Octreotide for recurrent intestinal variceal bleeding in patients without portal hypertension.
We report on the efficacy of octreotide acetate in two patients with intestinal phlebectasia and no evidence of portal hypertension or mesenteric thrombosis. Patient 1 was a 46-year-old woman with primary pulmonary arterial hypertension. She required repeated transfusions for recurrent episodes of gastrointestinal bleeding (GIB). Intraoperative enteroscopy revealed wide-spread small bowel phlebectasia and intestinal resection was not performed. Blue rubber-bleb syndrome, portal hypertension and mesenteric thrombosis were ruled out. Octreotide acetate long-acting release was started. A transient interruption in treatment was followed by severe overt GIB. This was effectively controlled with continuous infusion of octreotide acetate. After this episode, octreotide acetate long-acting release was resumed and no further episodes of GIB have been reported until the most recent follow up (total duration of 74 months). Patient 2 was a 51-year-old woman with a history of recurrent GIB requiring multiple blood transfusions since young adulthood with negative endoscopic investigations. An enteroscopy showed numerous submucosal serpiginous varices in the colon and the terminal ileum. All putative causes including portal hypertension or mesenteric thrombosis were ruled out. Monthly intramuscular injections of long-acting octreotide acetate were initiated, and no GIB occurred since then (27 months of follow up). Somatostatin analogues are known to reduce splanchnic blood flow, to increase vascular resistance, to enhance platelet aggregation; and are thus efficacious in preventing GIB secondary to various vascular lesions (portal hypertension, intestinal angiodysplasia and blue rubber-bleb syndrome). These case reports suggest that they are also effective in preventing GIB in intestinal phlebactasia without portal hypertension.


[Modified evaluation of allergic skin reactions].
Our modified evaluation of the results of investigating experimental allergy includes, apart from the percentage of sensitized animals as in all hitherto applied evaluations, appraisal of "challenge" reactions and results of supplementary in vitro studies in the examined animals' blood. Basing on the formula of the percentage index of the total evaluation of the study - W% = (formula: see text) X100 (a - percentage of sensitized animals; b - index of the total evaluation of reactions intensity, c - results of auxiliary tests in peripheral blood), the effects of allergens were differentiated. Introduction of our own evaluating criteria enabled differentiation of the intensity of effects of the test allergens, which was unfeasible with the hitherto applied Magnusson and Kligman criterion.


Rh(III)-catalyzed dual directing group assisted sterically hindered C-H bond activation: a unique route to meta and ortho substituted benzofurans.
A new strategy for the synthesis of highly substituted benzofurans from meta-substituted hydroxybenzenes and alkynes via a rhodium(III)-catalyzed activation of a sterically hindered C-H bond is demonstrated. A possible mechanism involving dual directing group assisted ortho C-H bond activation is proposed.


Intense exercise training and immune function.
Regular moderate exercise reduces the risk of infection compared with a sedentary lifestyle, but very prolonged bouts of exercise and periods of intensified training are associated with increased infection risk. In athletes, a common observation is that symptoms of respiratory infection cluster around competitions, and even minor illnesses such as colds can impair exercise performance. There are several behavioral, nutritional and training strategies that can be adopted to limit exercise-induced immunodepression and minimize the risk of infection. Athletes and support staff can avoid transmitting infections by avoiding close contact with those showing symptoms of infection, by practicing good hand, oral and food hygiene and by avoiding sharing drinks bottles and cutlery. Medical staff should consider appropriate immunization for their athletes particularly when travelling to international competitions. The impact of intensive training stress on immune function can be minimized by getting adequate sleep, minimizing psychological stress, avoiding periods of dietary energy restriction, consuming a well-balanced diet that meets energy and protein needs, avoiding deficiencies of micronutrients (particularly iron, zinc, and vitamins A, D, E, B6 and B12), ingesting carbohydrate during prolonged training sessions, and consuming - on a daily basis - plant polyphenol containing supplements or foodstuffs and Lactobacillus probiotics.


Bone strength and related traits in HcB/Dem recombinant congenic mice.
Fracture susceptibility depends jointly on bone mineral content (BMC), gross bone anatomy, and bone microarchitecture and quality. Overall, it has been estimated that 50-70% of bone strength is determined genetically. Because of the difficulty of performing studies of the genetics of bone strength in humans, we have used the HcB/Dem series of recombinant congenic (RC) mice to investigate this phenotype. We performed a comprehensive phenotypic analysis of the HcB/Dem strains including morphological analysis of long bones, measurement of ash percentage, and biomechanical testing. Body mass, ash percentage, and moment of inertia each correlated moderately but imperfectly with biomechanical performance. Several chromosome regions, on chromosomes 1, 2, 8, 10, 11, and 12, show sufficient evidence of linkage to warrant closer examination in further crosses. These studies support the view that mineral content, diaphyseal diameter, and additional nonmineral material properties contributing to overall bone strength are controlled by distinct sets of genes. Moreover, the mapping data are consistent with the existence of pleiotropic loci for bone strength-related phenotypes. These findings show the importance of factors other than mineral content in determining skeletal performance and that these factors can be dissected genetically.


Identification of tumor-associated proteins in oral tongue squamous cell carcinoma by proteomics.
Oral tongue carcinoma is an aggressive tumor that particularly affects chronic smokers, drinkers and betel squid chewers. Patients often present symptoms at a late stage, and there is a high recurrence rate after treatment. In this article, we report the first proteomic analysis of oral tongue carcinoma to globally search for tumor related proteins. Apart from helping us to understand the molecular pathogenesis of the carcinoma, these proteins may also have potential clinical applications as biomarkers, enabling the tumor to be identified at an early stage in high risk individuals, treatment response to be predicted, and residual or recurrent carcinoma to be detected sooner after treatment. The protein expression profiles of ten oral tongue squamous cell carcinomas and their matched normal mucosal resection margins were examined by two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization-time of flight mass spectroscopy. A number of tumor-associated proteins including heat shock protein (HSP)60, HSP27, alpha B-crystalline, ATP synthase beta, calgranulin B, myosin, tropomyosin and galectin 1 were consistently found to be significantly altered in their expression levels in tongue carcinoma tissues, compared with their paired normal mucosae. The expression profile portrays a global protein alteration that appears specific to oral tongue cancer. The potential of utilizing these tumor related proteins for screening cancer and monitoring recurrence warrants further investigation.


Integrative mRNA-miRNA interaction analysis associate with immune response of sea cucumber Apostichopus japonicus based on transcriptome database.
MicroRNAs (miRNAs) constitute a family of endogenous non-coding small RNAs that have been demonstrated to be the key effectors in mediating host-pathogen interactions. Additionally, high-throughput sequencing provides unexampled opportunities to identify the pathogenic mechanism underlying miRNAs. In the present study, the target genes of immune-related miRNAs (miR-31, miR-2008, miR-92a, miR-210 and miR-7) and specific miRNAs (miR-2004) in Echinodermata were predicted in silico and validated. Gene ontology (GO) analysis of the target genes of these six miRNAs were conducted to further understand the regulatory function in the host immunity of Apostichopus japonicus (A. japonicus). Among the putative target genes of the six miRNAs, various immune-related targets were annotated, such as Nephl, SEC14Ll, p105, GL2, LYS, FNIAL, mTOR, LITAF, SLC44, TLR3, Apaf-1, and CNTN4. This work will provide valuable genetic resources to understand the interaction of multiple mRNA-miRNAs and the regulation mechanism in the anti-bacterial process in the sea cucumber.


Analysis of a time-delayed mathematical model for tumour growth with an almost periodic supply of external nutrients.
In this paper, the existence, uniqueness and exponential stability of almost periodic solutions for a mathematical model of tumour growth are studied. The establishment of the model is based on the reaction-diffusion dynamics and mass conservation law and is considered with a delay in the cell proliferation process. Using a fixed-point theorem in cones, the existence and uniqueness of almost periodic solutions for different parameter values of the model is proved. Moreover, by the Gronwall inequality, sufficient conditions are established for the exponential stability of the unique almost periodic solution. Results are illustrated by computer simulations.


Clinical and Microbiological Characterization of Invasive Pulmonary Aspergillosis Caused by Aspergillus lentulus in China.
Invasive aspergillosis (IA) due to Aspergillus lentulus is associated with high mortality. In this study, we investigated the clinical and microbiological characteristics of 6 fatal cases of proven or probable IA caused by A. lentulus in China. Underlying immunosuppression, prior antifungal exposure, and intensive care unit (ICU) hospitalization were important risk factors for invasive A. lentulus infection. Phenotypic differences were observed for A. lentulus isolates including slower growth, reduced sporulation, and inability to grow at 48°C, compared with Aspergillus fumigatus complex. ITS sequencing was unable to distinguish A. lentulus from A. fumigatus, but sequencing of the benA, CaM, and rod A loci enabled reliable distinction of these closely related species. Phylogenetic analysis further confirmed that the ITS region had little variation within the Aspergillus section Fumigati while the benA gene offered the highest intraspecific discrimination. Microsatellite typing results revealed that only loci on chromosomes 1, 3, 5, and 6b generated detectable amplicons for identification. All A. lentulus isolates showed in vitro resistance to multiple antifungal drugs including amphotericin B (MIC range 4 to 8 μg/ml), itraconazole (MIC 2 μg/ml), voriconazole (MIC of 4-16 μg/ml), and posaconazole (MIC of 0.5-1 μg/ml). However, MECs for the echinocandin drugs ranged from 0.03-0.25, ≤0.008-0.015, and ≤0.015-0.03 μg/ml for caspofungin, micafungin, and anidulafungin, respectively. A. lentulus is an emerging fungal pathogen in China, causing fatal disease, and clinicians as well as laboratories should be alert to their increasing presence.


