Lung cancer risks in relation to vegetable and fruit consumption and smoking.
In a case-control study on lung cancer, risk was analysed in relation to smoking habits and frequency of vegetable and fruit consumption. Lung cancer cases in West Sweden and population controls were interviewed using a questionnaire where the frequency of consumption of dietary items and smoking habits were assessed. The material presented comprises 177 female and 359 male confirmed cases of lung cancer and 916 population controls. There was a dose-response relationship in regard to the number of cigarettes smoked and the number of years smoked, the latter factor being more important. After adjustment for number of cigarettes smoked/day and number of years smoked, the risk for those who seldom consumed vegetables was about twice of that among those who consumed vegetables frequently, both among nonsmokers, smokers and former smokers. This risk increase in relation to vegetable consumption also was present for different smoking categories. A similar tendency, although less pronounced, was found for fruit consumption. The results demonstrate that dietary factors are related to the risk for lung cancer, although smoking is the dominant risk factor.


Human CAAF1 gene--molecular cloning, gene structure, and chromosome mapping.
We have isolated and characterized a cDNA and the gene of the human homologue of CAAF1, a novel member of the S100 calcium-binding protein family. The 276-bp open reading frame encoded a 92-amino acid polypeptide with a predicted molecular mass of 10,575 Da. The deduced amino acid sequence of human CAAF1 showed 66% homology to bovine CAAF1. The human CAAF1 gene consisted of three exons, with the two EF hand motifs of the CAAF1 protein separately encoded by exons 2 and 3. This gene was expressed at a high level in polymorphonuclear leukocytes and at an intermediate level in esophageal mucosa. The tissue distribution of CAAF1 mRNA was different from that of other S100 proteins. Direct R-banding fluorescence in situ hybridization revealed that the human CAAF1 gene was mapped to chromosome 1q21.2-q22, where most of the S100 genes form a cluster.


Mutation detection in glycogen storage-disease type II by RT-PCR and automated sequencing.
A new method is described for detection of mutations in the lysosomal alpha-glucosidase gene (GAA) leading to Glycogen Storage Disease type II (GSDII). A key feature of the method is isolation and reverse transcription of mRNA followed by PCR amplification of lysosomal alpha-glucosidase cDNA with M13-extended primers. Dye labeled primers are used for cycle sequencing and an ABI PRISM 377 DNA sequencing system for analysis. The method is rapid and complementary to the automated sequencing of all the 19, PCR amplified, coding exons of the GAA gene. The advantages and pitfalls of this new method are discussed in the light of the results obtained with an infantile GSDII patient. A new splice site mutation in the GAA gene of this patient was identified, IVS16(+2T-->C), resulting in the deletion of 16 base pairs of exon 16.


Systematic review of lower urinary tract symptoms/benign prostatic hyperplasia surgical treatments on men's ejaculatory function: Time for a bespoke approach?
Although ejaculatory dysfunction is common for patients undergoing benign prostatic hyperplasia surgery, no clear evidence is present to counsel men seeking to preserve ejaculation. Our aim was to evaluate ejaculatory dysfunction in relation to benign prostatic hyperplasia surgery. We carried out a web and manual search using MEDLINE and Embase including randomized controlled trials reporting ejaculatory dysfunction after benign prostatic hyperplasia surgery: 42 randomized controlled trials comprising a total of 3857 patients were included. Only one study had ejaculatory dysfunction as a primary outcome, and just 10 evaluated ejaculatory dysfunction before and after surgery. The definition of ejaculatory dysfunction was not standardized. Similarly, just seven studies used internationally validated questionnaires to address ejaculatory dysfunction. The reported rates of ejaculatory dysfunction after resectional electrosurgery, laser procedures, coagulation, ablation and implant techniques were assessed and compared. Transurethral resection of the prostate and recent laser procedures including holmium, thulium and GreenLight cause similar rates of ejaculatory dysfunction, occurring in almost three out of four to five men. Although providing less symptomatic benefit compared with transurethral resection of the prostate, transurethral incision of the prostate, transurethral needle ablation and transurethral microwave thermotherapy should be considered for men aiming to maintain normal ejaculation. UroLift is also a recent promising option for this category of patients. The vast majority of studies reporting ejaculatory dysfunction after benign prostatic hyperplasia surgery used poor methodology to investigate this complication. Future studies able to address clear hypothesis and considering ejaculatory dysfunction anatomical and pathophysiological features are required to develop ejaculation preserving techniques and to increase the evidence to counsel men aiming to preserve ejaculation.


[Intrascrotal leiomyoma: report of a case].
A case of intrascrotal leiomyoma is reported. The patient was a 56-year-old male who complained of painless mass in the scrotum. He noticed the mass about 10 years ago and it had gradually enlarged. The mass was removed surgically. Pathohistological diagnosis of the specimen was leiomyoma. The literature revealed 13 cases of intrascrotal leiomyoma in Japan.


A new reducing agent of flavins and its application to the assay of bacterial luciferase.
Copper(I) plus ethylenediaminetetraacetic acid, Cu(I)-EDTA, reduces flavins. Using Cu(I)-EDTA reduction of riboflavin 5'-phosphate, a new assay method for bacterial luciferase is established. In previous assay methods, flavin and aldehyde substrates for luciferase have been routinely added to luciferase at different times; the new assay permits aldehyde and Cu(I)-reduced flavin to be injected simultaneously into air-saturated buffer containing luciferase. In the new assay method using Cu(I), bovine serum albumin is not required, the initial emission intensity is more than twice and the overall yield is about twice of that in the so-called standard assay for luciferase.


Pathology of lipomatous lesions in Proteus syndrome.
Proteus syndrome is an extremely rare, complex hamartomatous disorder with markedly variable clinical expression. We present a case of Proteus syndrome with multiple disfiguring soft tissue masses that were present since early childhood. The lesions involved predominantly the right side of the body and included scoliosis, macrodactyly, and limited hyperostosis in the right foot. There was no evidence of cranial or skin lesions. The patient underwent multiple resections of soft tissue masses, including an amputation of the right foot because of severe gait disturbance. All specimens exhibited lipomatous lesions that were probably hamartomatous rather than neoplastic. She carried a diagnosis of neurofibromatosis for more than a decade, but a re-evaluation of clinical features and pathological findings prompted the diagnosis of Proteus syndrome. We believe that a more informed evaluation of the pathology material may help to identify this rare entity.


Skin cooling for botulinum toxin A injection in patients with focal axillary hyperhidrosis: a prospective, randomized, controlled study.
Botulinum toxin A (BTX-A) injections are a commonly used and effective therapy for patients with focal axillary hyperhidrosis. However, injections are often painful. Therefore, we studied whether skin cooling decreases pain during injection. Thirty-one patients (n = 31) with focal axillary hyperhidrosis were enrolled in the present study. Patients were treated with 50 MU BTX-A (Botox; Allergan, Irvine, CA) in each axilla. One group (n = 21) received a skin cooling using a cold-air system (SmartCool; Cynosure, Westford, MA) versus no cooling on the other side. In the second group (n = 10), patients were cooled with the same cold air blower on one axilla and ice cubes on the other. For evaluation of the effect of cooling in both groups, relative pain scores using a visual analog scale (VAS) were recorded. In the first group, the air-cooled-side pain scores ranged from 0 to 4 (average: 2.5) versus 5 to 10 (average: 7.4) on the noncooled side. The air-cooled side showed a 66.2% higher reduction in pain score. In the second group, no significant difference was seen between air and ice cooling (average pain score 2.0 versus 2.4; P > 0.05). Skin cooling decreases pain during injection of BTX-A in patients with focal axillary hyperhidrosis, with ice and air cooling showing the same efficacy.


Investigation of the motor system in two siblings with Canavan's disease: a combined transcranial magnetic stimulation (TMS) - diffusion tensor imaging (DTI) study.
Canavan's disease (CD) is a hereditary leukodystrophy caused by mutations in the aspartoacylase gene (ASPA), leading to spongiform degeneration of the white matter and severe impairment of psychomotor development. We present the cases of two non-Jewish sisters with CD that have a milder and protracted clinical course compared to typical CD. MRI imaging revealed bilateral high-signal-intensity areas in the thalami and the internal capsule and MR spectroscopy showed typical findings for CD (a marked increase in N-acetylaspartate (NAA) levels). FA values of the right and left corticospinal tracts at the level of the posterior limb of the internal capsule, and the centrum semiovale were found to be significantly reduced compared to healthy controls. From a neurophysiological point of view, the peripheral motor system was normal. In contrast, cortical stimulation at maximal intensity failed to elicit facilitated or resting MEPs and silent periods (SPs) in upper and lower limbs, providing evidence for significant upper motor pathway dysfunction.


Genetic lineages, antimicrobial resistance, and virulence in Staphylococcus aureus of meat samples in Spain: analysis of immune evasion cluster (IEC) genes.
The objective of this study was to determine the rate of contamination by Staphylococcus aureus in 100 meat samples obtained during 2011-2012 in La Rioja (Northern Spain), to analyze their content in antimicrobial resistance and virulence genes, as well as in immune evasion cluster (IEC) genes, and to type recovered isolates. Seven of 100 samples (7%) contained S. aureus: 6 samples harbored methicillin-susceptible S. aureus (MSSA) and 1 pork sample harbored methicillin-resistant S. aureus (MRSA). The MRSA isolate corresponded to the ST398 genetic lineage with a multidrug resistance profile and the absence of human IEC genes, which pointed to a typical livestock-associated MRSA profile. MRSA isolate was ascribed to the spa-type t011, agr-type I, and SCCmec-V and showed resistance to erythromycin, clindamycin, tetracycline, and streptomycin, in addition to β-lactams. The remaining six MSSA strains belonged to different sequence types and clonal complexes (three isolates ST45/CC45, one ST617/CC45, one ST5/CC5, and one ST109/CC9), being susceptible to most antibiotics tested but showing a wide virulence gene profile. Five of the six MSSA strains (except ST617/CC45) contained the enterotoxin egc-cluster or egc-like-cluster genes, and strain ST109/CC9 contained eta gene (encoding exfoliatin A). The presence of human IEC genes in MSSA strains (types B and D) points to a possible contamination of meat samples from an undefined human source. The presence of S. aureus with enterotoxin genes and MRSA in food samples might have implications in public health. The IEC system could be a good marker to follow the S. aureus contamination source in meat food products.


Genetic therapy of human neoplastic disease.
Molecular biology has provided clinical investigators and basic scientists with the tools to identify those changes present within neoplastic hematopoietic and epithelial cells that lead to the evolution of unregulated patterns of cell growth. This information has made possible the development of therapy that involves genetic modification of either the normal hematopoietic cells (for chemoprotection), or the tumor cells themselves to suppress the growth of these cells. This article will summarize the clinical and laboratory data that is evolving in this area.


