Nonrandom distribution of aberrant promoter methylation of cancer-related genes in sporadic breast tumors.
In an effort to additionally determine the global patterns of CpG island hypermethylation in sporadic breast cancer, we searched for aberrant promoter methylation at 10 gene loci in 54 primary breast cancer and 10 breast benign lesions. Genomic DNA sodium bisulfate converted from benign and malignant tissues was used as template in methyl-specific PCR for BRCA1, p16, ESR1, GSTP1, TRbeta1, RARbeta2, HIC1, APC, CCND2, and CDH1 genes. The majority of the breast cancer (85%) showed aberrant methylation in at least 1 of the loci tested with half of them displaying 3 or more methylated genes. The highest frequency of aberrant promoter methylation was found for HIC1 (48%) followed by ESR1 (46%), and CDH1 (39%). Similar methylation frequencies were detected for breast benign lesions with the exception of the CDH1 gene (P = 0.02). The analysis of methylation distribution indicates a statistically significant association between methylation of the ESR1 promoter, and methylation at CDH1, TRbeta1, GSTP1, and CCND2 loci (P < 0.03). Methylated status of the BRCA1 promoter was inversely correlated with methylation at the RARbeta2 locus (P < 0.03). Our results suggest a nonrandom distribution for promoter hypermethylation in sporadic breast cancer, with tumor subsets characterized by aberrant methylation of specific cancer-related genes. These breast cancer subgroups may represent separate biological entities with potential differences in sensitivity to therapy, occurrence of metastasis, and overall prognosis.


Multiscale Determinants Drive Parasitization of Drosophilidae by Hymenopteran Parasitoids in Agricultural Landscapes.
(1) The management of agricultural landscapes for pest suppression requires a thorough understanding of multiple determinants controlling their presence. We investigated the ecological preferences of indigenous parasitoids and their drosophilid hosts to understand the role of native parasitoids as biological control agents of the invasive frugivorous Drosophila suzukii. (2) Using data from an extensive field survey across different habitat types we analyzed the influence of abiotic and biotic factors on parasitoid and drosophilid communities at multiscale levels. (3) Eight parasitoid and 27 drosophilid species were identified. Thirty-four percent variation in drosophilid communities was explained by factors at the landscape scale, and 52% of significant variation of parasitoids by local distribution of three drosophilid species, mainly collected in woodland. Parasitoid communities were significantly influenced by microhabitat type (ground versus canopy) rather than habitat type. All parasitoids except Pachycrepoideus vindemmiae preferred the ground microhabitat. All parasitoids, with the exception of Trichopria drosophilae and Spalangia erythromera, displayed significant preferences among the drosophilid species used in the baited traps. (4) Since they can tolerate a broad range of habitat factors, altogether pupal parasitoids investigated in this study could play a role in biological control programs to suppress D. suzukii, but non-target effects have to be regarded.


Depression of monocyte and polymorphonuclear leukocyte oxidative metabolism and bactericidal capacity by influenza A virus.
Decreased host defense against bacterial disease associated with influenza infection may be related to virus-induced changes in phagocytic cell function. Influenza A virus initiates the respiratory burst in peripheral blood monocytes and polymorphonuclear leukocytes, with a peak chemiluminescent response approximately 3 min after virus is added to the cells in vitro. Electron micrographs of phagocytic cells incubated with influenza virus demonstrated virus attached to the cell membrane and within phagocytic vacuoles. After 20 min of incubation of the virus with phagocytic cells, the chemiluminescent response to opsonized zymosan or phorbol myristate acetate was decreased by 30 to 90%. Phagocytic activity of monocytes and polymorphonuclear leukocytes incubate with influenza virus was normal, but the bactericidal activity was significantly depressed. Influenza A virus therefore stimulates an oxidative burst in monocytes as well as polymorphonuclear leukocytes, leading to a subsequent depression of the oxidative metabolic response and bactericidal capacity of the phagocytic cells.


Damage of supercoiled DNA by an ultrafast laser-driven electron x-ray source.
Using magnetic fields to differentiate the effects of electrons and x-rays, it was discovered that single strand breaks in supercoiled DNA were mainly caused by the energetic ultrafast electrons rather than the ultrafast x-ray photons emitted from the same table-top ultrafast x-ray source. At constant pulse energy of the driving laser pulses, shorter laser pulses produced more strand breaks than longer ones. This was attributed to the increased flux of electrons produced with the shorter laser pulses. Other factors contributing to the DNA damage were investigated and discussed.


Effects of cannabis smoking on the respiratory system: A state-of-the-art review.
The diminished perception of the health risks associated with the consumption of cannabis (marijuana) lead to a progressive increase in its inhalational use in many countries. Cannabis can be smoked through the use of joints, spliffs and blunts, and it can be vaporised with the use of hookah or e-cigarettes. Delta-9 tetrahydrocannabinol (THC) is the main psychoactive component of cannabis smoke but contains numerous other substances. While the recreational use of cannabis smoking has been legalised in several countries, its health consequences have been underestimated and undervalued. The purpose of this review is to critically review the impact of cannabis smoke on the respiratory system. Cannabis smoke irritates the bronchial tree and is strongly associated with symptoms of chronic bronchitis, with histological signs of airway inflammation and remodelling. Altered fungicidal and antibacterial activity of alveolar macrophages, with greater susceptibility to respiratory infections, is also reported. The association with invasive pulmonary aspergillosis in immunocompromised subjects is particularly concerning. Although cannabis has been shown to produce a rapid bronchodilator effect, its chronic use is associated with poor control of asthma by numerous studies. Cannabis smoking also represents a risk factor for the development of bullous lung disease, spontaneous pneumothorax and hypersensitivity pneumonitis. On the other hand, no association with the development of chronic obstructive pulmonary disease was found. Finally, a growing number of studies report an independent association of cannabis smoking with the development of lung cancer. In conclusion, unequivocal evidence established that cannabis smoking is harmful to the respiratory system. Cannabis smoking has a wide range of negative effects on respiratory symptoms in both healthy subjects and patients with chronic lung disease. Given that the most common and cheapest way of assumption of cannabis is by smoking, healthcare providers should be prepared to provide counselling on cannabis smoking cessation and inform the public and decision-makers.


[Propagating the Culture of Schistosomiasis Control and Promoting Its Sustainable Development in China].
Great achievements have been gained in schistosomiasis control in China due to the last half-century endeavor. These achievements not only indicate the success in disease control, but also represent a particularly successful social practice with a unique cultural property. Inspite of the accumulating reports on schistosomiasis prevention and control experience, there is a need to sublimate the experience to the "cultural" level, as historically the value of cultural and spiritual merits goes far beyond that of the achievements. Although the strategy and technology will be enriched with time, the cultural spirit remains especially important for the long- term promotion of schistosomiasis control. This paper materially dissected the meaning of "China's culture for schistosomiasis control", i.e., people-first, government-oriented, science-respected, collective wisdom and efforts, and diversity-embracing.


Nabilone as an adjunctive to gabapentin for multiple sclerosis-induced neuropathic pain: a randomized controlled trial.
Neuropathic pain (NPP) is a chronic syndrome suffered by patients with multiple sclerosis (MS), for which there is no cure. Underlying cellular mechanisms involved in its pathogenesis are multifaceted, presenting significant challenges in its management. A randomized, double-blind, placebo-controlled study involving 15 relapsing-remitting MS patients with MS-induced NPP was conducted to evaluate nabilone combined with gabapentin (GBP). Eligible patients stabilized on GBP (≥1,800 mg/day) with inadequate pain relief were recruited. Nabilone or placebo was titrated over 4 weeks (0.5 mg/week increase) followed by 5-week maintenance of 1 mg oral nabilone (placebo) twice daily. Primary outcomes included two daily patient-reported measures using a 100-mm visual analog scale (VAS), pain intensity (VASpain), and impact of pain on daily activities (VASimpact). Hierarchical regression modeling was conducted on each outcome to determine if within-person pain trajectory differed across study groups, during 63-day follow-up. After adjustment for key patient-level covariates (e.g., age, sex, Expanded Disability Status Scale, duration of MS, baseline pain), a significant group × time(2) interaction term was reported for both the VASpain (P < 0.01) and VASimpact score (P < 0.01), demonstrating the adjusted rate of decrease for both outcomes was statistically greater in nabilone vs placebo study group. No significant difference in attrition rates was noted between treatments. Nabilone was well tolerated, with dizziness/drowsiness most frequently reported. Nabilone as an adjunctive to GBP is an effective, well-tolerated combination for MS-induced NPP. The results of this study identify a novel therapeutic combination for use in this population of patients predisposed to tolerability issues that may otherwise prevent effective pain management.


AT1-receptor antagonism reverses the blood pressure elevation associated with diet-induced obesity.
Previous studies in our laboratory demonstrated that rats exhibiting obesity in response to a moderately high-fat (MHF) diet developed hypertension associated with activation of the local and systemic renin-angiotensin system. In this study, we examined the effect of the angiotensin type 1 (AT(1))-receptor antagonist, losartan, on blood pressure in obesity-prone (OP) and obesity-resistant (OR) rats fed a MHF diet. Using telemetry monitoring, we characterized the evolution of blood pressure elevations during the development of obesity. Male Sprague-Dawley rats were implanted with telemetry transducers for chronic monitoring of blood pressure, and baseline measurements were obtained. Rats were then switched to the MHF diet (32% kcal as fat) and were segregated into OP and OR groups at week 5. At week 9 on the MHF diet, OP rats exhibited significantly greater 24-h mean arterial blood pressure compared with OR rats (OP: 105 +/- 4 mmHg, OR: 96 +/- 2 mmHg; P < 0.05). Elevations in blood pressure in OP rats were manifest as an increase in systolic pressure. Administration of losartan to all rats at week 9 resulted in a reduction in blood pressure; however, losartan had the greatest effect in OP rats (percent decrease in mean arterial pressure by losartan; OP: 19 +/- 4, OR: 10 +/- 2%; P < 0.05). These results demonstrate that elevations in blood pressure occur subsequent to established obesity in rats fed a high-fat diet. Moreover, these results demonstrate the ability of losartan to reverse the blood pressure increase from diet-induced obesity, supporting a primary role for the renin-angiotensin system in obesity-associated hypertension.