Borrelidin has limited anti-cancer effects in bcl-2 overexpressing breast cancer and leukemia cells and reveals toxicity in non-malignant breast epithelial cells.
Clinically effective anti-cancer drugs have to tread a narrow line between selective cytotoxicity on tumor cells and tolerable adverse effects against healthy tissues. This causes the failure of many potential cancer drugs in advanced clinical trials, hence signifying the importance of a comprehensive initial estimate of the cytotoxicity of prospective anti-cancer drugs in preclinical studies. In this study, the cytotoxicity of borrelidin, a macrolide antibiotic with a high cytotoxic selectivity for proliferating endothelial cells and leukemia cells, was tested on malignant and non-malignant breast cells. Highly metastatic breast cancer cell lines (MDA-MB-231 and MDA-MB-435) showed promising results and exhibited good sensitivity to borrelidin at low nanomolar concentrations, but borrelidin was cytotoxic to a non-malignant breast epithelial cell line (MCF10A) as well. Furthermore, although a high sensitivity of endothelial cells (human umbilical vein endothelial cells; HUVEC) and individual leukemia cell lines (Jurkat and IM9) to borrelidin was confirmed in this study, another leukemia cell line (HL60) and an immortalized endothelial cell line (EA.hy926) displayed a significantly decreased sensitivity. Reduced sensitivity to borrelidin was associated with elevated bcl-2 expression in these cell lines. In conclusion, the results presented show that borrelidin displays high and selective cytotoxicity against subgroups of cancer cells and endothelial cells, but, owing to its non-specific toxicity to non-malignant cells, its clinical application might be restricted because of likely adverse effects and limited efficacy in bcl2-overexpressing cancer cells.


War of ontology worlds: mathematics, computer code, or Esperanto?
The use of structured knowledge representations-ontologies and terminologies-has become standard in biomedicine. Definitions of ontologies vary widely, as do the values and philosophies that underlie them. In seeking to make these views explicit, we conducted and summarized interviews with a dozen leading ontologists. Their views clustered into three broad perspectives that we summarize as mathematics, computer code, and Esperanto. Ontology as mathematics puts the ultimate premium on rigor and logic, symmetry and consistency of representation across scientific subfields, and the inclusion of only established, non-contradictory knowledge. Ontology as computer code focuses on utility and cultivates diversity, fitting ontologies to their purpose. Like computer languages C++, Prolog, and HTML, the code perspective holds that diverse applications warrant custom designed ontologies. Ontology as Esperanto focuses on facilitating cross-disciplinary communication, knowledge cross-referencing, and computation across datasets from diverse communities. We show how these views align with classical divides in science and suggest how a synthesis of their concerns could strengthen the next generation of biomedical ontologies.


Speciation and preconcentration of vanadium(V) and vanadium(IV) in water samples by flow injection-inductively coupled plasma optical emission spectrometry and ultrasonic nebulization.
An on-line separation, preconcentration and determination system for vanadium(IV) and vanadium(V) comprising inductively coupled plasma optical emission spectrometry (ICP-OES) coupled to a flow injection (FI) method with an ultrasonic nebulization (USN) system was studied. The vanadium species were retained on an Amberlite XAD-7 resin as a vanadium-2-(5-bromo-2-pyridylazo)-5-diethylaminophenol (V-5-Br-PADAP) complex at pH 3.7. Enhanced selectivity was obtained with the combined use of the formation on-line of the complexes and 1,2-cyclohexanediaminetetraacetic acid (CDTA) as masking agent. The vanadium complexes were removed from the microcolumn with 25% v/v nitric acid. A sensitivity enhancement factor of 225 was obtained with respect to ICP-OES using pneumatic nebulization (15-fold for USN and 15-fold for the microcolumn). The detection limit for the preconcentration of 10 mL of aqueous solution was 19 ng L-1. The precision for 10 replicate determinations at the 5 micrograms L-1 V level was 2.3% relative standard deviation (RSD), calculated from the peak heights obtained. The calibration graph using the separation and preconcentration system for vanadium species was linear with a correlation coefficient of 0.9992 at levels from near the detection limits up to at least 100 micrograms L-1. The method was successfully applied to the speciation of vanadium in river water samples.


Medical devices; hearing aids; technical data amendments. Direct final rule.
The Food and Drug Administration (FDA) is amending its regulations governing hearing aid labeling to reference the most recent version of the consensus standard used to determine the technical data to be included in labeling for hearing aids. We are amending the regulations to require that manufacturers may use state-of-the-art methods to provide technical data in hearing aid labeling. FDA is also amending the regulations to update an address and remove an outdated requirement. FDA is amending the regulations in accordance with its direct final rule procedures. Elsewhere in this issue of the Federal Register, we are publishing a companion proposed rule under FDA's usual procedures for notice and comment rulemaking to provide a procedural framework to finalize the rule in the event we receive a significant adverse comment and withdraw this direct final rule.


Effects of Wearing the Elevation Training Mask During Low-intensity Cycling Exercise on Intraocular Pressure.
Low-intensity aerobic exercise is recommended to reduce intraocular pressure (IOP) levels. However, this effect depends on several factors. We found that using an elevation training mask (ETM) during low-intensity aerobic exercise causes an IOP rise. The aim was to assess the influence of wearing an ETM on IOP during low-intensity endurance training. Sixteen physically active young adults (age=23.9±2.9 y) cycled during 30 minutes at 10% of maximal power production with and without an ETM in 2 different days and randomized order. A rebound tonometer was used to measure IOP at baseline, after a warm-up of 5 minutes, during cycling (6, 12, 18, 24, and 30 min), and recovery (5 and 10 min) by rebound tonometry. The use of an ETM significantly affects the IOP behaviour during exercise (P<0.001, ηp²=0.66). In the ETM condition, there was an IOP increment during exercise (P<0.001, ηp²=0.28) whereas an IOP-lowering effect was observed in the control condition (P<0.001, ηp²=0.41). Post hoc comparisons showed that there were greater IOP values during exercise in the ETM condition in comparison to the control condition (average IOP difference=3.7±2.2 mm Hg; corrected P<0.01, and the Cohen d's >1.10, in all cases). Low-intensity endurance exercise causes an increment in IOP when it is performed wearing an ETM and a decrease in IOP when the air flow is not restricted (control condition). Therefore, the ETM should be discouraged during low-intensity endurance exercise for individuals who need to reduce IOP levels (eg, glaucoma patients or those at risk). However, the external validity of these results needs to be addressed in future studies with the inclusion of glaucoma patients.


Genetic analysis of ion-beam induced extremely late heading mutants in rice.
Two extremely late heading mutants were induced by ion beam irradiation in rice cultivar 'Taichung 65': KGM26 and KGM27. The F2 populations from the cross between the two mutants and Taichung 65 showed clear 3 early: 1 late segregation, suggesting control of late heading by a recessive gene. The genes identified in KGM26 and KGM27 were respectively designated as FLT1 and FLT2. The two genes were mapped using the crosses between the two mutants and an Indica cultivar 'Kasalath'. FLT1 was located on the distal end of the short arm of chromosome 8. FLT2 was located around the centromere of chromosome 9. FLT1 might share the same locus as EHD3 because their chromosomal location is overlapping. FLT2 is inferred to be a new gene because no gene with a comparable effect to that of this gene was mapped near the centromere of chromosome 9. In crosses with Kasalath, homozygotes of late heading mutant genes showed a large variation of days to heading, suggesting that other genes affected late heading mutant genes.


Treatment of refractory aplastic anemia with plasmapheresis: report of a case in childhood with review of the literature.
Treatment of aplastic anemia may raise considerable problems in some patients. This report concerns a boy whose illness started at 11 years of age. At first admission laboratory data were: hemoglobin 7.5 g/l, and counts of leucocytes, neutrophils and platelets were 2.3, 0.6, and 8 x 10(9)/l, respectively. His bone marrow was hypoplastic with sparse erythropoiesis. The patient did not respond to traditional medical treatment. Serum contained a high concentration of erythropoietin but no antibodies against erythropoietin. The patient's serum did neither alone, nor supported with recombinant erythropoietin, stimulate erythropoiesis in a bioassay, suggesting that some factor(s) inhibiting erythropoietic activity was present. Based on this hypothesis, plasma exchange was performed. After 26 weeks of plasmapheresis the hematological parameters were normalized. We conclude that plasmapheresis might be an alternative in treatment of resistant aplastic anemia. Further diagnostic tools to identify patients who might benefit from such a treatment are required.


Life values, psychotherapy, and East-West integration.
This paper intends to examine life-styles and values of East and West and to note apparent differences and underlying commonalities relevant to psychotherapy and clinical issues. Topics discussed include a public versus private orientation, a pragmatic versus psychodynamic approach, and dependence versus independence.


Pre-West Nile virus outbreak: perceptions and practices to prevent mosquito bites and viral encephalitis in the United States.
Mosquitoes can transmit over 100 of the viruses that can cause encephalitis, meningitis, and hemorrhagic disease in humans (Chin 2000; Gubler 1996; Monath 1989). While much is known about the ecology, epidemiology, and clinical manifestations of the arboviral encephalitides (Campbell et al. 2002; Centers for Disease Control and Prevention 1997; Gubler 1998; Hayes 1989; Hubálek and Halouzka 1999), little empirical research exists regarding the U.S. population's knowledge of mosquitoes and arboviral encephalitis, particularly prior to the U.S. outbreak of West Nile virus (WNV) in 1999. A nationally representative 55-item survey instrument was successfully administered to 1,500 adults in the United States and an additional 250 adults in six states in the Northeast (Connecticut, Delaware, New Jersey, New York, Pennsylvania, and Rhode Island) regarding mosquitoes and mosquito-borne viral encephalitis. A summary outcome measure for mosquito bite prevention was created. Analyses revealed that the following were statistically significant predictors of behaviors taken to prevent mosquito bites: being concerned about being bitten by mosquitoes, perceived effectiveness of staying indoors in late afternoon and early evening was protective, perceived effectiveness that mosquito repellent is not harmful to health, owning dogs and/or cats as pets, being married, and being > or = 18-44 years old. Being concerned about being bitten by mosquitoes was the most robust predictor of behavioral action to prevent mosquito bites (OR = 7.3; 95% CI = 4.3, 12.2). Observed misperceptions and inadequate knowledge regarding insect repellents suggest increased promotion of the safety and efficacy of DEET-containing insect repellents is warranted.


Absence of pathogenic mutations in VSX1 and SOD1 genes in patients with keratoconus.
Keratoconus (KC) is a bilateral, noninflammatory, and progressive corneal ectasia that occurs mostly as a sporadic disorder, but it has long been recognized that a significant minority of patients also exhibit a family history. In recent years, several candidate genes, including VSX1 and SOD1, have been proposed and some disease-causing mutations have been identified. To investigate the role of the 2 genes in 113 Slovenian patients with sporadic and familial KC, the complete coding region with corresponding intronic sequences was analyzed. The same regions of both genes were also checked in 100 healthy blood donors. We also checked the relation of 627+23G>A polymorphism in the VSX1 gene with the hereditary form of the disease. No disease-causing mutations were identified in either gene. We did discover a significant association of 627+23G>A polymorphism distribution (VSX1) with unrelated patients diagnosed with the hereditary form of KC. The absence of pathogenic mutations in our large number of unrelated patients with KC indicates that other genetic factors are involved in the development of this disorder.