Evolution of human immunodeficiency virus type 1 envelope sequences in infected individuals with differing disease progression profiles.
Sequence variation displayed by the human immunodeficiency virus type 1 (HIV-1) has been proposed to be linked to the pathogenesis of acquired immunodeficiency syndrome (AIDS). To assess viral evolution during the course of infection, we evaluated sequence variability in the env variable domains in four HIV-1-infected individuals exhibiting differing profiles of CD4+ T cell decline when followed from seroconversion until the development of AIDS or loss of followup. Proviral sequences encoding the V3-V5 region of gp 120 were obtained following PCR amplification of peripheral blood mononuclear cell DNA and cloning. Virus in each patient was relatively homogeneous early in infection and then diverged with time, more consistently at its nonsynonymous sites. Just prior to or coincident with a rapid decline in CD4+ T cell numbers, sequences were found with basic amino acid substitutions clustered within and downstream of the gp 120 V3 domain. Within the constraints of the current data set, we conclude that the virus appears to continually accumulate changes in its amino acid sequences well into the time of marked CD4+ T cell decline.


Reaction of malondialdehyde with deoxyribonucleosides in the presence of acetaldehyde.
The reactivity of malondialdehyde (MDA) with deoxyribonucleosides in the presence of acetaldehyde (AA) was investigated. Although MDA is known to be reactive towards deoxyguanosine (GdR), deoxyadenosine (AdR) and deoxycytidine (CdR) under acidic conditions, MDA had only slight reactivity towards GdR under physiological pH. However, when AA was present, MDA exhibited much higher reactivity towards GdR, and a reaction with AdR also took place.


Carbon-11 acetate PET/CT based dose escalated IMRT in prostate cancer.
To demonstrate the theoretical feasibility of [(11)C]acetate PET/CT in delineating the malignant intraprostatic lesions (IPL's) in prostate cancer and to use the data in external beam radiotherapy to boost the biologically defined target volume (BTV). Twelve men with intracapsular prostate carcinoma were imaged with [(11)C]acetate PET/CT and the data were used to delineate the BTV. Six dynamic IMRT plans were generated to each patient: a standard IMRT (sIMRT) plan with a 77.9 Gy dose to PTV (prostate gland with a 6-mm margin) and a simultaneous integrated boost IMRT (SIB(IMRT)) plan to deliver 77.9 Gy, 81 Gy, 84 Gy, 87 Gy and 90 Gy to the BTV and 72 Gy to the rest of PTV. To study the theoretical dose escalation based on the delineation of BTV, tumor control probabilities (TCPs) and normal tissue complication probabilities (NTCPs) of bladder and rectum were calculated and compared between the treatment plans. [(11)C]Acetate was used to delineate the IPL's of all 12 patients. With every patient the TCP was increased with SIB(IMRT) without increasing the NTCP of the bladder or rectum. The probability of uncomplicated control (PUC) was increased on average by 28% with the SIB(IMRT) treatment plans. The highest PUC was achieved with an average dose of 82.1 Gy to the BTV. Our study indicates that [(11)C]acetate can be used to define the IPL's and in combination with SIB(IMRT) the defined areas can theoretically be treated to ultra high doses without increasing the treatment toxicity. These results motivate the formal validation of [(11)C]acetate PET for biological dose planning in prostate cancer.


Hypertension and kidney disease: is renalase a new player or an innocent bystander?
Most patients on dialysis are hypertensive and their blood pressure (BP) control is often poor. Renalase is preferentially expressed in proximal tubules, but it is also present in glomeruli and distant tubules, as well as in cardiomyocytes, liver, and skeletal muscle. It had been proposed that renalase had a flavin adenine dinucleotide (FAD)-binding domain and that FAD was an essential cofactor for its stability and monoamine oxidase activity. It was reported that renalase, secreted by the kidney and circulating in the blood, degraded catecholamines and might play a role in the regulation of sympathetic tone and BP. It has been also proposed that renalase-coding gene is a novel susceptibility gene for essential hypertension and its variations may influence BP. In addition, polymorphisms of the renalase gene in hemodialysed patients were associated with hypertension. However, several unresolved and controversial issues still remain such as how to measure renalase and its physiological activity. Furthermore, there are few data on possible activators and/or inhibitors of renalase. We are at the very beginning of solving the problem of whether renalase is a causative factor of hypertension in kidney disease or just an innocent bystander. Therefore, more research is needed to establish whether renalase can become a useful therapeutic target.


Synthesis of undoped and manganese-doped hgte nanoparticles using [Hg(TeCH2CH2NMe2)2] as a single source precursor.
The Reaction of [HgCl2(tmeda)] with NaTeCH2CH2NMe2 gave a mercury tellurolate, [Hg(TeCH2CH2. NMe2)2] (1) as a yellow crystalline solid, which was characterized by elemental analysis, UV-vis, mass and NMR (1H, 13C, 125Te, 199Hg) spectroscopy. Thermolysis of 1 in hexadecylamine (HDA) at 90 degrees C in the absence and presence of Mn(OAc)2.4H2O gave undoped and Mn-doped HgTe nanoparticles which were characterized by XRD, EDAX, TEM, EPR and magnetic measurements. These particles could be synthesized with mean particle size of 6-7 nm (from TEM). Manganese substitution at Hg site in HgTe lead to a linear decrease in lattice parameter with increasing concentration of Mn. Magnetization measurements showed ferromagnetic ordering at room temperature with very small coercive field (Hc, 50 Oe) for Hg0.973 Mn0.027 Te sample. This sample also exhibited distinct ferromagnetic resonance (FMR) in the EPR spectrum.


Paravesical abscess as an unusual late complication of inguinal hernia repair in children.
We analyzed pitfalls in the etiology, diagnosis and treatment of pediatric patients who had a paravesical abscess (PVA) resulting from previous inguinal hernia repair. We retrospectively reviewed the records of 6 children undergoing operation for PVA related to previous inguinal hernia repair between 1994 and 2002. All patients were male and 1.5 to 8 years old. The location of PVA was the right side of the bladder in 4 patients and the left side in 2. History showed that only 2 cases were complicated by early postoperative wound infection. Four patients were hospitalized with a relapse of symptoms following antibiotic treatment for possible urinary tract infection. The interval between initial inguinal hernia repair and the diagnosis of PVA was 6 to 48 months. Five patients had from recurrent lower urinary tract symptoms, 2 had ipsilateral groin discomfort and 1 had lower abdominal discomfort. There were swelling and tenderness at palpation of the ipsilateral groin in 5 patients not present at previous examinations. Only 1 patient had fever and leukocytosis. Urinalysis showed microscopic hematuria in all patients, of whom 2 had also leukocyturia. All patients had negative urine cultures. Ultrasound and computerized tomography findings suggested features of abscess formation at the paravesical space with concomitant focal thickening of the adjacent bladder wall. At surgery when entering the abscess cavity, thick pus and granulation tissues were débrided. Transfixing silk sutures were found to be secured to the adjacent bladder wall in 2 patients and in the area of the internal ring in 4. They were removed. The adjacent bladder walls needed no additional intervention. Biopsy specimens revealed only chronic inflammatory components. Antibiotics were continued for a mean of 7 days. Weekly ultrasound was performed to evaluate bladder wall thickening, which resolved completely within 3 to 5 weeks. Followup was 5 months to 6 years and no recurrence was noted. In children presenting with lower urinary tract symptoms (early period) plus findings of soft tissue infection at the ipsilateral inguinal region (late period) after inguinal hernia repair clinicians should be aware of the possibility of PVA as a primary problem to avoid insufficient treatment because its definitive treatment is removal of the infected suture material.


Lipoxins, leukocyte recruitment and the resolution phase of acute glomerulonephritis.
The resolution phase of inflammation is being increasingly recognized as a dynamic multifaceted process whose components may be amenable to pharmacological manipulation for therapeutic gain. Here, we review evidence that the lipoxins (LX), a family of lipoxygenase-derived eicosanoids generated during cell-cell interactions within the vascular lumen, are potential endogenous inhibitors of polymorphonuclear neutrophil (PMN) recruitment during glomerular inflammation. LX are generated in nanogram quantities in kidneys of rats with Concanavalin A-ferritin (Con A-F) immune complex glomerulonephritis and of mice with acute nephrotoxic serum nephritis (NSN). PMN-platelet transcellular pathways appear to be the major route to LX formation in these settings, PMN donating the labile epoxide intermediate leukotriene A4 for conversion by platelet LX synthase to LXA4. Complementary approaches using monoclonal antibodies and gene knockout suggest that PMN-platelet adhesion through P-selectin promotes transcellular LXA4 biosynthesis in vitro and in vivo. In support of a modulatory role in PMN trafficking; LXA4 and LXB4, the LX generated in greatest quantities by mammalian cells, inhibit PMN chemotaxis, adhesion to endothelial cells, and migration across endothelium and epithelium induced leukotrienes and some other mediators in vitro. Exposure of PMN to LXA4 ex vivo attenuates their recruitment in Con A-F glomerulonephritis. Furthermore, PMN recruitment is exaggerated during NSN in P-selectin knockout mice, coincident with reduced efficiency of transcellular LXA4 generation and reduced renal LXA4 levels. Replenishment of platelet P-selectin by transfusion of null mice with wild-type platelets reverses this defect in LXA4 synthesis and approximates PMN infiltrates in null and wild-type animals. Against this background, LXA4 stable analogues have been designed that retain the biologic activity of native LXA4 in vitro and should be useful tools for probing the therapeutic potential of LXA4 in disease. In the presence of aspirin, endothelial cell cyclooxygenase II (COX-II) transforms arachidonic acid to 15R-hydroxyeicosatetraenoic acid which, in the context of PMN-endothelial cell interaction, is converted by PMN 5-lipoxygenase to 15-epi-LX. Intriguingly, these novel LX also attenuate PMN adhesion and transmigration in model in vitro systems. Together, these observations suggest that LX may not only play important regulatory roles in the "stop programs" of renal inflammation, but also contribute to the anti-inflammatory activity of aspirin and related inhibitors of COX-II.


Absence of nematodes in farmed Atlantic salmon (Salmo salar L.) in Norway.
In the present study, a total of 1,180 samples of muscle or viscera from Norwegian-farmed salmon (Salmo salar L.) were examined for the presence of nematode larvae. The samples represented all salmon-producing counties in Norway. The method applied was based on the degradation of fish soft tissue in an acidified pepsin enzyme solution. None of the samples examined in this study contained nematodes.


