Retinoic acid activation and thyroid hormone repression of the human alcohol dehydrogenase gene ADH3.
Mammalian alcohol dehydrogenase (ADH) catalyzes the oxidation of retinol to retinaldehyde, the rate-limiting step in the synthesis of retinoic acid. There exists a family of ADH isozymes encoded by unique genes, and it is unclear which isozymes are most important for regulation of retinoic acid synthesis during differentiation or development. A region in the human ADH3 promoter from -328 to -272 base pairs was shown previously to function as a retinoic acid response element (RARE), prompting an hypothesis for a positive feedback mechanism controlling retinoic acid synthesis (Duester, G., Shean, M. L., McBride, M. S., and Stewart, M. J. (1991) Mol. Cell. Biol. 11, 1638-1646). The ADH3 RARE contains three direct AGGTCA repeats which constitute the critical nucleotides of RAREs present in other genes. We dissected the ADH3 RARE and determined that receptor binding as well as transactivation are dependent upon only the two downstream AGGTCA motifs separated by 5 base pairs, a structure noticed previously for a RARE in the promoter for the retinoic acid receptor beta (RAR beta) gene. ADH3 and RAR beta RAREs functioned similarly in transfection assays, suggesting that the feedback mechanisms controlling ADH3 and RAR beta utilize a common RARE. We also found that the normal functioning of the ADH3 RARE was abrogated by thyroid hormone receptor in the presence of thyroid hormone. A negative thyroid hormone response element in the human ADH3 promoter was found to colocalize with the RARE. Since ADH production in rat liver is known to be repressed by thyroid hormone, these findings suggest that human ADH production may also be subject to thyroid hormone repression and that the mechanism involves an interference with retinoic acid induction.


Ten unanswered questions in multimodal communication.
The study of multimodal communication has become an active and vibrant field. This special issue of Behavioral Ecology and Sociobiology brings together new developments in this rapidly expanding area. In this final contribution to the special issue, I look to the future and discuss ten questions in need of further work, touching on issues ranging from theoretical modeling and the evolution of behavior to molecular mechanisms and the development of behavior. In particular, I emphasize that the use of multimodal communication allows animals to switch between sensory channels when one channel becomes too noisy, and suggest that a better understanding of this process may help us both to understand the evolution of multisensory signaling and to predict the success of species facing environmental changes that affect signaling channels, such as urbanization and climate change. An expanded section is included on the effects of climate change on animal communication across sensory channels, urging researchers to pursue this topic due to the rapidity with which the environment is currently transforming.


Reduced 5-FU clearance in a patient with low DPD activity due to heterozygosity for a mutant allele of the DPYD gene.
5-fluorouracil pharmacokinetics, dihydropyrimidine dehydrogenase-activity and DNA sequence analysis were compared between a patient with extreme 5-fluorouracil induced toxicity and six control patients with normal 5-fluorouracil related symptoms. Patients were treated for colorectal cancer and received chemotherapy consisting of leucovorin 20 mg m(-2) plus 5-fluorouracil 425 mg m(-2). Blood sampling was carried out on day 1 of the first cycle. The 5-fluorouracil area under the curve(0-->3h) in the index patient was 24.1 mg h l(-1) compared to 9.8+/-3.6 (range 5.4-15.3) mg h l(-1) in control patients. The 5-fluorouracil clearance was 520 ml min(-1) vs 1293+/-302 (range 980-1780) ml min(-1) in controls. The activity of dihydropyrimidine dehydrogenase in mononuclear cells was lower in the index patient (5.5 nmol mg h(-1)) compared to the six controls (10.3+/-1.6, range 8.0-11.7 nmol mg h(-1)). Sequence analysis of the dihydropyrimidine dehydrogenase gene revealed that the index patient was heterozygous for a IVS14+1G>A point mutation. Our results indicate that the inactivation of one dihydropyrimidine dehydrogenase allele can result in a strong reduction in 5-fluorouracil clearance, causing severe 5-fluorouracil induced toxicity.


Augmenting the unified protocol for transdiagnostic treatment of emotional disorders with transcranial direct current stimulation in individuals with generalized anxiety disorder and comorbid depression: A randomized controlled trial.
The aim of the current study was to compare the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP) with and without transcranial direct current stimulation (tDCS) in individuals suffering from generalized anxiety disorder (GAD) and comorbid depression. A total of 43 individuals diagnosed with GAD and comorbid depression enrolled in a randomized controlled trial (IRCT20140929019334N1). Participants were randomly assigned to three groups including UP with tDCS (UP+tDCS; n = 15), UP alone (UP; n = 13) or wait-list control (n = 15). GAD and depression symptoms, worry severity, anxiety sensitivity, and intolerance of uncertainty were assessed at baseline, post-treatment and 3-month follow-up. Treatment with both UP+tDCS and UP alone resulted in significant lower ratings across all measures relative to wait-list controls at post-treatment and 3-month follow-up (all p-values <0.001). UP+tDCS showed significantly greater reductions in anxiety (p = 0.001 post-treatment; p = 0.003 follow-up), worry (p = 0.001 post-treatment; p = 0.002 follow-up), and anxiety sensitivity (p = 0.003 post-treatment; p = 0.002 follow-up) relative to UP alone. The present study had some limitations. First, the sample size was low. Another limitation was the use of a short-term follow-up. These results suggest augmenting UP treatment with tDCS may be an efficacious strategy to improve treatment outcomes in GAD with comorbid depression. Trial registration reference is IRCT20140929019334N1 (see https://irct.ir/trial/27988).


Comparison of different methods to measure contact angles of soil colloids.
We compared five different methods, static sessile drop, dynamic sessile drop, Wilhelmy plate, thin-layer wicking, and column wicking, to determine the contact angle of colloids typical for soils and sediments. The colloids (smectite, kaolinite, illite, goethite, hematite) were chosen to represent 1:1 and 2:1 layered aluminosilicate clays and sesquioxides, and were either obtained in pure form or synthesized in our laboratory. Colloids were deposited as thin films on glass slides, and then used for contact angle measurements using three different test liquids (water, formamide, diiodomethane). The colloidal films could be categorized into three types: (1) films without pores and with polar-liquid interactions (smectite), (2) films with pores and with polar-liquid interactions (kaolinite, illite, goethite), and (3) films without pores and no polar-liquid interactions (hematite). The static and dynamic sessile drop methods yielded the most consistent contact angles. For porous films, the contact angles decreased with time, and we consider the initial contact angle to be the most accurate. The differences in contact angles among the different methods were large and varied considerably: the most consistent contact angles were obtained for kaolinite with water, and illite with diiodomethane (contact angles were within 3 degrees); but mostly the differences ranged from 10 degrees to 40 degrees among the different methods. The thin-layer and column wicking methods were the least consistent methods.


Serum gastrin determination with a radioimmunosorbent technique.
A low utilization of antiserum has been reported in gastrin radioimmunoassay with a solid-phase procedure. As solid-phase immunoassays possess several advantages over their soluble counterparts for the assay of many hormones, a solid-phase radioimmunoassay for gastrin was examined. The results showed that this technique was suitable for gastrin determination without being wasteful to antibodies. Sensitivity and precision of the method were comparable to other investigations on gastrin immunoassay, as well as serum gastrin levels obtained for persons with no known gastro-intestinal disease, in patients with pernicious anemia and in patients with Zollinger-Ellison syndrome.


Kouprey (Bos sauveli) genomes unveil polytomic origin of wild Asian Bos.
The evolution of the genera Bos and Bison, and the nature of gene flow between wild and domestic species, is poorly understood, with genomic data of wild species being limited. We generated two genomes from the likely extinct kouprey (Bos sauveli) and analyzed them alongside other Bos and Bison genomes. We found that B. sauveli possessed genomic signatures characteristic of an independent species closely related to Bos javanicus and Bos gaurus. We found evidence for extensive incomplete lineage sorting across the three species, consistent with a polytomic diversification of the major ancestry in the group, potentially followed by secondary gene flow. Finally, we detected significant gene flow from an unsampled Asian Bos-like source into East Asian zebu cattle, demonstrating both that the full genomic diversity and evolutionary history of the Bos complex has yet to be elucidated and that museum specimens and ancient DNA are valuable resources to do so.


Headaches in the emergency department -a survey of patients' characteristics, facts and needs.
Headache is very often the cause for seeking an emergency department (ED). However, less is known about the different diagnosis of headache disorders in the ED, their management and treatment. The aim of this survey is to analyse the management of headache patients in two different ED in Europe. This retrospective survey was performed from September 2018 until January 2019. Patients were collected from the San Luca Hospital, Milan, Italy and the Ordensklinikum Barmherzige Schwestern, Linz, Austria. Only patients with a non-traumatic headache, as the primary reason for medical clarification, were included. Patients were analysed for their complexity and range of examination, their diagnoses, acute treatment and overall efficacy rate. The survey consists of 415 patients, with a mean age of 43.32 (SD ±17.72); 65% were female. Technical investigation was performed in 57.8% of patients. For acute treatment non-steroidal-anti-inflammatory drugs (NSAIDs) were the most used, whereas triptans were not given. A primary headache disorder was diagnosed in 45.3% of patients, being migraine the most common, but in 32% of cases the diagnosis was not further specified. Life-threatening secondary headaches accounted for less than 2% of cases. The vast majority of patients attending an ED because of headache are suffering from a primary headache disorder. Life-threatening secondary headaches are rare but seek attention. NSAIDs are by far the most common drugs for treating headaches in the ED, but not triptans.


Prospective application of an index of neonatal necrotizing enterocolitis.
Fifty-five patients were scored 1 to 3 according to the criteria: the character of stools, abdominal findings on palpation, x-ray evidence of pneumatosis intestinalis, the development of pulmonary insufficiency, and the duration of symptoms to positive x-rays. Fifteen patients with scores of less than five were considered to have subclinical NEC with one late death. Twenty-nine of 30 patients with scores of 5-10 responded to medical management with 2 deaths related to recurrent bouts of sepsis without recurrent NEC. Eleven patients required surgery with index scores of 10-14 with 6 deaths occurring uniformly in those patients with scores of 12 or more. Two patients were scored inappropriately low due to the lack of the passage of a stool for analysis. One patient with a score of 4 did not pass a stool but had the other diagnostic criteria for the single false negative of the series. This index correctly determined the severity of NEC of 53 of 55 patients, identified the patients who required surgical intervention and predicted survival.