[A case of ruptured posterior superior pancreaticoduodenal artery aneurysm successfully treated by emergency transcatheter embolization].
A man in his 40s with no remarkable past medical history was referred to our hospital with acute exacerbation of nonspecific epigastric pain by another hospital on the morning of the day of presentation. Though vital signs were stable, tenderness and guarding were observed over the entire abdomen. Contrast-enhanced computed tomography (CT) revealed a giant retroperitoneal hematoma due to a ruptured aneurysm close to the superior mesenteric artery. Emergency angiography of the superior mesenteric artery detected a ruptured 2-mm pseudoaneurysm of the posterior superior pancreaticoduodenal artery, for which embolization was immediately performed. The postoperative course was good, with the patient complaining only of transient abdominal pain due to exclusion of the hematoma on hospital day 6. His clinical symptoms disappeared with conservative treatment, and the patient was discharged on hospital day 18. Complete occlusion of the aneurysm and reduction of the hematoma was confirmed on follow-up CT. Pancreaticoduodenal artery aneurysm is an uncommon visceral artery aneurysm, and ruptured aneurysms typically result in fatal hemorrhage and high mortality. We herein report a case of ruptured aneurysm of the posterior pancreaticoduodenal artery where emergency transcatheter arterial embolization was able to save the patient's life. We also review 116 cases of pancreaticoduodenal artery aneurysm reported in Japanese literature.


Novel optical lens design with a light scattering freeform inner surface for LED down light illumination.
Using the precise mid field angular distribution model of the LED light source and the optical scattering surface property of the Harvey BSDF scattering model, we perform optical simulation to develop and design a novel solid plastic optical lens with freeform inner surface to achieve the optical performance of 89.89% light energy transmission optics for the sake of energy saving reason. The 70 degrees angular light distribution pattern defined at full width half maximum (FWHM) light energy level is performed and the optical utilization factor (OUF) of 51.8% is obtained within -45 degrees and 45 degrees range in the areas of interest with glare reduced for the down light illumination.


Local oxygen content in the skin is increased in chronic venous incompetence.
In skin lesions of chronic venous incompetence (CVI) transcutaneous oxygen pressure (tcpO(2)) at the ankle is often reduced. However, in some CVI patients the tcpO(2) during suprasystolic occlusion remains significantly higher than in healthy subjects. The aim of the present study was to investigate which kind of CVI patients develop this phenomenon and whether the higher tcpO(2) during occlusion is caused by a smaller oxygen consumption of the skin or by an increased local oxygen content. The oxygen consumption of the skin was measured by the pO(2) decrease (DeltatcpO(2)/Deltat) after stopping the arterial oxygen supply when the hemoglobin was saturated by oxygen inhalation, i.e., at tcpO(2) values above 120-130 mmHg. By multiplying the tcpO(2) with the mean oxygen solubility coefficient of the skin the content of physically dissolved oxygen is obtained. The decrease of tcpO(2) in the 55- to 45-mmHg range indicates the consumption of oxygen physically dissolved and chemically bound to hemoglobin. It gave a parameter for estimating the local hemoglobin content of the skin. These values and the minimal tcpO(2) after a 5-min arterial occlusion were measured in 14 healthy subjects, in 13 patients with varicose veins, but no skin lesions, in 10 patients with CVI lesions like white atrophy and lipodermatosclerosis and in 16 CVI patients with open venous ulcers. During suprasystolic occlusion tcpO(2) at the ankle remained significantly higher in CVI patients with skin lesions than in the healthy control subjects (25.6 +/- 18.9 versus 8.0 +/- 7.0 mmHg). The steepness of the tcpO(2) decrease caused by cutaneous oxygen consumption in healthy subjects was not significantly different from the CVI patients. In contrast, the decrease of tcpO(2) at the ankle between 55 and 45 mmHg was 1.9 +/- 2.0 mmHg/s in the control group and 0.7 +/- 0.5 mmHg/s in the group with open venous ulcers. These results indicate a higher hemoglobin content in the skin of the CVI patients than in healthy subjects. Obviously, the hemoglobin bound oxygen content in the skin of CVI patients is increased. Thus, a lack of oxygen is unlikely to be the primary reason for the development of skin lesions in CVI.


Total spondylectomy for primary malignant, aggressive benign, and solitary metastatic bone tumors of the thoracolumbar spine.
The records of 14 patients with malignant or aggressive benign vertebral tumors of the thoracolumbar spine who underwent total spondylectomy (TS) were evaluated retrospectively. Total spondylectomy was performed by bisecting the affected vertebra through the pedicle using fine threadwire saws and removing the vertebra en bloc through the posterior procedure alone or the one-stage anteroposterior combined procedure. Remarkable pain relief and ambulation after surgery were achieved in all 14 patients. No serious complications occurred. Nerve roots were sacrificed in seven cases. A marginal surgical margin was achieved in 10 cases and an intralesional surgical margin was achieved in four. At the site of the osteotomized pedicle, the surgical margin was marginal, with the possibility of tumor-cell contamination in 10 cases. Local recurrence was found in three cases of posterior total spondylectomy at 0.3 to 3.5 years (mean, 3.2 years) follow-up evaluation at the other site of the osteotomized pedicle. These results suggest that this type of total spondylectomy is effective in controlling local recurrence without incurring major complications and is a clinically useful procedure.


[Fifty-three atherosclerotic carotid stenoses in an irradiated environment].
Fifty-three atheromatous carotid stenosis in a previously irradiated zone were operated upon between January 1983 and December 1991. A case control (retrospective) study confirmed the reality, even within the context of multiple artery atheromatous localizations, of an atypical profile suggestive of incrimination of the radiation: extension of the atheromatous lesions distally in the common carotid, proximally beyond the bulb. An isolated atheromatous lesion in the common carotid is very suggestive of postradiation atheroma, which also presents specific histologic features: peri-adventitial inflammation, adventitial and medial sclerosis. These changes are not accompanied by any particular neurologic clinical manifestations, but require frequent changes in surgical strategy: bypass rather than endarterectomy; the extent of the lesions decides whether the proximal implantation of the bypass is in the lower part of the common carotid or the subclavian. Radiotherapy adds to the difficulty of dissection and provokes a slight increase in morbidity, but the long term prognosis is analogous to that of usual atheromatous lesions with, however, the risk of atherosclerotic changes proximally.


Synthesis and degradation of unassembled polypeptides of the coupling factor of photophosphorylation CF1 in 70S ribosome-deficient rye leaves.
The formation of polypeptides of the coupling factor CF1 was investigated in 70S ribosome-deficient rye leaves generated by growing the plants at a non-permissive elevated temperature of 32 degrees C, in order to analyse mechanisms coordinating subunit accumulation. Antibodies were raised in rabbits against total CF1 as well as against its five individual subunits purified from chloroplast thylakoids from rye leaves. Several immunological techniques applying these antibodies (immunoprecipitation, immunoblotting, antibody affinity chromatography) were unable to detect the presence of any of the CF1 subunits in heat-treated 70S ribosome-deficient leaves. After in vivo labeling with L-[35S]methionine and subsequent immunoprecipitation, however, radioactivity was found to be incorporated into the subunits gamma and delta, but not into alpha, beta and epsilon, in 70S ribosome-deficient leaves, demonstrating the cytoplasmic synthesis of CF1-gamma and CF1-delta. Chase experiments after in vivo labeling with L-[35S]methionine indicated that the unassembled subunits gamma and delta were rapidly and preferentially degraded, while they were stabilized when integrated into the complete CF1 complex in normal green leaves from permissive growth conditions. The apparent half-times of the unassembled subunits were 2 h for CF1-gamma and 4 h for CF1-delta in 32 degrees C-grown leaves. Several other, stromal, plastid proteins of cytoplasmic origin were stable in 32 degrees C-grown leaves during the period of chase. In etiolated leaves total CF1, including all subunits, appeared to be less stable than in green leaves grown under permissive temperature conditions in light. Rapid degradation of the excess of unassembled subunits is regarded as an important mechanism ensuring a constant stoichiometry and apparently synchronous development of CF1 subunits.


High-resolution magnetic field measurement system for recording heads and disks.
A high-resolution system for measuring the magnetic fields near recording heads and disks has been built. The perpendicular field components close to the head and disk surfaces are measured with an InSb Hall probe which is moved point-by-point under computer control. The computer also records the magnetic field strength as a function of position in a plane parallel to the head or disk surface. The active area of the probe is 2x2 microm and a roughly 1-microm separation between the probe and the surfaces being measured can be obtained. Measurements of the fields near transitions on a particulate disk and near the gap in in a ferrite recording head are presented and compared with calculated field distributions.


Hypothalamic neuronal responses to cytokines.
Fever has been extensively studied in the past few decades. The hypothesis that hypothalamic thermosensitive neurons play a major role in both normal thermoregulation and in fever production and lysis has particularly helped to advance our understanding of the neuronal mechanisms underlying the response to pyrogens. Furthermore, new data in the study of host defense responses induced by pyrogenic cytokines such as interleukin 1, interferon alpha 2, tumor necrosis factor alpha, and interleukin 6 have demonstrated that those factors have multiple, yet coordinated, regulatory activities in the central nervous system, so that our understanding of the role of the brain in the activity of these agents requires a new perspective and dimension. Thus, recent evidence from our laboratory indicates that blood-borne cytokines may be detected in the organum vasculosum laminae terminalis and transduced there into neuronal signals. Such signals may then affect distinct, but partially overlapping, sets of neuronal systems in the preoptic area of the anterior hypothalamus, mediating directly and/or indirectly the array of various host defense responses characteristic of infection that are thought to be induced by blood-borne cytokines.


