Linearity and non-linearity in cerebral hemodynamics.
Transcranial Doppler ultrasound has been extensively used to study cerebral hemodynamics, and yet the basic characteristics of the input/output system of blood pressure/velocity are little known. We examine whether this system can best be considered linear or non-linear. We assessed the adequacy of linear modeling in four ways: (1) Known properties of cerebral blood flow were reviewed and analyzed from a systems standpoint; (2) 1100 ARX & OE model types were tested with data from 29 normal subjects, with and without lowpass filtering; (3) time-frequency analysis was used to identify nonstationary behavior and markers of non-linearity (such as bifurcations, chirps, and intermittent autoregulatory impairment) in the same data sets; (4) simple computer models of autoregulation incorporating time delays and non-linear elements were tested for production of spontaneous oscillations. (1) Several aspects of cerebral hemodynamics are poorly described by linear models, (2) the ARX & OE models performed poorly, (3) time-frequency analysis showed non-linear and nonstationary behavior, (4) the computer models produced spontaneous oscillations similar to those observed in humans. There is strong evidence that the blood pressure/velocity system is non-linear.


Regulation of taurine transport in Ehrlich ascites tumor cells.
Taurine influx is inhibited and taurine efflux accelerated when the cell membrane of Ehrlich ascites tumor cells is depolarized. Taurine influx is inhibited at acid pH partly due to the concomitant depolarization of the cell membrane partly due to a reduced availability of negatively charged free carrier. These results are in agreement with a 2Na,1C1,1taurine cotransport system which is sensitive to the membrane potential due to a negatively charged empty carrier. Taurine efflux from Ehrlich cells is stimulated by addition of LTD4 and by swelling in hypotonic medium. Cell swelling in hypotonic medium is known to result in stimulation of the leukotriene synthesis and depolarization of the cell membrane. The taurine efflux, activated by cell swelling, is dramatically reduced when the phospholipase A2 is inhibited indirectly by addition of the anti-calmodulin drug pimozide, or directly by addition of RO 31-4639. The inhibition is in both cases lifted by addition of LTD4. The swelling-induced taurine efflux is also inhibited by addition of the 5-lipoxygenase inhibitors ETH 615-139 and NDGA. It is concluded that the swelling-induced activation of the taurine leak pathway involves a release of arachidonic acid from the membrane phospholipids and an increased oxidation of arachidonic acid into leukotrienes via the 5-lipoxygenase pathway. LTD4 seems to act as a second messenger for the swelling induced activation of the taurine leak pathway either directly or indirectly via its activation of the Cl- channels, i.e., via a depolarization of the cell membrane.


Paediatric family activation rapid response (FARR) in tertiary healthcare organisations: Protocol for an online, multi-lingual, application (app) intervention development study.
At least 85% of unplanned admissions to critical care wards for children and young people (CYP) are associated with clinical deterioration. CYP and their families play an integral role in the recognition of deterioration. The Paediatric Critical Care Outreach Team (PCCOT) supports the reduction of avoidable harm through earlier recognition and treatment of the deteriorating child, acting as a welcome conduit between the multiprofessional teams, helping ensure that CYP gets the right care, at the right time and in the right place. This positions PCCOT well to respond to families who call for help as part of family activation. This protocol details the methods and process of developing a family activation rapid response online application. This is a single-centre, sequential, multiple methods study design. Firstly, a systematic review of the international literature on rapid response interventions in paediatric family activation was conducted. Findings from the review aimed to inform the content for next stages; interviews/ focus groups and experience-based co-design (EBCD) workshops. parents / caregivers whose children have been discharged or admitted to an acute care hospital and healthcare professionals who care for paediatric patients (CYP). During interviews and workshops participants' opinion, views and input will be sort on designing a family activation rapid response online-app, detailing content, aesthetics, broad functionality and multi-lingual aspects. Further areas of discussions include; who will use the app, access, appropriate language and terminology for use. A suitable app development company will be identified and will be part of the stakeholders present at workshops. Data obtained will be used to develop a multi-lingual paediatric family activation rapid response web based application prototype. Full ethical approval was received from the Wales Research Ethics Committee 2. Cardiff; REC reference: 22/WA/0174. The findings will be made available to all stakeholders.