A critical appraisal of the immunohistochemical detection of the c-myc oncogene product in colorectal cancer.
Expression of c-myc was studied immunohistochemically in 100 colorectal carcinomas, using a monoclonal antibody, Myc 1-6E10, which is purported to recognize the oncoprotein (p62c-myc) in paraffin-embedded material. In normal epithelium, maturing crypt cells and terminally differentiated surface cells were positive, and proliferating basal crypt cells negative. All carcinomas stained positively, but intensity was independent of histological differentiation, Dukes' stage, DNA ploidy and survival. Staining was predominantly cytoplasmic despite the suspected nuclear location of p62c-myc and there was considerable staining of fibroblasts. When staining was compared in frozen and paraffin-embedded sections fixed in different ways, different patterns were observed. Acetone-fixed frozen sections exhibited weak nuclear and cytoplasmic staining or were negative. In formol-saline fixed frozen sections, there was stronger predominantly nuclear staining. In paraffin-embedded sections staining was predominantly cytoplasmic. This study suggests that c-myc expression is enhanced in the majority of colorectal carcinomas and although independent of clinical behaviour, may be a common event in malignant transformation. However, since staining is affected by fixation and processing, data obtained using Myc 1-6E10 on routinely processed specimens should be interpreted with caution.


Crossregulation of NF-kappaB by the APC/GSK-3beta/beta-catenin pathway.
Glycogen synthase kinase-3beta (GSK-3beta) and adenomatous polyposis coli (APC) play an important role in the regulation of beta-catenin. Inhibition of or defects in their functions can lead to activation of beta-catenin. beta-catenin has been recently found to interact with and inhibit nuclear factor kappa B (NF-kappaB). However, the regulatory roles of GSK-3beta/APC on the NF-kappaB signaling pathway are unknown because of their diverse effects. In this study, we investigated whether GSK-3beta/APC might regulate NF-kappaB activity through beta-catenin. We found that inhibition of GSK-3beta suppressed NF-kappaB activity, whereas reexpression of APC restored NF-kappaB activity in APC mutated cells. The regulatory effects were through beta-catenin because depletion of beta-catenin with small interfering RNA (siRNA) in the same systems reversed the effects. The regulatory relationship was further supported by the analysis of primary breast tumor tissues in vivo in which NF-kappaB target TRAF1 was inversely correlated with activated beta-catenin. Thus, APC/GSK-3beta, through beta-catenin, may crossregulate NF-kappaB signaling pathway.


Relationship between back muscle endurance and voluntary activation.
There is some evidence that the Biering-Sorensen endurance test can discriminate low back pain sufferers from healthy individuals and can predict future back pain. This test relies on the subject's ability to voluntarily drive the back muscles. This neural drive, termed voluntary activation (VA) can be measured using the twitch interpolation technique. The aim of the current study was to investigate the relationship between back muscle endurance and VA. Twenty-one healthy volunteers (10 males) participated. Bilateral electromyographic recordings were obtained from erector spinae and rectus abdominis. Back extensor torque was recorded using a dynamometer. The protocol consisted of measurement of VA (using magnetic stimulation of the brain and assessment of the sizes of the evoked twitches) and measurement of endurance. There was a linear correlation (r(2)=1, P<0.01) between voluntary torque and VA. The mean (SEM) endurance time was 174.9 (12.8)s. There was no correlation between endurance and VA at either 100% MVC (r(2)=0.01, P=0.72) or at 50% MVC (r(2)=0.11, P=0.16). These findings indicate that the endurance of the back muscles, as assessed using this widely utilised test does not appear to be related to a subject's ability to drive their back muscles voluntarily either maximally or submaximally.


Normal human blood density gradient lymphocyte subset analysis: I. An interlaboratory flow cytometric comparison of 85 normal adults.
An interlaboratory flow cytometric comparison of several commercially available human lymphocyte subset reagents was undertaken in three different laboratories. Fresh Hypaque-Ficoll purified blood mononuclear cells were stained at 4 degrees C or 22 degrees C. Direct or indirect surface immunofluorescence was carried out at all sites using an EPICS V flow cytometer. Fullbright, 10-micron fluorescent polystyrene microspheres were used for optical alignment and standardization. A log integral fluorescent histogram gated on forward and right angle scatter was collected on 1-2 X 10(4) cells for each reagent and the proportion, of positive cell determined for each reagent. With the exception of one reagent, anti-B1, which showed an approximately twofold variation, all three laboratories showed remarkable agreement. Thus there was no significant difference noted for the following reagents: OKT4, CCT4, Leu 3a, Leu 2a, OKT8, or CCT8. We attribute these findings to the availability of quality reagents, precision instrumentation, and a standard lymphocyte preparation.


Quantitative Assessment of In-Stent Stenosis After Pipeline Embolization Device Treatment of Intracranial Aneurysms: A Single-Institution Series and Systematic Review.
Very little is known about the incidence of in-stent stenosis after flow diverter treatment of intracranial aneurysms. We sought to evaluate the incidence and clinical significance of in-stent stenosis at angiographic follow-up after Pipeline embolization device (PED) placement using quantitative measures. The clinical and radiological records from all patients undergoing PED treatment of intracranial aneurysms at a major U.S. academic center from March 2013 to July 2017 were retrospectively reviewed. A modified version of the North American Symptomatic Carotid Endarterectomy criteria was used to quantify the degree of stenosis on the most recent postprocedural angiogram. The percentage of stenosis was calculated as 1 - (narrowest vessel diameter/maximal midstent diameter within the artery) at the first follow-up angiogram. The PubMed, Web of Science, and EMBASE databases were additionally searched from inception until April 2018 for the rates of in-stent stenosis after flow diversion. A total of 155 patients (mean age, 58.3 years; 30 males) with 162 aneurysms underwent treatment with the PED at our institution. In-stent stenosis was detected in 12 patients (7.1%) at 6 months. The mean percentage of stenosis was 39.7%. All 12 patients remained asymptomatic, except for 1 who developed hemiplegia secondary to an unrelated ischemic stroke. The aneurysm occlusion rates at 6 months were comparable between the stenosis and nonstenosis cohorts (76.9% and 71.6%, respectively). Within the stenosis cohort, further follow-up angiograms after 6 months were available for 6 patients, of whom 3 (50%) had either complete resolution or improvement. Of the 43 included studies, 28 reported on the use of the PED, with 2448 patients. The mean reported rate of in-stent stenosis after PED placement was 8.8% (range, 0%-39%). In-stent stenosis remains a rare complication of PED placement for intracranial aneurysms. When occurring, it appears to largely be self-limiting, with a benign clinical course.


Where's the action? The pragmatic turn in cognitive science.
In cognitive science, we are currently witnessing a 'pragmatic turn', away from the traditional representation-centered framework towards a paradigm that focuses on understanding cognition as 'enactive', as skillful activity that involves ongoing interaction with the external world. The key premise of this view is that cognition should not be understood as providing models of the world, but as subserving action and being grounded in sensorimotor coupling. Accordingly, cognitive processes and their underlying neural activity patterns should be studied primarily with respect to their role in action generation. We suggest that such an action-oriented paradigm is not only conceptually viable, but already supported by much experimental evidence. Numerous findings either overtly demonstrate the action-relatedness of cognition or can be re-interpreted in this new framework. We argue that new vistas on the functional relevance and the presumed 'representational' nature of neural processes are likely to emerge from this paradigm.


Changes in circulating iodothyronines in euthyroid and hyperthyroid subjects given ipodate (Oragrafin), an agent for oral cholecystography.
A dose (3 g) of sodium ipodate used routinely in oral cholecystography caused a fall in serum 3,5,3'-triiodothyronine and a rise in serum 3,3',5'-triiodothyronine in three patients taking thyroxine (T4), four euthyroid subjects,and four hyperthyroid patients. Serum T4 fell in patients with hperthyroidism, whereas it rose in the other two groups. Sodium ipodate appears to alter peripheral T4 metabolism and, in addition, produces thyroid-inhibiting effects in hyperthyroidism.


Concordance between glucose-6-phosphate dehydrogenase (G6PD) genotype and phenotype and rasburicase use in patients with hematologic malignancies.
Phenotypic rather than genotypic tests remain the gold standard for diagnosing glucose-6-phosphate dehydrogenase (G6PD) deficiency. However, with increasing use of genomic arrays and whole exome or genome sequencing, G6PD genetic data are increasingly available. We examined the utility of G6PD genetic data in patients with hematologic malignancies and the association of G6PD genotype and phenotype with rasburicase-induced methemoglobinemia. We analyzed G6PD activity for 990 patients. Genotype data were available from the Affymetrix DMET array (n = 379), whole exome sequencing (n = 374), and/or the Illumina exome array (n = 634) for 645 patients. Medical records of 341 patients with methemoglobin measures were assessed for the administration of rasburicase. We observed 5 non-synonymous SNPs, 4 of which were known to be associated with deficient G6PD activity (WHO Class I-III). Genotyping 367 males resulted in a positive predictive value of 81.8% (47.8-96.8%), and two males with a Class I-III allele having normal activity both received a red blood cell transfusion prior to the activity assay. However, genotyping males had only 39.1% (20.5-61.2%) sensitivity. Two of the 12 heterozygous females had deficient G6PD activity. Rasburicase-induced methemoglobinemia occurred in 6 patients, 5 of whom had at least one Class I-III allele, despite 2 of these having normal G6PD activity. We conclude that although an apparent nondeficient genotype does not necessarily imply a normal phenotype, a deficient genotype result indicates a deficient phenotype in those without transfusions, and may be a useful adjuct to phenotype to prevent adverse drug reactions.


Amelioration of ochratoxin-A induced cytotoxicity by prophylactic treatment of N-Acetyl-L-Tryptophan in human embryonic kidney cells.
Ochratoxin A (OTA) is known to induce nephro-toxicity via induction of cellular redox homeostasis perturbation, mitochondrial hyperpolarisation and depolarization, protein synthesis inhibition leading to apoptosis. In the present study, protective efficacy of N-Acetyl-L-Tryptophan (NAT) against OTA induced toxicity was evaluated using Human Embryonic Kidney (HEK-293) cells. Cells were treated with NAT (0-200 μg/ml) before OTA treatment (0-20 μg/ml) and protective efficacy of NAT was evaluated using MTT and SRB assay. OTA-induced intracellular ROS generation and its inhibition by NAT (2.5 μg/ml) pre-treatment was evaluated using 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA) probe. Effects of NAT pre-treatment on OTA treated cells were also evaluated in terms of cell cycle perturbations and mitochondrial membrane potential disturbance using flowcytometry. Results of the study demonstrated significant (∼89 % cell growth in comparison to 50% in OTA alone group; P < 0.05) protection by NAT to the HEK-293 cells against OTA mediated cell death in terms of cell viability. Further, significant reduction in ROS levels and mitochondrial membrane potential disturbance was also observed in NAT pre-treated plus OTA cells as compared to only OTA treated cells. Significant (p < 0.05) arrest in G0 and S phase of cell cycle was observed in OTA treated cells that was found to be inhibited by NAT pre-treatment to OTA treated cells. Also, molecular docking analysis demonstrated higher probability of NAT to bind with OTA binding pocket on phenylalanyl t-RNA synthetase, resulting in inhibition of OTA incorporation in the newly synthesized peptides and thus may ameliorate OTA induced protein synthesis inhibition. Conclusively, present study suggested that NAT offers protection against OTA toxicity in HEK-293 cells by counterbalancing oxidative stress, cell cycle regulation, mitochondrial membrane potential stabilization, protein synthesis inhibition and cell death retardation.