Clinical relevance of sensitive and quantitative STAT3 mutation analysis using next-generation sequencing in T-cell large granular lymphocytic leukemia.
Diagnosis of T-cell large granular lymphocytic leukemia (T-LGL) is often challenging because clinical and laboratory characteristics are overlapping with nonneoplastic conditions. Recently, mutation in the STAT3 gene has been identified as a recurrent genetic abnormality in T-LGL. STAT3 mutation, therefore, represents a promising marker in T-LGL diagnostics. We developed a new quantitative next-generation sequencing assay that allows sensitive analysis of the STAT3 gene. The assay was used to study the utility of STAT3 mutation analysis as a diagnostic tool in T-LGL. The study included 16 T-LGL patients. A total of 15 mutations, including 2 new mutations (G618R and K658R), were detected in 12 patients (75%), with mutation levels ranging from 2.5% to 45.6% mutation-positive alleles. Next-generation sequencing detected 50% more mutations than Sanger sequencing. Blood samples from 20 healthy blood donors all tested negative, thus demonstrating the specificity of the assay. The results also indicated that mutation levels in blood and bone marrow are not systematically different, and next-generation sequencing-based STAT3 mutation analysis represents a sensitive method for monitoring residual disease as demonstrated in a patient receiving pentostatin. We demonstrate the clinical relevance of next-generation sequencing-based STAT3 mutation analysis, which represents a sensitive and specific diagnostic marker in T-LGL that allows assessment of molecular residual disease, which may improve clinical decision making.


Convenient Monitoring System of Intracellular microRNA Expression during Adipogenesis via Mechanical Stimulus-Induced Exocytosis of Lipovesicular miRNA Beacon.
Noninvasive investigation of microRNAs (miRNAs) expression, which is deeply related to biological phenomena such as stem cell differentiation, in culture soup is particularly useful for monitoring of stem cell differentiation without phototoxicity of living cells, especially when cell morphologies remain unchanged during differentiation. However, real-time detection of miRNA in culture soup is not recommended because of insufficient miRNA amounts in culture soup. In this study, a convenient method is introduced for real-time assessing intracellular miRNA in culture soup by using lipovesicular miRNA beacon (Lipo-mB) and mechanical stimulus-mediated exocytosis. Pipetting-harvest of culture soup induces exocytosis-secretion of fluorescence signal of Lipo-mB from cytoplasm into culture soup. To demonstrate this method, Lipo-mB is applied for monitoring of adipogenesis by analyzing the expression levels of various intracellular miRNAs, which are related to adipogenesis regulators. The fluorescence intensity profile of the culture soup is correlated with the quantitative reverse-transcription-polymerase chain reaction data and absorbance of Oil Red O staining. These results demonstrate that Lipo-mB can successfully monitor stem cell differentiation by sensing changes in miRNA expression from culture soup of living cells. Lipo-mB can be further developed as an accurate sensing system for analyzing subtle differences in genotype, even when changes in phenotype cannot be observed.


Circumflex artery stenosis induced by intraoperative radiofrequency ablation.
We report a case of circumflex artery stenosis after intraoperative radiofrequency ablation for permanent atrial fibrillation in a patient who had a previous mitral valve replacement. The patient presented with acute pulmonary edema and severe angina 1 year after an uneventful recovery. The patient underwent a diagnostic angiography that showed the presence of stenosis of a long segment of the circumflex artery, adjacent to the radiofrequency ablation site, which was reopened successfully by angioplasty. Intraoperative radiofrequency ablation caused circumflex artery stenosis. We believe that this complication could have been avoided by applying the radiofrequency ablation more distally between the left pulmonary veins and the mitral valve.


Determination of a novel sigma receptor antagonist, DuP 734, in rat plasma by reversed-phase high-performance liquid chromatography with ultraviolet detection.
A selective high-performance liquid chromatographic (HPLC) assay for a sigma receptor antagonist, DuP 734 (I), in rat plasma has been developed. Compound I and internal standard, XC031 (I.S.), were first extracted from plasma into an ethyl acetate-toluene mixture (3:7, v/v) and then back-extracted into freshly prepared phosphoric acid (0.03 M). Separation of I and I.S. with no interference from endogenous substances was achieved on a reversed-phase octyl column and detection was by UV at 229 nm. The mobile phase consisted of acetonitrile-glacial acetic acid-triethylamine-0.05 M ammonium acetate (670:4:2:2000, v/v). Using 0.5 ml of rat plasma for extraction, the limit of quantitation was 43 ng/ml and the assay was linear from 43 to 8536 ng/ml. The intra- and inter-day coefficients of variation ranged from 0.7 to 3.0%, and from 1.4 to 14.5%, respectively, over the entire concentration range. The accuracy was within 16.1% of the spiked concentrations. I was stable in frozen plasma at -20 degrees C for at least 68 days.


Co-expression of Arabidopsis thaliana phytochelatin synthase and Treponema denticola cysteine desulfhydrase for enhanced arsenic accumulation.
Arsenic is one of the most hazardous pollutants found in aqueous environments and has been shown to be a carcinogen. Phytochelatins (PCs), which are cysteine-rich and thio-reactive peptides, have high binding affinities for various metals including arsenic. Previously, we demonstrated that genetically engineered Saccharomyces cerevisiae strains expressing phytochelatin synthase (AtPCS) produced PCs and accumulated arsenic. In an effort to further improve the overall accumulation of arsenic, cysteine desulfhydrase, an aminotransferase that converts cysteine into hydrogen sulfide under aerobic condition, was co-expressed in order to promote the formation of larger AsS complexes. Yeast cells producing both AtPCS and cysteine desulfhydrase showed a higher level of arsenic accumulation than a simple cumulative effect of expressing both enzymes, confirming the coordinated action of hydrogen sulfide and PCs in the overall bioaccumulation of arsenic.


Dietary regulation of adenosine deaminase activity in stomach, small intestine and spleen of mice.
Activity of adenosine deaminase (ADA) and its regulation by dietary restriction were studied in the stomach, small intestine and spleen of mice. ADA activity (U/mg protein) was highest in the stomach, followed by small intestine and spleen of mice on normal diet. The activity decreased significantly in the stomach (41%) and small intestine (45%) of 24 hr fasted mice, when compared to mice fed ad-libitum. However, ADA activity in spleen did not show any change by dietary intervention. Refeeding of fasted mice for 24 hr restored the activity of ADA in tissues. In addition, dietary restriction (alternate days of feeding for three months) had a cumulative effect, whereby ADA activity decreased significantly in the stomach (53% on the day of feeding and 60% on the day of fasting) and small intestine (50% and 54% on the day of feeding and fasting, respectively) without any change in activity in spleen. These findings indicate that dietary restriction reduces ADA activity in a tissue-specific manner. Long-term dietary restriction leads to a cumulative adaptation in lowering the ADA activity of GIT, but not in spleen.


The histidine triad nucleotide-binding protein 1 supports mu-opioid receptor-glutamate NMDA receptor cross-regulation.
A series of pharmacological and physiological studies have demonstrated the functional cross-regulation between MOR and NMDAR. These receptors coexist at postsynaptic sites in midbrain periaqueductal grey (PAG) neurons, an area implicated in the analgesic effects of opioids like morphine. In this study, we found that the MOR-associated histidine triad nucleotide-binding protein 1 (HINT1) is essential for maintaining the connection between the NMDAR and MOR. Morphine-induced analgesic tolerance is prevented and even rescued by inhibiting PKC or by antagonizing NMDAR. However, in the absence of HINT1, the MOR becomes supersensitive to morphine before suffering a profound and lasting desensitization that is refractory to PKC inhibition or NMDAR antagonism. Thus, HINT1 emerges as a key protein that is critical for sustaining NMDAR-mediated regulation of MOR signaling strength. Thus, HINT1 deficiency may contribute to opioid-intractable pain syndromes by causing long-term MOR desensitization via mechanisms independent of NMDAR.


Antiplatelet Effect of Ketorolac in Children After Congenital Cardiac Surgery.
Ketorolac is used for pediatric analgesia after surgery despite its known platelet inhibition via the arachidonic acid (AA) pathway. The degree of platelet inhibitory effect after cardiac surgery is not well characterized. Thromboelastography with platelet mapping (TEG-PM) is emerging as a frequently used test to evaluate platelet inhibition via the AA pathway. Post hoc analysis of a data set collected in a prospective observational cohort study evaluating platelet inhibition in children after congenital heart surgery with cardiopulmonary bypass (CPB). Categorization into two groups: (1) received ketorolac and (2) did not receive ketorolac for analgesia after surgery. The TEG-PM was evaluated at two time points (prior to surgery and 12-48 hours after CPB). Fifty-three children were studied; mean age was 6.6 (range: 0.07-16.7) years and 45% (n = 24) were female. Participants were distributed into two groups by ketorolac use, 41 within the ketorolac group and 12 in the no ketorolac group. All 41 participants who received ketorolac had platelet inhibition and 11 (91.7%) of 12 participants who did not receive ketorolac had normal platelet function after surgery ( P < .0001). There was no difference in patient characteristics or clinical data between the two groups. Ketorolac use in a cohort of children after congenital cardiac surgery was associated with platelet inhibition via the AA pathway when evaluated by TEG-PM.


Determination of tissue polypeptide antigens (TPA) and carcinoembryonic antigen (CEA) in serum: its value in the preliminary cancer risk assessment in asbestos exposed workers.
Seeking the changes at the cellular level or at the level of cellular metabolism products, present in the biological fluids, in order to detect early stages of the carcinogenic process is an essential step in preventing cancer development among asbestos exposed workers. Carcinogenic biomarkers such as tissue polypeptide antigens (TPA) and carcinoembryonic antigen (CEA) were found very useful in this attempt. The objective of this work was to identify individuals at critical cancer risk in the population of workers exposed to asbestos and to evaluate the value of TPA and CEA determinations for this particular purpose. The study was carried out in the group of workers exposed to asbestos (n = 274). Age, exposure duration, smoking habits and the kind of job performed, were considered in the analysis of the results. To sum up, it should be concluded that in 22 persons exposed to asbestos TPA values exceeded the cut off concentrations, established on the basis of the studies performed in the control group, and CEA value accounted for 10 ng/lm. Statistically significant differences in the percentage of TPA increased values between two groups under study were indicated. Such a relationship did not apply to CEA. In the exposed group, an evident effect of the age and exposure duration on the number of persons with TPA concentrations above the cut off, was also revealed. These changes show a growing tendency and statistical significance for TPA only. Smoking had a great impact on the occurrence of TPA increased concentrations. Three kinds of jobs were considered: operation of the production line, white collar workers and miscellaneous'. The significant differences in TPA concentrations between the operators and miscellaneous, and between white collar workers and miscellaneous were found. Therefore, it may be concluded that a similar percentage of TPA increased values was observed in the group of operators and white collar workers. The study allowed to identify, among those exposed to asbestos, 22 persons who should be covered with target medical care. It also indicated that TPA determination was more useful than that of CEA in this kind of investigations.


