided into three groups. Control group was provided daily with 185 g of food increased to 200 g from the 15th day of gestation. R(1) was offered daily a restricted amount of food (60% restriction, 111 g) for the first half of pregnancy and then offered 200 g of food daily till parturition. R(2) was provided with 185 g of food daily through the first half of pregnancy and then offered daily a restricted amount of food (60% restriction, 120 g) for the second half. After parturition, food was provided adlibitum. Maternal body weights, litter size, litter weight, and average body weight of kits at kindling of R(1) showed no change, whereas R(2) showed significant reduction in the weights of does at the 4th week of pregnancy and at kindling. The birth weight and weaning weight of R(2) were significantly reduced. The highest mortality was recorded in kits of R(2). No significant differences in blood parameters or serum prolactin were observed. The serum protein was significantly reduced R(2).


Genome‑wide DNA methylation profile of thymomas and potential epigenetic regulation of thymoma subtypes.
The aim of the present study was to examine the whole‑genome DNA methylation status of thymomas and identify differences in thymoma DNA methylation profiles. DNA methylation profiles of tissues (n=12) were studied using the Infinium MethylationEPIC BeadChip microarray (850K) and analyzed in relation to gene expression data. Functional annotation analysis of DNA methylation between the different groups was performed using the online tool GeneCodis3. In order to assess the diagnostic value of candidate DNA methylation markers, receiver operation characteristic (ROC) analysis was performed using the pROC package. A total of 10,014 CpGs were found to be differentially methylated (Δβ>0.2) between two thymoma types (type A and B). Combination analysis showed that 36 genes had differentially methylated CpG sites in their promoter region. 'Pathways in cancer', 'focal adhesion' and 'regulation of actin cytoskeleton' were the most enriched KEGG pathways of differentially methylated genes between tumor and controls. Among the 29 genes that were hypomethylated with a high expression, zinc finger protein 396 and Fraser extracellular matrix complex subunit 1 had the largest area under the curve. The present results may provide useful insights into the tumorigenesis of thymomas and a strong basis for future research on the molecular subtyping of epigenetic regulation in thymomas.


Bloom's syndrome.
Bloom's syndrome is a rare autosomal recessive disorder that characteristically shows a telangiectatic, sun-sensitive facial rash in conjunction with stunted growth. These patients are prone to respiratory and gastrointestinal infections along with immunologic abnormalities. Chromosomal aberrations include an elevated frequency of sister chromatid exchange in cultured lymphocytes, a phenomenon pathognomonic for this disorder. These patients exhibit a great tendency for neoplasia, particularly acute leukemia and lymphoma. Three cases are reported, including a follow-up of a patient diagnosed 16 years ago.


A Novel Human Diabetes Biomarker Recognition Approach Using Fuzzy Rough Multigranulation Nearest Neighbour Classifier Model.
The selection of gene identifier from microarray databases is a challenging task since microarray contains large number of gene attributes for a few samples. This article proposes a novel fuzzy-rough set-based gene expression features selection using fuzzy-rough reduct under multi-granular space for human diabetes patient. Firstly, fuzzy multi-granular gain has been computed from the expression datasets via fuzzy entropy which reduces the dimension of the database. Thereafter, the features have been selected from microarray using the fuzzy rough reduct and information gain with respect to their expression patterns. To reduce the computational cost, a decision making scheme has been designed using a rough approximation of a fuzzy concept in the field of multi-granulation framework. Finally, we have recognized the association among the genomes that have expressively different expression patterns from controlled state to the diabetic state with respect to their impression using modified fuzzy-rough nearest neighbour classifier (FRNNC). Five standard diabetic microarray datasets have been considered to quantify the efficiency of the designed FRNNC model and are validated with F measure using diabetes gene expression NCBI database and it performs superior compared to existing methods.


Integrating subvolume dose and myocardial perfusion imaging parameters to assess the impact of radiation therapy on heart function in breast cancer patients: A comparative analysis between left- and right-sided breast cancer.
This study aimed to utilize an innovative method of integrating the 20 subvolume dose of left ventricle and the Tl-201 single photon emission computed tomography (SPECT) with myocardial perfusion imaging (MPI) parameters in patients with left- and right-sided breast cancer after radiation therapy. Female patients with breast cancer underwent SPECT MPI before commencing radiotherapy and 12 months later were enrolled from January 2014 to December 2018. The images of CT simulation and SPECT MPI were integrated into the treatment planning system. The differences of doses and parameters of MPI in all cardiac subvolumes between left- and right-sided breast cancer patients were analyzed. Patients with left-sided breast cancer (n = 61) received a higher radiation dose to the heart, left ventricular, and its territories and subvolumes, compared to patients with right-sided breast cancer (n = 19). The 20-segment analysis also showed statistically significant disparities in the average radiation doses received by the two groups. In different coronary artery territories, the end-diastolic perfusion and end-systolic perfusion showed a decrease in both sides, with no significant differences. However, the wall motion and wall thickening showed a significant decline in subregions within the left- and right-sided coronary artery territories. This study demonstrates an innovative integrated method combining the left ventricular 20 regional doses with SPECT MPI which shows that left-sided breast cancer patients receive a higher subvolume dose than right-sided breast cancer patients. Further research is needed to confirm the potential impact on heart function after radiotherapy on both sides.


Optimising diffusion-weighted MR imaging for demonstrating pancreatic cancer: a comparison of respiratory-triggered, free-breathing and breath-hold techniques.
To compare respiratory-triggered, free-breathing, and breath-hold DWI techniques regarding (1) image quality, and (2) signal intensity (SI) and ADC measurements in pancreatic ductal adenocarcinoma (PDAC). Fifteen patients with histopathologically proven PDAC underwent DWI prospectively at 1.5 T (b = 0, 50, 300, 600 and 1,000 s/mm(2)) with the three techniques. Two radiologists, independently and blindly, assigned total image quality scores [sum of rating diffusion images (lesion detection, anatomy, presence of artefacts) and ADC maps (lesion characterisation, overall image quality)] per technique and ranked them. The lesion SI, signal-to-noise ratio, mean ADC and coefficient of variation (CV) were compared. Total image quality scores for respiratory-triggered, free-breathing and breath-hold techniques were 17.9, 16.5 and 17.1 respectively (respiratory-triggered was significantly higher than free-breathing but not breath-hold). The respiratory-triggered technique had a significantly higher ranking. Lesion SI on all b-values and signal-to-noise ratio on b300 and b600 were significantly higher for the respiratory-triggered technique. For respiratory-triggered, free-breathing and breath-hold techniques the mean ADCs were 1.201, 1.132 and 1.253 × 10(-3) mm(2)/s, and mean CVs were 8.9, 10.8 and 14.1 % respectively (respiratory-triggered and free-breathing techniques had a significantly lower mean CV than the breath-hold technique). In both analyses, respiratory-triggered DWI showed superiority and seems the optimal DWI technique for demonstrating PDAC. • Diffusion-weighted magnetic resonance imaging is increasingly used to detect pancreatic cancer • Images are acquired using various breathing techniques and multiple b-values • Breathing techniques used: respiratory-triggering, free-breathing and breath-hold • Respiratory-triggering seems the optimal breathing technique for demonstrating pancreatic cancer.