Online blind source separation using incremental nonnegative matrix factorization with volume constraint.
Online blind source separation (BSS) is proposed to overcome the high computational cost problem, which limits the practical applications of traditional batch BSS algorithms. However, the existing online BSS methods are mainly used to separate independent or uncorrelated sources. Recently, nonnegative matrix factorization (NMF) shows great potential to separate the correlative sources, where some constraints are often imposed to overcome the non-uniqueness of the factorization. In this paper, an incremental NMF with volume constraint is derived and utilized for solving online BSS. The volume constraint to the mixing matrix enhances the identifiability of the sources, while the incremental learning mode reduces the computational cost. The proposed method takes advantage of the natural gradient based multiplication updating rule, and it performs especially well in the recovery of dependent sources. Simulations in BSS for dual-energy X-ray images, online encrypted speech signals, and high correlative face images show the validity of the proposed method.


Projecting the radiation oncology workforce in Australia.
Research on radiation oncologists has indicated that there is a shortage in supply of specialist workers in this field internationally, and also within Australia. However, there are no current estimates as to what the future Australian radiotherapy workforce will look like. This paper aims to review the current status and capacity of the three main disciplines that make up the radiation oncology workforce in Australia and project the workforce supply and demand for 2014 and 2019. Using data on the workforce from a survey of all radiotherapy facilities operating in Australia in 2008 a workforce model was constructed. This study found that there will be a future shortfall of radiation oncologists, radiation therapists and radiation oncology medical physicists working in radiation oncology treatment. By 2014 there will be 109 fewer radiation oncologists than what will be demanded, and by 2019 this figure will increase to a shortfall of 155 radiation oncologists. There was a projected shortfall of 612 radiation therapists by 2014, with this figure slightly decreasing to a shortfall of 593 radiation therapists in 2019. In 2014, there was projected to be a deficit of 104 radiation oncology medical physicists with a persisting shortfall of 78 in 2019. This future projected shortage highlights the need for radiation oncology workforce planning.


Roles of prices, poverty, and health in Medicare and private spending in Texas.
To investigate the roles of prices, poverty, and health in divergences between Medicare and private spending in Texas. Retrospective observational design using 2011 Blue Cross Blue Shield of Texas claims data and publicly available Medicare data. We measured market-level spending per enrollee among the privately insured. Variation in Medicare and private spending per person are decomposed into prices and quantities, and their associations with poverty are measured. Markets are divided into 4 groups and are compared based on the ratio of Medicare to private spending: "high-private," "proportional," "high-Medicare," and "extremely high-Medicare." Among the privately insured, poverty appears to have large spillover effects; it is strongly associated with lower prices, quantities, and spending. Among Medicare beneficiaries, health status is a key driver of spending variation. The 2 markets with extremely high Medicare-to-private spending ratios (Harlingen and McAllen) are predominantly Hispanic communities with markedly higher rates of poverty and lack of insurance and also extremely low physician supply. The markets with relatively high private spending stand out for having good health-system performance and health outcomes, and higher than average hospital prices. Variation in private spending appears to reflect the ability of the local population to pay for healthcare, whereas variation in Medicare is more heavily driven by health status, and presumably, by clinical need. These findings highlight the inadvisability of using Medicare spending as a proxy for systemwide spending, and the need for comprehensive market-level spending data that allow comparisons among populations with different sources of insurance coverage.


Immunolocalization of Jasmonates and Auxins in Pea Roots in Connection with Inhibition of Root Growth under Salinity Conditions.
Inhibition of root elongation is an important growth response to salinity, which is thought to be regulated by the accumulation of jasmonates and auxins in roots. Nevertheless, the mechanisms of the interaction of these hormones in the regulation of the growth response to salinity are still not clear enough. Their better understanding depends on the study of the distribution of jasmonates and auxins between root cells. This was achieved with the help of immunolocalization of auxin (indoleacetic acid) and jasmonates on the root sections of pea plants. Salinity inhibited root elongation and decreased the size of the meristem zone and the length of cells in the elongation zone. Immunofluorescence based on the use of appropriate, specific antibodies that recognize auxins and jasmonates revealed an increased abundance of both hormones in the meristem zone. The obtained data suggests the participation of either auxins or jasmonates in the inhibition of cell division, which leads to a decrease in the size of the meristem zone. The level of only auxin and not jasmonate increased in the elongation zone. However, since some literature evidence argues against inhibition of root cell division by auxins, while jasmonates have been shown to inhibit this process, we came to the conclusion that elevated jasmonate is a more likely candidate for inhibiting root meristem activity under salinity conditions. Data suggests that auxins, not jasmonates, reduce cell size in the elongation zone of salt-stressed plants, a suggestion supported by the known ability of auxins to inhibit root cell elongation.


pAMT11, a novel plasmid isolated from a Thermococcus sp. strain closely related to the virus-like integrated element TKV1 of the Thermococcus kodakaraensis genome.
A novel extrachromosomal element that we called pAMT11 was discovered in a deep-sea vent isolate belonging to the hyperthermophilic euryarchaeal order Thermococcales. It consists of a double-stranded DNA of 20,534bp which encodes 30 putative open reading frames (ORFs) of which six could be assigned to a putative function on the basis of sequence similarity to known genes or to protein domain families. Most of the ORFs of pAMT1 showed homology and synteny with a genomic island of Thermococcus kodakaraensis KOD1. This region, named TKV1, was previously described as a "virus-like integrated element" and assumed to integrate into the host chromosome by a site-specific recombination mechanism similar to that of Sulfolobus solfataricus virus 1. While most of the genes shared by pAMT11 and TKV1 encode putative membrane proteins presumably involved in virus particle formation, attempts to induce production of virus particles by mitomycin treatment of AMT11 cultures failed, suggesting that pAMT11 may represent the genome of a defective virus or a plasmid. Genomes of mobile elements usually contain two regions: a core of conserved genes mainly involved in replication, maintenance or spreading of the genetic element, and a variable set of accessory genes. Surprisingly, genes presumably implied in the replication process are quite divergent between TKV1 and pAMT11. Indeed, TKV1 possesses a MCM-like protein that may function as a replication initiator, while pAMT11 encodes a putative non-conventional protein distantly related to the Rep protein previously described in a small plasmid of Pyrococcus sp. strain JT1, assumed to replicate by a rolling-circle (RC) mechanism. However, in the case of pAMT11, this mode of plasmid replication could not be experimentally proven and is questionable given the lack of significant similarities with any other members of the RC-Rep superfamily and its unusual large size compared to other RC plasmids.


Zanamivir: a review of clinical safety.
Preclinical and clinical studies have clearly demonstrated that zanamivir, a potent and highly selective inhibitor of the influenza A and B virus neuraminidase, has an impressive safety profile. This report describes the safety and tolerability findings from the clinical studies completed up to the 17 July 1998 involving over 6000 adult and adolescent patients from North America, Europe and the Southern Hemisphere. Serious adverse events from an ongoing Japanese clinical programme are also reported. Zanamivir was administered in various dose forms and frequencies and was found to have a comparable safety profile with placebo when given for both the treatment and prophylaxis of influenza-like illness. These findings were independent of age and underlying medical condition. 4152 patients received zanamivir and the most commonly reported adverse events were consistent with the signs and symptoms of influenza-like illness. Most of the adverse events were mild and did not result in patient withdrawal from the studies. Less than 1% of zanamivir and placebo recipients reported a serious adverse event. In addition, 490 healthy volunteers received zanamivir in clinical pharmacology studies. It was well tolerated and the incidence of adverse events was similar in zanamivir and placebo recipients. In addition, no clinically significant laboratory abnormalities were detected. Results from in vitro and in vivo animal studies suggest that zanamivir has low acute toxicity and no significant systemic toxicity or respiratory tract irritancy at plasma exposures more than 100-fold higher than those anticipated following clinical use. Neither genotoxic nor reproductive types of toxicity have been observed in toxicology studies at doses equal to 17 to 197 times the current therapeutic dose (20 mg/day). The characteristics of the molecule and the low systemic exposure indicate a very low potential for drug interactions with the inhaled route. Furthermore, repeated 600mg intravenous doses were well tolerated in healthy volunteers. The observed safety profile of zanamivir compares favourably with currently available agents with anti-influenza virus activity, such as rimantadine and amantadine, as well as GS4104, a neuraminidase inhibitor currently in phase III development. This may be attributed to the low systemic bioavailability of zanamivir, which is given by oral inhalation, direct to the primary site of viral replication. The potential advantages of this include a reduced risk of drug-drug interactions, other nontarget organ toxicities (e.g. brain) and drug clearance issues from both kidney and liver. Therefore, the safety profile of zanamivir supports its use in the management of influenza.


Effects of protein source and nutrient density in the diets of male broilers from 8 to 21 days of age on their subsequent growth, blood constituents, and carcass compositions.
The effects of protein source and amino acid (AA) and AME levels in the diets of male broilers from 8 to 21 d of age on subsequent growth and blood and carcass traits were investigated in the current study. Fourteen Ross × Ross 708 male broiler chicks were randomly allocated to each of 80 floor pens arranged in a randomized complete block design. Each diet contained 1 of 2 dietary protein sources (high inclusion of distillers dried grains with solubles or high inclusion of meat and bone meal), 1 of 2 AA densities (moderate or 10% higher), and 1 of 2 AME densities (2,998 or 3,100 kcal/kg). Experimental diets were fed from 8 to 21 d of age, and common diets from 1 to 7 and 21 to 55 d of age. The higher AME density in high inclusion of meat and bone meal diets increased serum triglyceride and cholesterol levels on d 20. The dietary inclusion of high inclusion of distillers dried grains with solubles or lower levels of AA increased high-density lipoprotein cholesterol on d 20. Feeding the high-AA-density diet decreased feed intake without affecting BW gain, which resulted in a lower feed conversion ratio (FCR). A high-AME-density diet lowered feed intake but increased BW gain, which resulted in a lower FCR from 8 to 21 d of age. Feed intake, BW gain, FCR from 21 to 54 d of age, and carcass weight on 42 and 55 d of age were not affected by treatments from 8 to 21 d of age. However, early dietary manipulation from 8 to 21 d of age affected fat and meat yield at 42 and 55 d of age. Moreover, a high-AME diet decreased feed cost per carcass weight gain from 8 to 55 d of age. In conclusion, high AA or AME densities during the grower phase, from d 8 to 21 of age, may improve growth during the grower feeding phase, but may also affect meat yield during the latter grow-out phases. Furthermore, high-AME diets from 8 to 21 d of age may save on feed costs for meat production.