Transwell In Vitro Cell Migration and Invasion Assays.
Cell migration and invasion have essential roles in both normal physiology and disease. As such, methodologies to assess cell migratory and invasive capacities are necessary to elucidate normal cell processes and underlying mechanisms of disease. Here, we describe commonly used transwell in vitro methods for the study of cell migration and invasion. The transwell migration assay involves the chemotaxis of cells through a porous membrane after the establishment of a chemoattractant gradient using two medium-filled compartments. The transwell invasion assay involves the addition of an extracellular matrix on top of the porous membrane which only permits chemotaxis of cells which possess invasive properties such as tumor cells.


Photochromism of a Spiropyran in the Presence of a Dendritic Fibrous Nanosilica; Simultaneous Photochemical Reaction and Adsorption.
The photoinduced adsorption of a photochromic spiropyran (1-(2-hydroxyethyl)-3,3-dimethylindolino-6'-nitrobenzopyrylospiran) onto a dendritic fibrous nanosilica (DFNS) was investigated. By UV irradiation, the colorless suspension containing the spiropyran and DFNS changed to blue without stirring, while it turned to red by the irradiation under stirring. These two colors were attributed to the photogenerated merocyanine in a non polar environment (in toluene, blue) and on a protic environment (on DFNS, red). The long lifetime of the adsorbed merocyanine on DFNS (red) and the easy separation of DFNS from the suspension made it possible to follow the kinetics of the photoinduced adsorption as a pseudo-first order reaction with the rate constant of 0.0279 s-1. The rate limiting process was suggested to be the adsorption of the merocyanine onto DFNS.


A new alternative treatment for entrapped stone basket in the distal ureter.
We describe an alternative method for the treatment of an entrapped stone basket. When efforts to remove an engaged stone through the intramural ureter met with marked resistance, the basket with the stone within it was advanced into the renal pelvis. Extracorporeal shock wave lithotripsy then was used to pulverize the stone, allowing successful removal of the basket.


Leaf transcriptome profiling of contrasting sugarcane genotypes for drought tolerance under field conditions.
Drought is the most detrimental abiotic stress to sugarcane production. Nevertheless, transcriptomic analyses remain scarce for field-grown plants. Here we performed comparative transcriptional profiling of two contrasting sugarcane genotypes, 'IACSP97-7065' (drought-sensitive) and 'IACSP94-2094' (drought-tolerant) grown in a drought-prone environment. Physiological parameters and expression profiles were analyzed at 42 (May) and 117 (August) days after the last rainfall. The first sampling was done under mild drought (soil water potential of -60 kPa), while the second one was under severe drought (soil water potential of -75 kPa). Microarray analysis revealed a total of 622 differentially expressed genes in both sugarcane genotypes under mild and severe drought stress, uncovering about 250 exclusive transcripts to 'IACSP94-2094' involved in oxidoreductase activity, transcriptional regulation, metabolism of amino acids, and translation. Interestingly, the enhanced antioxidant system of 'IACSP94-2094' may protect photosystem II from oxidative damage, which partially ensures stable photochemical activity even after 117 days of water shortage. Moreover, the tolerant genotype shows a more extensive set of responsive transcription factors, promoting the fine-tuning of drought-related molecular pathways. These results help elucidate the intrinsic molecular mechanisms of a drought-tolerant sugarcane genotype to cope with ever-changing environments, including prolonged water deficit, and may be useful for plant breeding programs.


Racial Differences in Positive Airway Pressure Adherence in the Treatment of Sleep Apnea.
Although data are limited, studies suggest on average lower positive airway pressure use in Black, indigenous, and people of color (BIPOC) compared with Whites in most but not all studies. Most of these observational studies are certainly limited by confounding by socioeconomic status and other unmeasured factors that likely contribute to differences. The etiology of these observed disparities is likely multifactorial, due in part to financial limitations, differences in sleep opportunity, poor sleep quality due to environmental disruptions, and so forth. These disparities in sleep health are likely related to chronic inequities, including experiences of racism, neighborhood features, structural, and contextual factors. Dedicated studies focusing on understanding adherence in BIPOC are lacking. Further research is needed to understand determinants of PAP use in BIPOC subjects and identify feasible interventions to improve sleep health and reduce sleep apnea treatment disparities.


Clavicular osteotomy in shoulder arthroplasty.
We present an approach to the shoulder which is easily performed, offers unrivalled exposure for the accurate placement of prostheses or reconstruction of complicated fractures and is easily closed. We have used this approach since 1977 and report our results in 128 patients.