Increased effective activity of rat liver catalase by dietary restriction.
While dietary restriction (DR) increases maximum life span in many animal species, the mechanisms by which this is achieved remain unclear. One possibility is that DR may act in part to reduce free radical levels by retarding age-related declines in rat liver catalase activity. We measured liver cytosolic catalase activity at various times of day in 9-12 month old male (BN X F344)F1 rats fed ad libitum (AL) or subjected to a 30% DR from 14 weeks of age. Catalase activity (expressed as μmol·min(-1)·g liver(-1)) in both diet groups reached minimums at 0600 h but activity was 26% higher in DR as compared to AL rats. This traditional expression of catalase activity did not significantly differ between diet groups at other times of day. One must be careful in the interpretation of such data, however, since catalase is rapidly inactivated by its substrate (H2O2), thus displaying abnormal enzyme kinetics. In order to avoid this difficulty we evaluated the time period during which the reaction remained linear and multiplied it by its activity to yield the effective catalase activity. Using this method we found a significant increase in catalase activity in DR animals at several H2O2 concentrations during the light span. At 1800 h (the beginning of the dark span when the controls initiated peak food intake), fewer and smaller dietary differences were observed and no dietary effects were observed at 2400 h. These data suggest that DR reduces the rate of accumulation of inactive catalase and may contribute to an increased capacity in DR animals to remove free radicals.


Serum and urine osmolality: 8 hours, 24 hours and 1-month sample stability.
The body of literature varies significantly regarding serum and urine osmolality stability. Therefore, our aim was to investigate the stability of serum and urine osmolality at different temperatures (room temperature (RT) 4-8 °C, -20 °C) and time conditions (8 h, 24 h, 1 month). The stability study was conducted following the CRESS guidelines, including 40 serum and urine samples. Samples were aliquoted into three aliquots and stored as follows: primary tube stored at RT for 8 h; two capped aliquots stored at 4-8 °C for 8 h and 24 h; one aliquot stored at -20 °C for 1 month. To minimize imprecision error, serum and urine osmolality were measured by the freezing point depression method in triplicate on OSMOMAT 3000 (Gonotech, Germany) analyzer. Percentage difference (PD%) against baseline measurement was calculated. Deviations were assessed against a reference change value of 5.0%. The PD% for serum and urine osmolality was below 2.0% for all time/temperature conditions. For serum samples: primary tube after 8 h at RT PD% (95% CI) = 0.0% (-0.3, 0.2%); 8 h at 4-8 °C PD% (95% CI) = -0.4% (-0.7, 0.0%); 24 h at 4-8 °C PD% (95% CI) = -0.7% (-0.7, -0.6%); 1 month at -20 °C PD% (95% CI) = -2.1% (-2.4, -1.5%). For urine samples: after 8 h at RT PD% (95% CI) =0.6% (0.2, 0.9%); 8 h at 4-8 °C PD% (95% CI) = -0.2% (-0.5, 0.1%); 24 h at 4-8 °C PD% (95% CI) = -0.2% (-0.5, 0.0%); 1 month at -20 °C PD% (95% CI) = -2.0% (-3.0, -1.0%). Changes in osmolality for tested conditions for serum and urine samples, were within acceptance criteria. Reflex and add-on osmolality testing can be performed within the same day in samples kept at RT for 8 h in primary tube and within 24 h, in aliquoted refrigerated samples, without compromising the reliability of test results. For longer storage, samples should be kept at -20 °C.


Disparities in greenspace associated with sleep duration among adolescent children in Southern California.
More than half of adolescent children do not get the recommended 8 hours of sleep necessary for optimal growth and development. In adults, several studies have evaluated effects of urban stressors including lack of greenspace, air pollution, noise, nighttime light, and psychosocial stress on sleep duration. Little is known about these effects in adolescents, however, it is known that these exposures vary by socioeconomic status (SES). We evaluated the association between several environmental exposures and sleep in adolescent children in Southern California. In 2010, a total of 1476 Southern California Children's Health Study (CHS) participants in grades 9 and 10 (mean age, 13.4 years; SD, 0.6) completed a questionnaire including topics on sleep and psychosocial stress. Exposures to greenspace, artificial light at night (ALAN), nighttime noise, and air pollution were estimated at each child's residential address, and SES was characterized by maternal education. Odds ratios and 95% confidence intervals (95% CIs) for sleep outcomes were estimated by environmental exposure, adjusting for age, sex, race/ethnicity, home secondhand smoke, and SES. An interquartile range (IQR) increase in greenspace decreased the odds of not sleeping at least 8 hours (odds ratio [OR], 0.86 [95% CI, 0.71, 1.05]). This association was significantly protective in low SES participants (OR, 0.77 [95% CI, 0.60, 0.98]) but not for those with high SES (OR, 1.16 [95%CI, 0.80, 1.70]), interaction P = 0.03. Stress mediated 18.4% of the association among low SES participants. Residing in urban neighborhoods of greater greenness was associated with improved sleep duration among children of low SES but not higher SES. These findings support the importance of widely reported disparities in exposure and access to greenspace in socioeconomically disadvantaged populations.


Ocular aspergillosis isolated in the anterior chamber.
In all cases in which ocular involvement has been reported in endogenous aspergillosis, the posterior segment of the eye was involved. The authors examined a patient who had been intubated and treated with corticosteroid therapy for status asthmaticus and in whom a mass later developed in the anterior chamber of the right eye. Computed tomography showed a solitary lesion in the left lower pulmonary lobe and multiple brain lesions that enhanced with contrast. Aspergillus fumigatus was cultured from the endotracheal tube. However, ocular and blood cultures were negative, as were the results of a bone marrow biopsy, lung biopsy, and anterior chamber paracentesis. Disseminated aspergillosis was confirmed when a biopsy of the anterior chamber mass was performed, and results of histopathologic examination showed the presence of hyphae. The patient responded to a regimen of antifungal drugs. This is the first known reported case in which the diagnosis of disseminated aspergillosis was confirmed with biopsy of an anterior chamber mass. This case demonstrates that Aspergillus organisms may disseminate to the anterior chamber of the eye without involving the posterior segment.


Ankle swelling in a 6-year-old boy with unusual presentation: report of a rare case.
A 6-year-old boy with a history of pain and swelling in the right ankle was referred to our medical center. A cascading algorithm helped us to better evaluate this case of an osteochondroma of talus. The diagnosis was based on clinical and radiologic findings and on histopathologic analysis of the excised tissue. Although osteochondroma, or osteocartilaginous exostosis, is a common skeletal neoplasm, it is rarely seen in the foot. The rare location, a young age group, and an inexperienced surgeon may make the diagnosis confusing. We presented a case that shows the importance of an orderly evaluation of a musculoskeletal neoplasm. This may be helpful for the physician to better understand the clinical implications of any case before attempting a surgical intervention.


RNAi knockdown of the Akt1 gene increases the chemosensitivity of gastric cancer cells to cisplatin both in vitro and in vivo.
To examine the in vitro and in vivo effects of a combined treatment of cis-d iamminedichloroplatinum(II) (cisplatin) with downregulation of Akt1 expression in gastric cancer cells. Lentivirus-mediated RNA interference (RNAi) was used to silence the Akt1 gene. pGCSIL-Akt1 small hairpin RNA (shRNA) was stably transfected into gastric cancer cells (SGC7901 and BGC823). Next, the effects of Akt1 downregulation on the growth and apoptosis of SGC7901 (BGC823) cells in the presence or absence of cisplatin were investigated by real-time polymerase chain reaction (RT-PCR), Western blot analysis, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-d-iphenyltetrazolium bromide) assay, Hoechst assay, flow cytometric analysis of annexin V-FITC/PI staining, and TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling). Finally, the effects of downregulation of Akt1 expression on the sensitivity of SGC7901 cells in a tumor xenograft model of cisplatin were also determined. Akt1 silencing reduced gastric cancer proliferation and increased cell apoptosis both in vitro and in vivo. The chemosensitivity of SGC7901 (BGC823) cells to cisplatin increased significantly following the downregulation of Akt1 expression, which might be associated with the inactivation of the PI3K/Akt1 signaling pathway, followed by the induced expression of the pro-apoptotic protein Bax and a concomitant decrease of Bcl-2 expression. This study confirmed that downregulation of Akt1 reduced chemotherapy tolerance of gastric cancer cells to cisplatin treatment. Thus, Akt1 silencing and cisplatin appear to be an effective combination treatment strategy for gastric cancer.


Stop codons and UGG promote efficient binding of the polypeptide release factor eRF1 to the ribosomal A site.
To investigate the codon dependence of human eRF1 binding to the mRNA-ribosome complex, we examined the formation of photocrosslinks between ribosomal components and mRNAs bearing a photoactivable 4-thiouridine probe in the first position of the codon located in the A site. Addition of eRF1 to the phased mRNA-ribosome complexes triggers a codon-dependent quenching of crosslink formation. The concentration of eRF1 triggering half quenching ranges from low for the three stop codons, to intermediate for s4UGG and high for other near-cognate triplets. A theoretical analysis of the photochemical processes occurring in a two-state bimolecular model raises a number of stringent conditions, fulfilled by the system studied here, and shows that in any case sound KD values can be extracted if the ratio mT/KD<<1 (mT is total concentration of mRNA added). Considering the KD values obtained for the stop, s4UGG and sense codons (approximately 0.06 microM, 0.45 microM and 2.3 microM, respectively) and our previous finding that only the stop and s4UGG codons are able to promote formation of an eRF1-mRNA crosslink, implying a role for the NIKS loop at the tip of the N domain, we propose a two-step model for eRF1 binding to the A site: a codon-independent bimolecular step is followed by an isomerisation step observed solely with stop and s4UGG codons. Full recognition of the stop codons by the N domain of eRF1 triggers a rearrangement of bound eRF1 from an open to a closed conformation, allowing the universally conserved GGQ loop at the tip of the M domain to come into close proximity of the peptidyl transferase center of the ribosome. UGG is expected to behave as a cryptic stop codon, which, owing to imperfect eRF1-codon recognition, does not allow full reorientation of the M domain of eRF1. As far as the physical steps of eRF1 binding to the ribosome are considered, they appear to closely mimic the behaviour of the tRNA/EF-Tu/GTP complex, but clearly eRF1 is endowed with a greater conformational flexibility than tRNA.