A ruthenium-containing organometallic compound reduces tumor growth through induction of the endoplasmic reticulum stress gene CHOP.
Cisplatin-derived anticancer therapy has been used for three decades despite its side effects. Other types of organometallic complexes, namely, some ruthenium-derived compounds (RDC), which would display cytotoxicity through different modes of action, might represent alternative therapeutic agents. We have studied both in vitro and in vivo the biological properties of RDC11, one of the most active compounds of a new class of RDCs that contain a covalent bond between the ruthenium atom and a carbon. We showed that RDC11 inhibited the growth of various tumors implanted in mice more efficiently than cisplatin. Importantly, in striking contrast with cisplatin, RDC11 did not cause severe side effects on the liver, kidneys, or the neuronal sensory system. We analyzed the mode of action of RDC11 and showed that RDC11 interacted poorly with DNA and induced only limited DNA damages compared with cisplatin, suggesting alternative transduction pathways. Indeed, we found that target genes of the endoplasmic reticulum stress pathway, such as Bip, XBP1, PDI, and CHOP, were activated in RDC11-treated cells. Induction of the transcription factor CHOP, a crucial mediator of endoplasmic reticulum stress apoptosis, was also confirmed in tumors treated with RDC11. Activation of CHOP led to the expression of several of its target genes, including proapoptotic genes. In addition, the silencing of CHOP by RNA interference significantly reduced the cytotoxicity of RDC11. Altogether, our results led us to conclude that RDC11 acts by an atypical pathway involving CHOP and endoplasmic reticulum stress, and thus might provide an interesting alternative for anticancer therapy.


Appropriate drug therapy for improving outcomes in diabetic nephropathy.
Diabetic nephropathy is the leading cause of end-stage kidney disease in the United States. The majority of these cases are attributed to those with type 2 diabetes. Elevated blood pressure, proteinuria, and increased activity of the renin-angiotensin-aldosterone system (RAAS) play a major role in the development and progression of chronic kidney disease attributed to diabetes mellitus. Moreover, drugs that inhibit angiotensin II synthesis or block the angiotensin II type I receptor lower blood pressure, reduce proteinuria, and improve outcomes in patients with chronic kidney disease caused by diabetes. This article highlights improvements in the current management of diabetic nephropathy afforded by agents that inhibit the RAAS, discusses their limitations, and considers novel strategies to prevent onset and progression of diabetic nephropathy. Current opinions concerning combination drug therapy with agents that block the RAAS at multiple sites, as well as combining calcium channel blockers with either angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists, are also discussed.


Regulation of the wild-type and Y1235D mutant Met kinase activation.
Met receptor tyrosine kinase plays a crucial role in the regulation of a large number of cellular processes and, when deregulated by overexpression or mutations, leads to tumor growth and invasion. The Y1235D mutation identified in metastases was shown to induce constitutive activation and a motile-invasive phenotype on transduced carcinoma cells. Wild-type Met activation requires phosphorylation of both Y1234 and Y1235 in the activation loop. We mapped the major phosphorylation sites in the kinase domain of a recombinant Met protein and identified the known residues Y1234 and Y1235 as well as a new phosphorylation site at Y1194 in the hinge region. Combining activating and silencing mutations at these sites, we characterized in depth the mechanism of activation of wild-type and mutant Met proteins. We found that the phosphotyrosine mimetic mutation Y1235D is sufficient to confer constitutive kinase activity, which is not influenced by phosphorylation at Y1234. However, the specific activity of this mutant was lower than that observed for fully activated wild-type Met and induced less phosphorylation of Y1349 in the signaling site, indicating that this mutation cannot entirely compensate for a phosphorylated tyrosine at this position. The Y1194F silencing mutation yielded an enzyme that could be activated to a similar extent as the wild type but with significantly slower activation kinetics, underlying the importance of this residue, which is conserved among different tyrosine kinase receptors. Finally, we observed different interactions of wild-type and mutant Met with the inhibitor K252a that may have therapeutic implications for the selective inhibition of this kinase.


Thoracoscopic management of thoracic duct injury: Is there a place for conservatism?
Thoracic duct injury is a rare but serious complication following chest surgeries and major neck dissections. Clinically, it can present as cervical chylous fistula, chylothorax or chylopericardium. Without treatment, the mortality is up to 50% and thus, early aggressive therapy is indicated. Traditional conservative management includes low-fat diet, parenteral nutrition, careful monitoring of fluid and electrolytes, and drainage of the neck wound or chylothorax. Patients with failed conservative management require definitive treatment in the form of ligation of the thoracic duct, which has traditionally been done by thoracotomy. The advent of Video-Assisted-Thoracoscopic-Surgery (VATS) over the last decade has changed the approach towards the management of numerous chest diseases. Thoracoscopic ligation of the thoracic duct has also been reported. We report herein a case of postoperative cervical chylous fistula managed successfully by VATS thoracic duct ligation and present a systematic analysis of the English literature to highlight the current trends in the management of thoracic duct injury.


HLA-B27 Prevalence in Arab Populations and Among Patients with Ankylosing Spondylitis.
To investigate prevalence of HLA-B27 among general Arab populations and among patients with ankylosing spondylitis (AS), and to review published data. The prevalence of HLA-B27 was studied among 2579 unrelated healthy Jordanians, almost equally divided among Palestinian refugees and natives of Jordan, reflecting the general population of Jordan. The prevalence of HLA-B27 was also studied among 129 patients with AS, 70 from Jordan, and the remaining 59 from Qatar. HLA typing was performed by standard 2-stage micro-lymphocytotoxicity method. We also reviewed published English language studies of HLA-B27 in Arab patients with AS and general populations retrieved through Medline and cross-reference search. We observed that the general prevalence of HLA-B27 among Jordanians is 2.4%; while the reported prevalence ranges between 2% and 5% among major Arab populations. The prevalence of HLA-B27 among patients with AS is 71% in Jordan and 73% in Qatar, while the reported prevalence from pooled published data from various Arab populations is 64%. From these data one can conclude that HLA-B27 is present in about 2% to 5% among major Arab populations and that its prevalence in Arab patients with AS is closer to 70%.


Histocompatibility antigens in familial Creutzfeldt-Jakob disease.
Histocompatibility antigens were defined in 25 members of a Finnish family in which Creutzfeldt-Jakob disease (CJD) was diagnosed clinically in 4 cases and neuropathologically in 3 cases; 3 further cases had a history of presenile dementia. 2 HLA haplotypes were defined in 3 patients and deduced in a further 3 cases; only one haplotype could be deduced in 2 patients. CJD was not linked with a single haplotype, but at least 7 out of 8 patients with this disease apparently shared the HLA antigens A28 and B8.


Subcellular localizations of guanylate cyclase and 3',5'-cyclic nucleotide phosphodiesterase in sea urchin sperm.
The subcellular localizations of guanylate cyclase and 3',5'-cyclic nucleotide phosphodiesterase in sea urchin sperm were examined. Both the specific and total activities of these two enzymes were much higher in sperm flagella (tails) than in the heads. In addition to the observation that guanylate cyclase in the flagella was particulate-bound and solubilized by Triton X-100, more than 80% of the cyclase activity in the flagella was found in the plasma membrane fraction, whereas the activity of cyclic nucleotide phosphodiesterase was observed in both the axonemal and plasma membrane fractions. The observations indicated that the cyclase in the flagella appeared to be associated with the plasma membrane. Cyclic nucleotide phosphodiesterase in the plasma membrane fraction as well as the axonemal fraction hydrolyzed both cyclic GMP and cyclic AMP; however, the rates of hydrolysis for cyclic GMP were obviously higher than those for cyclic AMP. The enzymic properties of guanylate cyclase and cyclic nucleotide phosphodiesterase in sperm flagella were also briefly described.


Efficient bio-deodorization of aniline vapor in a biotrickling filter: metabolic mineralization and bacterial community analysis.
A biotrickling filter inoculated with commercial mixed microorganisms B350 was employed to treat N-containing odorous vapor - aniline. Results indicated no aniline could be detected when empty bed residence time (EBRT) was larger than 110s at inlet concentration of 0.30 g m(-3). The variation of inlet concentration did not change removal efficiencies when concentration is less than 0.21 g m(-3) at fixed EBRT 110s. Biodegradation mechanism of aniline was tentatively proposed based on identified intermediates and predicted biodegradation pathway as well as final mineralized products. Aniline was firstly biodegraded to catechol, and then to levulinic acid and subsequently to succinic acid. Finally, about 62% aniline carbon was completely mineralized to CO(2), while about 91% aniline nitrogen was converted into ammonia and nitrate. Bacterial community in biotrickling filter was found that at least seven bands microbes were identified for high efficiencies of bioreactor at stable state. In all, biotrickling filter seeded with B350 would be a better choice for the purification odorous gas containing high concentration aniline.


The metabolism of salicylidene benzylamine, a pro-drug for salicylate, in rats and dogs.
1. Oral doses of [14C]salicylidene benzylamine were well absorbed by rats and dogs and excreted mainly in the urine (92% dose by rat in 24 h and 84% by dog in 48 h). 2. After 50, 100 and 300 mg/kg oral doses to rats, peak mean plasma 14C concn. (mainly salicylic acid) of 77, 243 and 396 micrograms equiv./ml respectively were reached between 2 and 4 h and maintained at this level until about 7.5 h. 14C was cleared more rapidly from the plasma of male rats than from that of female rats. After 44, 85 and 300 mg/kg oral doses to dogs, peak mean plasma 14C concn. (mainly salicylic acid) of 114, 194 and 320 micrograms equiv./ml respectively were reached at 4 h and then declined with a half-life of 6-7 h. 3. Tissue 14C concn. in both species were greatest at the times of peak plasma 14C concn., but in general were lower than those in the corresponding plasma. 4. The major components in rat and dog urine were salicyl alcohol, salicylic acid and salicyluric acid, the first two being excreted partly as glucuronic acid/sulphate conjugates. After initial hydrolysis of salicylidene benzylamine to salicylaldehyde, approximately equal amounts were reduced and oxidized to the corresponding alcohol and acid respectively.