Validation of Toxtree and SciQSAR in silico predictive software using a publicly available benchmark mutagenicity database and their applicability for the qualification of impurities in pharmaceuticals.
The draft ICH M7 guidance (US FDA, 2013) recommends that the computational assessment of bacterial mutagenicity for the qualification of impurities in pharmaceuticals be performed using an expert rule-based method and a second statistically-based (Q)SAR method. The public nonproprietary 6489 compound Hansen benchmark mutagenicity data set was used as an external validation data set for Toxtree, a free expert rule-based SAR software. This is the largest known external validation of Toxtree. The Toxtree external validation specificity, sensitivity, concordance and false negative rate for this mutagenicity data set was 66%, 80%, 74% and 20%, respectively. This mutagenicity data set was also used to create a statistically-based SciQSAR-Hansen mutagenicity model. In a 10% leave-group-out internal cross validation study the specificity, sensitivity, concordance and false negative rate for the SciQSAR mutagenicity model was 71%, 83%, 77% and 17%, respectively. Combining Toxtree and SciQSAR predictions and scoring a positive finding in either software as a positive mutagenicity finding reduced the false negative rate to 7% and increased sensitivity to 93% at the expense of specificity which decreased to 53%. The results of this study support the applicability of Toxtree, and the SciQSAR-Hansen mutagenicity model for the qualification of impurities in pharmaceuticals.


Performance of one-view breast tomosynthesis as a stand-alone breast cancer screening modality: results from the Malmö Breast Tomosynthesis Screening Trial, a population-based study.
To assess the performance of one-view digital breast tomosynthesis (DBT) in breast cancer screening. The Malmö Breast Tomosynthesis Screening Trial is a prospective population-based one-arm study with a planned inclusion of 15000 participants; a random sample of women aged 40-74 years eligible for the screening programme. This is an explorative analysis of the first half of the study population (n = 7500). Participants underwent one-view DBT and two-view digital mammography (DM), with independent double reading and scoring. Primary outcome measures were detection rate, recall rate and positive predictive value (PPV). McNemar's test with 95 % confidence intervals was used. Breast cancer was found in sixty-eight women. Of these, 46 cases were detected by both modalities, 21 by DBT alone and one by DM alone. The detection rate for one-view DBT was 8.9/1000 screens (95 % CI 6.9 to 11.3) and 6.3/1000 screens (4.6 to 8.3) for two-view DM (p < 0.0001). The recall rate after arbitration was 3.8 % (3.3 to 4.2) for DBT and 2.6 % (2.3 to 3.0) for DM (p < 0.0001). The PPV was 24 % for both DBT and DM. Our results suggest that one-view DBT might be feasible as a stand-alone screening modality. One-view DBT as a stand-alone breast cancer screening modality has not been investigated. One-view DBT increased the cancer detection rate significantly. The recall rate increased significantly but was still low. Breast cancer screening with one-view DBT as a stand-alone modality seems feasible.


Suppression of fertility in male mice by immunization against LH receptor.
We have investigated the potential contraceptive effects of immunization against the luteinizing hormone (LH) receptor in male mice at the prepubertal stage. Two N-terminal fragments of the porcine LH receptor encoding amino acids 1-297 and 1-370 were produced in large quantities through the Baculovirus insect cell system. We have immunized three-week-old mice from two Balb/c stocks of differing fecundity with Sf9 insect cells producing the short (1-297) or long (1-370) recombinant LH receptor. A booster injection was performed at six weeks using purified antigens. Ten days later, the immunized male mice were mated over a period of two weeks with adult untreated females. After weaning of the first litters, the same partners were mated once again under the same conditions. There was no decrease in the antiserum titers against the antigens over a two-month period. The circulating testosterone decreased as the anti-LH receptor antibodies increased. The fertility of the treated male mice was reduced up to 75%, depending on the mouse stock, the antigen used and the time separating immunization and mating. The impaired fertility was mostly due to male sterilization (up to 60% of sterile mates). The delay between mating and birth was enhanced by the treatment, reflecting delayed fertility and/or delayed male behaviour acquisition.


Motor imagery in a locked-in patient: evidence from transcranial magnetic stimulation.
Motor evoked potentials (MEPs) to transcranial magnetic stimulation were evaluated in a case of locked-in syndrome due to a large pontine infarction. In this patient, magnetic resonance imaging (MRI) and somatosensory evoked potentials demonstrated a tegmental involvement. One month after the attack, no MEP could be recorded from the right abductor digiti minimi (ADM) or either tibialis anterior muscle. On the contrary, MEPs were obtained from the left ADM, although with a prolonged latency and a reduced amplitude. When the patient was requested to think about the abduction of her paralyzed left little finger, the latency and the elicitability of these responses improved as compared with the relaxed condition. These severe MEP alterations correctly predicted a poor recovery of motor function in the chronic stage. However, although the tegmental involvement raises the question of an insufficient cortical motor arousal, preserved motor imagery suggested a normal cortical motor area activation.