Disease resistance conferred by expression of a gene encoding H2O2-generating glucose oxidase in transgenic potato plants.
Plant defense responses to pathogen infection involve the production of active oxygen species, including hydrogen peroxide (H2O2). We obtained transgenic potato plants expressing a fungal gene encoding glucose oxidase, which generates H2O2 when glucose is oxidized. H2O2 levels were elevated in both leaf and tuber tissues of these plants. Transgenic potato tubers exhibited strong resistance to a bacterial soft rot disease caused by Erwinia carotovora subsp carotovora, and disease resistance was sustained under both aerobic and anaerobic conditions of bacterial infection. This resistance to soft rot was apparently mediated by elevated levels of H2O2, because the resistance could be counteracted by exogenously added H2O2-degrading catalase. The transgenic plants with increased levels of H2O2 also exhibited enhanced resistance to potato late blight caused by Phytophthora infestans. The development of lesions resulting from infection by P. infestans was significantly delayed in leaves of these plants. Thus, the expression of an active oxygen species-generating enzyme in transgenic plants represents a novel approach for engineering broad-spectrum disease resistance in plants.


[Patterns in the correlations between the indices of the hydration-electrolyte profile of the brain].
The hydration-electrolyte profile was studied in 18 CNS structures of dogs. The frequencies of correlation coefficients were found to be placed in diminishing order as follows: H2O/H2O, K/K, H2O/K, Na/Na, H2O/Na, Na/K. The closest relations were detected in the frontal cortex, the least number of interactions were characteristic of the spinal cord and the hippocampus. The interrelations based on functional, anatomic, embryo-phylogenetic principles were most frequently observed in the thalamic and caudate-frontal systems as well as in the cortex and in mesencephalon.


Surgical intervention and accommodative responses, I: centripetal ciliary body, capsule, and lens movements in rhesus monkeys of various ages.
To determine how surgically altering the normal relationship between the lens and the ciliary body in rhesus monkeys affects centripetal ciliary body and lens movement. In 18 rhesus monkey eyes (aged 6-27 years), accommodation was induced before and after surgery by electrical stimulation of the Edinger-Westphal nucleus. Accommodative amplitude was measured by coincidence refractometry. Goniovideography was performed before and after intra- and extracapsular lens extraction (ICLE, ECLE) and anterior regional zonulolysis (ARZ). Centripetal lens/capsule movements, centripetal ciliary process (CP) movements, and circumlental space were measured by computerized image analysis of the goniovideography images. Centripetal accommodative CP and capsule movement increased in velocity and amplitude after, compared with before, ECLE regardless of age (n = 5). The presence of the lens substance retarded capsule movement by approximately 21% in the young eyes and by approximately 62% in the older eyes. Post-ICLE compared with pre-ICLE centripetal accommodative CP movement was dampened in all eyes in which the anterior vitreous was disrupted (n = 7), but not in eyes in which the anterior vitreous was left intact (n = 2). After anterior regional zonulolysis (n = 4), lens position shifted toward the lysed quadrant during accommodation. The presence of the lens substance, capsule zonular attachments, and Wieger's ligament may play a role in centripetal CP movement. The capsule is still capable of centripetal movement in the older eye (although at a reduced capacity) and may have the ability to produce approximately 6 D of accommodation in the presence of a normal, young crystalline lens or a similar surrogate.


A Retrospective Evaluation of the Epithelial Changes/Lesions and Neoplasms of the Gallbladder in Turkey and a Review of the Existing Sampling Methods: A Multicentre Study.
As there is continuing disagreement among the observers on the differential diagnosis between the epithelial changes/lesions and neoplasms of the gallbladder, this multicentre study was planned in order to assess the rate of the epithelial gallbladder lesions in Turkey and to propose microscopy and macroscopy protocols. With the participation of 22 institutions around Turkey that were included in the Hepato-Pancreato-Biliary Study Group, 89,324 cholecystectomy specimens sampled from 2003 to 2016 were retrospectively evaluated. The numbers of adenocarcinomas, dysplasias, intracholecystic neoplasms/adenomas, intestinal metaplasias and reactive atypia were identified with the review of pathology reports and the regional and countrywide incidence rates were presented in percentages. Epithelial changes/lesions were reported in 6% of cholecystectomy materials. Of these epithelial lesions, 7% were reported as adenocarcinoma, 0.9% as high-grade dysplasia, 4% as low-grade dysplasia, 7.8% as reactive/regenerative atypia, 1.7% as neoplastic polyp, and 15.6% as intestinal metaplasia. The remaining lesions (63%) primarily included non-neoplastic polypoids/hyperplastic lesions and antral/pyloric metaplasia. There were also differences between pathology laboratories. The major causes of the difference in reporting these epithelial changes/lesions and neoplasms include the differences related to the institute's oncological surgery frequency, sampling protocols, geographical dissimilarities, and differences in the diagnoses/interpretations of the pathologists. It seems that the diagnosis may change if new sections are taken from the specimen when any epithelial abnormality is seen during microscopic examination of the cholecystectomy materials.


[Classical monoamine oxidase inhibitor: not registered for, but still a place in the treatment of depression].
In the Netherlands monoamine oxidase (MAO) inhibitors are not registered for the treatment of patients with depression. The classical, nonselective MAO inhibitors--phenelzine and tranylcypromine--are effective but their use is associated with interactions (with tyramine in food, sympathicomimetics and serotonine re-uptake inhibitors) and side-effects (hypertension, hypotension, headache, sleep disturbances and neuromuscular symptoms in particular). Therefore, the classical MAO inhibitors are indicated only in depressive disorders that are unresponsive to the first stages of treatment. Taking this selection into account, treatment should be long-term to avoid relapse.


Effects of daily kangaroo care on cardiorespiratory parameters in preterm infants.
Kangaroo care (KC) has possible benefits for promoting physiological stability and positive developmental outcomes in preterm infants. The purpose of this study was to compare bradycardia and oxygen desaturation events in preterm infants in standard incubator care versus KC. Thirty-eight infants 27 to 30 weeks gestational age were randomly assigned to 2 hours of KC daily between days of life 5 to 10 or to standard incubator care. Infants were monitored for bradycardia (heart rate <80) or oxygen desaturation (<80%). Analysis of hourly events was based on three sets of data: standard care group 24 hours daily, KC group during incubator time 22 hours daily, and KC group during holding time 2 hours daily. The KC group had fewer bradycardia events per hour while being held compared to time spent in an incubator (p = 0.048). The KC group also had significantly fewer oxygen desaturation events while being held than while in the incubator (p = 0.017) and significantly fewer desaturation events than infants in standard care (p = 0.02). KC reduces bradycardia and oxygen desaturation events in preterm infants, providing physiological stability and possible benefits for neurodevelopmental outcomes.


Acute Liver Failure Induced by Joss Paper Ingestion.
We present a case of liver failure secondary to ingestion of Joss paper. A 44-year-old female initially presented with fever, nausea and vomiting and was subsequently diagnosed with acute liver failure. Prior to presentation she had consumed 1.3 gram of acetaminophen and 800 mg of ibuprofen. Her acetaminophen level was 18 mcg/mL initially and on repeat check was <10 mcg/ml and all viral hepatology antibodies and antigens were negative. History revealed that the patient ingested a ceremonial paper, Joss paper, daily, which is typically painted with heavy metals. Her mercury level was subsequently found to be elevated to 12 ug/L. Mercury can cause depletion of glutathione (GSH) through production of reactive oxygen species. Acetaminophen metabolism requires sufficient GSH to bind to a reactive metabolite to prevent cell death and hepatic injury. Daily exposure to mercury present in the Joss paper, likely accumulated in our patient's body and allowed hepatic injury from even therapeutic doses of acetaminophen.


The Canadian American Ticlopidine Study (CATS) in thromboembolic stroke. Design, organization, and baseline results.
The Canadian American Ticlopidine Study is a randomized, placebo-controlled, double-blind, multicenter study to assess the efficacy and safety of ticlopidine hydrochloride in patients who have suffered a thromboembolic stroke no less than 1 week and no more than 4 months before entry into the study. The primary assessment of efficacy will be based on the cluster of outcome events recurrent stroke, myocardial infarction, or vascular death. Twenty-five clinical centers, 12 in Canada and 13 in the United States, entered a total of 1,072 patients during a 3-year recruitment period; these patients were randomly allocated to receive either 250 mg ticlopidine or identical-appearing placebo tablets twice daily for up to 3 years. Patient recruitment was completed in December 1986. Patients were followed for a maximum of 3 years or until the close of the study in December 1987; at that time an average follow-up of 25 months had been achieved. We summarize the protocol and organization of the study and document the methods of execution and analysis, with corresponding criteria, before disclosure of the treatment code to any of the study investigators. We also provide a clinical description of the patients at entry into the study.


Molecular characterization of hypoxia-hypothermia-conditioned human endothelial cells and their interaction with human monocytes.
This in vitro study was designed to characterize the molecular profiling of human endothelial cells (ECs) during the early phase of hypoxia-hypothermia (HH) conditioning and to evaluate their interactions with allogeneic monocytes. The HH-conditioned ECs were analyzed using real-time quantitative polymerase chain reaction (RT-PCR). A cell adhesion assay was performed to assess adhesion of purified allogeneic monocytes as well as CD4- and CD8-positive T cells to HH-conditioned ECs with or without blocking antibodies specific for CD15s and CD162. Uptake of EC membrane by monocytes with or without scavenger receptor blockade was examined using fluorescence-activated cell scanning. The RT-PCR revealed up-regulation of gene transcripts for inflammatory cytokines, monocyte-associated growth factors, costimulatory, and apoptosis-related molecules in HH-conditioned ECs. Analysis using fluorescence-activated cell scanning showed minimal CD54 up-regulation in HH-conditioned ECs. We noted low-level adhesion of CD4- or CD8-positive cells to resting and HH-conditioned ECs. High-level adhesion of monocytes to HH-conditioned ECs was observed when compared with resting ECs. Blockade of CD15s and CD162 dramatically reduced monocyte adhesion to normal and HH-conditioned ECs. Monocytes but not T cells showed uptake of EC membranes during their interactions with HH-conditioned ECs, which was inhibited by scavenger receptor blockade. These data characterized the molecular features of ECs during early HH-conditioning. The EC transcripts related to monocyte recruitment and interaction between monocytes and HH-conditioned ECs dominated the early post-HH condition. Blockade of CD15s and CD162 prevented monocyte adhesion to ECs. These findings suggest that the initial interaction between monocytes and HH-conditioned ECs has a central role during the early phase of reperfusion injury.