Atrioventricular node fetal dispersion and His bundle fragmentation of the cardiac conduction system in sudden cardiac death.
This study sought to examine the frequency of persistent fetal dispersion of the atrioventricular (AV) node and fragmentation of the atrioventricular bundle (His) bundle in the cardiac conduction system of sudden cardiac death cases and control subjects to establish their importance as the cause of death. These are two of the most frequent lesions reported in published reports in the cardiac conduction system in unexplained sudden deaths. We have studied the conduction system of 347 hearts: 249 hearts from sudden cardiac death cases and 98 control hearts. The sudden cardiac death cases were divided, according to the pathology found, in three groups: group I: ischemic heart disease, 137 cases; group II: nonischemic heart disease, 48 cases, and group III: unexplained sudden cardiac deaths, 64 cases. The control group (group IV) consisted of patients with unnatural deaths and extracardiac natural deaths. Persistent fetal dispersion of the AV node was observed in 70 cases (20.17%) of all groups with a frequency (40.81%) statistically higher in the control group. Fragmentation of the His bundle was observed in 95 cases (31.77%), and the frequency was statistically higher in the control group, too (47.67%). Persistent fetal dispersion of the AV node and fragmentation of the His bundle can be a normal variation present during many years in life and must not be considered the anatomic substrate for arrhythmias and sudden death without electrocardiographic abnormalities.


Acute septicaemic pasteurellosis in Vietnamese pigs.
Sixteen isolates of Pasteurella multocida were cultured from cases diagnosed as acute septicaemic pasteurellosis in Vietnamese pigs. The HSB-PCR assay provided rapid presumptive determination of 10 isolates of P. multocida identified as haemorrhagic septicaemia (HS) causing type B cultures (B:2, B:5, B:2,5). Serological designation using the Carter and Heddleston typing systems confirmed these findings, and identified the six HSB-PCR negative cultures as either A:1, A:3 or D:3,4. Biochemical fermentation and REP-PCR revealed phenotypic and genotypic identity between P. multocida type A:1 isolated from Vietnamese pigs and poultry. Marked homogeneity was also demonstrated among HSB-PCR positive swine isolates, which were shown to possess genotypic identity with P. multocida type B:2 from buffaloes diagnosed with HS.


Feline thelaziosis caused by Thelazia callipaeda in Portugal.
Thelazia callipaeda (Spirurida, Thelaziidae) is a nematode that lives in the conjunctival sac of domestic and wild carnivores, rabbits and humans causing mild to severe symptoms (e.g., conjunctivitis, lacrimation, epiphora, blepharospasm, keratitis and even corneal ulceration) in infected animals. This report describes an autochthonous case of thelaziosis in a cat from the central region of Portugal, representing the most occidental record of thelaziosis in Europe. Adult nematodes recovered from alive animal were morphological identified as T. callipaeda. A portion of the mitochondrial cytochrome c oxidase subunit 1 gene (cox 1) from nematode specimens was amplified by PCR. Cox1 sequences of all specimens were identical to T. callipaeda haplotype 1. Additionally to these findings, a recent description of thelaziosis in the northern region of Portugal suggests that T. callipaeda has successfully established in Portugal.


Maternal anaemia in Abidjan--Its influence on placenta and newborns.
In a random population of 198 pregnant women, detailed haematological determinations were performed at delivery. The prevalence of anaemia (haemoglobin less than 10 g/100 ml) is 20%. Iron deficiency is even more frequent. Malaria is shown to play an important role. Maternal anaemia is also correlated with nutritional status. Primiparae are shown to be at higher risk of anaemia. The effect of maternal anaemia on anthropometric and haematological variables of the newborn are discussed. Mothers with sickle-cell or HbC trait are not at special risk of anaemia.


Dietary intake of metals by Mumbai adult population.
Daily intake of 12 metals (Na, K, Ca, Cu, Zn, Fe, Mn, Mg, Pb, Cd, Co and Ni) by Mumbai adult population were assessed by analysing duplicate diet samples. These metals were determined by flame atomic absorption spectrophotometry (AAS) and stripping voltammetric techniques. A total of 250 diet samples containing 170 vegetarian diet and 80 non-vegetarian diet collected during April 2003 to March 2004 were analysed during this study. Daily dietary intakes of 2.4 g Na and 1.2 g K were observed for Mumbai adults. Daily dietary intakes of Ca, Cu, Zn, Fe, Mn and Mg were 367, 1.0, 6.3, 6.7, 2.0 and 304 mg, respectively. Pb, Cd, Co and Ni intakes by Mumbai adults were 32.3, 2.2, 2.2 and 108 microg/day, respectively. From this study it has been observed that the intake of toxic metals such as Pb, Cd and Ni is much lower than the tolerable daily intake derived from PTWI given by FAO/WHO and could not be considered harmful in this group of subjects. Daily intake of the studied 12 metals was found to be higher in non-vegetarian diet compared to the vegetarian diet (P<0.02, 0.01).


Quality-control analytical methods: a discussion of United States pharmacopeia chapter 71 sterility tests.
It is apparent that the quality assurance program of a compounding pharmacy cannot adhere to the strict requirements of some of the general chapters in the United States Pharmacopeia. Those chapters containing such strict requirements that may impact pharmacy compounding should be studied thoroughly by the appropriate United States Pharmacoepia expert committee. Afterward, a determination should be made of which standards are reasonable and which can be modified and implemented to ensure timely preparation of quality compounded medications.


[7-Substituted theophyllines. V. Azabenzhydrylaminoalkyl derivatives].
Some 7-(azabenzhydrylaminoalkyl)theophyllines were prepared and pharmacologically screened. They showed low toxicity, antidepressant properties and, in some cases, antithrombotic activity.


Development of a novel beta-glucan supplemented hydrogel spray formulation and wound healing efficacy in a db/db diabetic mouse model.
To relieve the severe economic and social burdens and patient suffering caused by the increasing incidence of chronic wounds, more effective treatments are urgently needed. In this study, we focused on developing a novel sprayable wound dressing with the active ingredient β-1,3/1,6-glucan (βG). Since βG is already available as the active ingredient in a commercial wound healing product provided as a hydrogel in a tube (βG-Gel), the sprayable format should bring clinical benefit by being easily sprayed onto wounds; whilst retaining βG-Gel's physical stability, biological safety and wound healing efficacy. Potentially sprayable βG hydrogels were therefore formulated, based on an experimental design setup. One spray formulation, named βG-Spray, was selected for further investigation, as it showed favorable rheological and spraying properties. The βG-Spray was furthermore found to be stable at room temperature for more than a year, retaining its rheological properties and sprayability. The cytotoxicity of βG-Spray in keratinocytes in vitro, was shown to be promising even at the highest tested concentration of 100 μg/ml. The βG-Spray also displayed favorable fluid affinity characteristics, with a capacity to both donate and absorb close to 10% fluid relative to its own weight. Finally, the βG-Spray was proven comparably effective to the commercial product, βG-Gel, and superior to both the water and the carrier controls (NoβG-Spray), in terms of its ability to promote wound healing in healing-impaired animals. Contraction was found to be the main wound closure mechanism responsible for the improvement seen in the βG-treatment groups (βG-Spray and βG-Gel). In conclusion, the novel sprayable βG formulation, confirmed its potential to expand the clinical use of βG as wound dressing.


Functional assessment of the liver with gadolinium-ethoxybenzyl-diethylenetriamine penta-acetate-enhanced MRI in living-donor liver transplantation.
A precise estimation of the capacity of the remnant liver following partial liver resection is important. In this study, the regional function of the liver in patients undergoing living-donor liver transplantation was evaluated by gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid (EOB)-enhanced MRI, with special reference to the congested region. EOB-MRI analysis was performed before hepatectomy in donors, and 7 days after surgery in the donor and recipient. In the hepatocyte phase, from images obtained 15 min after Primovist® injection, the signal intensity in each liver segment was measured and divided by the signal intensity of the erector spinae muscle (liver to muscle ratio, LMR) for standardization. Inter-regional differences in LMRs were analysed in donors and recipients. Thirty-two living donors and 31 recipients undergoing living-donor liver transplantation were enrolled. In donors, the LMRs of the remnant left lobe were almost equivalent among the liver segments. In the remnant right lobe without the middle hepatic vein, the mean(s.d.) LMR for congested segments (S5 and S8) was significantly lower than that for non-congested segments (S6 and S7): 2·60(0·52) versus 3·64(0·56) respectively (P < 0·001). After surgery, values in the non-congested region were almost identical to those in the preoperative donor liver. LMR values in the left and right lobe graft were significantly lower than those in the corresponding segment before donor surgery (P < 0·001). The function of the congested region secondary to outflow obstruction in the remnant donor liver was approximately 70 per cent of that in the non-congested region. EOB-MRI is a promising tool to assess regional liver function, with good spatial resolution.


The mechanism and kinetics of decomposition of 5-aminotetrazole.
The pathway and ab initio direct kinetics of the decomposition 5-aminotetrazole (5-ATZ) to HN(3) and NH(2)CN was investigated. Reactant, products and transition state were optimized with MP2 and B3LYP methods using 6-311G** and aug-cc-pVDZ basis sets. The intrinsic reaction coordinate curve of the reaction was calculated using the MP2 method with 6-311G** basis set. The energies were refined using CCSD(T)/6-311G**. Rate constants were evaluated by conventional transition-state theory (CVT) and canonical variational transition-state theory (TST), with tunneling effect over 300 to 2,500 K. The results indicated that the tunneling effect and the variational effect are small for the calculated rate constants. The fitted three-parameter expression calculated using the CVT and TST methods are k(T) = 4.07 x 10(11) x T(0.84) x e((-2.42 x 10(4))/T)s(-1) and k(T) = 2.09 x 10(11) x T(0.89) x e((-2.36 x 10(4))/T)s(-1), respectively.


Five-step protocol for carotid endarterectomy in the managed health care era.
We developed a protocol combining 5 cost-effective strategies to determine whether elective carotid endarterectomy (CEA) could be performed safely without adversely affecting well-established low morbidity and mortality rates and with significant hospital cost savings. Between April 1, 1995, and December 31, 1996, 109 of 141 patients were prospectively enrolled as candidates into a 5-step CEA protocol: (1) duplex ultrasonography (DU) performed at an accredited vascular laboratory as the sole diagnostic carotid preoperative study, (2) admission the day of operation, (3) cervical block anesthesia to eliminate intraoperative electroencephalogram monitoring, (4) transfer from the recovery room after a 4-hour observation period to the vascular ward, and (5) discharge the first postoperative morning. The other 32 patients were excluded from analysis; 16 patients were treated by vascular surgeons not participating in the protocol, 9 were treated concomitantly for other medical problems, and 7 were admitted emergently. One patient died of carotid hemorrhage the first postoperative morning, and one had an intraoperative embolic stroke for a combined mortality-stroke rate of 1.8% (2 of 109). Of the 109 patients, 70% (76) underwent operation using DU as the sole diagnostic study, 95% (104) were admitted the day of operation, 76% (83) had cervical block anesthesia, 59% (64) were transferred to the floor the day of operation, and 83% (90) were discharged the morning after operation. None of the 109 patients were adversely affected by these 5 cost-saving strategies except potentially the patient who bled the first postoperative morning. The predicted charges of a patient treated with a perioperative protocol that many vascular surgeons currently use (preoperative arteriography, general anesthesia with intraoperative electroencephalogram monitoring, overnight intensive care unit stay, discharge on postoperative day 2) was $16,073 compared with $10,437 for a patient who completed all 5 steps of the protocol detailed above. On the basis of these results documenting significant cost savings and acceptably low morbidity and mortality rates, this 5-step protocol may be considered the standard for performing CEA in this era of cost containment. These results may be compared with endovascular intervention, which has recently been proposed as a less expensive technique to treat carotid disease.