The SOS-SAH questionnaire in clinical practice: a multi-method evaluation study.
In patients with mild disabilities after aneurysmal subarachnoid hemorrhage (aSAH), invisible symptoms might be easily overlooked during consultations in the outpatient clinic. We hypothesize that the Questionnaire for the Screening of Symptoms in aneurysmal Subarachnoid Hemorrhage (SOS-SAH), a disease-specific patient-reported outcome measure, might aid in screening for symptoms after aSAH. The objective of this explorative study is to evaluate the perceived impact of using the SOS-SAH in daily clinical practice for patients after aSAH, as well as to explore potential barriers to further implementation. This multi-method study consists of a quantitative and a qualitative component. To evaluate differences in quality of care, a patient experience survey was sent to patients receiving usual care and to patients who received the SOS-SAH. A multiple linear regression model was applied, with the intervention group and case mix adjusters as independent variables. We described differences in the number of symptoms discussed between patients receiving usual care and those receiving care post-implementation. Following implementation, 16 patients and 6 healthcare professionals were interviewed about their perceptions concerning the impact of and barriers to using the SOS-SAH. A thematic analysis was performed to identify the main themes. The survey did not reveal any differences between the usual-care group and the post-implementation group on the scales of the patient experience survey. After implementation of the SOS-SAH, the number of symptoms discussed during consultation did not increase. The interviews suggest that the SOS-SAH may improve the preparation of patients by providing them with greater insight into their complaints and by raising issues for the consultation. It could also enhance the structure and efficiency of consultation, in addition to improving communication about issues that matter to patients. All patients and healthcare professionals recommended continuing the use of the SOS-SAH in daily practice. Although no quantitative improvements were found in patient experience and symptoms discussed during consultation, implementation of the SOS-SAH could aid in screening for symptoms in patients after aSAH, and it might have a positive influence on patient preparation, while helping to structure consultations between patients and healthcare professionals.


[Quantitative analysis of dyes for automated studies of cell preparations].
Spectral studies were made of the dyes in solutions and also of the cytology preparations stained by these dyes. 14 dyes of the blue-violet spectral region were examined. Absorbtion and transmission coefficients of the cell nucleus and cytoplasm were measured. The data obtained allowed to elaborate a quantitative estimation of dye selection. According to this method cresyl-violet was selected as the dye for Videocon LI-421.


Inhibiting change: effects of memory on auditory selective attention.
Two experiments investigated the behavioral and electrophysiological effects on human auditory selection of the psychophysical discriminability of a distractor channel in memory. Participants performed a set of baseline (single distractor) and filtering (multiple distractors) tasks, classifying the pitch of targets, while ignoring pitch variation in temporally distinct distractors, which differed from targets in timbre (Experiment 1) or loudness (Experiment 2). Increased distractor change progressively disrupted target accuracy and reaction time, and fostered confusion in distinguishing target from distractor channels. Physiologically, relative discriminability only affected distractor waveforms, whether or not distractor values physically differed across tasks, enhancing the N1 response while reducing an inhibitory slow-wave component. The results suggest that inhibition fails as distractors activate a wider range of the task-relevant continuum in working memory.


Effects of neural stimuli on blood flow through vasa vasorum in dogs.
The purpose of this study was to determine whether neural stimuli alter blood flow through vasa vasorum in the thoracic aorta. We measured flow with microspheres in anesthetized dogs and observed responses to sympathetic stimulation and baroreceptor stimulation. During these interventions, changes in arterial pressure were prevented with propranolol or an arterial reservoir, to minimize indirect effects on vasa vasorum mediated through changes in aortic wall tension. Electrical stimulation of the stellate ganglion at 10 Hz reduced blood flow to vasa vasorum in the thoracic aorta from 11 +/- 1.6 (mean +/- SE to 6.8 +/- 1.1 ml/min per 100 g (p less than 0.05). Aortic diameter, measured with a sonomicrometer technique, did not change during sympathetic stimulation. Thus, the reduction in blood flow through vasa vasorum during sympathetic stimulation appears to be a direct effect, and not the result of constriction of the aorta and compression of vasa. To determine effects of physiological alterations in neurogenic vasoconstrictor activity, we examined responses to stimulation of carotid baroreceptors. When pressure in isolated, perfused carotid sinus baroreceptors was raised from 81 +/- 3 to 198 +/- 2 mm Hg, blood flow to vasa vasorum of the thoracic aorta increased from 3.7 +/- 0.6 to 10 +/- 2.2 ml/min per 100 g (P less than 0.05). We conclude that vasa vasorum are responsive to neural stimuli, since they constrict during sympathetic stimulation and dilate in response to baroreceptor stimulation.


Diffusivity of 125I-labelled macromolecules through collagen: mechanism of diffusion and effect of adsorption.
Diffusion of angiotensin II, albumin and aldolase was studied through collagen membranes with swelling ratios between 4 and 15. The diffusion coefficient was measured from the time-lag for the onset of steady-state flux through the membrane. Binding of macromolecules to collagen was evaluated from the results of sorption studies conducted as a function of macromolecular concentration. Results presented indicate that the diffusion of macromolecules through collagen membrane is slowed by electrostatic and hydrogen bonding between individual macromolecular chains and collagen. The extent of adsorption is increased as the molecular weight of the diffusant increases. Diffusion of water soluble macromolecules through collagen occurs rapidly, suggesting that diffusion occurs through water filled channels as opposed to between collagen molecules. The results of these studies are useful in understanding diffusion through connective tissues and in the design of drug delivery systems based on collagen.


Transient Receptor Potential Ankyrin 1 Is Up-Regulated in Response to Lipopolysaccharide via P38/Mitogen-Activated Protein Kinase in Dental Pulp Cells and Promotes Mineralization.
Increased expression of the transient receptor potential ankyrin 1 (TRPA1) channel has been detected in carious tooth pulp, suggesting involvement of TRPA1 in defense or repair of this tissue after exogenous noxious stimuli. This study aimed to elucidate the induction mechanism in response to lipopolysaccharide (LPS) stimulation and the function of TRPA1 in dental pulp cells. Stimulation of human dental pulp cells with LPS up-regulated TRPA1 expression, as demonstrated by quantitative RT-PCR and Western blotting. LPS stimulation also promoted nitric oxide (NO) synthesis and p38/mitogen-activated protein kinase (MAPK) phosphorylation. NOR5, an NO donor, up-regulated TRPA1 expression, whereas 1400W, an inhibitor of inducible nitric oxide synthase, and SB202190, a p38/MAPK inhibitor, down-regulated LPS-induced TRPA1 expression. Moreover, JT010, a TRPA1 agonist, increased the intracellular calcium concentration and extracellular signal-regulated kinase 1/2 phosphorylation, and up-regulated alkaline phosphatase mRNA in human dental pulp cells. Icilin-a TRPA1 agonist-up-regulated secreted phosphoprotein 1 mRNA expression and promoted mineralized nodule formation in mouse dental papilla cells. In vivo expression of TRPA1 was detected in odontoblasts along the tertiary dentin of carious teeth. In conclusion, this study demonstrated that LPS stimulation induced TRPA1 via the NO-p38 MAPK signaling pathway and TRPA1 agonists promoted differentiation or mineralization of dental pulp cells.