Cloning and characterization of an alpha-enolase of the oral pathogen Streptococcus mutans that binds human plasminogen.
Streptococcus mutans is the etiologic agent of dental caries and is a causative agent of infective endocarditis. While the mechanisms by which S. mutans cells colonize heart tissue is not clear, it is thought that bacterial binding to extracellular matrix and blood components is crucial in the development of endocarditis. Previously, we have demonstrated that S. mutans cells have the capacity to bind and activate plasminogen to plasmin. Here we report the first cloning and characterization of an alpha-enolase of S. mutans that binds plasminogen. The functional identity of the purified recombinant alpha-enolase protein was confirmed by its ability to catalyze the conversion of 2-phosphoglycerate to phosphoenolpyruvate. The protein exhibited a Km of 9.5 mM and a Vmax of 31.0 mM/min/mg. The alpha-enolase protein was localized in the cytoplasmic, cell wall and extracellular fractions of S. mutans. Binding studies using an immunoblot analysis revealed that human plasminogen binds to the enolase enzyme of S. mutans. These findings identify S. mutans alpha-enolase as a binding molecule used by this oral pathogen to interact with the blood component, plasminogen. Further studies of this interaction may be critical to understand the pathogenesis of endocarditis caused by S. mutans.


Chronic estrogen exposure affects gene expression in the rostral ventrolateral medulla of young and aging rats: Possible role in hypertension.
Chronic exposure to estradiol-17β (E2) in adult female rats increases mean arterial pressure by stimulating superoxide production in the rostral ventrolateral medulla (RVLM). However the mechanisms behind this phenomenon are unknown. We hypothesized that E2 exposure induces the gene expression of cytokines, chemokines and NADPH oxidase (Nox) in the RVLM that promotes superoxide production and aging would exacerbate this effect. Young adult (3-4 month old) and middle-aged (6-8 month old) female Sprague Dawley rats were sham-implanted (YS and MS respectively) or implanted s.c. with slow-release E2 pellets (20 ng of E2/day for 90 days; YE and ME respectively). Blood pressure (BP) was measured during the last 3 weeks of exposure in a separate set of rats. At the end of treatment, the animals were sacrificed and RVLM was isolated from the brainstem. PCR array and Quantitative RT-PCR were performed with the tissue to quantify genes associated with hypertension and superoxide production. Superoxide dismutase (SOD) activity was also measured in the RVLM from a different set of animals. E2 exposure increased mean arterial pressure in both YE and ME animals. Inflammatory genes such as interleukin-1β, interleukin-6 and monocyte chemoattractant protein-1 were significantly up-regulated in the RVLM of ME treated female rats compared to YS rats, but not in YE rats. Endothelin-1 (ET-1) gene was up-regulated in the RVLM of both YE and ME rats that were exposed to E2. Furthermore, chronic E2 treatment increased the mRNA levels of Nox1 and Nox2 genes in the RVLM of YE but not ME animals. SOD activity was reduced in MA animals, compared to young animals. E2 treatment had no significant effect on SOD activity. Chronic E2 exposure stimulates the expression of inflammatory genes in older animals and increases the expression of Nox subunits in the RVLM of younger animals. SOD activity was reduced in older animals. This suggests increased superoxide production in younger animals, but reduced superoxide elimination in older animals. On the other hand, E2 exposure stimulates ET-1 expression in both young and aging animals. These findings suggest that hypertension caused by chronic E2 exposure may involve different molecular mediators in young and aging animals, however ET-1 and superoxide could be common mediators for both age groups.


The liberal state and the rogue agency: FDA's regulation of drugs for mood disorders, 1950s-1970s.
The theory of the liberal state does not generally contemplate the possibility that regulatory agencies will turn into "rogues," regulating against the interests of their clients and, indeed, the public interest. In the years between circa 1955 and 1975 this seems to have happened to one of the prime regulatory agencies of the US federal government: the Food and Drug Administration (FDA). Intent upon transforming itself from a traditional "cop" agency to a regulatory giant, the FDA campaigned systematically to bring down some safe and effective drugs. This article concentrates on hearings in the area of psychopharmacology regarding several antianxiety drugs, namely meprobamate (Miltown), chlordiazepoxide (Librium) and diazepam (Valium). In addition, from 1967 to 1973 this regulatory vengefulness occurred on a broad scale in the Drug Efficacy Study Implementation (DESI), an administrative exercise that removed from the market almost half of the psychopharmacopoeia. The article explores possible bureaucratic motives for these actions.