Trivalvular nonbacterial thrombotic endocarditis in a patient with colon adenocarcinoma: a case report.
Nonbacterial thrombotic endocarditis is a rare complication of prothrombotic states such as neoplasms that can cause valvular dysfunction and life-threatening complications. Nonbacterial thrombotic endocarditis usually affects the left-sided valves; however, only a minority of cases involving the tricuspid valve have been reported in medical literature. The current report describes trivalvular involvement by nonbacterial thrombotic endocarditis in a 54-year-old Azeri female patient with metastatic colorectal carcinoma. This case underlines the necessity of evaluating nonbacterial thrombotic endocarditis as a possible consequence in cancer patients. When thromboembolic events are found in the presence of a hypercoagulable state (such as malignancy) and no growth on blood cultures, nonbacterial thrombotic endocarditis could be suspected as the cause. It is critical to achieve early diagnosis in such a setting to initiate treatment plans and prevent further complications rapidly.


[Radiation exposure in the vicinity of patients after administration of Tc-99m-DPD].
Dose rate measurements were performed in 0.5, 1 and 2 m distance from the surface of the bodies of 16 patients within the first 4 h after they had received 600 +/- 30 MBq of 99mTc-DPD. The various individual time to dose rate courses are discussed. The radiation dose rates around the patients were determined and the possible radiation exposure of other patients, attendants, and nurses in the surroundings of the "radiating" patients were estimated. The doses were far below the limits set by radiation protection regulations.


Phase II trial of syncopated thalidomide, lenalidomide, and weekly dexamethasone in patients with newly diagnosed multiple myeloma.
Thalidomide and lenalidomide, in combination with dexamethasone, provide response rates ranging from 63%-79% after 4 cycles of therapy. Because of toxicities such as neuropathy and myelosuppression for thalidomide and lenalidomide, respectively, dose escalation has not been pursued. We evaluated a syncopated regimen of alternating weeks of thalidomide and lenalidomide to determine if a modified schedule allows for fewer dose reductions and, subsequently, superior efficacy. Although well tolerated, this phase II trial did not show superior efficacy compared with conventional dosing and scheduling of these agents. Over the past decade, the novel agents thalidomide, lenalidomide, and bortezomib have emerged as effective treatment in patients with multiple myeloma (MM). Initially used in the relapse setting, these agents have been incorporated into frontline treatment algorithms. They have been combined in doublets with corticosteroids, in triplets with alkylators, or with each other. Because thalidomide and lenalidomide have different clinical activity and toxicity profiles, we designed a trial to evaluate a syncopated schedule of thalidomide and lenalidomide with weekly dexamethasone in patients with newly diagnosed MM to determine response and toxicity. Twenty-two patients with newly diagnosed MM were treated with syncopated thalidomide (200 mg on days 1-7 and 15-21), lenalidomide (25 mg on days 8-14 and 22-28 for the first cycle and 50 mg on the same schedule for subsequent cycles) with weekly dexamethasone (40 mg). Each cycle lasted 28 days. MM parameters were assessed at the end of each cycle. It was intended that the patients proceed to stem cell mobilization and autologous transplantation after 4 cycles of therapy. The median number of cycles administered was 3.5. The overall response was 68%. The regimen was well tolerated by the majority of the patients; only patient discontinued treatment because of toxicity. We conclude that a syncopated schedule of thalidomide and lenalidomide with weekly dexamethasone was tolerated well, with no unexpected toxicities. However the response rate, even using lenalidomide at 50 mg, was not superior to standard dosing of thalidomide or lenalidomide plus dexamethasone.


Long-term performance of sediment microbial fuel cells with multiple anodes.
This study constructed multiple-anode SMFCs with different anode spacing and investigated their long-term performance. Results show that multiple anodes extended electricity generation from SMFCs due to increased anode surface area, but the distance between the anodes showed limited effects on power output. Power generation was seriously inhibited when temperature was below 20°C, but system recovered once temperature rose based to ambient condition. The degradation of readily oxidizable organic matter (ROOM) and decomposition of refractory organics occurred simultaneously. Worms' growth in the sediment destabilized power output, caused the increase of COD and decrease of pH and DO in water layer, and affected the microbial communities in sediments. ANME-2D related to anaerobic oxidation of methane was enriched around anodes and might benefit electron transfer in SMFCs.


Which evaluation criteria of the short-term efficacy can better reflect the long-term outcomes for patients with nasopharyngeal carcinoma?
To compare the consistency of one-dimensional Response Evaluation Criteria in Solid Tumors (1D-RECIST), two-dimensional WHO criteria (2D-WHO), and three-dimensional (3D) measurement for therapeutic response assessment of nasopharyngeal carcinoma (NPC). Retrospective data of 288 newly diagnosed NPC patients were reviewed. Tumor size was assessed on magnetic resonance imaging (MRI) according to the 1D-RECIST, 2D-WHO, and 3D measurement criteria. Agreement between tumor responses was assessed using unweighted k statistics. The receiver operating characteristic (ROC) curve was used to determine the optimal cut-off point of the PTV. The Kaplan-Meier method and Cox regression were used for the survival analysis. The optimal cut-off point of the PTV for progression-free survival (PFS) was 29.6%. Agreement with PTV measurement was better for 1D measurement than for 2D and 3D measurements (kappa values of 0.646, 0.537, and 0.577 for 1D, 2D, and 3D measurements, respectively; P < 0.05). The area under the curve of the 1D measurement (AUC=0.596) was similar to that of the PTV measurement (AUC=0.621). Compared with 2D and 3D measurements, 1D measurement is superior for predicting prognosis in NPC (C-index of 0.672, 0.663, and 0.646 were for 1D, 2D, and 3D measurements, respectively; P < 0.005). Survival analysis showed that patients with non-responders had worse prognosis (P < 0.05). The 1D measurement more closely agreed with the PTV measurement than the 2D and 3D measurements for predicting therapeutic responses in NPC. Therefore, we recommend using the less time-consuming 1D-RECIST criteria in routine clinical practice.


Assessment of Fallopian tube patency by HyCoSy: comparison of a positive contrast agent with saline solution.
To compare the efficiency of air-filled albumin microspheres (Infoson) with saline solution in determining Fallopian tube patency during hysterosalpingo contrast sonography (HyCoSy). This was a prospective randomized multicenter study with a sequential design. Over a 10-month period, 23 patients (mean age, 33 years) referred for infertility were examined by HyCoSy (saline or Infoson) before conventional hysterosalpingography (Iopamiron 370), performed during the same session. Contrast agents were administered through a 5-F Ackrad balloon catheter inserted transcervically into the uterine cavity. HyCoSy was performed with a 7-MHz transvaginal probe using both B-mode and color Doppler, and tubal patency was demonstrated by the appearance of contrast agent in the peritoneal cavity near the ovaries. Data were registered for each patient during the examination and the results were monitored by sequential analysis. Mean volumes of contrast injections were 35.3 mL of saline, 14.4 mL of Infoson, and 13.8 mL of Iopamiron 370. Infoson-enhanced HyCoSy provided a significantly larger (P = 0.006) number of correct diagnoses (20/22 Fallopian tubes) than did saline HyCoSy (12/24 Fallopian tubes), and the same number as that achieved by hysterosalpingography. A positive ultrasound contrast agent appears to be more efficient than saline solution at determining Fallopian tube patency in infertile women by means of HyCoSy, and as efficient as an iodinated contrast agent in the same population explored by HSG. HyCoSy could be used to screen infertile women, thereby avoiding the use of iodinated contrast medium and exposure to ionizing radiation during conventional HSG in patients with patent Fallopian tubes.


Parasellar dermoid tumor with intra-tumoral hemorrhage.
We report a case of parasellar dermoid tumor with intra-tumoral hemorrhage. It is rare for a dermoid tumor that hemorrhage was detected as high attenuation on the initial CT. In the present case, the tumor content included a little fat component and mostly cholesterin-rich fluid which resulted in extremely low signal intensity on T2-weighted and high signal on T1-weighted MR images. In addition to this, hemosiderin accumulation in the tumor could be the reason for low signal intensity on T2-weighted images.


Interaction between carbamazepine, zonisamide and voltage-sensitive Ca2+ channel on acetylcholine release in rat frontal cortex.
To clarify the mechanisms of action of antiepileptic drugs (AEDs), carbamazepine (CBZ) and zonisamide (ZNS), on exocytosis mechanisms, the present study determined the concentration-dependent action of CBZ and ZNS, as well as the interaction between these AEDs and voltage-sensitive Ca(2+) channel (VSCC) activity on basal, Ca(2+)- and K(+)-evoked acetylcholine (ACh) release in frontal cortex of freely moving rat using in vivo microdialysis. Perfusion with therapeutic-relevant concentrations of CBZ and ZNS increased basal ACh release, which was regulated by N-type VSCC predominantly and P-type VSCC weakly, whereas supratherapeutic-relevant concentrations of these AEDs reduced this release. The 3.4 mM Ca(2+)-evoked release, which was regulated by N-type VSCC selectively, but not by P-type VSCC, was increased by therapeutic-relevant concentrations of CBZ and ZNS, whereas this release was reduced by supratherapeutic-relevant concentrations of them. The 50 mM K(+)-evoked release, which was regulated by P-type VSCC predominantly and N-type VSCC weakly, was decreased by CBZ and ZNS, in a concentration-dependent manner. These findings indicate that the interplay between enhancement of basal ACh release and reduction of depolarization-related ACh release in the frontal cortex are at least partially involved in a common mechanism of antiepileptic action between CBZ and ZNS.