Recurrent chromosome abnormalities in adult T-cell lymphomas of peripheral T-cell origin.
Cytogenetic studies were performed on 11 Japanese patients with adult T-cell lymphoma of peripheral T-cell origin. All patients had a histologic diagnosis of diffuse lymphoma, and were treated with intensive combination chemotherapy; their median survival was 6 months. Lymphomas were categorized on the basis of the classification proposed by the Lymphoma Study Group of Japan: 5 patients had the features of pleomorphic lymphoma; 3, mixed lymphoma; 2, large-cell lymphoma; and 1, medium-sized-cell lymphoma. The modal chromosome number of abnormal cells was near-diploid in 7, and hypotetraploid in 4 including 3 patients with pleomorphic lymphoma. Abnormalities of the clonal chromosomes were observed in all 11 patients. A translocation of the short arm of 19 at band 19p13 was found in 2 patients with pleomorphic lymphoma and in one patient each with mixed lymphoma and medium-sized-cell lymphoma. A translocation of the short arm of 14, with a break at band 14p12, occurred in 4 patients with pleomorphic lymphoma. In one patient each with mixed lymphoma and large-cell lymphoma, an extra chromosome 3 was found. The numerical change was unique because their lymphomas were further categorized as "angioimmunoblastic lymphadenopathy with dysproteinemia" and "large-cell immunoblastic lymphoma", respectively. Our findings suggest that characteristic chromosome abnormalities occur in adult T-cell lymphoma, and dividing cells in the tetraploid range tend to be predominant in pleomorphic lymphoma.


Co-clinical quantitative tumor volume imaging in ALK-rearranged NSCLC treated with crizotinib.
To evaluate and compare the volumetric tumor burden changes during crizotinib therapy in mice and human cohorts with ALK-rearranged non-small-cell lung cancer (NSCLC). Volumetric tumor burden was quantified on serial imaging studies in 8 bitransgenic mice with ALK-rearranged adenocarcinoma treated with crizotinib, and in 33 human subjects with ALK-rearranged NSCLC treated with crizotinib. The volumetric tumor burden changes and the time to maximal response were compared between mice and humans. The median tumor volume decrease (%) at the maximal response was -40.4% (range: -79.5%-+11.7%) in mice, and -72.9% (range: -100%-+72%) in humans (Wilcoxon p=0.03). The median time from the initiation of therapy to maximal response was 6 weeks in mice, and 15.7 weeks in humans. Overall volumetric response rate was 50% in mice and 97% in humans. Spider plots of tumor volume changes during therapy demonstrated durable responses in the human cohort, with a median time on therapy of 13.1 months. The present study described an initial attempt to evaluate quantitative tumor burden changes in co-clinical imaging studies of genomically-matched mice and human cohorts with ALK-rearranged NSCLC treated with crizotinib. Differences are noted in the degree of maximal volume response between the two cohorts in this well-established paradigm of targeted therapy, indicating a need for further studies to optimize co-clinical trial design and interpretation.


Discovery of the first potent and orally efficacious agonist of the orphan G-protein coupled receptor 119.
GPR119 is a rhodopsin-like GPCR expressed in pancreatic beta-cells and incretin releasing cells in the GI tract. As with incretins, GPR119 increases cAMP levels in these cell types, thus making it a highly attractive potential target for the treatment of diabetes. The discovery of the first reported potent agonist of GPR119, 2-fluoro-4-methanesulfonyl-phenyl)-{6-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-5-nitro-pyrimidin-4-yl}-amine (8g, AR231453), is described starting from an initial inverse agonist screening hit. Compound 8g showed in vivo activity in rodents and was active in an oral glucose tolerance test in mice following oral administration.


[Migration and integration policies within the Andean Pact].
"After a review of the institutions belonging to the 1969 Andean Pact, migration topics within this context are analyzed, considering three main issues: labor migration,...circulation of persons, where a series of agreements tending to simplify procedures at bordersites are still not practically in force for reasons concerning internal safety, drug traffic and unemployment, and migration across borders as related to borderline integration, which was dealt with in the Macchu Picchu Summit in 1990 and in a Decision Project in 1991." The five pact countries are Bolivia, Chile, Colombia, Ecuador, and Peru. (SUMMARY IN ENG)


Aftercare services.
The author discusses the need for postplacement or "aftercare" services for youth leaving placement to live on their own, and explains how a statewide pilot project is helping to meet that need.


Personal remarks on the future of protein crystallography and structural biology.
Protein crystallography, the main experimental method of structural biology, has undergone in the recent past three revolutionary changes leading to its unexpected renaissance. They were connected with (i) the introduction of synchrotron radiation sources for X-ray diffraction experiments, (ii) implementation of Se-Met multiwavelength anomalous diffraction (MAD) for phasing, and (iii) initiation of structural genomics (SG) programs. It can be foreseen that in the next 10-15 years protein crystallography will continue to be in this revolutionary phase. We can expect not only an avalanche of protein crystal structures from SG centers, but also attacking of more demanding projects, such as the structure of membrane proteins and of very large macromolecular complexes. On the technological front, the introduction of X-ray radiation from free-electron lasers will revolutionize the experimental possibilities, making feasible even the imaging of single molecules and of intact biological cells.


TASK1 modulates inflammation and neurodegeneration in autoimmune inflammation of the central nervous system.
We provide evidence that TWIK-related acid-sensitive potassium channel 1 (TASK1), a member of the family of two-pore domain potassium channels relevant for setting the resting membrane potential and balancing neuronal excitability that is expressed on T cells and neurons, is a key modulator of T cell immunity and neurodegeneration in autoimmune central nervous system inflammation. After induction of experimental autoimmune encephalomyelitis, an experimental model mimicking multiple sclerosis, TASK1(-/-) mice showed a significantly reduced clinical severity and markedly reduced axonal degeneration compared with wild-type controls. T cells from TASK1(-/-) mice displayed impaired T cell proliferation and cytokine production, while the immune repertoire is otherwise normal. In addition to these effects on systemic T cell responses, TASK1 exhibits an independent neuroprotective effect which was demonstrated using both a model of acutely prepared brain slices cocultured with activated T cells as well as in vitro cultivation experiments with isolated optic nerves. Anandamide, an endogenous cannabinoid and inhibitor of TASK channels, reduced outward currents and inhibited effector functions of T cells (IFN-gamma production and proliferation); an effect completely abrogated in TASK1(-/-) mice. Accordingly, preventive blockade of TASK1 significantly ameliorated experimental autoimmune encephalomyelitis after immunization. Therapeutic application of anandamide significantly reduced disease severity and was capable of lowering progressive loss of brain parenchymal volume as assessed by magnetic resonance imaging. These data support the identification and characterization of TASK1 as potential molecular target for the therapy of inflammatory and degenerative central nervous system disorders.


Scale-dependent effects of nonnative plant invasion on host-seeking tick abundance.
Nonnative, invasive shrubs can affect human disease risk through direct and indirect effects on vector populations. Multiflora rose (Rosa multiflora) is a common invader within eastern deciduous forests where tick-borne disease (e.g. Lyme disease) rates are high. We tested whether R. multiflora invasion affects blacklegged tick (Ixodes scapularis) abundance, and at what scale. We sampled host-seeking ticks at two spatial scales: fine-scale, within R. multiflora-invaded forest fragments; and patch scale, among R. multiflora-invaded and R. multiflora-free forest fragments. At a fine scale, we trapped 2.3 times more ticks under R. multiflora compared to paired traps 25 m away from R. multiflora. At the patch scale, we trapped 3.2 times as many ticks in R. multiflora-free forests compared to R. multiflora-invaded forests. Thus, ticks are concentrated beneath R. multiflora within invaded forests, but uninvaded forests support significantly more ticks. Among all covariates tested, leaf litter volume was the best predictor of tick abundance; at the patch scale, R. multiflora-invaded forests had less leaf litter than uninvaded forests. We suggest that leaf litter availability at the patch-scale plays a greater role in constraining tick abundance than the fine-scale, positive effect of invasive shrubs.


Solid-State Polymerization of Poly(Ethylene Furanoate) Biobased Polyester, II: An Efficient and Facile Method to Synthesize High Molecular Weight Polyester Appropriate for Food Packaging Applications.
The goal of this study was to synthesize, through a facile strategy, high molecular weight poly(ethylene furanoate) (PEF), which could be applicable in food packaging applications. The efficient method to generate PEF with high molecular weight consists of carrying out a first solid-state polycondensation under vacuum for 6 h reaction time at 205 °C for the resulting polymer from two-step melt polycondensation process, which is catalyzed by tetrabutyl titanate (TBT). A remelting step was thereafter applied for 15 min at 250 °C for the obtained polyester. Thus, the PEF sample was ground into powder, and was then crystallized for 6 h at 170 °C. This polyester is then submitted to a second solid-state polycondensation (SSP) carried out at different reaction times (1, 2, 3.5, and 5 h) and temperatures 190, 200, and 205 °C, under vacuum. Ultimately, a significant increase in intrinsic viscosity is observed with only 5 h reaction time at 205 °C during the second SSP being needed to obtain very high molecular weight PEF polymer greater than 1 dL/g, which sufficient for manufacturing purposes. Intrinsic viscosity (IV), carboxyl end-group content (⁻COOH), and thermal properties, via differential scanning calorimetry (DSC), were measured for all resultant polyesters. Thanks to the post-polymerization process, DSC results showed that the melting temperatures of the prepared PEF samples were steadily enhanced in an obvious way as a function of reaction time and temperature increase. It was revealed, as was expected for all SSP samples, that the intrinsic viscosity and the average molecular weight of PEF polyester increased with increasing SSP time and temperature, whereas the number of carboxyl end-group concentration was decreased. A simple kinetic model was also developed and used to predict the time evolution of polyesters IV, as well as the carboxyl and hydroxyl end-groups of PEF during the SSP.


Cementing techniques for hip resurfacing arthroplasty: in vitro study of pressure and temperature.
Cementing irregularities have been associated with femoral failures of resurfacing arthroplasties in retrieval studies. We used an in vitro model to measure pressure, temperatures, and cement penetration as a function of 6 different cementing techniques. Filling the component with cement can lead to overpenetration or increase the resistance to component seating with resultant polar cement mass. Both conditions result in high and long-lasting cement pressures, cement defects, as well as peak temperatures higher than 50°C. Manual application of cement provides complete penetration of the available fixation area with the lowest cement pressures, the smallest total cement mass, and a peak temperature of 36.0°C ± 4.1°C. Application of the principles elucidated by this study may reduce the risk of cement overpenetration and incomplete seating.