Differentiation in the murine B cell lymphoma I.29: inductive capacities of lipopolysaccharide and Mycoplasma fermentans products.
Cells from the murine B lymphoma I.29, expressing IgM or IgA of identical idiotype, were found inducible by lipopolysaccharide to differentiate into plasma cells. Within 3 days, differentiating cells lost membrane-bound immunoglobulin (Ig) and accumulated large quantities of intracytoplasmic Ig. At day 6 of culture, IgA secretion increased 50-100-fold, as determined by enzyme-linked immunoassay. Proliferation increased for the first days of culture but decreased thereafter; by day 10 very few viable cells were present in lipopolysaccharide-stimulated cultures. Similar results were obtained by culturing I.29 cells in the presence of supernatants of certain B cell lines (e.g. BFO.3). The finding of a strict correlation between the inductive activity and presence of contaminating Mycoplasma fermentans suggested that factor(s) released by mycoplasma were responsible for the mitogenic activities. This was further indicated by the findings that: the supernatants of BFO.3 that were rendered free of mycoplasma were not inductive, and a nonactive cell line could be made active by infection with supernatants of BFO.3 cells containing viable microorganisms. Thus, supernatants of mycoplasma-infected cell lines may act as potent polyclonal activators on both normal and malignant B lymphocytes. The ability to induce membrane Ig on 70Z/3 cells indicates that mycoplasma-related mitogens are also active on pre-B cells. The possibility of mycoplasma contamination should thus be carefully excluded when presumptive factors of cloned cell lines are being evaluated.


Combined assessment of regional perfusion and wall motion in patients with coronary artery disease with technetium 99m tetrofosmin.
Technetium 99m tetrofosmin is a new 99mTc-labeled myocardial perfusion agent that can be labeled easily and provides excellent myocardial perfusion images. In addition, bolus administration of the tracer allows first-pass radionuclide ventriculography. This study examined the diagnostic value of combined assessment of regional perfusion by tetrofosmin tomography and wall motion by first-pass radionuclide ventriculography both at rest and during stress in 24 patients suspected of having coronary artery disease. All patients underwent stress-rest tetrofosmin tomography, stress-delayed thallium 201 tomography, and coronary angiography. Stress tetrofosmin tomography showed abnormal perfusion in all 23 patients with angiographic evidence of coronary artery disease, whereas stress 201Tl tomography showed abnormal perfusion in 22 of the 23 patients. For detection of significant (> or = 50% diameter stenosis) stenotic coronary arteries, the two perfusion studies showed similar sensitivities (62% with 201Tl and 69% with tetrofosmin) and specificities (88% and 100%, respectively). When analysis of regional wall motion was combined with perfusion study, a slightly higher sensitivity was obtained (77%), with similar specificity. The regional wall motion score was concordant with the regional perfusion score in only 42% of the segments at rest and 50% during exercise. These results suggest that stress tetrofosmin perfusion tomography and stress 201Tl tomography provided similar diagnostic accuracy for detection of coronary artery disease. The combined assessment of perfusion and function that is feasible with tetrofosmin may enhance diagnostic accuracy in patients with coronary artery disease.


Bronchiectasis detected with thin-section CT as a predictor of chronic lung allograft rejection.
To evaluate bronchiectasis detected with thin-section computed tomography (CT) as a potential early finding of chronic lung allograft rejection. Forty patients were studied at least 6 months after transplantation. Follow-up CT scans were obtained 6-48 months after transplantation and were retrospectively reviewed for evidence and anatomic extent of bronchiectasis. Irreversible dysfunction of the lung transplant, called the bronchiolitis obliterans syndrome (BOS), was staged according to pulmonary function testing. Pathologic proof of bronchiolitis obliterans was obtained. BOS occurred in 14 (35%) of the 40 patients. When considering bronchiectasis preceding BOS, bronchiectasis was a predictor of chronic rejection with a sensitivity of 14%, a specificity of 77%, a positive predictive value of 25%, and a negative predictive value of 63%. Bronchiectasis appeared concomitantly with BOS in eight (67%) of 12 patients. The diagnosis of chronic rejection relies on the degree of impairment of pulmonary function. When the diagnosis is only suspected on the basis of minimal impairment, CT can aid in the diagnosis of rejection by depicting early pulmonary changes.


Climate-diameter growth relationships of black spruce and jack pine trees in boreal Ontario, Canada.
To predict the long-term effects of climate change - global warming and changes in precipitation - on the diameter (radial) growth of jack pine (Pinus banksiana Lamb.) and black spruce (Picea mariana [Mill.] B.S.P.) trees in boreal Ontario, we modified an existing diameter growth model to include climate variables. Diameter chronologies of 927 jack pine and 1173 black spruce trees, growing in the area from 47°N to 50°N and 80°W to 92°W, were used to develop diameter growth models in a nonlinear mixed-effects approach. Our results showed that the variables long-term average of mean growing season temperature, precipitation during wettest quarter, and total precipitation during growing season were significant (alpha = 0.05) in explaining variation in diameter growth of the sample trees. Model results indicated that higher temperatures during the growing season would increase the diameter growth of jack pine trees, but decrease that of black spruce trees. More precipitation during the wettest quarter would favor the diameter growth of both species. On the other hand, a wetter growing season, which may decrease radiation inputs, increase nutrient leaching, and reduce the decomposition rate, would reduce the diameter growth of both species. Moreover, our results indicated that future (2041-2070) diameter growth rate may differ from current (1971-2000) growth rates for both species, with conditions being more favorable for jack pine than black spruce trees. Expected future changes in the growth rate of boreal trees need to be considered in forest management decisions. We recommend that knowledge of climate-growth relationships, as represented by models, be combined with learning from adaptive management to reduce the risks and uncertainties associated with forest management decisions.


Selection of optimal combinations of target genes for therapeutic multi-gene silencing based on miRNA co-regulation.
Therapeutic gene silencing is a promising approach for treatment of cancer. Despite substantial efforts, however, only few such therapeutic methods have been clinically tested. The heterogeneity in gene expression profiles among malignant tissues and the dynamic control of gene expression in individual tumors makes identifying universal and effective targets a challenge. Further development of gene silencing therapy requires new approaches to comprehend and manage gene expression in cancer cells. In this study, we proposed and evaluated experimentally a new approach to design multi-gene silencing therapy. Using a simplified model of gene expression control, we show that genes commonly regulated by the same microRNA represent optimal combinations of targets for small hairpin RNA/small interfering RNA-based gene silencing. The proposed method of target gene selection and co-silencing can be explored as an algorithm for personalized cancer gene therapy.


Identifies KCTD5 as a novel cancer biomarker associated with programmed cell death and chemotherapy drug sensitivity.
More and more studies have demonstrated that potassium channel tetramerization domain-containing 5 (KCTD5) plays an important role in the development of cancer, but there is a lack of comprehensive research on the biological function of this protein in pan-cancer. This study systematically analyzed the expression landscape of KCTD5 in terms of its correlations with tumor prognosis, the immune microenvironment, programmed cell death, and drug sensitivity. We investigated a number of databases, including TCGA, GEPIA2, HPA, TISIDB, PrognoScan, GSCA, CellMiner, and TIMER2.0. The study evaluated the expression of KCTD5 in human tumors, as well as its prognostic value and its association with genomic alterations, the immune microenvironment, tumor-associated fibroblasts, functional enrichment analysis, and anticancer drug sensitivity. Real-time quantitative PCR and flow cytometry analysis were performed to determine the biological functions of KCTD5 in lung adenocarcinoma cells. The results indicated that KCTD5 is highly expressed in most cancers and that its expression is significantly correlated with tumor prognosis. Moreover, KCTD5 expression was related to the immune microenvironment, infiltration by cancer-associated fibroblasts, and the expression of immune-related genes. Functional enrichment analysis revealed that KCTD5 is associated with apoptosis, necroptosis, and other types of programmed cell death. In vitro experiments showed that knockdown of KCTD5 promoted apoptosis of A549 cells. Correlation analysis confirmed that KCTD5 was positively correlated with the expression of the anti-apoptotic genes Bcl-xL and Mcl-1. Additionally, KCTD5 was significantly associated with sensitivity to multiple antitumor drugs. Our results suggest that KCTD5 is a potential molecular biomarker that can be used to predict patient prognosis, immunoreactions and drug sensitivity in pan-cancer. KCTD5 plays an important role in regulating programmed cell death, especially apoptosis.