Environmentally and economically efficient utilization of coal processing waste.
High concentrations of hazardous anthropogenic emissions (sulfur, nitrogen and carbon oxides) from solid fuel combustion in coal burning plants cause environmental problems that have been especially pressing over the last 20-30 years. A promising solution to these problems is a switch from conventional pulverized coal combustion to coal-water slurry fuel. In this paper, we pay special attention to the environmental indicators characterizing the combustion of different coal ranks (gas, flame, coking, low-caking, and nonbaking coals) and coal-water slurry fuels based on the coal processing waste - filter cakes. There have been no consistent data so far on the acceptable intervals for the anthropogenic emissions of sulfur (SOx), nitrogen (NOx) and carbon (CO, CO2) oxides. Using a specialized combustion chamber and gas analyzing system, we have measured the concentrations of typical coal and filter-cake-based CWS combustion products. We have also calculated the typical combustion heat of the fuels under study and measured the ratio between environmental and energy attributes. The research findings show that the use of filter cakes in the form of CWS is even better than coals in terms of environment and economy. Wide utilization of filter cakes solves many environmental problems: the areas of contaminated sites shrink, anthropogenic emissions decrease, and there is no need to develop new coal mines anymore.


Co-Designing a New Yoga-Based Mindfulness Intervention for Survivors of Stroke: A Formative Evaluation.
Movement-based mindfulness interventions (MBI) are complex, multi-component interventions for which the design process is rarely reported. For people with stroke, emerging evidence suggests benefits, but mainstream programs are generally unsuitable. We aimed to describe the processes involved and to conduct a formative evaluation of the development of a novel yoga-based MBI designed for survivors of stroke. We used the Medical Research Council complex interventions framework and principles of co-design. We purposefully approached health professionals and consumers to establish an advisory committee for developing the intervention. Members collaborated and iteratively reviewed the design and content of the program, formatted into a training manual. Four external yoga teachers independently reviewed the program. Formative evaluation included review of multiple data sources and documentation (e.g., formal meeting minutes, focus group discussions, researcher observations). The data were synthesized using inductive thematic analysis. Three broad themes emerged: (a) MBI content and terminology; (b) manual design and readability; and (c) barriers and enablers to deliver the intervention. Various perspectives and feedback on essential components guided finalizing the program. The design phase of a novel yoga-based MBI was strengthened by interdisciplinary, consumer contributions and peer review. The 12-week intervention is ready for testing among survivors of stroke.


A comparison of children with ADHD in a natural and built setting.
A link has been suggested between children's disconnection from nature and the recent surge in childhood disorders such as Attention Deficit Hyperactivity Disorder (ADHD). Research on benefits of nature for healthy children provides some support for such a link. However, only a few studies have directly examined the influence of contact with nature on children with ADHD. The aim of the present research was to gain more insight into the behaviour and emotional and cognitive functioning of children with ADHD in a natural and built setting. Two groups of six children (age 9-17) who stayed at care farms for children with ADHD in the Netherlands were systematically observed, questioned, and tested during visits to a wooded area and a small town. Both groups performed better on a concentration task in the woods than in the town, despite the fact that all children visited the town after the woods and thus their scores in the town were possibly inflated by learning effects. However, the behaviour and emotional functioning in the two settings differed between the groups. One group of children liked the woods better than the town and displayed more positive behaviours and feelings in the natural environment. The other group of children liked the town equally well as the woods and displayed positive behaviours and feelings in both settings, although they showed somewhat more non-social, aggressive, inattentive, impulsive and hyperactive behaviour in the town than in the woods. These results suggest that natural areas provide a consistent positive environment for children with ADHD. However, more research is needed to obtain a fuller understanding of the influences of the physical environment on children with ADHD.


Effects of the systemic administration of alendronate on bone formation in a porous hydroxyapatite/collagen composite and resorption by osteoclasts in a bone defect model in rabbits.
Several bisphosphonates are now available for the treatment of osteoporosis. Porous hydroxyapatite/collagen (HA/Col) composite is an osteoconductive bone substitute which is resorbed by osteoclasts. The effects of the bisphosphonate alendronate on the formation of bone in porous HA/Col and its resorption by osteoclasts were evaluated using a rabbit model. Porous HA/Col cylinders measuring 6 mm in diameter and 8 mm in length, with a pore size of 100 μm to 500 μm and 95% porosity, were inserted into a defect produced in the lateral femoral condyles of 72 rabbits. The rabbits were divided into four groups based on the protocol of alendronate administration: the control group did not receive any alendronate, the pre group had alendronate treatment for three weeks prior to the implantation of the HA/Col, the post group had alendronate treatment following implantation until euthanasia, and the pre+post group had continuous alendronate treatment from three weeks prior to surgery until euthanasia. All rabbits were injected intravenously with either saline or alendronate (7.5 μg/kg) once a week. Each group had 18 rabbits, six in each group being killed at three, six and 12 weeks post-operatively. Alendronate administration suppressed the resorption of the implants. Additionally, the mineral densities of newly formed bone in the alendronate-treated groups were lower than those in the control group at 12 weeks post-operatively. Interestingly, the number of osteoclasts attached to the implant correlated with the extent of bone formation at three weeks. In conclusion, the systemic administration of alendronate in our rabbit model at a dose-for-weight equivalent to the clinical dose used in the treatment of osteoporosis in Japan affected the mineral density and remodelling of bone tissue in implanted porous HA/Col composites.


Higher Glucose Enhances Breast Cancer Cell Aggressiveness.
Cancer cells overexpress several transcription factors and motor proteins, such as NFkB and kinesin, to accommodate their high energy demand as well as migratory needs via enhanced glycolysis. We hypothesize that high glucose drives cancer progression and cell aggressiveness by decreasing actin expression, increasing NFkB, and kinesin expressions, and by activating Epithelial Mesenchymal Transition (EMT). Using lowly metastatic MCF-7 and highly metastatic MDA-MB231 (MB231) breast cancer cells - highly incident cancer types - we establish how glucose metabolism regulates actin and the biochemical changes that lead to alterations of cell mechanical properties. We find that higher glucose (15 and 30 mM) increases glycolytic enzymes, glucose uptake, migration speed, kinesin, Ki-67, and NFkB expressions (biomarkers), and hybrid EMT phenotype activation (adhesion molecules/cadherins). Downregulation of actin, increased expressions of motor protein and NFkB, and decreased nuclear stiffness - induced by higher glucose - result in a significant increase in the migration speed. Moreover, glucose deprivation using the glucose analog 2-deoxyglucose decreases significantly the migration speed in both cancer cells. Thus, higher glucose promotes a more aggressive phenotype that promises to be a new target for cancer therapy and can help prevent cancer progression in diabetic patients by inhibiting glucose activated mechanisms.


Experimental cord stretchability and the tethered cord syndrome.
Much remains to be learned about the embryology and pathophysiology of the "tethered cord syndrome." Of particular importance in tethered cord syndrome is spinal cord stretchability and its relation to resultant cord dysfunction. In this study, cord elongation was observed in fresh fetuses and in animals by applying weights or forceps traction at the conus medullariscauda equina region. The results show that maximum cord elongation occurs in the lumbar region, some occurs in the thoracic area, and minimal to no elongation occurs in the cervical region. These results are concordant with clinically observed lumbosacral cord dysfunction and oxidative and electrophysiologic impairment of the lumbosacral cord in tethered cord syndrome as shown by other investigators.


[Fundamental research--a basis for the synthesis of new hypotensive drugs].
The paper presents the data showing the important significance of basic research into the mechanisms of circulation regulation in synthesizing new classes of antihypertensive agents. It also considers the hemodynamic mechanisms responsible for the antihypertensive effect of calcium antagonists, postsynaptic alpha 1-adrenoreceptor blockers and angiotensin-converting enzyme blockers to treat hypertensive disease. The paper gives the data suggesting the effects of the drugs on the adrenergic and humoral mechanisms of vascular tone regulation.


Glucosamine sulfate for osteoarthritis.
To characterize the usefulness of glucosamine sulfate in the treatment of patients with osteoarthritis (OA). Pertinent citations were identified via a MEDLINE search (January 1975-March 1997). Only trials available in the English language involving human subjects, OA, and glucosamine sulfate were selected for review. OA is the most common form of arthritis and represents a major cause of morbidity and disability in the elderly. The main symptom of OA is pain and most of the commonly prescribed medications (e.g. acetaminophen, nonsteroidal antiinflammatory drugs) have been targeted at relieving the pain. Some of these medications have serious adverse effects and do not necessarily change the natural course of the disease. Glucosamine sulfate, a nutritional supplement, has recently emerged as an alternative treatment option for patients with OA. The beneficial effects of this chondroprotective agent have been reported to reverse or at least stop the progression of the disease without inducing serious adverse effects. Limited data from short-term human trials suggest that glucosamine sulfate administered orally, intravenously, intramuscularly, and intraarticularly may produce a gradual and progressive reduction in joint pain and tenderness, as well as improved range of motion and walking speed. Results of the trials have also shown that glucosamine has produced consistent benefits (> 50% overall improvement in symptom scores) in patients with OA and that, in some cases, it may be equal or superior to ibuprofen in controlling symptoms. There is evidence that glucosamine sulfate may provide pain relief, reduce tenderness, and improve mobility in patients with OA. Most of the current data, however, are derived from the European and Asian literature and there are no studies supporting the use of this agent in the US. The studies published to date have been done in small numbers of patients; adequate long-term trials examining the safety, efficacy, and optimal dosage requirements of glucosamine sulfate are lacking. Most of the available clinical data are difficult to interpret due to serious deficiencies in study design. Furthermore, studies evaluating the appropriate place of glucosamine sulfate in the therapeutic armamentarium of OA remain to be done.