201Tl and 99mTc-MIBI gated SPECT in patients with large perfusion defects and left ventricular dysfunction: comparison with equilibrium radionuclide angiography.
Left ventricular ejection fraction (LVEF) is a major prognostic factor in coronary artery disease and may be computed by 99mTc-methoxyisobutyl isonitrile (MIBI) gated SPECT. However, 201Tl remains widely used for assessing myocardial perfusion and viability. Therefore, we evaluated the feasibility and accuracy of both 99mTc-MIBI and 201Tl gated SPECT in assessing LVEF in patients with myocardial infarction, large perfusion defects and left ventricular (LV) dysfunction. Fifty consecutive patients (43 men, 7 women; mean age 61 +/- 17 y) with a history of myocardial infarction (anterior, 26; inferior, 18; lateral, 6) were studied. All patients underwent equilibnum radionuclide angiography (ERNA) and rest myocardial gated SPECT, either 1 h after the injection of 1110 MBq 99mTc-MIBI (n = 19, group 1) or 4 h after the injection of 185-203 MBq 201Tl (n = 31, group 2) using a 90 degrees dual-head camera. After filtered backprojection (Butterworth filter: order 5, cutoff 0.25 99mTc or 0.20 201Tl), LVEF was calculated from reconstructed gated SPECT with a previously validated semiautomatic commercially available software quantitative gated SPECT (QGS). Perfusion defects were expressed as a percentage of the whole myocardium planimetered by bull's-eye polar map of composite nongated SPECT. Gated SPECT image quality was considered suitable for LVEF measurement in all patients. Mean perfusion defects were 36% +/- 18% (group 1), 33% +/- 17% (group 2), 34% +/- 17% (group 1 + group 2). LVEF was underestimated using gated SPECT compared with ERNA (34% +/- 12% and 39% +/- 12%, respectively; P = 0.0001). Correlations were high (group 1, r= 0.88; group 2, r = 0.76; group 1 + group 2, r = 0.82), and Bland-Altman plots showed a fair agreement between gated SPECT and ERNA. The difference between the two methods did not vary as LVEF, perfusion defect size or seventy increased or when the mitral valve plane was involved in the defect. LVEF measurement is feasible using myocardial gated SPECT with the QGS method in patients with large perfusion defects and LV dysfunction. However, both 201Tl and 99mTc-MIBI gated SPECT similarly and significantly underestimated LVEF in patients with LV dysfunction and large perfusion defects.


[Thoracic surgery in neonates and infants with congenital malformations].
Congenital malformations of the lung and diaphragm are a challenge in paediatric surgery. Depending on the malformation they show a broad spectrum of symptoms and a varying age at manifestation. Thus there are many diagnostic and therapeutic options, which require a good knowledge of the pathology. The treatment of these complex cases should lead to early referral to paediatric centres containing an interdisciplinary team with neonatologists, paediatric pulmonologists and cardiologists, ENT surgeons, anaesthesiologists, radiologists and paediatric surgeons. Some malformations are diagnosed prenatally and need intrauterine interventions. Decisive is the early diagnosis and treatment of these malformations. Nowadays the surgical therapy of neonates and infants with malformations of the lung and diaphragm is enriched by a number of endoscopic and endoluminal techniques, which are discussed critically in this article.


Evaluation of sputum smears concentrated by cytocentrifugation for detection of acid-fast bacilli.
Early identification and isolation of tuberculosis patients is of utmost importance to minimize the risk of further epidemic spread of the disease. The traditional concentrated acid-fast smears are not very reliable tools for the presumptive diagnosis of tuberculosis. Acid-fast bacillus (AFB) smears from 120 patients specimens and 80 simulated AFB samples were processed according to standard laboratory procedures and by cytocentrifugation (Cyto-Tek, Ames Division, Miles Laboratories, Inc., Elkhart, Ind.). Prior to dispensing of samples into the Cyto-Tek chambers, specimens were liquefied and decontaminated by mixture with an equal volume of 5% sodium hypochlorite (household bleach). Culture and smear results were correlated. Of 120 patient specimens, 43 were culture and smear negative by both methods. Ten specimens were overgrown with mold and bacteria, but 2 of them had positive AFB smears by cytocentrifugation only. There were 67 positive AFB cultures, with 67 positive cytocentrifuge smears and 34 positive smears by the conventional technique. Of the 80 simulated positive AFB samples, all grew mycobacteria on culture. Smears from the 10(5)- to 10(3)-CFU/ml specimens were positive by both methods. The simulated samples with 10(2) CFU/ml yielded smears positive only by cytocentrifugation. The Cyto-Tek AFB smears had a greater correlation with positive culture than did the smears from concentrated specimens. The sensitivity, efficiency, and rapidly of the Cyto-Tek AFB smear technique resulted in increased detection of mycobacteria in clinical specimens. The simplicity and safety of this method will enable qualified mycobacteriology technologists to rapidly and accurately perform sputum smears for AFB at clinics, emergency rooms, and field sites, as well as in the traditional laboratory setting.


Closure vs non-closure of the visceral and parietal peritoneum at cesarean delivery: 16 year study.
To determine whether non-closure of visceral and parietal peritoneum at LSCS has advantages over peritoneal closure with regard to postoperative complication and adhesions. Prospective randomized controlled trial. Paholpolpayuhasena Hospital, Kanchanaburi province, Thailand Three hundred and sixty full-term pregnant women undergoing first cesarean section were divided into 3 groups (N = 120). Group A: non-closure of both visceral and parietal peritoneum. Group B. non-closure of only visceral peritoneum. Group C: closure of both visceral and parietal peritoneum. Postoperative complications were compared. Adhesions were evaluated in 65 patients returning for a second LSCS and compared for severity of adhesions. The three groups were compared using statistical analysis. There was no significant statistical difference between group A and C, group B and C for postoperative complications or number of adhesion formation. However, adhesions in the closure group were more severe. Closure of visceral and parietal peritoneum has no benefit over non-closure of visceral peritoneum and non-closure of both visceral and parietal peritoneum at LSCS.


A multi-disciplinary approach to implementation science: the NIH-PEPFAR PMTCT implementation science alliance.
In resource-limited countries, interventions to prevent mother-to-child HIV transmission (PMTCT) have not yet realized their full potential health impact, illustrating the common gap between the scientific proof of an intervention's efficacy and effectiveness and its successful implementation at scale into routine health services. For PMTCT, this gap results, in part, from inadequate adaptation of PMTCT interventions to the realities of the implementation environment, including client and health care worker behaviors and preferences, health care policies and systems, and infrastructure and resource constraints. Elimination of mother-to-child HIV transmission can only be achieved through understanding of key implementation barriers and successful adaptation of scientifically proven interventions to the local environment. Central to such efforts is implementation science (IS), which aims to investigate and address major bottlenecks that impede effective implementation and to test new approaches to identifying, understanding, and overcoming barriers to the adoption, adaptation, integration, scale-up, and sustainability of evidence-based interventions. Advancing IS will require deliberate and strategic efforts to facilitate collaboration, communication, and relationship-building among researchers, implementers, and policy-makers. To speed the translation of effective PMTCT interventions into practice and advance IS more broadly, the US National Institutes of Health, in collaboration with the President's Emergency Plan for AIDS Relief launched the National Institutes of Health/President's Emergency Plan for AIDS Relief PMTCT IS Alliance, comprised of IS researchers, PMTCT program implementers, and policy-makers as an innovative platform for interaction and coordination.


Preliminary report of the Cardiovascular Diseases and Alimentary Comparison Study: the Israeli experience.
The relationship between blood pressure and dietary constituents including potassium, sodium, calcium, and protein was studied in 183 randomly selected men and women, 50-54 years of age. Twenty-five of the subjects were drug-controlled hypertensive patients. Subjects were investigated by automated BP measurements, 24-h urine collection, and blood sampling. Mean systolic BP (SBP) was 119 +/- 17 mm Hg, placing the sample between Shanghai and Sweden on the distribution chart of the Cardiovascular Diseases and Alimentary Comparison (CARDIAC) Study. Salt intake estimated by 24-h sodium excretion was 8.5 +/- 3.4 g/day, between Australia and Okinawa on the distribution chart. Potassium was 48.55 +/- 20 20 mEq/day, between Urumqi (China), and Beppu and Ohda (Japan). Calcium was 162.3 +/- 89.9 mg/day. Urea nitrogen, which might reflect protein intake, was 9.5 +/- 3.1 g/day. Cholesterol was 195.1 +/- 38.1 mg/dl, between Brazil and Hirosaki. The Israeli results, as well as the data on other countries participating in the CARDIAC Study, show wide variability in the profiles generated by the investigated parameters. Each parameter placed Israel with a different CARDIAC Study group.


Characterization of a Dehydratase and Methyltransferase in the Biosynthesis of Ribosomally Synthesized and Post-translationally Modified Peptides in Lachnospiraceae.
As a result of the exponential increase in genomic data, discovery of novel ribosomally synthesized and post-translationally modified peptide natural products (RiPPs) has progressed rapidly in the past decade. The lanthipeptides are a major subset of RiPPs. Through genome mining we identified a novel lanthipeptide biosynthetic gene cluster (lah) from Lachnospiraceae bacterium C6A11, an anaerobic bacterium that is a member of the human microbiota and which is implicated in the development of host disease states such as type 2 diabetes and resistance to Clostridium difficile colonization. The lah cluster encodes at least seven putative precursor peptides and multiple post-translational modification (PTM) enzymes. Two unusual class II lanthipeptide synthetases LahM1/M2 and a substrate-tolerant S-adenosyl-l-methionine (SAM)-dependent methyltransferase LahSB are biochemically characterized in this study. We also present the crystal structure of LahSB in complex with product S-adenosylhomocysteine. This study sets the stage for further exploration of the final products of the lah pathway as well as their potential physiological functions in human/animal gut microbiota.


Lithium nephrotoxicity revisited.
Lithium is widely used to treat bipolar disorder. Nephrogenic diabetes insipidus (NDI) is the most common adverse effect of lithium and occurs in up to 40% of patients. Renal lithium toxicity is characterized by increased water and sodium diuresis, which can result in mild dehydration, hyperchloremic metabolic acidosis and renal tubular acidosis. The concentrating defect and natriuretic effect develop within weeks of lithium initiation. After years of lithium exposure, full-blown nephropathy can develop, which is characterized by decreased glomerular filtration rate and chronic kidney disease. Here, we review the clinical and experimental evidence that the principal cell of the collecting duct is the primary target for the nephrotoxic effects of lithium, and that these effects are characterized by dysregulation of aquaporin 2. This dysregulation is believed to occur as a result of the accumulation of cytotoxic concentrations of lithium, which enters via the epithelial sodium channel (ENaC) on the apical membrane and leads to the inhibition of signaling pathways that involve glycogen synthase kinase type 3beta. Experimental and clinical evidence demonstrates the efficacy of the ENaC inhibitor amiloride for the treatment of lithium-induced NDI; however, whether this agent can prevent the long-term adverse effects of lithium is not yet known.