MicroRNA-379-5p inhibits tumor invasion and metastasis by targeting FAK/AKT signaling in hepatocellular carcinoma.
Some microRNAs (miRNAs) have been implicated in hepatocellular carcinoma (HCC) development and progression. However, the roles and mechanisms of several miRNAs in HCC remain poorly understood. Here, we report that miR-379-5p, which is down-regulated in HCC tissues and cell lines, is associated with advanced TNM stage and metastasis in HCC. The ectopic overexpression of miR-379-5p inhibited HCC cell migration, invasion, epithelial-to-mesenchymal transition (EMT) and metastasis both in vitro and in vivo. Conversely, miR-379 knockdown increased migration, invasion and EMT in HCC cells. Moreover, miR-379-5p exerted this function by directly targeting focal adhesion kinase (FAK) 3'-UTR and repressing FAK expression, thus leading to suppression of AKT signaling. Furthermore, the tumor suppressive effects of miR-379-5p in HCC cells were reversed by activating AKT signaling or restoring FAK expression. In clinical samples of HCC, miR-379-5p negatively correlated with FAK, which was up-regulated in HCC. Taken together, our findings highlight the important role of miR-379-5p in regulating the EMT and metastasis of HCC by targeting FAK/AKT signaling, suggesting that miR-379-5p may represent a novel potential therapeutic target and prognostic marker for HCC.


Dr. Zhang's experience in massotherapy for treatment of vertebral-artery-type cervical spondylopathy.
Thirty cases of vertebral-artery-type cervical spondylopathy were treated by Dr. Zhang Tao's technique. The cure rate was 50%, and the total effective rate was 100%.


Follicular cervicitis--colposcopic appearances and association with Chlamydia trachomatis.
Follicular cervicitis was recognised in 15 (44 per cent) of 34 women who were examined colposcopically and who were sexual partners of men with non-gonococcal urethritis. Valid results of culture for Chlamydia trachomatis were obtained in 26 cases: the organism was isolated from the cervix of five of 11 women in whom follicular cervicitis had been diagnosed, but from only one of 15 whose cervices did not have this change. A similar correlation was not found for infection with Mycoplasma hominis or Ureaplasma urealyticum.


Ultrasensitive detection of amifostine and alkaline phosphatase based on the growth of CdS quantum dots.
In this study, we reported a simple and sensitive fluorescence nanosensor for rapid detection of amifostine and alkaline phosphatase (ALP). The novel nanosensor was based on the fluorescence "turn on-off" of CdS quantum dots (QDs). Firstly, Cd(2+) cation could react with S(2-) anion to generate fluorescent CdS QDs in the presence of amifostine. The fluorescence (FL) intensity of amifostine-capped CdS QDs (Amifostine-CdS QDs) was increased with the increasing amounts of amifostine, and could be used for amifostine detection. However, amifostine could be converted to 2-(3-aminopropylamino) ethanethiol (WR1065) in the presence of ALP based on the dephosphorylation of ALP. Under the optimum conditions, the affinity of WR1065 to CdS QDs was weaker than that of amifostine. Therefore the new generation of WR1065-CdS QDs would reduce the FL intensity with the increase of ALP concentration, and the fluorescence of CdS QDs was turn off. The metabolic process of amifostine in the presence of alkaline phosphatase could be also studied via the change of FL intensity of CdS QDs. The present method was cost-effective, convenient, and does not require any complicated synthetic procedures.


Elevated Toxoplasma IgG antibody in patients tested for infectious mononucleosis in an urban emergency department.
There are many infectious causes of fatigue, sore throat, and fever, including mononucleosis and toxoplasmosis. Toxoplasma antibody testing is rarely performed in most emergency departments; as a result, toxoplasmosis is diagnosed infrequently. We obtained Toxoplasma IgG IFA titers on ED patients who had mononucleosis testing performed to determine the frequency of toxoplasmosis in this population. Two hundred sixty patients were included in our study. Eleven (4.2%) had a positive mononucleosis test, and 14 (5.4%) had a positive Toxoplasma titer. In the detection of toxoplasmosis, Toxoplasma IgG titers of 1:1,024 or greater have been shown to be a sensitive means of detecting infection in the first six months. Further testing with IgM titers is needed to establish a positive diagnosis when necessary. We found more patients with elevated Toxoplasma IgG titers than with positive heterophil antibody titers in an ED population tested for mononucleosis over a two-year period. We conclude that toxoplasmosis may be as common as mononucleosis in our ED and that clinicians should consider this pathogen when working up patients with appropriate symptoms.


Quantitative histochemistry of the lysosomal dipeptidyl aminopeptidase II in the proximal tubule of the rat kidney.
The activity of the lysosomal dipeptidyl aminopeptidase II (DAP II) was measured by quantitative histochemical methods in the S1/S2 segments of the proximal tubule using freeze dried and celloidin mounted cryostat sections (FDC sections) of rat kidney. The methodological studies show that there is a linear relationship between the amount of reaction product and reaction time for the first 5 min, as well as section thickness between 4 and 10 microns. Maximal DAP II activities were demonstrated at pH 5.5. The Km of DAP II was about 2.3 mM. In addition to the methodological studies, DAP II activity was also measured in the proximal tubule (S1/S2 segments) of experimental animals (sham-operated and castrated male and female rats). Sham-operated females showed significantly higher DAP II activities than males. DAP II activity increased significantly in castrated males so that there were no significant differences between castrated males, sham-operated and castrated females. The quantitative histochemical results are largely in agreement with biochemical data published earlier.


Bilateral skin conductance activity, clinical symptoms and CSF monoamine metabolite levels in unmedicated schizophrenics, differing in rate of habituation.
Bilateral skin conductance (SC) and heart rate (HR) were recorded for 18 RDC-diagnosed unmedicated recently admitted psychotic patients (13 schizophrenic and 5 paranoid) and for age- and sex-matched controls, during rest and tone stimulation (85 dBA, 1000 Hz, 1 sec duration and 0.25 msec rise time). Schizophrenics had more SC spontaneous fluctuations and faster HR, indicating higher arousal. SC spontaneous fluctuations were more frequent in left hand and showed an increasing trend over the session. Several SC measures indicated higher responsivity and a more irregular responding pattern in schizophrenics. These patients had higher levels of the noradrenaline metabolite (MHPG). Paranoid psychotic patients had a more stable SC habituation course than controls, and higher levels of the dopamine (HVA) and serotonin metabolites (5-HIAA). Schizophrenic nonhabituators had fewer positive psychotic symptoms than habituators, suggesting that poor habituation is not due to interference by symptoms. It may be related to higher arousal, or to deficient information processing.


Study on possibilities of reconstructive--plastic surgery in patients with stage III breast cancer.
This population based study aimed to use reconstructive-plastic surgery with autologous tissue as a treatment of patients with stage III breast cancer. We identified women (374) diagnosed with stage III breast cancer between 2000 and 2009 years. We compared radical operations with and without a plastic step, where 29 patients underwent the surgery in combination with an immediate radical resection with LD-flap replacement, mastectomy concurrently to TRAM-flap reconstruction in 103 patients. We examined the immediate and remote results of therapy. In data analysis, there were higher summarized indices of physical and mental health rates in patients who underwent the reconstruction plastic surgery compared to patients with mastectomy. All treated women 5 -year survival rate was 77.4+3.6 %, 63.5+3.2% and 40.1+3.1 % in stages IIIa, IIIb, IIIc respectively. In the control group, the rates were 78.6+3.4 %, 64.0+3.3 %, and 39.3+3.1 % (p<0.05) respectively. Our results showed that women with stage III breast cancer who underwent reconstructive-plastic surgeries had a chance to improve their quality of life, and did not increase the frequency, neither did reduce 5 year survival (Tab. 2, Fig. 4, Ref. 19). Full Text in free PDF www.bmj.sk.


Head trauma in children younger than 2 years: are there predictors for complications?
To determine the incidence of skull fracture (SF) and intracranial injury (ICA) among children younger than 2 years evaluated in a pediatric emergency department for head trauma; whether historical features and/or physical findings are predictive of injury type; and whether clinical criteria could allow a selective approach to radiographic imaging. Retrospective medical record review. Tertiary pediatric emergency department. Case series of 278 children aged younger than 24 months evaluated for head injury. Presence of SF and/or ICA. Diagnoses at discharge included 227 minor head injuries, 39 isolated SF, 9 ICA with SF, and 3 isolated ICA. Children younger than 12 months had the highest incidence of SF/ICA (29%) vs 4% for children aged 13 to 24 months (P<.001). Seven percent of complications from SF/ICA resulted from falls 3 ft (0.9 m) or less [corrected]. Incidence of behavioral change, loss of consciousness, emesis, and seizures did not differ significantly between those with minor head injuries and those with SF/ICA. Scalp abnormalities were more common in children with SF/ICA (P<.001). Sixty-two percent of children with isolated SF and 58% of children with ICA had no history of loss of consciousness, emesis, seizure, or behavioral change. Ninety-two percent of children with isolated SF and 75% of children with ICA had normal levels of consciousness and nonfocal neurologic examinations at diagnosis. Among children who fell 3 ft or less (0.9 m) [corrected] and had no loss of consciousness, emesis, seizure, behavioral change, or scalp abnormality, none of 31 (95% confidence interval [CI], 0-0.10) children younger than 24 months and none of 20 (95% CI, 0-0.15) children younger than 12 months had SF/ICA. Both SF and ICA are common in children younger than 2 years evaluated for head trauma. Children younger than 12 months are at highest risk. Injuries resulted from relatively minor falls and occurred in alert, neurologically normal children. Clinical signs and symptoms were insensitive predictors of SF/ICA; however, a grouping of features (fall < or = 3 ft [0.9 m], no history of neurologic symptoms, and normal scalp physical examination results) identified a subset of children at low risk for complications.


Transformation of mouse bone marrow cells by transfection with a human oncogene related to c-myc is associated with the endogenous production of macrophage colony stimulating factor 1.
We recently derived a series of transformed cell lines by transfecting mouse bone marrow cells highly enriched for macrophage progenitors with a newly described human gene, R-myc, which has homology to the c-myc oncogene. In this report, we show that these lines share some features characteristic of cells of the mononuclear phagocyte lineage. Specifically, all cell lines had macrophage- or monocytelike morphology, contained nonspecific esterase, were phagocytic for latex beads, secreted lysozyme, bore the Mac-1 antigen, and contained a minority of cells with Fc receptors. However, only a single monocytelike clone had appreciable numbers of cells which bore complement receptor 1, and none were phagocytic for antibody or complement-coated particles, or constitutively secreted Interleukin-1. All these cell lines secreted a growth factor capable of supporting the in vitro proliferation of bone marrow macrophages. Radioimmunoassay and receptor binding studies indicate that this factor is colony stimulating factor 1.


Characteristics of slow waves on EEG associated with epileptic spasms.
The high-voltage slow waves (HVSs) on EEG associated with epileptic spasms were investigated to clarify their characteristics and their relation to the pathophysiology of spasms in West syndrome and related disorders. In 14 patients, digitally recorded EEG segments showing the ictal HVSs were extracted and their traces were overlaid by using an average reference. The ictal HVSs were also averaged to build maps for investigation of the pattern of potential distribution over the scalp. In a total of 685 recorded spasms, 346 (50.5%) with minimal artifacts were selected to demonstrate that the ictal HVSs had a largely consistent waveform and distribution in each patient. The ictal HVSs were symmetrical in 10 patients and asymmetrical in the other four, and were relatively negative over the posterior region and positive over the frontal or temporal regions in 11 patients. Two symptomatic patients showed a marked deviation of the distribution of HVSs to the pathologically more involved hemisphere. An infant with Aicardi syndrome had two different types of spasms, each type showing a consistent pattern of HVSs with a lateralized distribution. The patterns of distribution of the ictal HVS may be related to the abnormal activation of the brain in the generation of spasms.