Utility of Gram's stain and efficacy of quantitative cultures for posttraumatic pneumonia: a prospective study.
This prospective trial examined the efficacy of using bronchoalveolar lavage (BAL) for the diagnosis of pneumonia (PN) and the utility of Gram's stain (GS) for dictating empiric therapy. Posttraumatic nosocomial PN remains a significant cause of morbidity and mortality. However, its diagnosis is elusive, especially in multiply injured patients. The systemic inflammatory response syndrome of fever, leukocytosis, and a hyperdynamic state is common in trauma patients, especially patients with pulmonary contusion. Bronchoscopy with BAL with quantitative cultures of the lavage effluent may distinguish between PN and systemic inflammatory response syndrome, and GS of the lavage effluent may guide empiric therapy before quantitative culture results. Mechanically ventilated trauma patients with a clinical diagnosis of PN (fever, leukocytosis, purulent sputum, and new or changing infiltrate on chest radiograph) underwent bronchoscopy with BAL. Effluent was sent for GS and quantitative cultures. The diagnostic threshold for PN was > or =10(5) colony-forming units (CFU)/mL, and antibiotics were continued. Antibiotics were stopped for < 10(5) CFU/mL and the diagnosis of systemic inflammatory response syndrome was made. Causative organisms for PN were compared to GS. Over a 2-year period, 232 patients underwent 443 bronchoscopies with BAL (71% men, 29% women; mean age, 41). The mean injury severity score was 30. Sixty percent of the patients had pulmonary contusion, and 59% were cigarette smokers. The overall incidence of PN was 39% and was no different regardless of the number of BALs a patient had. The false-negative rate of BAL was 7%. GS identified gram-positive organisms in 80% of patients with gram-positive PN and 40% of patients with gram-negative PN. GS identified gram-negative organisms in 52% of patients with gram-positive PN and 77% with gram-negative PN. The duration of the intensive care unit stay relative to the timing of BAL was beneficial for guiding empiric therapy. BAL in week 1 primarily identified Haemophilus influenzae and gram-positive organisms; Acinetobacter sp. and Pseudomonas sp. were more common after week 1. Bronchoscopy with BAL is an effective method to diagnose PN and avoids prolonged, unnecessary antibiotic therapy. Empiric therapy should be adjusted to the duration of the intensive care unit stay because the causative bacteria flora changes over time. GS of BAL effluent correlates poorly with quantitative cultures and is not reliable for dictating empiric therapy.


[Experience with chemotherapy for advanced pancreatic carcinoma].
The effectiveness of different regimens of chemotherapy for advanced pancreatic cancer was compared in 74 cases (1995-1999). 5-fluorouracil (5FU), adriamycin and mitomycin C (FAM) were given to 12 patients, 5FU alone--23, 5FU plus leukovorin--29, and gemcitabine alone--10. Metastases to the liver were detected in 42 (57%) patients. Partial response (40) was registered in: FAM--1 (8%); 5FU--1 (4%); 5FU + leukovorin--3 (10%); gemcitabine--3 (30%). Mean duration (40) was 5.4; 4; 6.1 and 9 months, respectively. Stabilization was recorded in 17 (23%), mean duration--4.4 months; tumor progression--49 (66%). Toxic side-effects of all the regimens were insignificant. Mean survival rates following FAM, 5FU, 5FU + leukovorin were 4.4; 4.2 and 5.6 months, respectively, while that for gemcitabine varied 3-24 months (on average--7.9 months). Survival in patients responsive to chemotherapy was 9.8; remaining patients--4.7 (p (0.05). Chemotherapy for advanced pancreatic carcinoma is a measure of palliation; its use was followed by a 20% increase in survival. Gemcitabine treatment appeared most effective.


Antioxidants and vision health: facts and fiction.
A number of nutritional supplements containing antioxidants are advertised for better vision health. Do they benefit the average consumer? The literature was examined for the effectiveness of antioxidants for human eye health, and for the intricacies in collection of such evidence. The following diseases were considered: cataract, glaucoma, age-related macular degeneration (AMD), retinopathy, retinitis pigmentosa, eye infections, and uveitis. The literature indicates that antioxidant supplements plus lutein have a reasonable probability of retarding AMD. For glaucoma, such supplements were ineffectual in some studies but useful in others. In some studies, antioxidant rich fruits and vegetables were also useful for protection against glaucoma. For diabetic retinopathy, antioxidant supplements may have a small benefit, if any, but only as an adjunct to glycemic control. In very high-risk premature retinopathy and retinitis pigmentosa, antioxidant supplements may be beneficial but those with excess Vitamin E should be avoided. For cataract, there is no evidence for an advantage of such nutritional supplements. However, lubricant drops containing N-acetylcarnosine may be helpful in initial stages of the disease. For eye infections and other causes of uveitis, antioxidants have not been found useful. We recommend that a diet high in antioxidant rich foods should be developed as a habit from an early age. However, when initial signs of vision health deterioration are observed, the appropriate nutritional supplement products may be recommended but only to augment the primary medical treatments.


Disparities in hormone replacement therapy use by socioeconomic status in a primary care population.
The use of hormone replacement therapy (HRT) is a controversial decision for many women, yet few studies have evaluated the socio-demographic, psychological, and behavioral correlates of HRT use. This cross-sectional, mailed survey evaluated the associations of socioeconomic status, preventive health behaviors, knowledge and perceptions about HRT-related risks and benefits with HRT use among 428 women 50-70 years old in Vermont. The overall prevalence of HRT use was 40%. Women of moderate to high income were three times more likely than those of low income to use HRT. HRT use was significantly higher among women whose physician had encouraged use (58%) than among those who received ambivalent recommendations from their physicians (20%). Hysterectomy, higher income, younger age, regular adherence to cervical cancer screening, and recommendation by a provider were significantly associated with HRT use in multivariate analyses. There were no differences in HRT use according to level of concern about heart disease, osteoporosis, or breast cancer. A recommendation by a health care provider is a powerful predictor of HRT use, but disparities in use exist by socioeconomic status. Future research should examine why lower income women are less likely to use HRT and whether the discrepancy is due to inconsistent recommendations by health care providers.


The multiple effects of thyroid disorders on bone and mineral metabolism.
Differently from most hormones, which commonly are specialized molecules able to influence other cells, tissues and systems, thyroid hormones (TH) are pleiotropic peptides, whose primordial function is difficult to identify. The complex action of TH on human economy can be easily witnessed by examining the diverse consequences of TH excess and deficiency during development and after maturity. In particular, different manifestations in bone modeling and remodeling reflect the circumstantial consequences of thyroid disturbances, which are age dependent. While hyperthyroidism during childhood enhances bone mineralization and accelerates epiphyseal maturation, in adults it induces bone loss by predominant activation of osteoclast activity. Furthermore, the syndrome of TH resistance is a multifaceted condition in which different sites exhibit signs of hormone excess or deficiency depending on the configuration of the TH receptor isoform. The investigation of the impact of TH resistance on the skeleton still remains to be elucidated. We present here a thorough review of the action of TH on bone and of the impact of thyroid disorders, including hyper- and hypothyroidism and the syndrome of TH resistance, on the skeleton.


Bayesian inference for generalized linear mixed models.
Generalized linear mixed models (GLMMs) continue to grow in popularity due to their ability to directly acknowledge multiple levels of dependency and model different data types. For small sample sizes especially, likelihood-based inference can be unreliable with variance components being particularly difficult to estimate. A Bayesian approach is appealing but has been hampered by the lack of a fast implementation, and the difficulty in specifying prior distributions with variance components again being particularly problematic. Here, we briefly review previous approaches to computation in Bayesian implementations of GLMMs and illustrate in detail, the use of integrated nested Laplace approximations in this context. We consider a number of examples, carefully specifying prior distributions on meaningful quantities in each case. The examples cover a wide range of data types including those requiring smoothing over time and a relatively complicated spline model for which we examine our prior specification in terms of the implied degrees of freedom. We conclude that Bayesian inference is now practically feasible for GLMMs and provides an attractive alternative to likelihood-based approaches such as penalized quasi-likelihood. As with likelihood-based approaches, great care is required in the analysis of clustered binary data since approximation strategies may be less accurate for such data.


Attention Modifies Spatial Resolution According to Task Demands.
How does visual attention affect spatial resolution? In texture-segmentation tasks, exogenous (involuntary) attention automatically increases resolution at the attended location, which improves performance where resolution is too low (at the periphery) but impairs performance where resolution is already too high (at central locations). Conversely, endogenous (voluntary) attention improves performance at all eccentricities, which suggests a more flexible mechanism. Here, using selective adaptation to spatial frequency, we investigated the mechanism by which endogenous attention benefits performance in resolution tasks. Participants detected a texture target that could appear at several eccentricities. Adapting to high or low spatial frequencies selectively affected performance in a manner consistent with changes in resolution. Moreover, adapting to high, but not low, frequencies mitigated the attentional benefit at central locations where resolution was too high; this shows that attention can improve performance by decreasing resolution. Altogether, our results indicate that endogenous attention benefits performance by modulating the contribution of high-frequency information in order to flexibly adjust spatial resolution according to task demands.


Semiclassical evaluation of frequency splittings in coupled optical microdisks.
When two microdisks are placed close to each other and the evanescent fields of their whispering gallery modes are overlapped, a strong coupling can be induced in the modes and lead to a doublet state. We attempt to evaluate the frequency splittings of the doublets by applying a semiclassical analysis in the regime of small wavelengths. Since a whispering gallery mode in a microdisk is a leaky mode, an established semiclassical method that deals with coupled closed systems is modified. As a result, we attain an analytic formula which can conveniently compute the frequency splittings of coupled whispering gallery modes. The derived formula is verified by demostrating a perfect agreement with numerical solutions of Maxwell's equations.


Exome-assistant: a rapid and easy detection of disease-related genes and genetic variations from exome sequencing.
Protein-coding regions in human genes harbor 85% of the mutations that are associated with disease-related traits. Compared with whole-genome sequencing of complex samples, exome sequencing serves as an alternative option because of its dramatically reduced cost. In fact, exome sequencing has been successfully applied to identify the cause of several Mendelian disorders, such as Miller and Schinzel-Giedio syndrome. However, there remain great challenges in handling the huge data generated by exome sequencing and in identifying potential disease-related genetic variations. In this study, Exome-assistant (http://126.96.36.199/exomeassistant), a convenient tool for submitting and annotating single nucleotide polymorphisms (SNPs) and insertion/deletion variations (InDels), was developed to rapidly detect candidate disease-related genetic variations from exome sequencing projects. Versatile filter criteria are provided by Exome-assistant to meet different users' requirements. Exome-assistant consists of four modules: the single case module, the two cases module, the multiple cases module, and the reanalysis module. The two cases and multiple cases modules allow users to identify sample-specific and common variations. The multiple cases module also supports family-based studies and Mendelian filtering. The identified candidate disease-related genetic variations can be annotated according to their sample features. In summary, by exploring exome sequencing data, Exome-assistant can provide researchers with detailed biological insights into genetic variation events and permits the identification of potential genetic causes of human diseases and related traits.