Valacyclovir combined with artesunate or rapamycin improves the outcome of herpes simplex virus encephalitis in mice compared to antiviral therapy alone.
Despite antiviral therapy, the mortality rate of herpes simplex virus encephalitis (HSE) remains high and many surviving patients harbor neurological sequelae. Although viral replication is responsible for substantial neurological damages, an exaggerated inflammatory response could also contribute to this process. Artesunate (ART) and rapamycin (RAPA) have shown some benefits in the treatment of herpes simplex virus infections. Herein, we evaluated the benefit of combining ART or RAPA with valacyclovir (VACV) in a murine model of HSE. Infected mice were treated with VACV (1mg/mL in drinking water) from day 3 post-infection (p.i.) combined or not with daily intraperitoneal administration of ART (30mg/kg) or RAPA (20mg/kg) from days 4 to 13 p.i. Viral load, infectious titers, cytokine and chemokine levels were measured in brain homogenates on days 5, 7 and 9. The survival rates of mice treated with VACV and ART or RAPA were higher than with VACV alone (71.9% versus 43.2% for ART and 66.7% versus 43.2% for RAPA; both P⩽0.05) but no significant difference was seen in the brain viral loads. Levels of IL-1β, IL-2 (both P⩽0.05), IL-6, IFN-γ (both P⩽0.01), CCL2 (P⩽0.01), CCL3 and CCL4 (both P⩽0.05) were reduced in mice treated with VACV combined with ART versus VACV alone. Levels of IL-6, IL-1β and IFN-γ slightly increased on day 7 in mice treated with VACV combined with RAPA compared to VACV alone and then decreased on day 9. Our results suggest that immunomodulatory compounds such as ART or RAPA could benefit antiviral therapy in HSE.


Alpha-1 antitrypsin reduces ovariectomy-induced bone loss in mice.
Proinflammatory cytokines are primary mediators of bone loss in estrogen deficiency. This study determined whether alpha-1 antitrypsin (AAT), a multifunctional protein with proteinase inhibitor and anti-inflammatory activities, mitigates bone loss induced by estrogen deficiency. Mice were either sham-operated or ovariectomized and injected with either AAT or phosphate buffered saline (PBS). Ovariectomy resulted in decreased wet uterus weight, significant bone loss, increased serum leptin concentrations, and higher body weight compared to sham. AAT injection increased tibial trabecular bone volume/total volume and trabecular thickness compared to PBS injection in ovariectomized mice. Ovariectomized mice with AAT treatment had higher uterus weight, lower serum osteocalcin levels, fewer bone marrow tartrate-resistant acid phosphatase-positive osteoclasts, and less expression of calcitonin receptor in bone than that in PBS-injected mice. These data demonstrate that AAT mitigates ovariectomy-induced bone loss in mice possibly through inhibiting osteoclast activity and bone resorption.


N-methyl N-nitrosourea induced functional and structural alterations in mice brain-role of curcumin.
Curcumin is being widely used both as an herbal drug and a food additive in Asian countries. However, its prophylactic potential in containing certain brain disorders is yet to be fully explored. The present study was conceived with an idea that curcumin may prove to be effective in ameliorating N-methyl N-nitrosourea (MNU)-induced adverse effects in cerebrum and cerebellum of mice. Male laca mice received either intravenous MNU treatment at a dose of 10 mg/kg body weight in sterile double distilled water, curcumin alone 60 mg/kg body weight in drinking water via oral gavage, or combined MNU and curcumin treatment on alternate days for a total duration of 2 months. MNU treatment resulted in significant alteration in neurobehavior, reactive oxygen species, lipid profile and histoarchitecture which showed appreciable signs of improvements upon curcumin supplementation. Therefore, the study concludes that prophylactic treatment with curcumin shall prove to be effective in containing MNU-induced neurotoxicity.


Hyperactivity of fibroblasts cultured from psoriatic skin: II. Synthesis of macromolecules.
Glycosaminoglycans and protein synthesis were assessed in fibroblasts cultured from the involved (PSA strains) and uninvolved (PSB strains) forearm skin of patients with severe generalized psoriasis and compared with that in fibroblasts from the forearm skin of control subjects of similar ages (NSF strains). Average rates of glycosaminoglycan secretion were 19% (PSA) and 28% higher (PSB) in psoriatic strains. Although these differences were not significant in themselves, the relationship between glycosaminoglycan secretion and fibroblast density (cells/cm2) was significantly different (P = 0.02) for the psoriatic and control groups, with the psoriatic cells secreting appreciably more glycosaminoglycans at higher cell densities. The nature of the glycosaminoglycans produced was the same in psoriatic and normal strains; 90% was recovered in the culture medium and the bulk of this appeared to be hyaluronic acid with only small amounts of sulphated components. Collagen synthesis was 77% higher in PSA and PSB strains (P less than 0.01), while other protein synthesis was increased by 44% (P less than 0.05). These findings confirm that fibroblasts from psoriatic skin are hyperactive in vitro. The data are compatible with the results of studies of psoriatic skin in vivo and suggest that the entire skin is abnormal.


Inattention in health professions education scholarship.
In this editorial, the Editor-in-Chief considers inattention to details and the implications thereof in education scholarship and academic writing.


Interstitial lung diseases specific measures in exercise interventions: A systematic review of measurement properties.
Effects of exercise-based interventions (EBIs) on people with interstitial lung disease (ILD) are not yet fully understood. Reasons may include the limited use of ILD-specific measures and/or the lack of adequate information regarding their measurement properties. The purpose of this review was to summarize the ILD-specific outcome measures used in EBI studies and their measurement properties. This was a two-phase systematic review: phase 1 identified ILD-specific measures used in EBI studies; phase 2 reviewed their measurement properties. PubMed, Web of Science, Scopus, EBSCO and EMBASE were searched up to March 2021. One reviewer extracted data, and 2 reviewers independently assessed studies risk of bias as well as the quality of measurement properties using the Consensus-Based Standards for the Selection of Health Status Measurement Instruments (COSMIN) recommendations. Phase 1 identified 18 records. The St George's Respiratory Questionnaire for Interstitial Pulmonary Fibrosis (SGRQ-IPF) was the only ILD-specific outcome measure used (n = 2 trials). Phase 2 resulted in 31 eligible records; measurement properties were reported for 12 measures. Measures presented sufficient content validity, internal consistency (Cronbach's alpha 0.61-0.96), test-retest reliability (intraclass correlation coefficient 0.39; 0.96), hypothesis testing and responsiveness but were insufficient for measurement error and indeterminate for cross-cultural and structural validity. The outcome measures King's Brief Interstitial Lung Disease and SGRQ-IPF had higher evidence of adequate measurement properties than other measures. Quality of the evidence was mostly very low to moderate. ILD-specific outcome measures are used infrequently in EBI trials, and there is scarce information regarding their measurement properties. CRD42018112466.