Antiamoebin I in methanol solution: rapid exchange between right-handed and left-handed 3(10)-helical conformations.
Antiamoebin I (Aam-I) is a membrane-active peptaibol antibiotic isolated from fungal species belonging to the genera Cephalosporium, Emericellopsis, Gliocladium, and Stilbella. Antiamoebin I has the amino acid sequence: Ac-Phe(1)-Aib-Aib-Aib-Iva-Gly-Leu-Aib(8)-Aib-Hyp-Gln-Iva-Hyp-Aib-Pro-Phl(16). By using the uniformly (13)C,(15)N-labeled sample of Aam-I, the set of conformationally dependent J couplings and (3h)J(NC) couplings through H-bonds were measured. Analysis of these data along with the data on magnetic nonequivalence of the (13)C(beta) nuclei (Deltadelta((13)C(beta))) in Aib and Iva residues allowed us to draw the univocal conclusion that the N-terminal part (Phe(1)-Gly(6)) of Aam-I in MeOH solution is in fast exchange between the right-handed and left-handed 3(10)-helical conformations, with an approximately equal population of both states. An additional conformational exchange process was found at the Aib(8) residue. The (15)N-NMR-relaxation and CD-spectroscopy measurements confirmed these findings. Molecular modeling and Monte Carlo simulations revealed that both exchange processes are correlated and coupled with significant hinge-bending motions around the Aib(8) residue. Our results explain relatively low activity of Aam-I with respect to other 15-amino acid residue peptaibols (for example, zervamicin) in functional and biological tests. The high dynamic 'propensity' possibly prevents both initial binding of the antiamoebin to the membrane and subsequent formation of stable ionic channels according to the barrel-stave mechanism.


Response of postpartum beef cows to exogenous progestogens and gonadotropin releasing hormone.
Plasma progesterone (P4) profile and estrous detection were used during three experiments to evaluate the effects of exogenous progestogens on the life span of gonadotropin releasing hormone (GnRH)-induced corpora lutea (CL) in postpartum (pp) beef cows. Experiment 1 utilized primiparous fall-calving cows (n = 28, trial 1); and spring-calving cows (n = 29, trial 2). On d 18 to 27 pp (d 0) all cows received intravaginal devices containing either P4 or no P4 (NP) for 5 d. On d 5 the devices were removed and calves were either removed (CR) or were present (CP) with half of the cows within steroid group. At 50 h after device removal, 500 micrograms of GnRH was given (iv) to all cows, and weaned calves were reunited with their dams. The induced CL had a normal life span (greater than 16 d) in 17 and 86% (trial 1) and 8 and 79% (trial 2) of NP and P4 cows, respectively. Calf removal did not affect (P greater than .10) the life span of the CL. In Exp. 2, spring-calving multiparous cows (d 18 to 24 pp; d 0) received either no P4 (NP; n = 19), P4 for 6 d via intravaginal devices (P4H; n = 19) or a single im injection of 300 mg P4 (P4 IM; n = 18). At 48 h after device removal or at 8 d after the injection of P4, half of the cows within steroid group received either 500 micrograms GnRH or saline. Corpora lutea had a normal life span in 0, 11, and 80% of NP, P4 IM and P4H cows, respectively, that received GnRH and in 22% of P4-saline cows. In Exp. 3, fall-calving multiparous and primiparous cows (d 25 to 31 pp) received either no progestogen (NP; n = 20), P4 via intravaginal devices for 5 d (P4H; n = 21) or melengestrol acetate (MGA; .5 mg.head-1.d-1 for 5 d orally, n = 15). At 48 d after device removal or at 72 h after the last MGA feeding, all cows received 500 micrograms GnRH. Progesterone post-GnRH injection was increased (greater than 1 ng/ml) at d 7 in 64, 100 and 100%, and remained elevated at d 14 in 11, 46 and 100% of NP, MGA and P4H cows, respectively. For all experiments plasma P4 was increased (range 2 to 5 ng/ml) when the devices containing P4 were in place, then decreased (less than 1 ng/ml) by 48 to 50 h after device removal.(ABSTRACT TRUNCATED AT 400 WORDS)


[Influence of diphenylhydantoine on delta sharp-waves in coma. A clinical contribution (author's transl)].
A patient with severe drug intoxication developed the well known EEG stages, starting with burst suppression activity until the pattern with delta waves and sharp waves was reached. At this stage it was treated with diphenylhydantoine intravenously. During injection the sharp elements disappeared and the pattern of faster waves was established. Thus it may be concluded that the sharp wave delta pattern indicates activity similar to that seen in epilepsy and that such a pattern needs anticonvulsant therapy.


Capability of questionnaire of social and psychological factors to predict coronary heart disease and stroke.
It is well known that the incidence of stroke is higher in Japan than in the US, and that, conversely, the incidence of heart disease is higher in the US than in Japan. To clarify this fact, a socio-cultural investigation is indicated. This study was therefore conducted from that viewpoint. A questionnaire was devised and a survey conducted to investigate the effect of social, cultural, and psychological factors on coronary heart disease and stroke. The survey was based on the hypothesis that cultural differences between Japan and the US contribute heavily to differences in the incidence of stroke and heart disease between the two countries. The questionnaire was analysed and correlated with physical examination findings, using Hayashi's quantification method type II. Discrimination between two distinct groups for each disease was clear and the predictive capability of the questionnaire was thus ascertained. In this report we concentrated on use of the prediction table use of sample data, and prediction of the probability of abnormality.


Mobile medics? The mobility of doctors in the European Economic Area.
The Treaty of Rome seeks to generate a common European market whereby all barriers to the free movement of produce, capital, services and labour are removed. Current EU policy on the free movement of labour requires that healthcare workers, who are EU citizens and meet certain training criteria, have the right to register to practice in member states other than the one in which they trained. This policy is underpinned by the EEC Directives. For example, the Medical Directive 93/16/EEC describes the framework for the mutual recognition of medical diplomas, certificates and other evidence of qualifications through out the European Economic Area (EEA). The potential impact of this for health policy is clear-workforce planning and the demand for doctors, (and also nurses and other health care professionals), could be particularly affected by new forces impacting on their supply. This paper reports on the reality of labour mobility today, and on the factors upon which mobility depends, by the means of a case study which, investigated the movement into UK of doctors from the EEA. At a formal level there is mutual recognition of diplomas, certificates and other evidence of qualifications. However, formal and 'real life' recognition could be in tension equating in policy terms to an implementation deficit. As a result, there is a 'mixed picture' which makes predicting the future (both for individual countries and for the European Union) even more difficult. Furthermore, different policy objectives have to be reconciled. Do we want high mobility; or do we want to preserve national manpower planning?


[Reproducibility of emesis by orally administrated copper sulfate in cats].
Adult cats were administered oral threshold doses of copper sulfate every week. As the cats vomited in 70 out out 80 cases, the reproducibility was 88%. Peripheral vomiting threshold dose was 40 mg/head or less, while the threshold dose for oral copper sulfate emesis after T4 transection and vagotomy was more than 160 mg/head. The following method is thus proposed for application in evaluating an antimetic for oral copper sulfate. Adult cats are to be given the emetic once a week. The threshold dose should be determined in three dose levels; 10, 20, 40 mg/head. The cats with a threshold of more than 40 mg or latency of less than 5 min or of more than 45 min are to be excluded. Inhibition of emesis or a considerable prolongation of latency is the sign of an antimetic action. A positive action of an antiemetic must be followed by another test with the threshold dose of copper sulfate alone. If the cat does not respond to the threshold dose after 2 administrations, the case must be excluded. It is considered positive when 3 cases are inhibited among 4 or more than 50% among more than 5.


All that glitters is not gold.
Solitary pulmonary nodules (SPN) are a diagnostic dilemma with a long list of differential diagnosis which extends to include both horizons i.e., benign as well as malignant conditions. Fortunately, there are some factors which favour benign over malignant; one such factor is presence of fat.1 We present here a case of a 40 years old male who underwent x-ray due to haemoptysis and cough which demonstrated a coin lesion; subsequently, PET-CT scan was requested for characterization of the lesion and concurrent staging which revealed mildly avid fat containing lesion in right lung diagnostic of pulmonary hamartoma.


The effect of anterior cruciate ligament graft rotation on knee biomechanics.
The purpose of this study was to evaluate the effects on knee biomechanics of rotating the distal end of the bone-patellar tendon graft 90° in anatomic single-bundle (SB) anterior cruciate ligament (ACL) reconstruction with a porcine model. Twenty (n = 20) porcine knees were evaluated using a robotic testing system. Two groups and three knee states were compared: (1) intact ACL, (2) deficient ACL and (3) anatomic SB ACL reconstruction with (a) non-rotated graft or (b) rotated graft (anatomic external fibre rotation). Anterior tibial translation (ATT), internal (IR) and external rotation (ER) and the in situ tissue force were measured under an 89-N anterior tibial (AT) load and 4-N m internal and external tibial torques. A significant difference from the intact ACL was found in ATT at 60° and 90° of knee flexion for rotated and non-rotated graft reconstructions (p < 0.05). There was a significant difference in the in situ force from the intact ACL with AT loading for rotated and non-rotated graft reconstructions at 60° and 90° of knee flexion (p < 0.05). Under IR loading, the in situ force was significantly different from the intact ACL at 30° and 60° of knee flexion for rotated and non-rotated graft reconstructions (p < 0.05). There were no significant differences in ATT, IR, ER and the in situ force between rotated and non-rotated reconstructions. Graft rotation can be used with anatomic SB ACL reconstruction and not have a deleterious effect on knee anterior and rotational biomechanics. This study has clinical relevance in regard to the use of graft rotation to better reproduce the native ACL fibre orientation in ACL reconstruction.


Segmental, Domain-Selective Perdeuteration and Small-Angle Neutron Scattering for Structural Analysis of Multi-Domain Proteins.
Multi-domain proteins play critical roles in fine-tuning essential processes in cellular signaling and gene regulation. Typically, multiple globular domains that are connected by flexible linkers undergo dynamic rearrangements upon binding to protein, DNA or RNA ligands. RNA binding proteins (RBPs) represent an important class of multi-domain proteins, which regulate gene expression by recognizing linear or structured RNA sequence motifs. Here, we employ segmental perdeuteration of the three RNA recognition motif (RRM) domains in the RBP TIA-1 using Sortase A mediated protein ligation. We show that domain-selective perdeuteration combined with contrast-matched small-angle neutron scattering (SANS), SAXS and computational modeling provides valuable information to precisely define relative domain arrangements. The approach is generally applicable to study conformational arrangements of individual domains in multi-domain proteins and changes induced by ligand binding.