A rate-independent continuum model for bone tissue with interaction of compressive and tensile micro-damage.
Low bone strength is a major risk factor for osteoporotic fractures and is only partially determined by clinical densitometry. Accumulated micro-damage induces residual strains, degrades elastic modulus and reduces bone strength independently of bone mineral density. Histologically, overloading of bone in compression and tension leads to distinct crack size, distribution and orientation which interact during combined loading scenarios. Statistics of rheological models can describe this process and reproduce experimental stress-strain curves with an unprecedented realism, but are computationally expensive and therefore difficult to generalize to 3D. Accordingly, the aim of this work is to formulate a continuum damage model that describes the key features of bone micro-damage, namely the accumulation of residual strains, the degradation of elastic modulus and the reduction of strength in compression, tension and especially in their sequential application. The promising qualitative agreement of the model with the experiments will motivate a generalization to 3D and allow the biomechanical investigation of bones and bone-implant systems subjected to cyclic overloading in tension and/or compression.


Inter-Rater Agreement in the Assessment of Video Recordings of Eye Drop Instillation by Glaucoma Patients.
To create a standardized method for evaluating the video recordings of patients self-instilling eye drops and to determine the level of agreement of eye drop instillation efficacy, safety and efficiency ratings by three masked graders. Prospective cross-sectional study. 78 patients with open-angle glaucoma or ocular hypertension who had at least 6 months of experience with the use of eye drop medications. Participants were video recorded while self-instilling artificial tears sequentially to both eyes. Three masked observers graded these video recordings on three criteria: efficacy (the determination of whether an eye drop was instilled on the ocular surface), safety (assessment of whether the tip of the medication bottle made contact with the ocular surface or eyelids), and efficiency (the number of eye drops expressed from the bottle). After grading the video recordings based on efficacy, safety, and efficiency, kappa statistics were used to estimate inter-rater agreement. The mean kappa level of agreement for efficacy, safety, and efficiency was 0.64 (95% confidence interval (CI), 0.42-0.87), 0.73 (95% CI, 0.58-0.88), and 0.62 (95% CI, 0.42-0.81), respectively. We demonstrated good inter-rater reproducibility of the masked analysis of video recordings of patients self-instilling eye drops based on three criteria: efficiency, safety, and efficacy.


Association of interleukin 23 receptor gene with sarcoidosis.
Interleukin 23 receptor (IL23R) gene has been reported as a genetic factor strongly associated with inflammatory bowel disease, psoriasis, and ankylosing spondylitis. We investigated the association between IL23R gene single nucleotide polymorphisms (SNPs) and susceptibility to sarcoidosis, including the clinical manifestation of uveitis. Ninety-one sarcoidosis subjects (58 with and 33 without uveitis) and 104 healthy controls were genotyped for eleven IL23R SNPs. DNA was amplified using specific PCR primers and genotyped by denaturing HPLC and/or direct DNA sequencing. Case-control frequency comparisons were analyzed using Chi square test. Three IL23R SNPs, rs7517847 (intron 6), rs11465804 (intron 8), and rs11209026 (exon 9, c.1142G>A, p.Arg381Gln) were associated with sarcoidosis in our population (p<0.05): rs7517847 showed increased frequencies in sarcoidosis compared to controls, but rs11465804 and rs11209026 were decreased. Two of these SNPs were associated with the uveitis subgroup compared to controls: rs11465804 (0.9% vs. 7.2%, OR=0.11, P=0.013) and rs11209026 (1.8% vs. 7.3%, OR=0.23, P=0.038). This finding indicates the association of IL23R polymorphism with sarcoidosis, especially with sarcoid uveitis. IL23R may be a common susceptibility gene shared by several autoimmune disorders including inflammatory bowel disease, psoriasis, and ankylosing spondylitis and sarcoid uveitis.


The therapeutic aspects of affect.
A satisfactory psychoanalytic definition and theory of affects has not yet been evolved. In spite of this, analysts work with affects using, for practical purposes, a common-sense definition leading to a therapeutic advantage in coordinating affective and cognitive structures as they appear in the course of a prolonged analysis. Undoing of defenses facilitates this process, allowing the ego's integrative capacities to function more adequately and satisfactorily in relation to inner and outer reality. A developmental hierarchy of affects emerges in this way ranging from primitive--all or none--affective experiences to adult, modified expression of such ego experiences. A brief historical survey of the changing forms of the theory of affects is included, as are clinical vignettes illustrating the therapeutic aspects of dealing with affective expression in the psychoanalytic situation. The therapeutic gains of such work comes about through the integration of earlier affective experiences into more developed cognitive structures allowing a variety of ego functions greater control over adult experiences.


Anesthetics release unfreezable and bound water in partially hydrated phospholipid lamellar systems and elevate phase transition temperature.
A dimyristoylphosphatidylcholine multilamellar system with varied water content was prepared by dessiccating sonicated vesicles in vacuo. The water content in the sample was determined by gas chromatography after dissolving the multilamellar system in water-free benzene. Differential scanning microcalorimetry revealed several endothermic peaks in the heating scan at subzero temperature, ranging from -25 to -3 degrees. The peaks that appeared in the subzero temperature range indicate the existence of water molecules bound to the lipid head groups, differing from free water that freezes at 0 degrees. The difference between the amount of water molecules that froze in calorimetry and the total amount of water detected by gas chromatography indicates the presence of unfreezable, tightly bound water molecules. The relative amount of free, intermediate, and unfreezable water was estimated by comparing the differential scanning microcalorimetry data with gas chromatography measurements. The addition of halothane and 1-hexanol significantly decreased the intermediately bound water peaks. The anesthetics dehydrated the lamellar system. The phase polymorphism of partially hydrated phospholipid multilayers is well known, and the temperature that corresponds to the main phase transition of fully hydrated lipid membranes shifts to a higher temperature. The addition of anesthetics increased the phase transition temperature when the water content was less than 18 wt%. This result is the complete reverse of the depressant action of anesthetics in fully hydrated lipid membranes. The present anesthetic effect upon the elevation of the transition temperature is apparently caused by anesthetic-induced dehydration of the lipid-water interface at the present experimental condition.


Dhh1 regulates the G1/S-checkpoint following DNA damage or BRCA1 expression in yeast.
Heterologous expression of the tumor suppressor BRCA1 in the yeast Saccharomyces cerevisiae is lethal. To identify potential new BRCA1-interacting gene targets, we characterized highly conserved ionizing radiation (IR) sensitive gene deletions that suppress BRCA1-induced lethality in yeast. Previously, we exposed an isogenic collection of yeast strains individually deleted for 4746 nonessential genes to IR and identified 199 radiation sensitive deletion strains. A subset (n = 130) of these were screened for those that suppressed the G1 arrest and lethality observed following galactose-induced expression from a GAL::BRCA1 plasmid in wild type yeast. We found that deletions of two core components of the highly conserved CCR4-NOT transcription complex (CCR4 or DHH1) rescued BRCA1-induced G1 arrest and lethality in yeast. This was not because of down regulation of the GAL promoter since both deletion strains produce large amounts of BRCA1 that is rapidly degraded. In addition, heterologous expression of BRCA1 results in increased transcription of the DNA damage-inducible reporter construct DIN::LacZ. Reduced viability following IR and nitrogen starvation was observed among strains deleted for CCR4 or DHH1 because of a defect in G1 to S phase checkpoint transition. Lethality following nitrogen starvation and IR was partially rescued in dhh1Delta strains by expressing the human ortholog of DHH1 (DDX6) which has been identified as a breakpoint oncogene.T CONCLUSIONS: hese results suggest that BRCA1 may promote genomic stability in human cells by interacting with the highly conserved ortholog of DHH1 (DDX6) to properly activate G1/S checkpoint arrest following DNA damage.


Interactions between NKT cells and Tregs are required for tolerance to combined bone marrow and organ transplants.
We used a model of combined bone marrow and heart transplantation, in which tolerance and stable chimerism is induced after conditioning with fractionated irradiation of the lymphoid tissues and anti-T-cell antibodies. Graft acceptance and chimerism required host CD4(+)CD25(+) Treg production of IL-10 that was in-turn enhanced by host invariant natural killer (NK) T-cell production of IL-4. Up-regulation of PD-1 on host Tregs, CD4(+)CD25(-) conventional T (Tcon) cells, and CD8(+) T cells was also enhanced by NKT cell production of IL-4. Up-regulated PD-1 expression on Tregs was linked to IL-10 secretion, on CD8(+) T cells was linked to Tim-3 expression, and on CD4(+) Tcon cells was associated with reduced IFNγ secretion. Changes in the expression of PD-1 were induced by the conditioning regimen, and declined after bone marrow transplantation. In conclusion, NKT cells in this model promoted changes in expression of negative costimulatory receptors and anti-inflammatory cytokines by Tregs and other T-cell subsets in an IL-4-dependent manner that resulted in tolerance to the bone marrow and organ grafts.


Withholding and withdrawal of life-sustaining treatments in low-middle-income versus high-income Asian countries and regions.
To compare the attitudes of physicians towards withholding and withdrawing life-sustaining treatments in intensive care units (ICUs) in low-middle-income Asian countries and regions with those in high-income ones, and to explore differences in the role of families and surrogates, legal risks, and financial considerations between these countries and regions. Questionnaire study conducted in May-December 2012 on 847 physicians from 255 ICUs in 10 low-middle-income countries and regions according to the World Bank's classification, and 618 physicians from 211 ICUs in six high-income countries and regions. After we accounted for personal, ICU, and hospital characteristics on multivariable analyses using generalised linear mixed models, physicians from low-middle-income countries and regions were less likely to limit cardiopulmonary resuscitation, mechanical ventilation, vasopressors and inotropes, tracheostomy and haemodialysis than those from high-income countries and regions. They were more likely to involve families in end-of-life care discussions and to perceive legal risks with limitation of life-sustaining treatments and do-not-resuscitate orders. Nonetheless, they were also more likely to accede to families' requests to withdraw life-sustaining treatments in a patient with an otherwise reasonable chance of survival on financial grounds in a case scenario (adjusted odds ratio 5.05, 95 % confidence interval 2.69-9.51, P < 0.001). Significant differences in ICU physicians' self-reported practice of limiting life-sustaining treatments, the role of families and surrogates, perception of legal risks and financial considerations exist between low-middle-income and high-income Asian countries and regions.