Faster algorithms for counting subgraphs in sparse graphs.
Given a k-node pattern graph H and an n-node host graph G, the subgraph counting problem asks to compute the number of copies of H in G. In this work we address the following question: can we count the copies of H faster if G is sparse? We answer in the affirmative by introducing a novel tree-like decomposition for directed acyclic graphs, inspired by the classic tree decomposition for undirected graphs. This decomposition gives a dynamic program for counting the homomorphisms of H in G by exploiting the degeneracy of G, which allows us to beat the state-of-the-art subgraph counting algorithms when G is sparse enough. For example, we can count the induced copies of any k-node pattern H in time 2 O ( k 2 ) O ( n 0.25 k + 2 log n ) if G has bounded degeneracy, and in time 2 O ( k 2 ) O ( n 0.625 k + 2 log n ) if G has bounded average degree. These bounds are instantiations of a more general result, parameterized by the degeneracy of G and the structure of H, which generalizes classic bounds on counting cliques and complete bipartite graphs. We also give lower bounds based on the Exponential Time Hypothesis, showing that our results are actually a characterization of the complexity of subgraph counting in bounded-degeneracy graphs.


Non-Invasive Brain Stimulation for the Treatment of Symptoms Following Traumatic Brain Injury.
Traumatic brain injury (TBI) is a common cause of physical, psychological, and cognitive impairment, but many current treatments for TBI are ineffective or produce adverse side effects. Non-invasive methods of brain stimulation could help ameliorate some common trauma-induced symptoms. This review summarizes instances in which repetitive Transcranial Magnetic Stimulation (rTMS) and transcranial Direct Current Stimulation (tDCS) have been used to treat symptoms following a TBI. A subsequent discussion attempts to determine the value of these methods in light of their potential risks. The research databases of PubMed/MEDLINE and PsycINFO were electronically searched using terms relevant to the use of rTMS and tDCS as a tool to decrease symptoms in the context of rehabilitation post-TBI. Eight case-studies and four multi-subject reports using rTMS and six multi--subject studies using tDCS were found. Two instances of seizure are discussed. There is evidence that rTMS can be an effective treatment option for some post-TBI symptoms, such as depression, tinnitus, and neglect. Although the safety of this method remains uncertain, the use of rTMS in cases of mild TBI without obvious structural damage may be justified. Evidence on the effectiveness of tDCS is mixed, highlighting the need for additional investigations.


Time series hyperspectral chemical imaging data: challenges, solutions and applications.
Hyperspectral chemical imaging (HCI) integrates imaging and spectroscopy resulting in three-dimensional data structures, hypercubes, with two spatial and one wavelength dimension. Each spatial image pixel in a hypercube contains a spectrum with >100 datapoints. While HCI facilitates enhanced monitoring of multi-component systems; time series HCI offers the possibility of a more comprehensive understanding of the dynamics of such systems and processes. This implies a need for modeling strategies that can cope with the large multivariate data structures generated in time series HCI experiments. The challenges posed by such data include dimensionality reduction, temporal morphological variation of samples and instrumental drift. This article presents potential solutions to these challenges, including multiway analysis, object tracking, multivariate curve resolution and non-linear regression. Several real world examples of time series HCI data are presented to illustrate the proposed solutions.


Concentration of Fibroblasts in the Vocal Fold of Elderly.
To study the concentration of fibroblasts in the vocal folds of elderly people. The vocal folds of 13 cadavers were removed and divided into two age groups: Control group: n-5, 18-40 years; Elderly group: n-8, ≥75 years). The vocal folds were dissected and prepared for immunohistochemical analysis using the SA100 antibody to fibroblasts. The sites analyzed were maculae flavae and medial (or vibrating) portion of the vocal folds. The AVsoft program was used to count the cells. A higher concentration of fibroblasts was identified in the maculae flavae of the larynx of young adults and in the medial portion of the vocal folds of the elderly. However, these results did not determine statistically significant differences, allowing us to conclude that there was no effect of age on the concentration of fibroblasts in the vocal folds. In the larynx of the elderly, the fibroblast population remains similar to the young adults, both in the maculae flavae and in the body of the vocal folds, possibly being responsible for the constant production of fibrous matrix in the lamina propria. Functional changes in these cells are probably more marked than quantitative ones.


Successful therapy with donor buffy coat transfusions in patients with relapsed chronic myeloid leukemia after bone marrow transplantation is associated with high frequencies of host-reactive interleukin 2-secreting T helper cells.
Six patients treated for relapsed chronic myeloid leukaemia after allogeneic bone marrow transplantation with donor buffy coat transfusions were investigated. In the 5 patients who achieved molecular remission high frequencies of host-reactive interleukin 2-secreting T helper cell precursors (Th-p) were detectable by limiting dilution analysis. In four of the patients the presence of Th-p was associated with a clinical syndrome similar to transfusion GVHD suggesting a T cell response to minor histocompatibility antigens (minor H) expressed by both malignant haemopoiesis and host tissues. In the fifth responding patient no GVHD or bone marrow hypoplasia was observed. The nature of the antigens recognised by these donor Th-p remains unknown. No host-reactive Th-p were detectable in the non-responder and host-reactive cytotoxic T cell precursors (CTL-p) were not consistently detectable in the responding patients.


Tuning the Organ Tropism of Polymersome for Spleen-Selective Nanovaccine Delivery to Boost Cancer Immunotherapy.
The past few decades have witnessed explosive development in drug delivery systems. However, in vivo delivery suffers from non-specific distribution in non-targeted organs or tissues, which may cause undesired side effects and even genotoxicity. Here, a general strategy that enables tuning the tropism of polymersomes for liver- and spleen-selective delivery is reported. By using a library screening approach, spleen-targeted polymersome PH9-Aln-8020 and liver-targeted polymersome PA9-ZP3-5050 are identified accordingly. Meanwhile, the second near-infrared (NIR-II) fluorescence imaging allows for in vivo dynamic evaluation of their spatial and temporal accumulation in specific tissues. O ur findings indicate that both polymer composition and protein corona on the surface are essential to determine the in vivo fate of polymersomes and tendency for specific organs. Importantly, PH9-Aln-8020 is employed as a systemic nanocarrier to co-deliver the antigen and adjuvant, which remarkably boost splenic immune responses in acute myeloid leukemia, melanoma, and melanoma lung metastasis mouse models. This study may open a new frontier for polymersomes in organ-selective delivery and other biomedical applications.


A new head-mounted lip-jaw movement transduction system for the study of motor speech disorders.
A new head-mounted lip and jaw transduction system is described, which features (a) an ultra-low mass tubular aluminum headmount mainframe with a unique coupling apparatus, (b) a low mass transducer unit, (c) nonrestraint of the head, and (d) a transduction artifact of .1 mm or less under most recording conditions. The importance of observing labial and mandibular movements in addition to electromyographic and aerodynamic signals is emphasized by reference to actual recordings of speech from subjects with neuromotor disorders.