Independent prognostic importance of microvessel density in clinically localized prostate cancer.
Previous studies have reported a possible prognostic importance of microvessel density (MVD) in prostate cancer, although the significance after radical prostatectomy is not clear. The purpose of this study was to assess the prognostic value of MVD in clinically localized prostatic adenocarcinomas, focusing on moderately-differentiated tumours. We examined a series of 104 patients treated for presumed organ-confined cancer in the period 1988-94. The area of highest tumour grade was selected from the prostatectomy specimens and vessels were high-lighted by staining for factor-VIII-related antigen. MVD was quantitated in the "hot spot" area and related to biochemical failure and clinical recurrence. In moderately differentiated tumours (WHO grade) (n = 66), MVD was associated with preoperative s-PSA and positive surgical margins. In univariate 5-year analysis, microvessel density (MVDmean > 122 mm-2, median) (p = 0.0074), s-PSA, tumour dimension, capsular penetration, seminal vesicle invasion and positive surgical margins were all significant predictors of biochemical failure, while MVDmean (p = 0.0084) was the only statistically significant predictor of clinical recurrence. In multivariate Cox' analysis, MVDmean (p = 0.0003), capsular penetration and tumour dimension remained as independent predictors of biochemical failure. Assessment of MVD in moderately differentiated prostatic adenocarcinomas may improve the prognostic stratification of patients after radical prostatectomy.


The effect of EDTA as an anticoagulant on the osmotic fragility of erythrocytes.
The osmotic fragility test is used to determine the extent of red blood cell haemolysis produced by osmotic stress. Since the quality of this test may easily be influenced by environmental and technical factors we have determined osmotic fragility reference values in our own conditions. The results show significantly increased osmotic resistance of erythrocytes in our conditions vs the published values for blood samples anticoagulated with heparin. Furthermore, the use of EDTA as an anticoagulant increased the osmotic fragility of red blood cells as compared with heparin. We conclude that EDTA can be used as an anticoagulant for the osmotic fragility test in order to simplify routine procedures. However, every laboratory should determine its own reference values which would reflect the local environmental and technical factors.


The institutionalization of pharmaceutical administration after the korean liberation: focusing on regulating the pharmaceutical affairs law(yaksabeop) in 1953.
The pharmaceutical administration under U.S Military Government in Korea and government of the Republic of Korea aimed at cleaning up the vestiges of Japanese imperialism which the pharmaceutical administration attached police administration and preparing with legal and systemic basis after the Korean liberation. The pharmaceutical bureau under U.S Military Government in Korea was reorganized as the independent division. The pharmaceutical bureau focused on preserving order, narcotics control and the distribution of relief drug. U.S Military Government proceeded supply side pharmaceutical policy for the distribution of relief drug without constructing human and material infrastructure. After the Korean War, Korean society asked the construction of system for nation building. Korean national assembly regulated National Medical Law(Gukmin uiryobeop) for promotion of public health in 1951. The Pharmaceutical Affairs Law(Yaksabeop) was regulated in 1953, and it prescribed the job requirement of pharmacist, apothecary, and drug maker and seller, and presented the frame of managing medical supplies. The Pharmaceutical Law originally planned the ideal pharmaceutical administration, but it rather secured the status of traditional apothecary, and drug maker and seller. On the contrary, though the Pharmaceutical Law guaranteed the traditional druggists, it did not materialize reproduction system such as educational and license system. It means that the traditional druggists would be degenerated in the near future. After the armistice agreement in 1953, Korean was in medical difficulties. Korean government was suffered from the deficiency of medical resources. Because of destruction of pharmaceutical facilities, Korean had to depend on United States and international aid. The Pharmaceutical Affairs Law did not cleaned up the vestiges of Japanese imperialism, and compromised with reality lacked human and material infrastructure. As a result, the law became the origin of pharmaceutical disputes such as pharmacist voluntary prescription, the separation of pharmacy and clinic, the compounding of traditional medicines, and the traditional pharmacist system. However, it was meaningful that the law was the turning point of the institutionalization of pharmaceutical administration after the Korean Liberation.


Novel anti-flavivirus drugs targeting the nucleolar distribution of core protein.
The risk of infectious diseases caused by Flavivirus is increasing globally. Here, we developed a novel high-throughput screening (HTS) system to evaluate the inhibitory effects of compounds targeting the nuclear localization of the flavivirus core protein. We screened 4000 compounds based on their ability to inhibit the nuclear localization of the core protein, and identified over 20 compounds including inhibitors for cyclin dependent kinase and glycogen synthase kinase. The efficacy of the identified compounds to suppress viral growth was validated in a cell-based infection system. Remarkably, the nucleolus morphology was affected by the treatment with the compounds, suggesting that the nucleolus function is critical for viral propagation. The present HTS system provides a useful strategy for the identification of antivirals against flavivirus by targeting the nucleolar localization of the core protein.


Postsurgical cerebral perfusion changes in idiopathic normal pressure hydrocephalus: a statistical parametric mapping study of SPECT images.
Our goal was to study cerebral blood flow (CBF) changes after surgery in a group of 15 patients with idiopathic normal pressure hydrocephalus (NPH). We used hexamethylpropyleneamine oxime SPECT and statistical parametric mapping (SPM), an image analysis method that does not require prior selection of regions of interest. Our study showed areas of significant increase in perfusion in specific regions of both frontal lobes and the right parietal lobe. Regions of increased perfusion were found in the left prefrontal dorsolateral areas (Brodmann's areas 9 and 45 or 47), right frontal premotor area (Brodmann's area 44), right medial prefrontal region (Brodmann's area 10 or 32), right frontal white matter area (superior longitudinalis fasciculus), and right basal ganglia (lenticular nucleus, putamen, and globus pallidus). In the right hemisphere, another region of increased perfusion was found in the inferior parietal lobule (Brodmann's area 40). The 2 areas most related to clinical improvement were Brodmann's area 32 and the frontal part of the left lobule of Reil insula. The results obtained with the SPM method of image analysis confirm and expand on previous CBF literature in NPH, with specific CBF regions located in frontal and parietal areas that improve after surgery in idiopathic NPH.


High-pressure phases and transitions of the layered alkaline earth nitridosilicates SrSiN(2) and BaSiN(2).
We investigate the high-pressure phase diagram of SrSiN(2) and BaSiN(2) with density-functional calculation. Searching a manifold of possible candidate structures, we propose new structural modifications of SrSiN(2) and BaSiN(2) attainable in high-pressure experiments. The monoclinic ground state of SrSiN(2) transforms at 3 GPa into an orthorhombic BaSiN(2) type. At 14 GPa a CaSiN(2)-type structure becomes the most stable configuration of SrSiN(2). A hitherto unknown Pbcm modification is adopted at 85 GPa and, finally, at 131 GPa a LiFeO(2)-type structure. The higher homologue BaSiN(2) transforms to a CaSiN(2) type at 41 GPa and further to a Pbcm modification at 105 GPa. Both systems follow the pressure-coordination rule: the coordination environment of Si increases from tetrahedral through trigonal bipyramidal to octahedral. Some high-pressure phases are related in structure through simple group-subgroup mechanisms, indicating displacive phase transformations with low activation barriers.


The loss of student idealism in the 3rd-year clinical clerkships.
The purpose of this study was to specify how student attitudes toward different types of patients and the profession change during clinical rotations. A questionnaire was given to all medical students prior to 3rd-year rotations regarding their attitudes toward the medical profession and patient types. It was given again after students completed their 16-week medicine-surgery clerkship. Eighty-eight of 96 students responded to pre- and posttests. Students became less idealistic toward two patient groups: the elderly and people with chronic pain. After clerkship, students believed a greater percentage of the elderly were demented (26% increasing to 35%, p = .09 and that a greater percentage of patients with chronic pain are drug seekers (15% increasing to 24%, p = .004). The authors conclude that in the 3rd year of medical school students become less idealistic toward elderly patients, those with chronic pain, and the profession.


Test characteristics of the respiratory syncytial virus enzyme-linked immunoabsorbent assay in febrile infants < or = 60 days of age.
The test characteristics of rapid tests for respiratory syncytial virus (RSV) in infants may differ from older children secondary to a lower likelihood of previous illness with RSV. Our main goal was to establish the test characteristics of the RSV Abbott Testpack (TP) enzyme-linked immunoabsorbent assay (EIA) in febrile infants < or = 60 days of age. Our secondary goal was to determine the likelihood of RSV given a particular clinical syndrome and a negative or positive EIA. A prospective sample of infants with a temperature > or = 38.0 degrees C was evaluated during 2 successive RSV seasons. Conventional tissue and shell vial viral cultures were utilized as the reference standard. The RSV Abbott Testpack EIA had a sensitivity of 75% (95% CI 60-90%), a specificity of 98% (95% CI 96-100%), a positive predictive value of 89% (95% CI 77-100%), a negative predictive value of 95% (95% CI 91-98%), a likelihood ratio for a positive test of 35.5 (95% CI 11.4-110.7), and a likelihood ratio for a negative test of 0.26 (95% CI 0.14-0.47). Even with a negative EIA, patients with lower and upper respiratory tract illness still had a 22.3% and 5.5% chance of harboring RSV, respectively. The RSV Abbott Testpack is a useful diagnostic tool in the detection of RSV in febrile infants but has limitations. During months typically associated with RSV disease, a positive RSV TP indicates a high likelihood of illness, but clinicians should be wary of false negatives.


Insulin-like growth factor 1 (IGF-1), IGF-1 density, and IGF-1/PSA ratio for prostate cancer detection.
Recent studies suggest an association between increased serum levels of insulin-like growth factor 1 (IGF-1) and an increased risk of prostate cancer (PCa). We prospectively analyzed the value of IGF-1, IGF-density (IGFD), and IGF-1/prostate-specific antigen (PSA) ratio for early detection of prostate cancer. IGF-1, IGFD, and IGF-1/PSA ratio were determined prospectively during an 11-month period in the serum from 245 consecutive white men with PSA levels between 2.5 and 15 ng/mL. Octant biopsy (including transition zone biopsy) was performed. A second biopsy was performed 6 weeks later if the first biopsy was negative. Prostate volume was measured using transrectal ultrasound and the prolate ellipsoid method. Receiver operating characteristic curves were performed to compare tests. No evidence of malignancy was found in 174 patients (71%), and PCa was found in 71 (29%). The mean age for patients with no evidence of malignancy and those with PCa was 67.7+/-9 and 65.7+/-6 years, respectively (P = 0.17). IGF-1, IGFD, IGF-1/PSA ratio, and PSA were significantly higher in patients with PCa than in those with benign disease (P = 0.03, P = 0.045, P = 0.001, and P = 0.018, respectively). The area under the curve value derived from the receiver operating characteristic curves for IGF-1/PSA ratio, PSA, IGFD, and IGF-1 was 71%, 61%, 60%, and 58%, respectively. At 95% sensitivity, the specificity of the IGF-1/PSA ratio was significantly greater than that of all other parameters (P<0.0001 ). An IGF-1/PSA cutoff value of 25 afforded a 95% sensitivity for detecting PCa and would have avoided unnecessary biopsies in 24.1% of patients. Although IGF-1 and IGFD were unable to enhance the performance of PSA in our study, the IGF-1/PSA ratio significantly improved PCa detection over the use of PSA alone. Thus, increased IGF-1 levels (i.e., the IGF-1/PSA ratio) may not only be associated with an increased PCa risk but may also be a useful tool for early detection.