Tay-Sachs heterozygote screening: specificity and sensitivity.
Heterozygotes for the Tay-Sachs allele can be identified by plotting the heat-labile hexosaminidase activity in serum against the heat-stable activity. Quadratic discriminants can be constructed from homozygous normal and obligate heterozygous data and the probability of misclassification computed. The cost of counseling and the classification error is diminished by the use of 2 tests.


Alcoholic hepatitis: from pathogenesis to treatment.
Alcoholic hepatitis is a serious complication of alcohol abuse due to its high mortality rates particularly at short term. It may complicate pre-existing alcoholic fatty liver or cirrhosis and is mainly diagnosed on clinical and laboratory grounds although liver biopsy is occasionally needed to exclude other pathology and confirm the diagnosis. Accumulating evidence suggests that cytokines and immunity are actively involved in its pathogenesis. Management includes abstinence and supportive care. Treatment with corticosteroids has been studied in several clinical trials with conflicting results. However, recent evidence supporting the beneficial effect of TNF-alpha inhibition provides an encouraging alternative. Here we summarise the current state in diagnosis and management of alcoholic hepatitis and briefly review the latest advances in pathophysiology that may lead to new therapeutic strategies for this difficult clinical condition. Medline 1966-2005, EMBASE/Excerpta Medica 1980-2005, The Cochrane Library (2005 Issue 2) and contact with authors of published reports.


Dynamic compression improves biosynthesis of human zonal chondrocytes from osteoarthritis patients.
We hypothesize that chondrocytes from distinct zones of articular cartilage respond differently to compressive loading, and that zonal chondrocytes from osteoarthritis (OA) patients can benefit from optimized compressive stimulation. Therefore, we aimed to determine the transcriptional response of superficial (S) and middle/deep (MD) zone chondrocytes to varying dynamic compressive strain and loading duration. To confirm effects of compressive stimulation on overall matrix production, we subjected zonal chondrocytes to compression for 2 weeks. Human S and MD chondrocytes from osteoarthritic joints were encapsulated in 2% alginate, pre-cultured, and subjected to compression with varying dynamic strain (5, 15, 50% at 1 Hz) and loading duration (1, 3, 12 h). Temporal changes in cartilage-specific, zonal, and dedifferentiation genes following compression were evaluated using quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR). The benefits of long-term compression (50% strain, 3 h/day, for 2 weeks) were assessed by measuring construct glycosaminoglycan (GAG) content and compressive moduli, as well as immunostaining. Compressive stimulation significantly induced aggrecan (ACAN), COL2A1, COL1A1, proteoglycan 4 (PRG4), and COL10A1 gene expression after 2 h of unloading, in a zone-dependent manner (P < 0.05). ACAN and PRG4 mRNA levels depended on strain and load duration, with 50% and 3 h loading resulting in highest levels (P < 0.05). Long-term compression increased collagen type II and ACAN immunostaining and total GAG (P < 0.05), but only S constructs showed more PRG4 stain, retained more GAG (P < 0.01), and developed higher compressive moduli than non-loaded controls. The biosynthetic activity of zonal chondrocytes from osteoarthritis joints can be enhanced with selected compression regimes, indicating the potential for cartilage tissue engineering applications.


Structure of polypeptide-based diblock copolymers in solution: stimuli-responsive vesicles and micelles.
Polypeptide-based diblock copolymers forming either well-defined self-assembled micelles or vesicles after direct dissolution in water or in dichloromethane have been studied combining light and neutron scattering with electron microscopy experiments. The size of these structures could be reversibly manipulated as a function of environmental changes such as pH and ionic strength in water. Compared to other pH-responsive self-assembled systems based on "classical" polyelectrolytes, these polypeptide-based nanostructures present the ability to give a response in highly salted media as the chain conformational ordering can be controlled. This makes these micelles and vesicles suitable for biological applications: they provide significant advantages in the control of the structure and function of supramolecular self-assemblies.


A simplified model for en bloc double lung xenotransplantation from hamster to rat.
We present a simplified model of lung xenotransplantation from hamster to rat with a total non-suture technique using 14G cuffs for the main pulmonary artery, the trachea and the left atrium. This technique provides a technically easier and more reliable model to study xenotransplantation of the lung.