The effect of zimelidine and amitriptyline on the brain concentration of some indolic and phenolic monoamines in the mouse.
The increase in mouse brain tryptamine accumulation rate and 5-hydroxytryptamine (5-HT) concentration and the reduction in 5-hydroxyindole acetic acid concentration observed after zimelidine administration suggest that the treatment reduces the brain tryptophan availability. Amitriptyline produced no significant changes on tryptamine, 5-HT or 5-hydroxyindole acetic acid. Also, zimelidine reduced mouse brain p-tyramine, increased m-tyramine and increased homovanillic acid. Similar effects were observed after amitriptyline administration. The experiments show that both drugs affect dopamine turnover and tyramine concentration in a similar fashion to that observed for the antipsychotic group of drugs, thus suggesting that they may have some antipsychotic effects, especially if administered at the high dose levels. In addition, it may also possess some of the undesirable effects of this group of drugs.


Engineered iron-carbon-cobalt (Fe3O4@C-Co) core-shell composite with synergistic catalytic properties towards hydrogen generation via NaBH4 hydrolysis.
Cobalt (Co) nanoparticle supported catalysts have better dispersion and recyclability than unsupported Co. However, the surface chemistry and limited surface area (SA) of supports limit their Co loading which lowers activity. Currently, supports with high SA and functionality which allow high Co loading are been developed. However, a smarter solution would be to develop "active" supports which can boost the activity of Co, even at low loading. The value of such a support lies in the ability to use low catalyst loading without scarifying activity. Herein, we demonstrate how via a simple annealing process the chemical properties of Fe3O4 and physico-electrical properties of carbon (C) in Fe3O4@C can be effectively combined to prepare an "active" support for Co. The unique properties of the "active" Fe3O4@C triggers a synergistic catalytic reaction involving Co, Fe3O4 and C during NaBH4 hydrolysis. Consequently, the hydrogen generation rate (1746 ml g-1 min-1) and activation energy (47.3 kJ mol-1) of Fe3O4@C-Co are significantly enhanced compared to reported catalyst even though its Co loading is significantly lower. Additionally, Fe3O4@C-Co is highly recyclable which demonstrates its stability. Our study gives a new perspective on the role supports can play in catalyst design.


Editorial Commentary: It is Never Wrong to Perform Anterior Cruciate Ligament Revision Reconstruction as a Two-Stage Procedure.
Revision anterior cruciate ligament (ACL) reconstruction can be performed in a single surgery, but in some instances, it requires 2 stages to get it right. The most common reasons for staged reconstruction include dilated bone tunnels on the tibial or femoral side (>13 mm), imperfectly placed bone tunnels that cannot be reused but cannot be avoided, and/or the need to combine the revision ACL reconstruction with meniscus and/or cartilage allograft transplantation. In my practice, we use prefabricated bone dowels, sizing up 0.5 to 1 mm relative to the size of the tunnel (after debridement) for both the femoral side and tibial side. The benefits are efficiency and reproducibility, while the challenges include cost and the potential need for multiple dowels if the prefabricated dowels are not long enough. We will occasionally add demineralized bone matrix, particularly on the tibial side, in the event that there is <5 mm of unfilled tunnel using the bone dowel. We wait ∼3 months before proceeding to the second stage using only plain radiographs to assess healing (advanced imaging such as computed tomography scan is not routinely used). We have also begun to push the limits of single-stage revision reconstruction, using dowels in a single setting. No matter what, it is never wrong to perform ACL revision reconstruction as a 2-stage procedure. When performed for the appropriate indications, outcomes tend to be good, regardless of the chosen technique.


[Spinal catheter-associated cerebrospinal fluid leak].
Cerebrospinal fluid leak, with its typical postdural puncture headache, occurs in 8-25 % of patients after insertion of a spinal catheter for treatment with an intrathecal pain pump. Symptoms are usually self-limiting; only rarely is an epidural blood patch used. In this case of a 49-year-old woman, we assumed a postdural puncture headache after replacement of the spinal catheter. Because of the persistence of symptoms and serous wound secretion around the paravertebral incision, we decided to test the catheter under radiological control with a contrast agent. Leakage could be seen within the spinal catheter, which was responsible for the symptoms. Because of an ongoing infection accompanied by meningitis the whole system had to be removed.


[Anti-papillomavirus vaccines and prevention of cervical cancer: progress and prospects].
Human papillomaviruses (HPV) cause the development of various cutaneous and mucosal lesions. Some genotypes play a role in the genesis of cervical cancer, which is the second most common cancer in women. HPV types 16 and 18 account for 60 to 72% of all HPV-associated cervical cancers, while types 6 and 11 cause genital warts. Despite the various escape strategies viruses use to fight the natural immune system, more than 90% of the infections clear spontaneously. It should therefore be possible to prepare prophylactic vaccines. The HPV major capsid protein L1 self-assembles into virus-like particles (VLP). Immunization after parenteral vaccination with it provided very good protection against experimental infection in different animal models. The first clinical trials revealed the satisfactory tolerance and excellent immunogenicity of these vaccines. Two vaccine approaches were selected: one based on protection against cervical cancer from a bivalent VLP L1 vaccine containing the two genotypes most frequently involved in cervical cancer (type 16 and 18) and the other, protecting against warts as well as cervical cancer, with a quadrivalent HPV VLP L1 vaccine containing genotypes 6, 11, 16 and 18. Initial results with these vaccines show an efficacy of more than 90% against infection and 100% against the onset of dysplastic lesions. Despite these hopeful results, a vaccined strategy sould still be defined. Meanwhile, the cytology screening program should be carried on until the beginning of the vaccination.


A study of the role of the reactive thiol group of rabbit muscle creatine kinase with a chromophoric reporter group.
Substrate- and ligand-induced conformational changes were studied in a series of thiol-modified derivatives of rabbit muscle creatine kinase that retained different amounts of enzymic activity. The results indicate that the 'reactive' thiol group of the enzyme is required for the conformational changes associated with formation of a 'transition-state analogue' complex.


Electroacupuncture and splinting versus splinting alone to treat carpal tunnel syndrome: a randomized controlled trial.
The effectiveness of acupuncture for managing carpal tunnel syndrome is uncertain, particularly in patients already receiving conventional treatments (e.g., splinting). We aimed to assess the effects of electroacupuncture combined with splinting. We conducted a randomized parallel-group assessor-blinded 2-arm trial on patients with clinically diagnosed primary carpal tunnel syndrome. The treatment group was offered 13 sessions of electroacupuncture over 17 weeks. The treatment and control groups both received continuous nocturnal wrist splinting. Of 181 participants randomly assigned to electroacupuncture combined with splinting (n = 90) or splinting alone (n = 91), 174 (96.1%) completed all follow-up. The electroacupuncture group showed greater improvements at 17 weeks in symptoms (primary outcome of Symptom Severity Scale score mean difference [MD] -0.20, 95% confidence interval [CI] -0.36 to -0.03), disability (Disability of Arm, Shoulder and Hand Questionnaire score MD -6.72, 95% CI -10.9 to -2.57), function (Functional Status Scale score MD -0.22, 95% CI -0.38 to -0.05), dexterity (time to complete blinded pick-up test MD -6.13 seconds, 95% CI -10.6 to -1.63) and maximal tip pinch strength (MD 1.17 lb, 95% CI 0.48 to 1.86). Differences between groups were small and clinically unimportant for reduction in pain (numerical rating scale -0.70, 95% CI -1.34 to -0.06), and not significant for sensation (first finger monofilament test -0.08 mm, 95% CI -0.22 to 0.06). For patients with primary carpal tunnel syndrome, chronic mild to moderate symptoms and no indication for surgery, electroacupuncture produces small changes in symptoms, disability, function, dexterity and pinch strength when added to nocturnal splinting. Chinese Clinical Trial Register no. ChiCTR-TRC-11001655 (www.chictr.org.cn/showprojen.aspx?proj=7890); subsequently deposited in the World Health Organization International Clinical Trials Registry Platform (apps.who.int/trialsearch/Trial2.aspx?TrialID=ChiCTR-TRC-11001655).


A randomized controlled trial of pentoxifylline for the prevention of post-ERCP pancreatitis.
Pentoxifylline can ameliorate pancreatitis in animal models because of its anti-tumor necrosis factor properties. Our purpose was to study the safety and efficacy of pentoxifylline in the prevention of post-ERCP pancreatitis. Patients due to undergo ERCP for various indications were randomized to receive pentoxifylline 400 mg orally 3 times, beginning the day before ERCP (2 and 10 pm) until the night after the procedure (6 am and 2 and 10 pm) or to receive no preventive medication. Serum amylase values were determined before and 6 and 24 hours after ERCP. Diagnosis and grading of the severity of complications was performed according to consensus criteria. One hundred fifty-eight patients received pentoxifylline (group A) and 162 had no medication (group B). The groups were similar in distributions of sex, biliary sphincterotomy, pancreatography, pancreatic duct cannulations, stone extraction, stent placement, and presence of periampullary diverticulum. Group A patients were younger (mean age 63 vs 68 years, P<.05) and biliary colic was a more frequent indication (30 vs 12, P<.05). Nine (5.6%) patients in group A and 5 (3%) in group B had pancreatitis (2 and 1 severe, respectively; P=.28). Serum amylase values were similar in baseline and 6- and 24-hour samples. Two (1.2%) patients in group A and 7 (4.3%) in group B had hemorrhage. This was not a double-blind trial. In this study pentoxifylline did not protect against post-ERCP pancreatitis or hyperamylasemia.


The exponential model for a regulatory enzyme: a computer program to determine the constants for the binding of a single ligand.
The paper describes a non-linear multiple regression program to analyse data arising from the binding of a single ligand by a protein under the assumption that the reaction can be represented by the exponential model for a regulatory enzyme.