X-ray sources based on subpicosecond-laser-produced plasmas.
The production of an efficient user friendly ultrafast x-ray source requires an understanding of the role of the various factors which affect the x-ray emission. Here we examine several issues which control the source brightness and the pulse duration. Picosecond time-resolved, high spectral resolution spectroscopy is used to study plasmas produced by a subpicosecond laser pulse with intensity between 1016 W/cm2 and 5 × 1018 W/cm2.


Determination of phenyltoloxamine salicylamide, caffeine, paracetamol, codeine and phenacetin by HPLC.
A reversed-phase high-performance liquid chromatographic method for the determination of six common analgesics (phenyltoloxamine dihydrogen citrate, salicylamide, caffeine, paracetamol, codeine phosphate and phenacetin) is presented. The method is specific for detection and determination of each of these compounds in a complex mixture, without pretreatment. A 10-mum C(18) silica gel stationary phase is used with a methanol-acetonitrile-water-tetrahydrofuran mixture (20:20:55:5 v/v) and spectrophotometric detection at 254 nm. All six components are eluted within 7 min. The method has given good results for three commercial products containing two, three and five active ingredients respectively. Phenacetin, a common analgesic which might be found in other formulations, is used as an internal standard.


Cellulosilyticum ruminicola gen. nov., sp. nov., isolated from the rumen of yak, and reclassification of Clostridium lentocellum as Cellulosilyticum lentocellum comb. nov.
An obligate anaerobic, Gram-staining-negative, mesophilic, cellulolytic bacterium, strain H1(T), was isolated from the rumen content of yak. Cells were straight to slightly curved rods, 0.8-1.0 x 3.0-4.0 microm in size, non-motile and encapsulated with mucous materials. Elliptical and terminal spores that swelled the cells were produced occasionally. The strain grew at 25-45 degrees C (optimum, 38 degrees C) and pH 6.0-7.8 (optimum, pH 6.7). Cellulose, cellobiose, xylan, xylose and maltose were used as carbon and energy sources, but not glucose. Products from cellulose and cellobiose fermentation were formic acid, acetic acid, carbon dioxide and trace amounts of ethanol, lactic acid and succinic acid. The genomic DNA G+C content was 33.7+/-1.2 mol%. The predominant fatty acids were C(16 : 0) (27.1 %), C(14 : 0) (9.2 %) and iso-C( 16 : 0) (6.4%). Based on the 16S rRNA gene sequence analysis, strain H1(T) was affiliated to the clostridial rRNA cluster XIVb and showed the highest 16S rRNA gene sequence similarity to Clostridium lentocellum DSM 5427(T) (96.0 %). These two strains formed a distinct lineage of the family 'Lachnospiraceae '. Based on data from this polyphasic taxonomic study, a new genus, Cellulosilyticum gen. nov., is proposed. Cellulosilyticum ruminicola sp. nov. is proposed for strain H1(T). The type strain of Cellulosilyticum ruminicola sp. nov. is strain H1(T) (=CGMCC 1.5065(T)=JCM 14822(T)). Clostridium lentocellum was reclassified in the new genus as Cellulosilyticum lentocellum comb. nov. (type strain RHM5(T)=ATCC 49066( T)=DSM 5427(T)=NCIMB 11756(T)).


Habituation of LG-mediated tailflip in the crayfish.
Crayfish escape from threatening stimuli by tailflipping. If a stimulus is applied to the rear, crayfish escape up and forwards in a summersault maneuver that is mediated by the activation of lateral giant (LG) interneurons. The occurrence probability of LG-mediated tailflip, however, diminishes and habituates if a stimulus is repeatedly applied. Since crayfish have a relatively simple CNS with many identifiable neurons, crayfish represent a good animal to analyze the cellular basis of habituation. A reduction in the amplitude of the EPSP in the LGs, caused by direct chemical synaptic connection from sensory afferents by repetitive stimulations, is essential to bring about an inactivation of the LGs. The spike response of the LGs recovers within several minutes of habituation, but the LGs subsequently fail to spike when an additional stimulus is applied after specific periods following habituation. These results indicate that a decline in synaptic efficacy from the mechanosensory afferents recovers readily after a short delay, but then the excitability of the LGs themselves decreases. Furthermore, the processes underlying habituation are modulated depending on a social status. When two crayfish encounter each other, a winner-loser relationship is established. With a short interstimulus interval of 5 s, the rate of habituation of the LG in both socially dominant and subordinate crayfish becomes lower than in socially isolated animals. Serotonin and octopamine affect this social status-dependent modulation of habituation by means of activation of downstream second messenger system of cAMP and IP3 cascades, respectively.


Integrating advances in insulin into clinical practice: Effective utilization of insulin in patient management.
The management of a patient with type 2 diabetes mellitus (T2DM) is typically a long-term process characterized by evolving strategies to meet and maintain the patient's glycemic, cardiovascular, lifestyle, and other goals.


Cardiovascular symptoms and longitudinal declines in processing speed differentially predict cerebral white matter lesions in older adults.
It is well established that cerebral white matter lesions (WML), present in the majority of older adults, are associated with cardiovascular and cerebrovascular diseases and also with cognitive decline. However, much less is known about how WML are related to other important individual characteristics and about the generality vs. brain region-specificity of WML. In a longitudinal study of 112 community-dwelling adults (age 50-71 years at study entry), we used a machine learning approach to evaluate the relative strength of 52 variables in association with WML burden. Variables included socio-demographic, lifestyle, and health indices-as well as multiple cognitive abilities (modeled as latent constructs using factor analysis)-repeatedly measured at three- to six-year intervals. Greater chronological age, symptoms of cardiovascular disease, and processing speed declines were most strongly linked to elevated WML burden (accounting for ∼49% of variability in WML). Whereas frontal lobe WML burden was associated both with elevated cardiovascular symptoms and declines in processing speed, temporal lobe WML burden was only significantly associated with declines in processing speed. These latter outcomes suggest that age-related WML-cognition associations may be etiologically heterogeneous across fronto-temporal cerebral regions.


Two new species of Ascarophis (Nematoda: Cystidicolidae) in marine fishes from Chile.
In this study, we describe 2 new species of Ascarophis van Beneden, 1871 (Nematoda: Cystidicolidae), found in fishes from southern Chile. Ascarophis carvajali n. sp. was found in Austrolycus depressiceps and Patagonotothen cornucola, whereas Ascarophis draconi n. sp. was taken from Champsocephalus gunnari. These new Ascarophis species differ from other species in a combination of several morphometric and morphological characteristics. Although A. carvajali n. sp. was morphologically close to Ascarophis minuta, the new species has a larger ratio between glandular and muscular esophagus, filaments on both egg poles, and a shorter right spicule than A. minuta. Ascarophis draconi n. sp. was morphologically similar to Ascarophis adioryx and Ascarophisfiliformis. However, A. adioryx has eggs without filaments, a smaller ratio between glandular and muscular esophagus length, and a smaller ratio between left and right spicule lengths in contrast to A. draconi n. sp., whereas A. filiformis has a shorter glandular esophagus and left spicule length than A. draconi n. sp. Only 1 Ascarophis species has been recorded in a single fish from Chile (i.e., Ascarophis sebastodis in Sebastes capensis). Consequently, this study constitutes not only new species and records of Ascarophis in fishes from Chile, but also new records for the Pacific coast of South America.


The development of a febrile response to pyrogen in the thyroid-deficient rabbit.
The development of the febrile response to E. coli lipopolysaccharide (1.5 micrograms/kg, i.v.) in thyroid-deficient rabbits has been studied. Twenty-eight New Zealand White rabbits weighing 2.1-2.3 kg were used. Hypothyroidism was induced by treatment with propylthiouracil (100 or 200 mg/kg body wt./15 days). Thyroid-deficient animals showed a reduction in the febrile response to lipopolysaccharide, but the effect was significantly different (p less than 0.01) from the control only for rabbits treated with 200 mg/kg of propylthiouracil. Propranolol (2 mg/kg, i.p.) given 30 min before lipopolysaccharide also reduced (p less than 0.01) the fever response in control rabbits. The results of this experiment are consistent with the hypothesis that the reduction in the febrile response of thyroid-deficient rabbits is due to the reduced number of beta-adrenergic receptors, or to a change in the availability of neurotransmitter in thermogenically active tissues, such as brown fat.


During transitions proteins make fleeting bonds.
How do proteins efficiently and precisely shift from one conformation to another? Gardino et al. (2009) show that transient hydrogen bonds are critical to the conformational transition of the nitrogen regulatory protein NtrC between its native state and its active state.


Differences in faecal bacteria populations and faecal bacteria metabolism in healthy adults and celiac disease patients.
Differences in the intestinal microbiota between children and adults with celiac disease (CD) have been reported; however, differences between healthy adults and adults with CD have not been clearly demonstrated. The aim of this study was to evaluate the differences in the intestinal microbiota between adults with CD and healthy individuals. Microbial communities in faecal samples were evaluated by PCR-denaturing gradient gel electrophoresis (DGGE) and gas-liquid chromatography of short chain fatty acids (SCFAs). The study group included 10 untreated CD patients, 11 treated CD patients and 11 healthy adults (in normal gluten diet and in GFD). UPGMA clustered the dominant microbial communities of healthy individuals together and separated them from the dominant microbial communities of the untreated CD patients. Most of the dominant microbial communities of the treated CD patients clustered together with those of healthy adults. The treated CD patients showed a reduction in the diversity of Lactobacillus and Bifidobacterium species. The presence of Bifidobacterium bifidum was significantly higher in untreated CD patients than healthy adults. There was a significant difference between untreated CD patients and healthy adults, as well as between treated CD patients and healthy adults, regarding acetic acid, propionic acid, butyric acid, and total SCFAs. healthy adults have a different faecal microbiota from that of untreated CD patients. A portion of the treated CD patients displayed a restored "normal" microbiota. The treated CD patients significantly reduce the Lactobacillus and Bifidobacterium diversity. Healthy adults have a different faecal SCFAs content from that of CD patients.