Metabolic complications in liver transplant recipients.
The metabolic syndrome (MS), which includes obesity, dyslipidaemia, hypertension and hyperglycaemia according to the most widely accepted definitions now used, is one of the most common post-transplant complications, with a prevalence of 44%-58%. The MS, together with the immunosuppression, is considered the main risk factor for the development of cardiovascular disease (CVD) in transplant recipients, which in turn accounts for 19%-42% of all deaths unrelated to the graft. The presence of MS represents a relative risk for the development of CVD and death of 1.78. On the other hand, non-alcoholic fatty liver disease (NAFLD), considered as the manifestation of the MS in the liver, is now the second leading reason for liver transplantation in the United States after hepatitis C and alcohol. NAFLD has a high rate of recurrence in the liver graft and a direct relation with the worsening of other metabolic disorders, such as insulin resistance or diabetes mellitus. Consequently, it is vitally important to identify and treat as soon as possible such modifiable factors as hypertension, overweight, hyperlipidaemia or diabetes in transplanted patients to thus minimise the impact on patient survival. Additionally, steroid-free regimens are favoured, with minimal immunosuppression to limit the possible effects on the development of the MS.


Applicability of factor analysis in solid state NMR.
Factor analysis has been used to deduce the composition of multicomponent magic angle spinning NMR spectra comprised of overlapping isotropic peaks. The technique has been used to determine the number of constituents present and was combined with a target transformation minimization procedure to identify the component MAS spectra. The new analysis procedure is compared to the conventional least-squares approach and is found to be superior in all cases.


Carbon dynamics and environmental controls of a hilly tea plantation in Southeast China.
Tea plantations are widely distributed and continuously expanding across subtropical China in recent years. However, carbon flux exchanges from tea plantation ecosystems are poorly understood at the ecosystem level. In this study, we use the eddy covariance technique to quantify the magnitude and temporal variations of the net ecosystem exchange (NEE) in tea plantation in Southeast China over four years (2014-2017). The result showed that the tea plantation was a net carbon sink, with an annual NEE that ranged from -182.40 to -301.51 g C/m2, which was a much lower carbon sequestration potential than other ecosystems in subtropical China. Photosynthetic photon flux density (PPFD) explained the highest proportion of the variation in NEE and gross primary productivity (GPP) (for NEE: F = 389.89, p < .01; for GPP: F = 1,018.04, p < .01), and air temperature (Ta) explained the highest proportion of the variation in ecosystem respiration (RE) (F = 13,141.81, p < .01). The strong pruning activity in April not only reduced the carbon absorption capacity but also provided many plant residues for respiration, which switched the tea plantation to a carbon source from April to June. Suppression of NEE at higher air temperatures was due to the decrease in GPP more than the decrease in RE, which indicated that future global warming may transform this subtropical tea plantation from a carbon sink to carbon source.


Admission Blood Glucose Level and Its Association With Cardiovascular and Renal Complications in Patients Hospitalized With COVID-19.
To investigate the association between admission blood glucose levels and risk of in-hospital cardiovascular and renal complications. In this multicenter prospective study of 36,269 adults hospitalized with COVID-19 between 6 February 2020 and 16 March 2021 (N = 143,266), logistic regression models were used to explore associations between admission glucose level (mmol/L and mg/dL) and odds of in-hospital complications, including heart failure, arrhythmia, cardiac ischemia, cardiac arrest, coagulation complications, stroke, and renal injury. Nonlinearity was investigated using restricted cubic splines. Interaction models explored whether associations between glucose levels and complications were modified by clinically relevant factors. Cardiovascular and renal complications occurred in 10,421 (28.7%) patients; median admission glucose level was 6.7 mmol/L (interquartile range 5.8-8.7) (120.6 mg/dL [104.4-156.6]). While accounting for confounders, for all complications except cardiac ischemia and stroke, there was a nonlinear association between glucose and cardiovascular and renal complications. For example, odds of heart failure, arrhythmia, coagulation complications, and renal injury decreased to a nadir at 6.4 mmol/L (115 mg/dL), 4.9 mmol/L (88.2 mg/dL), 4.7 mmol/L (84.6 mg/dL), and 5.8 mmol/L (104.4 mg/dL), respectively, and increased thereafter until 26.0 mmol/L (468 mg/dL), 50.0 mmol/L (900 mg/dL), 8.5 mmol/L (153 mg/dL), and 32.4 mmol/L (583.2 mg/dL). Compared with 5 mmol/L (90 mg/dL), odds ratios at these glucose levels were 1.28 (95% CI 0.96, 1.69) for heart failure, 2.23 (1.03, 4.81) for arrhythmia, 1.59 (1.36, 1.86) for coagulation complications, and 2.42 (2.01, 2.92) for renal injury. For most complications, a modifying effect of age was observed, with higher odds of complications at higher glucose levels for patients age <69 years. Preexisting diabetes status had a similar modifying effect on odds of complications, but evidence was strongest for renal injury, cardiac ischemia, and any cardiovascular/renal complication. Increased odds of cardiovascular or renal complications were observed for admission glucose levels indicative of both hypo- and hyperglycemia. Admission glucose could be used as a marker for risk stratification of high-risk patients. Further research should evaluate interventions to optimize admission glucose on improving COVID-19 outcomes.


A Bayesian Meta-analysis Method for Estimating Risk Difference of Rare Events.
Bayesian meta-analysis has been more frequently utilized for synthesizing safety and efficacy information to support landmark decision-making due to its flexibility of incorporating prior information and availability of computing software. However, when the outcome is binary and the events are rare, where event counts can be zero, conventional meta-analysis methods including Bayesian methods may not work well. Several methods have been proposed to tackle this issue but the prior knowledge of event rate was not utilized to increase precision of risk difference estimates. To better estimate risk differences, we propose a new Bayesian method, Beta prior BInomial model for Risk Differences (B-BIRD), which takes into account the prior information of rare events. B-BIRD is illustrated using a real data set of 48 clinical trials about a type 2 diabetes drug. In simulation studies, it performs well in low event rate settings.


Three-year survival after first-ever ischemic stroke is predicted by initial stroke severity: A hospital-based study.
We aimed to report 3-year survival and causes of death of first-ever ischemic stroke stratified by initial stroke severity. From September 1998 to October 1999, 360 acute first-ever ischemic stroke patients consecutively admitted were followed up prospectively. Patients' vital status and causes of death were identified from the National Death Registry, till December 31, 2002. Potential prognostic factors available at admission were evaluated using Cox proportional hazards regression analysis with bootstrap validation. Three hundred and sixty patients, 58% males with age 64.9 years on average, were followed up for 43.4 months with no lost follow-up. Ninety-two (25.6%) patients died, 25 in the first month. The cumulative case-fatality rates were 12.2%, 15.8%, 20.5% and 25.6% for years 1-4. The proportion of vascular deaths was 84% during the first 30 days and 71% for the subsequent 5 months. The hazard ratio (95% CI) was 1.08 (1.05-1.11) for age (1-year increment), 335.90 (20.72-5446.23) for NIHSS 16-38, 2.48 (1.39-4.42) for NIHSS 7-15, and 0.95 (0.91-0.99) for an interaction term of age and NIHSS 16-38. This study confirmed that the initial stroke severity and age were early prognostic factors for 3-year survival after first-ever ischemic stroke, and further demonstrated that the influence of age on survival time was slightly lower in patients with severe stroke.


Adult living donor liver transplantation in Singapore: the Asian centre for liver diseases and transplantation experience.
Living donor liver transplantation (LDLT) has progressed dramatically in Asia due to the scarcity of cadaver donors and is increasingly performed in Singapore. The authors present their experience with adult LDLT. Adult LDLTs performed at the Asian Centre for Liver Diseases and Transplantation, Singapore from 20 April 2002 until 20 March 2006 were reviewed. All patients received right lobe grafts and were managed by the same team throughout this period. Data were obtained by chart review. This study presents both recipient and donor outcomes in a single centre. A total of 65 patients underwent LDLT. Forty-three were genetically related while 22 were from emotionally-related donors. The majority were chronic liver failure while 14% were acute. The most common indication for LDLT was end-stage liver disease due to hepatitis B virus. A total of 22 patients with hepatoma were transplanted and overall 1-year disease specific survival was 94.4%. The mean model for end-stage liver disease (MELD) score was 17.4 +/- 9.4 (range, 6 to 40). Six patients had preoperative molecular adsorbent recycling system (MARS) dialysis with 83% transplant success rate. The mean follow-up was 479.2 days with a median of 356 days. One-year overall survival was 80.5%. There was 1 donor mortality and morbidity rate was 17%. Our series is in its early stage with good perioperative survival outcome with 1-month and 3-month actuarial survival rates of 95.4% and 87.3% respectively. The study demonstrates that LDLT can be done safely with good results for a variety of liver diseases. However, with dynamically evolving criteria and management strategies, further studies are needed to maximise treatment outcome.


Prolonged angiotensin II antagonism in spontaneously hypertensive rats. Hemodynamic and biochemical consequences.
The present study examines the effects of prolonged angiotensin II antagonism in spontaneously hypertensive rats by using an angiotensin II receptor antagonist (DuP 753) that is devoid of agonistic properties and selective for the subtype 1 of the angiotensin II (AT1) receptor. The antihypertensive effects of DuP 753 and its effects on circulating parameters of the renin-angiotensin system were compared with those of a converting enzyme inhibitor (benazeprilat). To minimize any influence of differences in the pharmacokinetic properties of the two blockers, administration was by continuous intravenous infusion. The experiments were performed in conscious, freely moving rats with continuous 24-hour monitoring of blood pressure. DuP 753 (10 or 30 mg/kg/day) lowered mean arterial pressure to the same extent as benazeprilat (3 or 10 mg/kg/day) during a 48-hour period. The antihypertensive effect was sustained when the treatment was extended to 7 days (DuP 753, 10 mg/kg/day; benazeprilat, 3 mg/kg/day). Neither of the compounds affected the baseline or diurnal rhythm of heart rate. Plasma concentrations of renin and angiotensin II were increased sevenfold and 10-fold, respectively, in the rats treated with DuP 753. In rats treated with benazeprilat, plasma renin concentration increased threefold, whereas angiotensin II was unchanged. Heart weights were significantly reduced to a similar extent by DuP 753 and benazeprilat. Both compounds also induced a smaller but significant decrease in blood pressure in Wistar-Kyoto rats. Our results indicate that the antihypertensive effects of converting enzyme inhibitors in spontaneously hypertensive rats are mainly due to the blockade of the renin-angiotensin system. In this rat model, angiotensin II appears to play an important role in the maintenance of hypertension that is mediated via the AT1 receptor.