Microtubules at focal adhesions - a double-edged sword.
Cell adhesion to the extracellular matrix is essential for cellular processes, such as migration and invasion. In response to cues from the microenvironment, integrin-mediated adhesions alter cellular behaviour through cytoskeletal rearrangements. The tight association of the actin cytoskeleton with adhesive structures has been extensively studied, whereas the microtubule network in this context has gathered far less attention. In recent years, however, microtubules have emerged as key regulators of cell adhesion and migration through their participation in adhesion turnover and cellular signalling. In this Review, we focus on the interactions between microtubules and integrin-mediated adhesions, in particular, focal adhesions and podosomes. Starting with the association of microtubules with these adhesive structures, we describe the classical role of microtubules in vesicular trafficking, which is involved in the turnover of cell adhesions, before discussing how microtubules can also influence the actin-focal adhesion interplay through RhoGTPase signalling, thereby orchestrating a very crucial crosstalk between the cytoskeletal networks and adhesions.


Giloy Ghanvati (Tinospora cordifolia (Willd.) Hook. f. and Thomson) Reversed SARS-CoV-2 Viral Spike-Protein Induced Disease Phenotype in the Xenotransplant Model of Humanized Zebrafish.
The current Severe Acute Respiratory Syndrome disease caused by Coronavirus-2 (SARS-CoV-2) has been a serious strain on the healthcare infrastructure mainly due to the lack of a reliable treatment option. Alternate therapies aimed at symptomatic relief are currently prescribed along with artificial ventilation to relieve distress. Traditional medicine in the form of Ayurveda has been used since ancient times as a holistic treatment option rather than targeted therapy. The practice of Ayurveda has several potent herbal alternatives for chronic cough, inflammation, and respiratory distress which are often seen in the SARS-CoV-2 infection. In this study we have used the aqueous extracts of Tinospora cordifolia (willd.) Hook. f. and Thomson in the form of Giloy Ghanvati, as a means of treatment to the SARS-CoV-2 spike-protein induced disease phenotype in a humanized zebrafish model. The introduction of spike-protein in the swim bladder transplanted with human lung epithelial cells (A549), caused an infiltration of pro-inflammatory immune cells such as granulocytes and macrophages into the swim bladder. There was also an increased systemic damage as exemplified by renal tissue damage and increased behavioral fever in the disease induction group. These features were reversed in the treatment group, fed with three different dosages of Giloy Ghanvati. The resultant changes in the disease phenotype were comparable to the group that were given the reference compound, Dexamethasone. These findings correlated well with various phyto-compounds detected in the Giloy Ghanvati and their reported roles in the viral disease phenotype amelioration.


Macroorganisation and flexibility of thylakoid membranes.
The light reactions of photosynthesis are hosted and regulated by the chloroplast thylakoid membrane (TM) - the central structural component of the photosynthetic apparatus of plants and algae. The two-dimensional and three-dimensional arrangement of the lipid-protein assemblies, aka macroorganisation, and its dynamic responses to the fluctuating physiological environment, aka flexibility, are the subject of this review. An emphasis is given on the information obtainable by spectroscopic approaches, especially circular dichroism (CD). We briefly summarise the current knowledge of the composition and three-dimensional architecture of the granal TMs in plants and the supramolecular organisation of Photosystem II and light-harvesting complex II therein. We next acquaint the non-specialist reader with the fundamentals of CD spectroscopy, recent advances such as anisotropic CD, and applications for studying the structure and macroorganisation of photosynthetic complexes and membranes. Special attention is given to the structural and functional flexibility of light-harvesting complex II in vitro as revealed by CD and fluorescence spectroscopy. We give an account of the dynamic changes in membrane macroorganisation associated with the light-adaptation of the photosynthetic apparatus and the regulation of the excitation energy flow by state transitions and non-photochemical quenching.


The usefulness of 99mTc-SestaMIBI scan in the diagnostic evaluation of thyroid nodules with oncocytic cytology.
To assess the relevance of (99m)Tc-SestaMIBI (MIBI) scan in the diagnostic evaluation of thyroid nodules with oncocytic cytology. Twenty-four patients with a single (or prevalent) 'cold' solid nodule with Hurthle cells (HC) at fine needle aspiration cytology (FNAC) were studied. Cytological diagnosis of oncocytic metaplasia (OM) or HC tumor (HCT) was made when HC on the smear were comprised 10-75%, or >75%. Nodules concentrating MIBI at early and late (2 h after washout) stages were considered MIBI-positive. In all cases histological findings were obtained after total thyroidectomy. FNAC was malignant or suspect for malignancy in 16 cases (six HCT and 10 OM) and not suspect in eight (two HCT and six OM). Histological examination revealed 14 malignant tumors (11 HCT and three OM), and 10 benign thyroid lesions (three HCT and seven OM). Sensitivity of FNAC for malignancy was 92.8% and specificity was 70.0%; HCT were identified by FNAC in only 35.7% and OM in 70.0% of cases. No significant difference in MIBI positivity was found between malignant and benign thyroid nodules. The highest percentage of MIBI positivity was found in HCT (78.5%), but MIBI-positive nodules were also observed in thyroid lesions with HC metaplasia (40.0%). MIBI scintiscan has no value in differentiating malignant from benign HC thyroid neoplasias. Most HCT are MIBI-positive, but this scan is not sufficiently specific to differentiate true HC neoplasias from other thyroid lesions showing HC at FNAC, although an MIBI-negative scan strongly supports the absence of true HCT.


[Effect of fenibut on cardiac hemodynamics in experimental hypertension from the aspect of age].
The effect of phenibut on cardiodynamics in 6-7-week-old rats and 14-16-week-old rats with spontaneous, renal and situational hypertension was studied in a 14-day chronic experiment. Phenibut in doses of 25 (young rats) and 50 (adult rats), mg/kg orally was found to exert the pressor effect in the first week and the hypotensive effect in the second week. In both age groups of rats with situational hypertension phenibut decreased arterial blood pressure.


Glial-cell cultures from brains of carbonic anhydrase II-deficient mutant mice: delay in oligodendrocyte maturation.
Carbonic anhydrase II (CAII) is a multifunctional enzyme found in oligodendrocytes and astrocytes in normal mouse brains. We have begun to compare the glial cells in primary cultures from neonatal genetically CAII-deficient (Car) mice to those from normal (con) mice in order to detect developmental defects, if any, in Car glial cells. In con cultures intensely CAII-positive cells costained with antibodies against the oligodendrocytic markers, O4 and myelin basic protein (MBP), respectively. Most (82%) of the CAII-positive cells were O4-positive, but only approximately 60% were MBP-positive. Some clumps of GFAP-positive cells were CAII-positive. At each respective number of days in vitro (DIV) total numbers of O4-positive cells were similar in Car and con cultures, and total numbers of galactocerebroside-positive cells also were similar in Car and con cultures. However, compared to cells in con cultures at 7 DIV, a lower percent of Car cells in the oligodendrocyte lineage expressed MBP, and morphological differentiation also was subnormal in that the Car cells showed fewer processes and membrane sheets. Car and con cultures expressed similar numbers of MBP-positive cells by 10 DIV. The results suggest a temporary delay in the maturation of Car oligodendrocytes.


Genetic Mechanisms Underlying the Evolution of Connectivity in the Human Cortex.
One of the most salient features defining modern humans is our remarkable cognitive capacity, which is unrivaled by any other species. Although we still lack a complete understanding of how the human brain gives rise to these unique abilities, the past several decades have witnessed significant progress in uncovering some of the genetic, cellular, and molecular mechanisms shaping the development and function of the human brain. These features include an expansion of brain size and in particular cortical expansion, distinct physiological properties of human neurons, and modified synaptic development. Together they specify the human brain as a large primate brain with a unique underlying neuronal circuit architecture. Here, we review some of the known human-specific features of neuronal connectivity, and we outline how novel insights into the human genome led to the identification of human-specific genetic modifiers that played a role in the evolution of human brain development and function. Novel experimental paradigms are starting to provide a framework for understanding how the emergence of these human-specific genomic innovations shaped the structure and function of neuronal circuits in the human brain.


ASSESSMENT OF THE QUALITY OF LIFE AND PREVALENCE OF POSSIBLE OSTEOPOROTIC CHANGES IN POSTMENOPAUSAL WOMEN IN YEREVAN BASED ON DATA OF THE ECOS-16 QUESTIONNAIRE.
The aim of the study was to conduct approximate assessment of the prevalence of osteoporotic changes and evaluate quality of life (QoL) in postmenopausal women using ECOS-16 questionnaire in Yerevan city. The cross-sectional survey was conducted for data collection among 196 postmenopausal women. The research material about QoL was collected using ECOS-16 questionnaire. The sample was randomly selected through a two-stage cluster sampling from the population of women served by five policlinics of Yerevan. The majority of surveyed women (70.3%) were in age group under 60. Slightly more than half of the study participants (57.7%) had higher education and worked (59.2%). Almost two thirds of respondents were married (65.3%). Half of the respondents (51.0%) noted their income at the subsistence level. 71.9%±3.21 of women reported back pain for a long time. The scores of all the scales of ECOS-16, as well the total score were significantly higher in women who reported chronic back pain, indicating a lower quality of life for them. Women in age group under 60 years old, as well as women indicating absence of risk factors at workplaces, had significantly higher quality of life. A statistically significant difference was also observed between groups of women based on such social and demographic characteristics, as marital status, and average monthly income level. Pairwise comparison of groups based on these characteristics revealed a higher quality of life among married women compared to widows (p=0.043) and among women with income higher and at the subsistence level compared to the group of women with income below the subsistence level (p= 0.010). Poor QoL was associated with low self-reported health status and presence of chronic diseases in women. Pairwise post-hoc analysis showed lower level of QoL in the study participants with a below average/low level of health compared to both, those with above average (p<0.001) and average (p<0.001) level of health. QoL was also lower in women with four or more chronic diseases compared to both, women without chronic diseases (p=0.001) and the group of women with 1-3 diseases (p=0.001). The prevalence of chronic back pain, which was considered as one of the manifestations of undiagnosed osteoporosis in postmenopausal women, was quite high. The scores calculated for all dimensions of ECOS-16 questionnaire, as well the total score indicated lower quality of life among women reported chronic back pain compared to those who did not have such a health problem. Age older 60, spouse's demise, income below the subsistence level, smoking, presence of risk factors at workplace, as well as poor self-reported health status, and presence of chronic diseases were the factors negatively affected the QoL of surveyed women.