[Hemophagocytic lymphohistiocytosis. Experience in 27 patients].
Hemophagocytic lymphohistiocytosis (HLH) is an aggressive and life-threatening syndrome of excessive immune activation Aim: To describe the clinical characteristics, causes and survival associated with HLH. Review of medical records of patients with HLH attended between 2004 and 2016. They were classified according to their probable cause in: associated with immunosuppression, cancer, post-infectious or idiopathic. Kaplan-Meier survival analysis was performed. Twenty seven patients with HLH aged 18 to 87 years (59% men), were detected. Fourteen (52%) were secondary to immunosuppression, six (22%) were post-infectious, five (18%) were associated with cancer and two (7%) were of unknown cause. There were no significant differences in clinical or laboratory features between these etiologies. Within the immunosuppressed group, 12 (86%) were patients with oncologic or hematologic diseases or bone marrow transplantation. Associated cancers were mostly oncohematologic diseases. Thirty-day mortality was 53.4% (95% confidence intervals (CI) 32.7-70.3%), despite the treatment. Mortality was significantly associated with the presence of renal failure with a hazard ratio (HR) of 3.4 (95% CI of 1.2-9.9, p =0.025). Treatment of the underlying disease proved to be protective against mortality with an HR of 0.3 (95% CI 0.1 to 0.98, p = 0.046). The prognosis of HLH could be related to the treatment of the underlying disease. The study of the pathophysiology of this syndrome will allow a better understanding and treatment.


Resveratrol neuroprotective effects during focal cerebral ischemia injury via nitric oxide mechanism in rats.
Our prior study showed that resveratrol could suppress infarct volume and exert neuroprotective effect on rats subjected to focal cerebral ischemia (FCI) injury. Recently, it has been reported in some literature that resveratrol protects the spinal cord, kidney, and heart from ischemia-reperfusion injury through upregulation of nitric oxide (NO). Therefore, this study was designed to investigate the role of nitric oxide on the neuroprotective mechanisms of resveratrol on rats after FCI injury. The FCI injury was induced by the middle cerebral artery (MCA) occlusion for 1 hour and then a 24-hour reperfusion followed in the anesthetized Long-Evans rats. Resveratrol was intravenously injected after 1 hour MCA occlusion. Treatment of resveratrol (0.1 and 1 microg/kg) decreased the lactate dehydrogenase (LDH) in plasma and malondialdehyde (MDA) in FCI injury brain tissue, whereas the level of NO in plasma was increased. In addition, resveratrol downregulated protein and mRNA expression of inducible nitric oxide synthase (iNOS), and upregulated protein and mRNA expression of endothelial nitric oxide synthase (eNOS), while the expression of protein and mRNA of neuronal nitric oxide synthase (nNOS) was unchanged. Pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME, the nonselective NOS inhibitor) or L-N(5)-(1-iminoethyl)-ornithine (L-NIO, the eNOS selective inhibitor) completely blocked the effect of resveratrol in decreasing infarction volumes. This study demonstrated the important role of NO in the neuroprotective effect of resveratrol in FCI injury.


False positive of an immunochromatography kit for detection of norovirus in neonatal feces.
Norovirus was detected in the feces from five neonates in the growing care unit by a rapid immunochromatography (ICG) kit. However, confirmation using reverse transcription polymerase chain reaction (RT-PCR), RT-loop-mediated isothermal amplification (RT-LAMP), and nested RT-PCR methods showed negative results from all the feces. In addition, the ICG test for the detection of norovirus was positive for four cases out of the 16 feces from other asymptomatic neonates/infants. Only one feces out of the four samples was positive by RT-LAMP. In this study, among the factors related to false positives with the norovirus ICG kit, there were no differences regarding the commencement of feeding, nutrition, and sample collection methods. Since the false positive rate of ICG in the diagnosis of norovirus infection in neonates and early infancy is high, ICG is not an appropriate method, and it is necessary to confirm the results using reliable methods like RT-PCR.


Defining and improving postoperative care.
Although much is known regarding the importance of postoperative care, the surveillance of patients after 30 days from the surgical procedure can be improved. It must be recognized that mortality between 30 and 90 days exceeds what is commonly considered "operative mortality"—death within 30 days of surgery. Significant effort should be dedicated to the design of predictive models to prevent readmission. More importantly, surgeons must develop better models to manage the complications that arise after readmission to prevent mortality in readmitted patients. Finally, current guidelines for oncologic surveillance are an area of controversy, and future studies are needed for better direction of resources.


Duplication of the internal carotid artery presenting with severe atherosclerotic stenosis.
Duplication of the extracranial internal carotid artery is a rare anatomic variant. We present the first patient with unilateral duplication of the cervical internal carotid artery with severe stenosis. Stent-assisted percutaneous transluminal angioplasty was successfully performed to restore blood flow. We discuss the angiographic findings and endovascular treatment.


Host defence versus intraspecific competition in the regulation of infrapopulations of the flea Xenopsylla conformis on its rodent host Meriones crassus.
Mechanisms that regulate parasite populations may influence the evolution of hosts and parasites, as well as the stability of host-parasite dynamics but are still poorly understood. A manipulation experiment on the grooming ability of rodent hosts (Meriones crassus) and flea (Xenopsylla conformis) densities on these hosts successfully disentangled two possible regulating mechanisms: (i) behavioural defence of the host and (ii) intraspecific competition among parasites, and revealed their importance in suppressing the feeding of fleas. Moreover, the results suggest that flea competition is direct and is not mediated by host grooming, immune response, or parasite-induced damage to the host. These mechanisms, together with interspecific competition and density-dependent parasite-induced host damage, may limit the parasite burden on an individual host and may prevent parasites from overexploiting their host population.


Physical recovery in intensive care unit survivors: a cohort analysis.
Some survivors of critical illness experience poor physical recovery, but which patients experience the most compromise during recovery is unknown. To identify factors associated with physical recovery by using the 6-minute walk test in adult survivors of critical illness 26 weeks after discharge from the hospital. A total of 195 adult survivors of a critical illness were enrolled in a multicenter trial of physical rehabilitation after discharge from the hospital. The 6-minute walk test, the 36-Item Short Form Health Survey, and sleep rated on a 5-point scale were completed at weeks 1 and 26. Clinical and demographic data were obtained from patient records. A total of 145 patients completed the 26-week test. Of these, 94 (65%) increased the distance walked in 6 minutes by at least 75 m from the 1-week value and were therefore considered to have improved on the test. Factors associated with improvement included moderate to severe sleeping problems in week 1, moderate to vigorous exercise in week 26, and higher vitality in week 26. Conversely, respiratory problems and higher social functioning in week 1 were associated with less improvement in the distance walked. Multiple factors are associated with physical recovery after critical illness. Interventions to target multidimensional aspects of recovery such as sleep and exercise may result in improved physical function after critical illness.


Edge Contact for Carrier Injection and Transport in MoS2 Field-Effect Transistors.
The contact properties of van der Waals layered semiconducting materials are not adequately understood, particularly for edge contact. Edge contact is extremely helpful in the case of graphene, for producing efficient contacts to vertical heterostructures, and for improving the contact resistance through strong covalent bonding. Herein, we report on edge contacts to MoS2 of various thicknesses. The carrier-type conversion is robustly controlled by changing the flake thickness and metal work functions. Regarding the ambipolar behavior, we suggest that the carrier injection is segregated in a relatively thick MoS2 channel; that is, electrons are in the uppermost layers, and holes are in the inner layers. Calculations reveal that the strength of the Fermi-level pinning (FLP) varies layer-by-layer, owing to the inhomogeneous carrier concentration, and particularly, there is negligible FLP in the inner layer, supporting the hole injection. The contact resistance is large despite the significantly reduced contact resistivity normalized by the contact area, which is attributed to the current-crowding effect arising from the narrow contact area.


Polarization controlled multi-wavelength Er-doped fiber laser using fiber Bragg grating written in few-mode side-hole fiber with an elliptical core.
We propose and experimentally demonstrate a novel method for multi-wavelength erbium-doped fiber laser by using fiber Bragg gratings written in few-mode side-hole fiber with an elliptical core. The resonance peaks can be made to split by properly adjusting the polarization state due to the high birefringence of the fiber with the elliptical core. The number of lasing wavelengths can thus be switched using the polarization controller. This multi-wavelength laser has the advantages of low cost, novel and simple configuration.


Optical approach to concurrence and polarization.
We address a recently established relationship, C2+P2=1, which engages concurrence (C) and polarization (P). This relationship has revealed a striking connection between two seemingly unrelated measures. Indeed, while C quantifies entanglement, which is widely seen as a quantum information resource, P quantifies the amount of coherence between optical field components. We discuss the conditions under which C and P may be related to one another and show how the optical approach discloses entanglement as a resource that may be found in both the quantum and the classical domain. This is confirmed by a proposed Bell violation that can be exhibited using either quantum or classical light.


[Frequency characteristics of central neurons of the electroreceptor system of the skate in response to exposure to electric and magnetic fields].
Responses of single units to sinusoidal homogenous electrical and magnetic field stimulation were studied in the lateral-line lobes of the skate Raja radiata. The voltage gradient thresholds were in the range of 0.03-10 microV/cm. Optimal frequency ranges for electrical and magnetic stimuli were 0.05-0.5 and 2-3 Hz, respectively. Possible mechanisms and functional significance of frequency characteristics of the neurons are discussed.


The research career of Richard B. Stein (1940-).
This report reviews the research and mentoring career of Richard B. Stein (1940-). In 1962, he completed a B.S. degree in physics at the Massachusetts Institute of Technology, USA, and thereafter an M.A. (1964), Ph.D. (1966), and postdoctoral training (1966-68) at the University of Oxford, UK. He subsequently assumed a faculty position at the University of Alberta (Canada), where he is currently an active researcher and mentor. To this point in 2004, Stein has trained and collaborated closely with over 160 scientists, largely neuroscientists and biomedical engineers, from 27 countries. He and his former trainees and collaborators have made important contributions on topics that span the cellular-to-behavioral spectrum of movement and rehabilitation-prosthetics neuroscience. His mentors, trainees, and collaborators include scientists whose countries of origin are: Australia, 2; Austria, 1; Belgium, 1; Bulgaria, 1; Canada, 64; China, 6; Denmark, 1; Germany, 1; Great Britain, 16; Hong Kong, 4; India, 5; Iraq, 2; Italy, 2; Japan, 10; Kenya, 1; New Zealand, 4; Pakistan, 1; Palestine, 1; Poland, 1; Romania, 1; South Africa, 1; Sri Lanka, 1; The Netherlands, 1; Turkey, 1; Uruguay, 1; USA, 21; and Yugoslavia, 6. In all instances, Stein's research collaborations and mentoring have advanced the careers of his trainees and junior collaborators, a well-deserved and important compliment to a stellar movement neuroscientist.