Perioperative enoximone infusion improves cardiac enzyme release after CABG.
To assess whether routine postoperative enoximone infusion compared with dobutamine improved clinical and biochemical results after coronary artery bypass grafting with cardiopulmonary bypass. Prospective nonrandomized study. Data collection was blinded to the choice of inotrope. Double-institutional clinical investigation. Two hundred sixteen consecutive patients undergoing myocardial revascularization between May 2000 and December 2002. Seventy-two patients underwent myocardial revascularization and were treated with enoximone, 5 microg/kg/min (group A). They were compared in a ratio of 1:2 to 144 patients treated with dobutamine at the same dose (group B) after aortic cross-clamp removal. The groups proved to be homogenous in preoperative and intraoperative characteristics. Hospital outcome, electrocardiogram, echocardiography, further inotropic support, and biochemical markers of ischemia were compared. Subsets of patients with comorbidities and total arterial revascularization were analyzed. Perioperative myocardial infarction, postoperative low-output syndrome, intra-aortic balloon pump, atrial fibrillation, ST-segment changes, postoperative echocardiographic findings, and intensive care and hospital durations were similar between groups. In the postoperative course, more patients belonging to group A maintained low-dose inotropic support, whereas more patients belonging to group B required higher doses. Troponin I and creatine kinase-MB values were higher in patients of group B, especially when subgroups with diabetes, left ventricular hypertrophy, or total arterial revascularization were included. Postoperative enoximone reduced troponin I release and need for inotropic support in patients undergoing on-pump myocardial revascularization. Subgroup data were confirmed in diabetes, left ventricular hypertrophy, and total arterial revascularization.


Chronic disease risk factors in vitamin/mineral supplement users and nonusers in a farm population.
Dietary, anthropometric, and chronic disease risk factors (CDRF) in vitamin/mineral supplement users (U) and non-users (NU) were measured in a farm population consisting of 162 subjects (46% females and 54% males; 20-79 years of age, mean age: 52 years). Subjects were white, except for two black males. Supplements were used by 62 subjects (38%); 47% of females and 31% of males used supplements; 43% of subjects over 50 years of age and 32% of subjects age 50 or under used supplements. Both dietary intake and energy expenditure were measured using 4-day records. Indices of adiposity included body weight, BMI, and estimated body fat. Total cholesterol (TC), high-density-lipoprotein cholesterol (HDL-C), serum ferritin, hemoglobin, hematocrit, zinc, copper, and vitamin C were based on 12-hr fasting blood samples. Dietary intake (excluding supplements) for vitamin/mineral U was greater than NU for vitamin C (p = 0.006), thiamin (p = 0.01), riboflavin (p = 0.03), niacin (p = 0.02), folic acid (p = 0.001), vitamin B6 (p = 0.01), and magnesium (p = 0.019). Vitamin C levels were significantly higher and the sum of four skinfolds was significantly lower among U than NU. In this population, 24% of males and 18% of females had TC levels over 240 mg%; 8% of both males and females had blood pressures (BP) greater than 140/90 mm Hg, while 49% of males and 46% of females had BP between 120/80 and 140/90; and 71% of males were more than 25% fat, and 56% of females were more than 35% fat. Despite the high prevalence of CDRF, there were no significant differences between supplement U and NU.


Blood thiocyanate levels and self-reported smoking habits compared in two large cardiovascular population studies.
In two representative population surveys (n1 = 1712, n2 = 3757, age-range: 25-64 years) from six towns in Northern Badenia (FRG) self-reported smoking habits and blood thiocyanate levels were compared. In Survey 1 the smoking prevalence was 44.1% in males and 32.9% in females, in Survey 2 45.0% in males and 26.5% in females. In agreement with previous studies it was proved that thiocyanate measurements allow to distinguish groups of non-smokers from smokers, whilst not being specific enough to reflect precisely the quantity of tobacco consumption of the individual. A quadratic regression of thiocyanate levels on cigarette consumption provided a better fit and a higher correlation coefficient than linear regression, indicating a saturation effect, i.e., there is no further increase of thiocyanate levels when more than about 30 cigarettes daily are consumed.


Neural substrates of respiratory sensory gating: A human fMRI study.
The involvement of neural substrates in respiratory sensory gating remained unclear. This study aimed to investigate cortical and subcortical activations associated with respiratory sensory gating by using functional magnetic resonance imaging. First, we hypothesized that paired occlusions would induce neural activation in cortical and subcortical areas, including the thalamus and sensorimotor cortices. Secondly, we hypothesized that, in terms of parameter estimates in the general linear model, the activation effect size β ratios (βpaired/βsingle) would be less than 2 due to central neural gating mechanism. Forty-six healthy participants were included in the study. Our analyses showed that the βpaired/βsingle ratios for the supramarginal gyrus, basal ganglia, thalamus, and middle frontal gyrus were less than 2. In conclusion, our results demonstrated a non-linear relationship regarding brain neural activations in response to paired versus single occlusions, suggesting that respiratory sensory information is gated at the subcortical and cortical levels.


Evaluation of the efficiency of a Venturi scrubber in particulate matter collection smaller than 2.5 µm emitted by biomass burning.
Energy demand has increased worldwide, and biomass burning is one of the solutions most used by industries, especially in countries that have a great potential in agriculture, such as Brazil. However, these energy sources generate pollutants, consisting of particulate matter (PM) with a complex chemical composition, such as sugarcane bagasse (SB) burning. Controlling these emissions is necessary; therefore, the aim was to evaluate PM collection using a rectangular Venturi scrubber (RVS), and its effects on the composition of the PM emitted. Considering the appropriate use of biomass as an industrial fuel and the emerging need for a technique capable of efficiently removing pollutants from biomass burning, this study shows the control of emissions as an innovation in a situation such as the industrial one with the use of a Venturi scrubber in fine particle collection, in addition to using portable and representative isokinetic sampling equipment of these particles. The pilot-scale simulation of the biomass burning process, the representative sampling of fine particles and obtaining parameters to control pollutant emissions for a Venturi scrubber, meets the current situation of concern about air quality. The average collection efficiency values were 96.6% for PM> 2.5, 85.5% for PM1.0-2.5, and 66.9% for PM< 1.0. The ionic analysis for PM< 1.0 filters showed potassium, chloride, nitrate, and nitrite at concentrations ranging from 20.12 to 36.5 μg/m3. As the ethanol and sugar plants will continue to generate electricity with sugarcane bagasse burning, emission control technologies and cost-effective and efficient portable samplers are needed to monitor particulate materials and improve current gas cleaning equipment projects.


Biomaterials use in Mulago National Referral Hospital in Kampala, Uganda: Access and affordability.
Students in Biomaterials BBE3102 at Makerere University in Kampala, Uganda were assigned semester long group projects in the first semester of the 2014-15 academic year to determine the biomaterials type and usage in Mulago National Referral Hospital, which is emblematic of large public hospitals across East Africa. Information gathering was conducted through student interviews with Mulago physicians because there were no archival records. The students divided themselves into seven project groups covering biomaterials use in the areas of wound closure, dental and oral surgery, cardiology, burn care, bone repair, ophthalmology and total joint replacement. As in the developed world, the majority of biomaterials used in Mulago are basic wound closure materials, dental materials, and bone fixation materials, all of which are comparatively inexpensive, easy to store, and readily available from either the government or local suppliers; however, there were significant issues with the implant supply chain, affordability, and patient compliance and follow-up in cases where specialty expertise and expensive implants were employed.


Light-induced surface wettability of a tethered DNA base.
We show that the DNA base thymine and other uracil derivatives, when alkylated with a hydrocarbon chain and assembled at a gold interface, dimerize when subjected to UV irradiation. The process is robust and reversible and is accompanied by a substantial decrease in wettability as well as a marked decrease in acidity constant when the dimer is formed. There is a concerted molecular reorientation that accompanies photodimerization, with the dimer displaying a marked affinity for the gold surface. The spatial requirements for this reorganization are satisfied during dimerization by the reduction in intermolecular distance that occurs when the cyclobutane ring is formed between adjacent bases. The structural changes observed here for a tethered DNA base provide a direct route for exploring reactions, in two dimensions, that are of central interest in biology.


Does a prediction model for pregnancy of unknown location developed in the UK validate on a US population?
A logistic regression model (M4) was developed in the UK to predict the outcome for women with a pregnancy of unknown location (PUL) based on the initial two human chorionic gonadotrophin (hCG) values, 48 h apart. The purpose of this paper was to assess the utility of this model to predict the outcome for a woman (PUL) in a US population. Diagnostic variables included log-transformed serum hCG average of two measurements, and linear and quadratic hCG ratios. Outcomes modeled were failing PUL, intrauterine pregnancy (IUP) and ectopic pregnancy (EP). This model was applied to a US cohort of 604 women presenting with symptomatic first-trimester pregnancies, who were followed until a definitive diagnosis was made. The model was applied before and after correcting for differences in terminology and diagnostic criteria. When retrospectively applied to the adjusted US population, the M4 model demonstrated lower areas under the curve compared with the UK population, 0.898 versus 0.988 for failing PUL/spontaneous miscarriage, 0.915 versus 0.981 for IUP and 0.831 versus 0.904 for EP. Whereas the model had 80% sensitivity for EP using UK data, this decreased to 49% for the US data, with similar specificities. Performance only improved slightly (55% sensitivity) when the US population was adjusted to better match the UK diagnostic criteria. A logistic regression model based on two hCG values performed with modest decreases in predictive ability in a US cohort for women at risk for EP compared with the original UK population. However, the sensitivity for EP was too low for the model to be used in clinical practice in its present form. Our data illustrate the difficulties of applying algorithms from one center to another, where the definitions of pathology may differ.