Calibration of mobile-gantry computed tomography for surgical navigation.
Image-guided interventions that use preoperative 3D computed tomography (CT) models are limited by the preoperative segmentation time 3D image and collection of intraoperative registration data. Intraoperative CT imaging can be ergonomically efficient in a direct navigation system if the imaging device is accurately calibrated. A mobile-gantry CT scanner offers improved patient safety but presents technical challenges beyond those of a conventional scanner. The goal was to calibrate an optoelectronic navigation system to mobile-gantry CT with millimeter-level accuracy. A custom calibration device was designed and manufactured. The calibrator contained optoelectronic markers for navigation reference and radio-opaque markers for CT reference. Calibrations were performed with a ceiling-mounted optoelectronic camera and with a portable camera, and then verified for accuracy. The component fiducial registration errors were extremely small, being 0.36 mm, with standard deviation of 0.16 mm, for the ceiling-mounted camera, and 0.05 mm, with standard deviation of 0.01 mm, for the portable camera. The net target registration error, measured as RMS deviation, was 1.58 mm for the ceiling-mounted camera and 0.73 mm for the portable camera. High-accuracy calibration of the mobile-gantry CT scanner was possible from a single preoperative CT image. A ceiling-mounted optoelectronic camera, which is ergonomically preferable, marginally met the accuracy criteria. The portable camera, which is in widespread use for conventional navigated surgery, had deep sub-millimeter error. This study demonstrates that high accuracy is achievable and offers a system developer options to trade off accuracy and user convenience in direct surgical navigation.


Bone graft substitutes in the upper extremity.
The development of effective bone graft substitutes is one of the most important innovations in musculoskeletal surgery. Bone graft substitutes provide an osteoconductive scaffolding similar to those of autogenous bone. They eliminate donor site morbidity,decrease operative time and complexity and treatment costs, and improve patient satisfaction. Osteoinductive and osteogenic elements may be added to further stimulate and enhance healing and incorporation of the scaffolding substance into the adjacent bone. Bone graft substitutes have proven effective in the spine and larger long bones of the extremities. The continuing development of bone graft substitutes, evaluation of their efficacy relative to autogenous bone grafts and to each other, and their use in the hand and wrist are emerging fields.


Recency judgements in Wernicke-Korsakoff and post-encephalitic amnesia: influences of proactive interference and retention interval.
This study further examines the performance of diencephalic and temporal lobe amnesics on the recency judgement task (Parkin, Leng and Hunkin, 1990). The two patient groups were represented by patients with Wernicke-Korsakoff syndrome (WKS) and post-Herpes simplex encephalitis (HSE). Experiment 1 demonstrated that poorer recency judgements by WKS patients were not due to a general proactive interference effect, but from an inability to remember which items had been designated targets on a given trial. Experiment 2 demonstrated that the superior performance of the HSE group was not attributable to a putative faster forgetting rate. In addition, the study found no relationship between recency judgements and degree of frontal lobe impairment. It is concluded that diencephalic damage has a particular effect on the ability to make recency judgements and that this represents a fundamental difference between diencephalic and temporal lobe amnesia. Theoretical interpretations of this difference are discussed.


Raise the anchor! Synthesis, X-ray and NMR characterization of 1,3,5-triazinanes with an axial tert-butyl group.
N-t-Bu-N',N''-Disulfonamide-1,3,5-triazinanes were synthesized and characterized by X-ray single crystal structure analysis. In the course of the X-ray structure elucidation, the first solid experimental evidence of the axial position of the tert-butyl group in unconstrained hexahydro-1,3,5-triazacyclohexanes was obtained. Dynamic low-temperature NMR analysis allowed to fully investigate a rare case of crystallization-driven unanchoring of the tert-butyl group in the chair conformation of saturated six-membered cycles. DFT calculations show that the use of explicit solvent molecules is necessary to explain the equatorial position of the t-Bu group in solution. Otherwise, the axial conformer is the thermodynamically stable isomer.


Modeling of palatable food intake in female young adults. Effects of perceived body size.
Laboratory taste-test studies have shown that social modeling effects on food intake are powerful. The aim of the present study was to examine the degree to which people model food intake in a more naturalistic eating setting. After completing a cover task, female participants (N=102) spent a 15-min break with a female confederate who ate a large amount or a small amount of M&Ms or no M&Ms at all. Further, the confederate had a slim or (subtly manipulated) normal-weight appearance. Females who were exposed to a confederate who ate much consumed more than those who were confronted with a confederate who ate only a little or nothing at all. Although the manipulation of the confederate's appearance had no significant main effect on the amount of food that participants consumed, a significant interaction effect was found, such that the modeling effect of eating was present only in the normal-weight appearance condition. Our findings suggest that normal-weight young women are more inclined to imitate the food intake of a female confederate if they are more similar to the confederate.


Comparison of dual-chamber pacing with nonsurgical septal reduction effect in patients with hypertrophic obstructive cardiomyopathy.
The aim of the study was to compare the influence of dual-chamber pacing vs. nonsurgical septal reduction on hemodynamic and morphological parameters in patients with obstructive form of hypertrophic cardiomyopathy. Nineteen patients with dual-chamber pacing (group I) and 9 patients who underwent nonsurgical septal reduction (group II) were studied at baseline and after a 6-month follow-up. The changes of left ventricular outflow tract gradient and posterior wall thickness (as an index of left ventricular hypertrophy regression) were compared. The baseline left ventricular outflow tract gradient was comparable between group I and group II (77+/-25 vs. 82+/-25 mm Hg, p>0.05). At 6-month follow-up, the left ventricular outflow tract gradient was reduced to a similar level in both groups (28+/-19 vs. 25+/-12 mm Hg, p>0.05). At baseline, posterior wall hypertrophy was comparable between groups (12.9+/-1.7 vs. 13.6+/-2.2 mm, p>0.05). During follow-up, the posterior wall thickness was unchanged in the pacing group (12.9+/-1.7 vs. 12.6+/-1.6 mm, p>0.05), whereas nonsurgical septal reduction induced regression of left ventricular hypertrophy in myocardial region remote from the infarcted septal segment (13.6+/-2.2 vs. 10.5+/-2.3 mm, p<0.003). Despite comparable reduction of instantaneous left ventricular outflow tract gradient, the nonsurgical septal reduction decreased posterior wall thickness, whereas pacing did not reduce left ventricular hypertrophy. Thus, regression of left ventricular hypertrophy that appeared solely after nonsurgical septal reduction may reflect the more permanent reduction of left ventricular pressure overload. Thus, not only hemodynamic but also morphological benefit from nonsurgical septal reduction seems to indicate the superiority of this method over dual-chamber pacing.


Antihypoxic and antinecrotic effect of mexidol in skin ischemia.
Course treatment with mexidol in a dose of 25 mg/kg for 3 days decreased activities of aspartate transaminase and creatine phosphokinase in the plasma on day 3 after the incidence of skin ischemia (by 1.3 and 1.66 times, respectively). Under these conditions the index of cytolysis decreased by 1.3 times. Therefore, mexidol prevented progression of necrotic processes in the skin. Mexidol therapy of animals with skin ischemia restored the reserve capacity of systems for energy supply and antioxidant defense. The systems of NADH-ubiquinone reductase and succinate-ubiquinone reductase served as the targets for the action of mexidol. Mexidol significantly decreased the damaging effect of reactive oxygen species. Dermatoprotective properties of mexidol were associated with its influence on the energy supply system (regulation of enzyme activity in the electron transport chain, ubiquinone metabolism) and antioxidant defense.


Development of a dedicated phantom for multi-target single-isocentre stereotactic radiosurgery end to end testing.
The aim of this project was to design and manufacture a cost-effective end-to-end (E2E) phantom for quantifying the geometric and dosimetric accuracy of a linear accelerator based, multi-target single-isocenter (MTSI) frameless stereotactic radiosurgery (SRS) technique. A perspex Multi-Plug device from a Sun Nuclear ArcCheck phantom (Sun Nuclear, Melbourne, FL) was enhanced to make it more applicable for MTSI SRS E2E testing. The following steps in the SRS chain were then analysed using the phantom: magnetic resonance imaging (MRI) distortion, planning computed tomography (CT) scan and MRI image registration accuracy, phantom setup accuracy using CBCT, dosimetric accuracy using ion chamber, planar film dose measurements and coincidence of linear accelerator mega-voltage (MV), and kilo-voltage (kV) isocenters using Winston-Lutz testing (WLT). The dedicated E2E phantom was able to successfully quantify the geometric and dosimetric accuracy of the MTSI SRS technique. MRI distortions were less than 0.5 mm, or half a voxel size. The average MRI-CT registration accuracy was 0.15 mm (±0.31 mm), 0.20 mm (±0.16 mm), and 0.39 mm (±0.11 mm) in the superior/inferior, left/right and, anterior/posterior directions, respectively. The phantom setup accuracy using CBCT was better than 0.2 mm and 0.1°. Point dose measurements were within 5% of the treatment planning system predicted dose. The comparison of planar film doses to the planning system dose distributions, performed using gamma analysis, resulted in pass rates greater than 97% for 3%/1 mm gamma criteria. Finally, off-axis WLT showed MV/kV coincidence to be within 1 mm for off-axis distances up to 60 mm. A novel, versatile and cost-effective phantom for comprehensive E2E testing of MTSI SRS treatments was developed, incorporating multiple detector types and fiducial markers. The phantom is capable of quantifying the accuracy of each step in the MTSI SRS planning and treatment process.


Safety and Efficacy of a Hybrid Approach Combining a Paclitaxel-Coated Balloon With a New Generation Drug-Eluting Stent in Patients With De Novo True Coronary Bifurcation Lesions.
The use of drug-coated balloon in the management of true bifurcation lesions appears to be an attractive option to reduce the rate of stent thrombosis and restenosis particularly at the level of the side branch ostium. We aim to assess the safety and the efficacy of a hybrid approach combining a drug-eluting stent in the main branch and a drug-coated balloon to treat the side branch ostium in patients with de novo true bifurcation. From September 2020 to March 2022, 45 patients with a de novo true bifurcation lesion Medina (1.1.1) or Medina (0.1.1) were enrolled. All patients underwent a percutaneous coronary intervention with the hybrid approach. Clinical assessment with functional stress imaging test was scheduled at 6 months. In case of documented ischemia, coronary angiography was performed. The primary endpoint was the composite of target lesion failure at 6 months including cardiac death, target vessel MI or ischemia-driven target lesion revascularization. The secondary endpoints were technical success, defined by performing the percutaneous coronary intervention without an additional drug-eluting stent at the level of the side branch ostium, and clinical success, defined by a technical success associated with the absence of severe complications during in-hospital phase. The immediate results show a technical success of the procedure in the majority of cases (88.9 %) with a low rate of bailout side branch stenting (11.1 %). The clinical success was obtained in 86.7 % and only one patient experienced a severe in-hospital complication. A side branch ostial lesion length > 10 mm was the only independent predictor of clinical failure of the procedure (OR 12.49, 95 % CI 1.17-133.6; p = 0.037). At 6 months, the TLF was low and occurred in 1 patient (2.2 %). No cardiac death was observed. No TVMI was observed. Importantly, at 6 months, no side branch thrombosis was observed. The use of a hybrid approach combining a drug-eluting stent in the main branch and a drug-coated balloon in the side branch to treat true bifurcation lesions appears to be safe and efficient with few immediate complications and with satisfactory results at mid-term follow up.