Rapid adaptation to neuronal membrane effects of ethanol and low temperature: some speculations on mechanism.
There is increasing evidence that ethanol exerts its primary effect at neuronal membranes by influencing specific lipid--protein or lipid--lipid interactions that control the state of organization of a specific membrane component; for example, a specific lipid--protein complex that controls a particular physiological property. This implies that tolerance to ethanol is the result of a change in the composition and/or state of organization of this critical membrane component. This altered state confers ethanol resistance. It may or may not have an effect on function in the absence of ethanol. One basis for these speculations comes from experiments using a sensitive and specific neurophysiological assay -- the rate of decay of posttetanic potentiation (PTP) at an identified synapse in an isolated, perfused Aplysia ganglion. We review evidence that PTP decay rate is strikingly accelerated by ethanol (a membrane-fluidizing agent) and strikingly decelerated below a transition temperature, presumably reflecting a transition in the structure of a membrane component. The ethanol and low-temperature effects are antagonistic. The system develops adaptation (tolerance) to either ethanol or low temperature within hours of its exposure. Tolerance persists for at least 12 hours, the longest interval tested thus far. In the absence of ethanol and at normal temperature the system behaves normally, that is it shows no "physical dependence". The system also has the remarkable property that when it becomes tolerant to either of these treatments, it shows tolerance to the other treatment that normally has the opposite effect. Therefore, the adaptation to either treatment cannot be a simple change in membrane composition governing overall membrane fluidity. A hypothesis which could explain the bidirectional cross-tolerance is considered in which adaptation to both treatments involves a shift from a homogeneous to a more heterogeneous composition of the critical membrane component, for example increasing heterogeneity in boundary lipid surrounding a critical membrane protein. It is becoming increasingly clear that ethanol exerts its primary effect by altering cell membrane structure -- by "fluidizing" or expanding neuronal and other membranes [1 - 6]. This effect results when ethanol, a somewhat hydrophobic molecule, intercalates between some fatty acid chains of membranes, reducing the degree of order of their alignment and increasing the lateral mobility of some membrane components. Decrease in the order of the fatty acid chains results in a measurable expansion of the membrane; and the change in fluidity is reflected in the change in mobility of appropriate probes that can be dissolved in the membrane [6, 7]. It is presumed that the physiological effects of ethanol are consequences of its fluidization of some critical membrane components; and that tolerance to ethanol is based on some form of resistance to this fluidization...


Bridging and downstaging role of trans-arterial radio-embolization for expected small remnant volume before liver resection for hepatocellular carcinoma.
To evaluate our initial experience of bridging role of trans-arterial radio-embolization (TARE) before major hepatectomy for hepatocellular carcinoma (HCC) in risky patients with small expected remnant liver volume (ERLV). We reviewed the data of patients with HCC who underwent major hepatectomy after TARE during the period between March and December 2017. Patients included had uni-lobar large HCC (>5 cm) requiring major hepatectomy with small ERLV. Five patients were included in our study. All patients were Child Pugh class A. A single session of TARE was applied in all patients. None developed any adverse events related to irradiation. The mean tumor size at baseline was 8.4 cm and 6.1 cm after TARE (p=0.077). The mean % of tumor shrinkage was 24.5%. ERLV improved from 354.6 ml at baseline to 500.8 ml after TARE (p=0.012). ERLV percentage improved from 27.2% at baseline to 38.1% after TARE (p=0.004). The mean % of ERLV was 39.5%. The mean interval time between TARE and resection was 99.6 days. Four patients (80%) underwent right hemi-hepatectomy and one patient (20%) underwent extended right hemi-hepatectomy. The mean operation time was 151 minutes, and mean blood loss was 56 ml. The mean hospital stay was 13.8 days, and one patient (20%) developed postoperative morbidity. After a mean follow-up of 15 months, all patients were alive with no recurrence. Yttrium-90 TARE can play a bridging role before major hepatectomy for borderline resectable HCC in risky patients with small ERLV.


Leucocyte locomotion: comparison of random and directed paths using a modified time-lapse film analysis.
A semi-automated method, using a graphic digitizing tablet, for analysing the the tracks of cells taken from time-lapse film is described and illustrated with sample data. Three film sequences of neutrophil leucocytes moving on protein-coated substrata are analysed, and in one of these the cells are moving in a non-random fashion. The randomness of the tracks is tested by an objective method. Cells in the non-random (directed) sequence move faster and make smaller angled turns. No correlation between step length and turning angle could be shown for the random sequences. The method described here should make it possible to undertake visual analyses of cell locomotion with considerably less effort.


New methods of dissecting the masticator space of the rhesus macaque ( Macaca mulatta).
The aim of our project was to develop a method to examine the deep masticator space of the rhesus macaque ( Macaca mulatta) in order to investigate the following particulars of the mandibular nerve: (1). its manner of entry into the masticator space, (2). its branching within spaces/canals in the spheno-temporal bony complex, and (3). the location of its principal divisions with reference to the lateral pterygoid plate and muscle heads. In order to access these structures it was necessary to develop novel lateral and medial approaches. These and the instruments used are described. The proximal branching of the mandibular nerve is described and contrasted with that of the human. The implications of nerve branching in humans with reference to (1). evolution, (2). electromyography and (3). anesthetic control are discussed.


Redescription of two Australian cladocerans of the subfamily Aloninae Dybowski amp; Grochowski (Cladocera: Anomopoda: Chydoridae).
Morphology of two Australian water fleas, Alona rigidicaudis (Smirnov, 1971) and Coronatella (Coronatella) novaezealandiae (Sars, 1904) (Crustacea: Cladocera) was studied by optical and scanning electron microscopy. Morphology of the thoracic limbs was studied in detail. Previously unknown ephippial females and males are described for both species. Alona rigidicaudis is close in morphology to the simplex-group of the genus Anthalona Van Damme, Sinev Dumont, 2011, but lack the main distinctive feature of Anthalona, the presence of cosmaria of lateral head pores. Morphology of Coronatella (Coronatella) novaezealandiae (Sars, 1904) is typical of the genus. Affinities and taxonomic position of studied species are discussed.


Unusual presentation of caustic ingestion and its surgical treatment: a case report.
Treatment and reconstruction of oral scar contracture, is always a challenging procedure to restore structure and functions of the oral cavity. We present a case of a patient with limited mouth opening who sustained extensive oral scar contracture with complete adhesion of tongue to floor of mouth following ingestion of caustic soda without his knowledge 4 years back. We performed a surgical release of the scar contractures from buccal mucosa on both sides, along with a release of the tongue from the floor of the mouth, followed by reconstruction of all sites using split skin grafts. Adequate mouth opening and tongue movement was achieved. There was a follow up period of 1 month with excellent mouth opening and tongue function.


Cavernous hemangioma of the temporal muscle.
Intramuscular cavernous hemangiomas are often found in the brain, but they are uncommon in the muscles of the head and neck region, with the masseter being the most frequent, followed by the trapezius and sternocleidomastoideus. Such a lesion in the temporal muscle is an extremely unusual situation. A 55-year-old man presented with intermittent headaches and painless swelling of the right temple region brought on by stress and bending forward. On MRI, T1-weighted imaging with enhancement after contrast medium showed a low signal-intense, fat-free lesion restricted to the temporal muscle. T2 weighting showed a hyperintense, high fluid content, low-flow lesion. There was no progression within 2 years. No resection was performed. In planning a treatment approach, one must bear in mind that cavernous hemangiomas in the temporal muscle or other muscles of the head and neck can be clinically distinguished from the more aggressive capillary ones. Complications are extremely rare (hemorrhage or functional deficits). These cavernomas should simply be followed up and only resected in case of any problems (cosmetic, neurological deficits).