Determination of methanogenic pathways through carbon isotope (δ13C) analysis for the two-stage anaerobic digestion of high-solids substrates.
This study used carbon isotope (δ(13)C)-based calculations to quantify the specific methanogenic pathways in a two-stage experimental biogas plant composed of three thermophilic leach bed reactors (51-56 °C) followed by a mesophilic (36.5 °C) anaerobic filter. Despite the continuous dominance of the acetoclastic Methanosaeta in the anaerobic filter, the methane (CH4) fraction derived from carbon dioxide reduction (CO2), fmc, varied significantly over the investigation period of 200 days. At organic loading rates (OLRs) below 6.0 gCOD L(-1) d(-1), the average fmc value was 33%, whereas at higher OLRs, with a maximum level of 17.0 gCOD L(-1) d(-1), the fmc values reached 47%. The experiments allowed for a clear differentiation of the isotope fractionation related to the formation and consumption of acetate in both stages of the plant. Our data indicate constant carbon isotope fractionation for acetate formation at different OLRs within the thermophilic leach bed reactors as well as a negligible contribution of homoacetogenesis. These results present the first quantification of methanogenic pathway (fmc values) dynamics for a continually operated mesophilic bioreactor and highlight the enormous potential of δ(13)C analysis for a more comprehensive understanding of the anaerobic degradation processes in CH4-producing biogas plants.


Image quality, contrast enhancement, and radiation dose of ECG-triggered high-pitch CT versus non-ECG-triggered standard-pitch CT of the thoracoabdominal aorta.
We sought to compare image quality, contrast enhancement, and radiation dose in patients undergoing ECG-triggered high-pitch helical CT or non-ECG-synchronized helical CT of the thoracoabdominal aorta. We retrospectively assessed data from 101 consecutive patients (81 men, 20 women; mean age, 71 ± 11 [SD] years) undergoing clinically indicated CT angiography (CTA) of the thoracoabdominal aorta on a dual-source scanner using either the ECG-triggered high-pitch helical mode (group 1, n = 52) or non-ECG-synchronized standard-pitch helical mode (group 2, n = 49) during the arterial phase. Two independent readers assessed image quality, noise, and contrast enhancement throughout the thoracoabdominal aorta. Scanner-reported dose-length product values were used to estimate effective dose values. Image quality at the root-proximal ascending level was higher in group 1 (mean ± SD, 2.81 ± 0.40) than in group 2 (1.22 ± 0.47; p < 0.0001), with similar quality for both groups noted at other levels. Group 1 scans displayed higher image noise at all levels. The groups received a similar volume of contrast material (p = 0.77), and similar percentages of cases with acceptable contrast enhancement (> 250 HU) were noted in the two groups. The estimated radiation burden was significantly lower in group 1 (mean ± SD, 5.4 ± 1.8 mSv) than in group 2 (14.4 ± 5.1 mSv; p < 0.0001). Imaging of the thoracoabdominal aorta with ECG-triggered high-pitch CTA provides higher quality images of the aortic root and ascending aorta with sufficient contrast enhancement and decreased estimated radiation dose compared with non-ECG-synchronized standard-pitch helical CT.


Papulosquamous eruptions: usefulness of biopsy in establishing diagnosis.
Papulosquamous dermatoses are caused by a variety of etiologic agents. T. rubrum in particular can produce clinicopathologic changes which mimic a spectrum of disorders. Of these, some are papulosquamos in character. Whenever patients are seen with atypical papulosquamous dermatoses, the clinical differential diagnosis should always include dermatophytosis caused by T. rubrum. If skin scrapings for direct microscopic examination and culture studies are negative, a biopsy should be seriously considered as the best procedure to aid in making the correct diagnosis. Periodically, tissue diagnoses of fungal disease are made by dermatopathologists when the problem has not even been suspected by the clinician. Clinicians and pathologists should maintain a high index of suspicion for the disease spectrum which T. rubrum can cause in the human host. T. rubrum represents a great mimicker of cutaneous diseases similar to eruptions caused by Treponema pallidum and drugs. Information T. rubrum and methods have been reported.


Synthesis of dimeric phenol derivatives and determination of in vitro antioxidant and radical scavenging activities.
In this study, di(2,6-dimethylphenol) (Di-DMP), di(2,6-diisopropylphenol) (Di-DIP, dipropofol) and di(2,6-di-t-butylphenol) (Di-DTP) were synthesized by the reaction of monomeric phenol derivatives with catalytic CuCl(OH). TMEDA and Na2S2O4. Their antioxidant capacity and radical scavenging activity were examined using different in vitro methodologies such as 1,1-diphenyl-2-picryl-hydrazyl (DPPH*) free radical scavenging, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical scavenging activity, total antioxidant activity by ferric thiocyanate, total reducing power by potassium ferricyanide reduction method, superoxide anion radical scavenging, hydrogen peroxide scavenging and ferrous ions chelating activities.


Prognostic Factors Affecting Postsurgical Outcomes of Adult Patients with Intracranial Meningioma: A Retrospective Study.
To identify the prognostic factors of surgical resection for meningioma and their relationship with patient outcomes. This retrospective study included 53 patients (≥16 years), who underwent surgical resection for intracranial meningioma at the King Abdulaziz University Hospital from 2012 to 2022. Data regarding tumor location and size, histopathological type, chief complaint, chief complaint duration, admission date, diagnosis, operation, and discharge date were collected. These data were subjected to univariate and bivariate analyses to investigate the relationship between the postsurgical outcomes of the patients with meningioma and the variables of age at surgery, sex, length of hospitalization, chief complaint, Glasgow outcome score, World Health Organization histopathological classification, body mass index, tumor size, and nature of surgical resection. The mean age of our study cohort was 49.09 ± 12.64 years, with a female preponderance (75.5%) and mean body mass index of 29.31 ± 5.52 kg/m2. length of hospitalization (mean: 26.92 ± 54.88 days) demonstrated a significant (P = 0.012) impact on prognosis after surgery. In addition, convexity meningiomas (21.2%), which were observed in the maximum number of cases, and mean tumor volume (28.67 ± 48.85 mm) were significantly (P = 0.049) associated with the outcome. Most patients (78.8%) underwent total surgical resection, and histopathological examinations revealed a higher frequency of grade 1 than grade 2 tumors. Short duration of hospitalization and superficial location of the tumor are associated with optimal outcomes after surgical resection for patients with meningioma.


Continuous and discrete T-maze alternation in rats: effects of intertrial and interrun intervals.
1. Recent concepts concerning animal memory have emphasized the kind of information processed in memory. Reference memory provides information relevant over several trials, i.e., it codes expectancy-based information. Working memory provides information critical for only one trial, i.e., it codes data-based information. Some investigators consider that a continuous alternation task in a T-maze depends on the reference memory of a series of left-right responses, whereas a discrete alternation task is thought to depend on working memory. 2. In the present report, we tested rats in a continuous alternation task with different intertrial intervals (ITI's). Rats were first subjected to 10 or 12 sessions at each of the following ITI's: 0, 55, 100, 200 and 600 s, and then tested at varying ITI's within each session for 12 sessions in the following sequence: 0, 55, 100, 200, 600 and 0 s. Next, the same rats were trained to perform discrete alternation with ITI's and interrun intervals (IRI's) varying across sessions but only IRI's changing within sessions, i.e., IRI = 0 or 55 with ITI = 0, 55, 100, 200 or 600 s across sessions, and IRI = 0, 55, 100, 200 and 600 s with ITI = 0 within sessions. 3. Rats performed both alternation tasks at high levels when ITI's and IRI's changed across sessions. However, when intervals changed within sessions, rats showed a better performance in the continuous task at intervals of 55, 100 and 200 s compared to their performance at these same intervals in the discrete task. In addition, for the discrete task with IRI's changing within sessions, errors probably due to proactive interference occurred more frequently with progressively increasing IRI's. 4. The hypothesis that performance of continuous alternation depends on reference memory and performance of discrete alternation depends on working memory is supported by these data.


Fundamental movement skill proficiency and objectively measured physical activity in children with bronchiectasis: a cross-sectional study.
Bronchiectasis is a major contributor to respiratory morbidity and healthcare utilization in children. Children with bronchiectasis exhibit low levels of physical activity (PA) and poor fundamental movement skills (FMS) may be a contributing factor. However, there are no data on FMS's in this population. The current study assessed FMS proficiency in children with bronchiectasis and examined associations with objectively measured PA. Forty-six children with bronchiectasis (mean age 7.5 ± 2.6 year, 63% Male) were recruited from the Queensland Children's Hospital, Brisbane. PA was measured using the ActiGraph GT3X + accelerometer. Raw accelerometer data were processed into daily time spent in sedentary activities, light-intensity activities and games, walking, running, and moderate-to-vigorous activities and games using a random forest (RF) PA classification algorithm specifically developed for children. Daily MVPA was calculated by summing time spent in walking, running, and moderate-to-vigorous activities and games. FMS were assessed using the Test of Gross Motor Development 2nd Edition (TGMD-2). Fewer than 5% of children demonstrated mastery in the run, gallop, hop, and leap; while fewer than 10% demonstrated mastery for the two-handed strike, overarm throw, and underarm throw. Only eight of the 46 children (17.4%) achieved their age equivalency for locomotor skills, while just four (8.7%) achieved their age equivalency for object control skills. One-way ANCOVA revealed that children achieving their age equivalency for FMS had significantly higher levels of MVPA than children not achieving their age equivalency (51.7 vs 36.7 min/day). When examined by the five activity classes predicted by the RF algorithm, children achieving their age equivalency exhibited significantly greater participation moderate-to-vigorous intensity activities and games (22.1 vs 10.7 min/day). No significant differences were observed for sedentary activities, light-intensity activities and games, walking, and running. Children with bronchiectasis exhibit significant delays in their FMS development. However, those who meet their age equivalency for FMS proficiency participate in significantly more daily MVPA than children who do not meet their age-equivalency. Therapeutic exercise programs designed to improve FMS proficiency are thus likely to be beneficial in this population.