Development of a Complex Intervention for Health Care Professionals' Care of Patients With African Background and HIV Infection Using the Behavior Change Wheel Method.
Introduction. Insufficient cultural competences among health care professionals (HCPs) working with ethnic minorities may result in poorer quality of care. This study aimed to develop a cultural intervention for HCPs. Method. The intervention was designed using the Behavior Change Wheel. The development phase contained empirical studies of patients with HIV and African background, literature review, observations from a migrant health clinic, and transcultural care theory. Results. Systematic development will facilitate an intervention tailored to focus on nurses' sensitivity and awareness, and aims to give them tools to identify narratives about patients' life situation and self-management as well as provide effective, compassionate, and culturally competent care. Discussion. Higher cultural competence among nurses may improve their support of patients to manage their disease.


Organocatalytic Regio- and Enantioselective [3 + 2]-Annulations of Ninhydrin-Derived Morita-Baylis-Hillman Carbonates with 3-Methyleneoxindoles.
A type of Morita-Baylis-Hillman (MBH) carbonates has been developed from ninhydrin. These MBH carbonates have been successfully employed as 3C-synthons in the organocatalytic asymmetric [3 + 2]-annulations of the isatin-derived electron-deficient olefins, affording structurally diverse spirooxindoles in high yield with excellent stereoselectivity. In particular, the regioselectivity of MBH carbonates was controlled by the reaction partner, 3-methyleneoxindoles with carbonyl groups (R = ArCO), affording β-selective products and 3-methyleneoxindoles with ester groups (R = CO2Me) furnishing γ-selective products. The representative scale-up reactions and transformation of product were examined. The reaction mechanism was expounded by control experiments.


Simulation of occupant response in space capsule landing configurations with suit hardware.
The purpose of this study was to compare the response of the total human model for safety (THUMS) human body finite element model (FEM) to experimental postmortem human subject (PMHS) test results and evaluate possible injuries caused by suit ring elements. Experimental testing evaluated the PMHS response in frontal, rear, side, falling, and spinal impacts. The THUMS was seated in a rigid seat that mirrored the sled buck used in the experimental testing. The model was then fitted with experimental combinations of neck, shoulder, humerus and thigh rings with a five-point restraint system. Experimental seat acceleration data was used as the input for the simulations. The simulation results were analyzed and compared to PMHS measurements to evaluate the response of the THUMS in these loading conditions. The metrics selected to compare the THUMS simulation to PMHS tests were the chest acceleration, seat acceleration and belt forces with additional metrics implemented in THUMS. The chest acceleration of the simulations and the experimental data was closely matched except in the Z-axis (superior/inferior) loading scenarios based on signal analysis. The belt force data of the model better correlated to the experimental results in loading scenarios where the THUMS interacted primarily with the restraint system compared to load cases where the primary interaction was between the seat and the occupant (rear, spinal and lateral impacts). The simulation output demonstrated low injury metric values for the occupant in these loading conditions. In the experimental testing, rib fractures were recorded for the frontal and left lateral impact scenarios. Fractures were not seen in the simulations, most likely due to variations between the simulation and the PMHS initial configuration. The placement of the rings on the THUMS was optimal with symmetric placement about the centerline of the model. The experimental placement of the rings had more experimental variation. Even with this discrepancy, the THUMS can still be considered a valuable predictive tool for occupant injury because it can compare results across many simulations. The THUMS also has the ability to assess a wider variety of other injury information, compared to anthropomorphic test devices (ATDs), that can be used to compare simulation results.


Prefrontal activity during experimental ostracism and daily psychache in suicide attempters.
Suicidal behaviors can result from a complex interaction between social stressors and individual vulnerability. Evidence suggests a specific neural processing of social cues in suicide attempters without knowledge of how it relates to real-world experiences. To investigate the association between brain activity during experimental social exclusion (measured by functional MRI) and psychological pain in daily life (assessed by Ecological Momentary Assessment) in patients with a lifetime history of suicide attempt. Thirty-three euthymic females with a history of a major depressive episode were recruited: 13 suicide attempters and 20 affective controls (no history of suicide attempt). Functional MRI scans were acquired while participants played the Cyberball game, a validated social exclusion paradigm. After fMRI, participants completed EMA for a one-week period. Five times per day, they were asked to rate their psychological pain, hopelessness and the negativity of daily events. EMA indices (psychological pain, hopelessness and their interaction with negative events) were correlated with cerebral activations using a ROI approach (orbitofrontal, dorsal and ventrolateral prefrontal cortices, anterior cingulate cortex and insula) in each group. We found a negative correlation between daily ratings of psychological pain and orbitofrontal activation for exclusion versus inclusion during the Cyberball game in suicide attempters but not in affective controls. We did not find correlations between cerebral activation and daily hopelessness ratings. Small sample size CONCLUSION: Scanner-based orbitofrontal activity during social exclusion relates to psychological pain in daily life which participates in suicide risk among vulnerable individuals.


Cumulative risk: toxicity and interactions of physical and chemical stressors.
Recent efforts to update cumulative risk assessment procedures to incorporate nonchemical stressors ranging from physical to psychosocial reflect increased interest in consideration of the totality of variables affecting human health and the growing desire to develop community-based risk assessment methods. A key roadblock is the uncertainty as to how nonchemical stressors behave in relationship to chemical stressors. Physical stressors offer a reasonable starting place for measuring the effects of nonchemical stressors and their modulation of chemical effects (and vice versa), as they clearly differ from chemical stressors; and "doses" of many physical stressors are more easily quantifiable than those of psychosocial stressors. There is a commonly held belief that virtually nothing is known about the impact of nonchemical stressors on chemically mediated toxicity or the joint impact of coexposure to chemical and nonchemical stressors. Although this is generally true, there are several instances where a substantial body of evidence exists. A workshop titled "Cumulative Risk: Toxicity and Interactions of Physical and Chemical Stressors" held at the 2013 Society of Toxicology Annual Meeting provided a forum for discussion of research addressing the toxicity of physical stressors and what is known about their interactions with chemical stressors, both in terms of exposure and effects. Physical stressors including sunlight, heat, radiation, infectious disease, and noise were discussed in reference to identifying pathways of interaction with chemical stressors, data gaps, and suggestions for future incorporation into cumulative risk assessments.


Cutaneous and splenic mastocytosis in a juvenile Malayan tiger.
A male Malayan tiger cub developed well-circumscribed, erythematous, alopecic lesions on the face, torso, and paws when 1-wk-old. Biopsies of a torso lesion and a right front paw lesion at 1-mo-old confirmed cutaneous mast cell tumors (MCTs). MCTs on the paws grew into pendulous masses up to 6.5 cm in diameter by 3-mo-old, but those on the face and torso regressed. Fine-needle aspiration of the spleen at 3-mo-old revealed marked mast cell infiltration. The spleen and the right paw cutaneous MCT were removed; the paw MCT recurred within 7 d. A 12-bp tandem duplication, suggesting a somatic mutation, was identified in exon 8 of c-KIT in DNA extracted from the cutaneous MCT on the right paw and from one over the torso, but not from the spleen. Remaining MCTs on the paws regressed slowly following splenectomy and had completely regressed by 1-y-old. At 7-y-old, there was no recurrence of any mast cell disease. Mast cell disease in this tiger cub is similar to a report in a domestic kitten and to pediatric mastocytosis in humans, which commonly begins in infancy, improves by adolescence, and is associated with somatic c-kit mutations. To our knowledge, mastocytosis has not been reported previously in a juvenile exotic felid.


[A clinical feature and therapeutic strategy in pituitary adenomas associated with intracranial aneurysms].
We studied the clinical feature and treatment strategy of pituitary adenomas associated with intracranial aneurysms. Among 102 pituitary adenoma patients (mean age: 54.8 years old) who received MR angiography and/or 3D-CT angiography, seven patients (6.9%) had intracranial aneurysms. The association of an aneurysm was more common in large size adenomas (p<0.05). According to the location of the aneurysms, five patients had these in the paraclinoid portion or cavernous portion of the internal carotid artery. Using MR images, we classified the aneurysms associated with pituitary adenomas as non-adjacent, adjacent, and intra-adenoma types. In non-adjacent types, an aneurysm is located apart from the adenoma, and has less chance of exposure during transsphenoidal surgery. In adjacent types, an aneurysm is located adjacent to the adenoma, and could be exposed during transsphenoidal surgery. In intra-adenoma types, an aneurysm is encased in the adenoma. In non-adjacent type aneurysms, a resection of the pituitary adenoma can be carried out before aneurysm treatment due to the low risk of rupture during surgery. In adjacent types, a tumor resection can precede aneurysm treatment in cases of low rupture risk aneurysms and untreatable aneurysms. In intra-adenoma types, adenoma resection should come after treatment of the aneurysms. Neurosurgeons should be careful about not only the presence of aneurysms in preoperative images during transsphenoidal surgery planning, but also their locations and proximity to adenomas. Such information may be crucial in deciding the order of treatment.


The effect of photodynamic therapy and polymer solution containing nano-particles of Ag /ZnO on push-out bond strength of the sealers AH-Plus and MTA Fillapex.
The aim of this in vitrostudy was to examine and compare the effect of photodynamic therapy and solution containing nano particles Ag/ZnO on adhesion of endodontic sealers to dentinal walls of human root canal. Ninty single-rooted human teeth were selected and their clinical crown was cut from the cemento-enamel junction zone. Canals were prepared by RaCe rotary system and the smear layer was removed using 17% EDTA and 5.25% NaOCl. Samples were randomly divided into two groups of AH Plus and MTA Fillapex based on the sealer type and each group based on antimicrobial method was divided into two sub-groups of photodynamic therapy and polymer containing nano particles of Ag / ZnO and a control sub-group (N = 15). After obturation of canals with gutta-percha and sealers mentioned, the samples were incubated for a week at a humidity of 95% and 37°C and then 2mm thick discs were prepared from the middle region of roots for Push-out test. The maximum failure force was recorded in newton and converted to MPa. Then, 3 random specimens of each subgroup were evaluated by scanning electron microscopy. Statistical analysis was performed by Two way ANOVA and (P<0.05) was considered significant. The highest (4.84 ± 1.63) and lowest (0.16 ± 0.075) push-out bond strength values were obtained in (AH Plus-PDT) and (MTA Fillapex-Ag/ZnO) respectively. Independent of antimicrobial method, AH Plus bond strength was significantly higher than the MTA Fillapex (p<0.001). For both sealers, PDT increased the bond strength significantly (p<0.001). Photodynamic therapy has a positive effect on the bond strength of AH Plus and MTA Fillapex sealers. Key words:AH Plus, MTA Fillapex, Nano particles, Photodynamic therapy, Push-out.