Bioconversion capacity of Streptomyces sp GE44282, a producer of the antibiotics heneicomycin and aurodox.
Streptomyces sp GE44282 was isolated in the course of a screening program for novel antibiotics. It co-produces heneicomycin and aurodox, two kirromycin-type antibiotics, which differ by the presence of an hydroxyl group at the C30 position of aurodox. Heneicomycin is converted into aurodox both by growing and resting cells of Streptomyces sp GE44282 and by the producer of aurodox, Streptomyces goldiniensis ATCC 21386. This bioconversion of heneicomycin is substrate-specific and is not observed using the producer of heneicomycin, Streptomyces filippiniensis NRRL 11044. The three strains show very similar taxonomic characteristics. These results suggest that heneicomycin is a precursor of aurodox, the production of which depends on the bioconversion capability expressed by the strain.


Aspirin inhibits the acute arterial and venous vasodilator response to captopril in patients with chronic heart failure.
The potentially beneficial hemodynamic effects of angiotensin-converting enzyme (ACE) inhibitors in heart failure may relate, in part, to their ability to increase the production of vasodilator prostanoids. Low dose aspirin is commonly prescribed in CHF and may attenuate the vasodilator effects of ACE inhibitors. We sought to determine the effects of low dose aspirin on the peripheral hemodynamic effects of captopril in patients with chronic heart failure (CHF). Nine patients with chronic heart failure were randomized in a placebo controlled, cross over study, to 75 mg of aspirin daily or placebo. After 7 days treatment the response to 25 mg of captopril was evaluated over 180 min using venous occlusion plethysmography. Forearm blood flow (FBF) and forearm venous capacitance (FVC) were measured. Mean arterial pressure and heart rate did not change. After placebo, FBF increased in response to captopril (+18%, 95%CI 24.2, 11.8), a response inhibited by aspirin (-1.4%, 2.9, -5.7), p < 0.005. After placebo, FVC increased in response to captopril (+7.6%, 9.8, 5.4), which was also inhibited by aspirin (+2.0%, 4.6, -0.6), aspirin vs. placebo, p = 0.02). In patients with chronic heart failure even low dose aspirin inhibits both the acute arterial and venous dilator responses to captopril. This action of aspirin may reduce the long-term clinical benefits of ACE inhibitors.


Energy-linked transhydrogenase. Characterization of a nucleotide-binding sequence in nicotinamide nucleotide transhydrogenase from beef heart.
Purified nicotinamide nucleotide transhydrogenase from beef heart was investigated with respect to labeling and subsequent sequence analysis of a nicotinamide nucleotide-binding site. A photo-activated azide derivative, 8-azidoadenosine 5'-monophosphate, was used as an active-site-directed photoaffinity label, which was shown to be specific for the NAD(H)-binding site in the dark. Light-activated incorporation of the label in transhydrogenase was accompanied by an inactivation, which approached 100% at the incorporation of about 1 mol label/mol transhydrogenase monomer. As expected from the assumed site-specificity of the label. NADH prevented both labeling and inactivation to some extent. However, NADPH also prevented labeling and inactivation marginally. The oxidized substrates NAD+ and NADP+ were inhibitory by themselves under these conditions, and the substrate analogs 5'-AMP and 2'-AMP were also poor protectors. The NAD(H)-site specificity of the azido compound was thus largely lost upon illumination and covalent modification. Radioactive labeling of transhydrogenase with 8-azido-[2-3H]-adenosine 5'-monophosphate followed by protease digestion, isolation of labeled peptides and amino-acid sequence analysis showed that Tyr 1006 in the sequence 1001-1027 close to the C-terminus was labeled. This sequence shows homologies with nucleotide-binding sequences in, e.g., F1-ATPase. On the basis of sequence homologies with other NAD(P)-dependent enzymes it is proposed that transhydrogenase contains 4 nucleotide-binding sites, of which 2 constitute the adenine nucleotide-binding domains of the catalytic sites for NAD(H) and NADP(H) close to the N- and C-terminals, respectively. Each of these domains has an additional vicinal nucleotide-binding sequence which may constitute a non-catalytic nucleotide-binding site or the nicotinamide nucleotide-binding domain of the catalytic site. The present results indicate that 8-azidoadenosine 5'-monophosphate is kinetically specific for the catalytic NAD(H)-binding site, but reacts covalently with Tyr 1006 of the putative non-catalytic site or nicotinamide nucleotide-binding domain formed by the 1001-1027 amino acid sequence of the catalytic NADP(H)-binding site. Interactions between the catalytic NAD(H) and NADP(H) binding sites, and the assumed non-catalytic sites, may be facilitated by a ligand-triggered formation of a narrow pocket, which normally allows an efficient hydride ion transfer between the natural substrates.


Decreased disappearance rate of 1-(2-tetrahydrofuryl)-5-fluorouracil (FT-207) from the blood and its unresponsiveness to tocophreyl nicotinate and indomethacin in patients with primary hepatocellular carcinoma.
The disappearance rates(K) of FT-207 from the blood in patients with primary hepatoma and advanced cirrhosis of the liver were significantly lower than those in control patients with cancer but normal liver function. Pretreatment with tocopheryl nicotinate and indomethacin increased the K values in the control subjects, but was without effect on the K values in patients with primary hepatoma.


In vitro fertilization in women under 35: counseling should differ by age.
The aim of this study is to evaluate the outcomes of in vitro fertilization (IVF), including cumulative live birth rate, among women <25 years, 25 to <30 years, and 30 to <35 years. A retrospective cohort study of all women 18 to <35 years of age at their first fresh-embryo, non-donor IVF cycle from January 1995 through December 2012 at a single center was conducted. A competing-risk regression model was used to estimate the cumulative probability and 95 % confidence interval (CI) of the first live birth in up to 6 cycles during the study period with IVF cycle number as the time metric. Among 7243 women who underwent 16,792 cycles, there were 163 (2.3 %) women <25 years, 1691 (23.3 %) women 25 to <30 years, and 5389 (74.4 %) women 30 to <35 years. Women <25 years had the lowest cumulative live birth rate after each cycle, followed by women 30 to <35 years. In both groups, the cumulative live birth rate after 6 cycles was significantly lower than that of women 25 to <30 years; these rates were 58 % (95 % CI 0.51-0.66) among women <25 years, 69 % (95 % CI 0.67-0.71) among women 25 to <30 years, and 64 % (95 % CI 0.63-0.65) among women 30 to <35 years. Our findings are consistent with other reports of less favorable IVF treatment outcomes in women <25 years of age following their first IVF cycle. This indicates that there are underlying factors in couples with a female <25 years of age that should lead to different treatment counseling when they attempt IVF.


Trace level determination of molybdenum in environmental and biological samples using surfactant-mediated liquid-liquid extraction.
A novel and sensitive spectrophotometric method for the determination of molybdenum at trace levels in environmental and biological samples is proposed. The method is based on the reaction of Mo (V) with thiocyanate (SCN(-)) and methyltrioctyl ammonium chloride (MTOAC) in acidic medium. The red colored complex of molybdenum is extracted with N-phenylbenzimidoyl thiourea (PBITU) in 1-pentanol for its determination by spectrophotometry. The sensitivity of the present method is higher than other conventional thiocyanate method, due to the use of MTOAC in liquid-liquid extraction. The value of molar absorptivity of the complex with respect to molybdenum is 7.6x10(4)Lmol(-1)cm(-1) at 470nm. The limit of detection of the metal is 5ngmL(-1). The system obeys Beer's law between 20 and 1000ngmL(-1) with slope, intercept and correlation coefficient values of 0.81, 2.5x10(-3) and +0.999, respectively. Most of the metal ions tested did not interfere in the determination of molybdenum. The proposed method has been successfully applied for the determination of the molybdenum in environmental and biological samples.


Hepatic Hypertrophy in Normal and Cirrhotic Livers Following Portal Vein Embolization: Comparative Assessment of 2 Different Embolic Regimens in a Large Animal Model.
To compare the mechanistic effects and hypertrophy outcomes using 2 different portal vein embolization (PVE) regimens in normal and cirrhotic livers in a large animal model. The Institutional Animal Care and Use Committee approved all experiments conducted in this study. Fourteen female Yorkshire pigs were separated into a cirrhotic group (CG, n = 7) and non-cirrhotic group (NCG, n = 7) and further subgrouped into those using microspheres and coils (MC, n = 3) or n-butyl cyanoacrylate (nBCA, n = 3) and their corresponding controls (each n = 1). A 3:1 ethiodized oil and ethanol mixture was administered intra-arterially in the CG to induce cirrhosis 4 weeks before PVE. Animals underwent baseline computed tomography (CT), PVE including pre-PVE and post-PVE pressure measurements, and CT imaging at 2 and 4 weeks after PVE. Immunofluorescence stainings for CD3, CD16, Ki-67, and caspase 3 were performed to assess immune cell infiltration, hepatocyte proliferation, and apoptosis. Statistical significance was tested using the Student's t test. Four weeks after PVE, the percentage of future liver remnant (FLR%) increased by 18.8% (standard deviation [SD], 3.6%) vs 10.9% (SD, 0.95%; P < .01) in the NCG vs CG. The baseline percentage of standardized future liver remnant (sFLR%) for the controls were 41.6% for CG vs 43.6% for NCG. Based on the embolic agents used, the sFLR% two weeks after PVE was 58.4% (SD, 3.7%) and 52.2% (SD, 0.9%) (P < .01) for MC and 46.0% (SD, 2.2%) and 47.2% (SD, 0.4%) for nBCA in the NCG and CG, respectively. Meanwhile, the sFLR% 4 weeks after PVE was 60.5% (SD, 3.9%) and 54.9% (SD, 0.8%) (P < .01) and 60.4% (SD, 3.5%) and 54.2% (SD, 0.95%) (P < .01), respectively. Ki-67 signal intensity increased in the embolized lobe in both CG and NCG (P < .01). This preclinical study demonstrated that MC could be the preferred embolic of choice compared to nBCA when a substantial and rapid FLR increase is needed for resection, in both cirrhotic and non-cirrhotic livers.


[Danger of delayed diagnosis in severe meningeal suppurations (author's transl)].
The necessity of unequivocal diagnosis is sometimes a fatal cause of delay in the medical or neurosurgical treatment of meningeal suppurations.


Cardioembolic and small vessel disease stroke show differences in associations between systemic C3 levels and outcome.
Activation of the complement system has been proposed to play a role in the pathophysiology of stroke. As the specific involvement of the complement proteins may be influenced by stroke etiology, we compared plasma C3 and C3a levels in patients with cardioembolic (CE) and small vessel disease (SVD) subtypes of ischemic stroke and control subjects and evaluated their association to outcome at three months and two years. Plasma C3 and C3a levels in 79 CE and 79 SVD stroke patients, sampled within 10 days and at three months after stroke, and age- and sex-matched control subjects from The Sahlgrenska Academy Study on Ischemic Stroke were measured by ELISA. Functional outcome was assesed with modified Rankin Scale. In the CE group, plasma C3 levels were elevated only in the acute phase, whereas C3a was elevated at both time points. The follow-up phase plasma C3 levels in the upper third were associated with an increased risk of unfavorable outcome at three months (OR 7.12, CI 1.72-29.46, P = 0.007) as well as after two years (OR 8.25, CI 1.61-42.28, P = 0.011) after stroke. These associations withstand adjustment for age and sex. Conversely, three-month follow-up plasma C3a/C3 level ratios in the middle third were associated with favorable outcome after two years both in the univariate analysis (OR 0.19, CI 0.05-0.82, P = 0.026) and after adjustment for age and sex (OR 0.19, CI 0.04-0.88, P = 0.033). In the SVD group, plasma C3 and C3a levels were elevated at both time points but showed no significant associations with outcome. Plasma C3 and C3a levels are elevated after CE and SVD stroke but show associations with outcome only in CE stroke.


Congenital tuberculosis.
We report a case of congenital tuberculosis diagnosed by liver biopsy in a 8-week-old infant presented with acute abdomen. Liver biopsy showed multiple lymphoepitheloid cell granulomas with Langhans' giant cells and central necrosis. The culture of caseous material from the liver showed Mycobacterium tuberculosis . Antituberculous treatment was started. Endometrial biopsy in the asymptomatic mother confirmed the source of infection.


Increased plasma levels of the soluble form of Fas ligand in patients with acute myocardial infarction and unstable angina pectoris.
To examine whether the Fas/Fas ligand system is involved in the pathogenesis of acute myocardial infarction (AMI), we measured the levels of the soluble form of the Fas ligand (sFasL) in the plasma of patients with AMI and stable or unstable angina pectoris (AP). The Fas ligand (FasL) is rapidly cleaved off by a metalloproteinase from the cell membrane to become a soluble form as a cytokine. Fas is expressed in most cells, including cardiomyocytes, whereas FasL is mainly expressed in inflammatory cells such as macrophages, which are greatly accumulated in unstable plaque. Thirty patients with AMI, 10 patients with unstable AP, 10 patients with stable AP and 30 control subjects were enrolled in the present study. Plasma sFasL levels were significantly elevated on hospital admission in patients with AMI and unstable AP, compared with control subjects. Time-course studies revealed that plasma sFasL levels rapidly decreased within 3 h and then increased again after percutaneous transluminal coronary angioplasty in patients with AMI, but not in patients with stable AP. Importantly, the sFasL levels were higher in the coronary sinus than in the circulation. In addition, in vitro studies showed that the expression of FasL messenger ribonucleic acid was upregulated in mononuclear cells isolated from patients with AMI and that hypoxia stimulated the release of sFasL from isolated mononuclear cells. This demonstration of elevated levels of sFasL in patients with AMI and unstable AP suggests that activation of the Fas/FasL system may play a pathogenic role in AMI and acute coronary syndromes.


Removal of formaldehyde, methanol, dimethylether and carbon monoxide from waste gases of synthetic resin-producing industries.
The removal of mixtures of gas-phase pollutants released from formaldehyde- and formaldehyde resin-producing industries was studied in different bioreactor systems. The waste gases contained formaldehyde, methanol, dimethylether and carbon monoxide. The use of a hybrid two-stage bioreactor, composed of a biotrickling filter and a conventional biofilter connected in series, led to very high elimination capacities and removal efficiencies close to 100% for overall pollutant loads exceeding 600g m(-3)h(-1). The presence of low concentrations of dimethylether in the gaseous mixture did not have a significant effect on the removal of formaldehyde or methanol under our operating conditions, although moderate concentrations of these compounds did negatively affect the biodegradation of dimethylether. When a mixture of all four compounds, at concentrations around 100, 100, 50 and 50mg m(-3) for formaldehyde, methanol, carbon monoxide and dimethylether, respectively, was fed to a conventional biofilter, removal efficiencies higher than 80% were obtained for the first three pollutants at empty bed retention time values above 30s. On the other hand, dimethylether was removed to a lower extent, although its reduced environmental impact allows to conclude that these results were satisfactory.