Clinical use of mood stabilizers beyond treatment for bipolar disorder: The REAP-MS study.
Mood stabilizers are psychotropic drugs mainly used to treat bipolar disorder in the acute phase or for maintenance therapy to prevent relapse. In clinical practice, mood stabilizers are commonly prescribed for conditions other than bipolar disorder. This study investigated the distribution of mood stabilizer prescriptions for different psychiatric diagnoses and studied differences in the drugs, dosage, and plasma concentration in 10 Asian countries including Taiwan, South Korea, Malaysia, China, Thailand, India, Pakistan, Singapore, Indonesia, and Myanmar. Patients prescribed mood stabilizers (lithium, carbamazepine, valproic acid, or lamotrigine) for a psychiatric condition other than bipolar disorder (codes F31.0-F31.9 in the International Classification of Diseases, 10th Edition, Clinical Modification) were recruited through convenience sampling. A website-based data entry system was used for data collection. In total, 1557 psychiatric patients were enrolled. Schizophrenia, schizotypal, delusional, and other non-mood psychotic disorders (F20-F29, 55.8 %) was the most common diagnosis, followed by non-bipolar mood disorders (F30, F31- F39, 25.3 %), organic mental disorder (F00-F09, 8.8 %), mental retardation (F70-F79, 5.8 %) and anxiety, dissociative, stress-related, somatoform and other nonpsychotic mental disorders (F40-F48, 4.4 %). The most frequently targeted symptoms (>20 %) were irritability (48 %), impulsivity (32.4 %), aggression (29.2 %), anger (20.8 %), and psychosis (24.1 %). Valproic acid was the most frequently used medication. Clinicians typically prescribe mood stabilizers as empirically supported treatment to manage mood symptoms in patients with diagnoses other than bipolar disorders, though there is on official indication for these disorders. The costs and benefits of this add-on symptomatic treatment warrant further investigation.


Obstructive Primary Cardiac T-Cell Lymphoma: A Case Report from Senegal.
BACKGROUND Cardiac lymphoma is a rare entity, defined by the non-extra cardiac location at diagnosis. CASE REPORT Our patient was a 32-year-old female with no particular medical history, who presented with right heart failure with recurrent ascites and pleural effusion. There was a progressive worsening exertional dyspnea. On admission, examination revealed an irregular tachycardia at 170 beats per minute (bpm) and congestive heart failure. The electrocardiogram scored full tachyarrhythmia by atrial fibrillation with an average ventricular rate of 179 cycles per minute. Doppler echocardiography showed dilatation and systolic dysfunction of the left ventricle. There were dilated atria. We noted a large mass in the right atrium, which was less mobile, heterogeneous, integral with the wall, and filling three quarters of the cavity. It clogged the tricuspid valve in diastole. CT scan showed a tissue process enhanced after contrast injection, occupying the predominant cavities in the right atrium and filling it. Its borders were irregular. The lesion was extended to the posterior mediastinum, in front of the vertebral axis. In addition, there was a thrombosis of the jugular vein and the inferior vena cava. There was no other tumor site noted. The patient died after presenting with cardiovascular shock associated with refractory right heart failure. Pathology examination confirmed T-cell lymphoma. CONCLUSIONS The primitive cardiac lymphoma is an entity of intra-cardiac masses. It is therefore to be considered even if the diagnosis is challenging.


ISOMAP induced manifold embedding and its application to Alzheimer's disease and mild cognitive impairment.
Neuroimaging data are high dimensional and thus cumbersome to analyze. Manifold learning is a technique to find a low dimensional representation for high dimensional data. With manifold learning, data analysis becomes more tractable in the low dimensional space. We propose a novel shape quantification method based on a manifold learning method, ISOMAP, for brain MRI. Existing work applied another manifold learning method, multidimensional scaling (MDS), to quantify shape information for distinguishing Alzheimer's disease (AD) from normal. We enhance the existing methodology by (1) applying it to distinguish mild cognitive impairment (MCI) from normal, (2) adopting a more advanced manifold learning technique, ISOMAP, and (3) showing the effectiveness of the induced low dimensional embedding space to predict key clinical variables such as mini mental state exam scores and clinical diagnosis using the standard multiple linear regression. Our methodology was tested using 25 normal, 25 AD, and 25 MCI patients.


Osteopontin-stimulated apoptosis in cardiac myocytes involves oxidative stress and mitochondrial death pathway: role of a pro-apoptotic protein BIK.
Increased osteopontin (OPN) expression in the heart, specifically in myocytes, associates with increased myocyte apoptosis and myocardial dysfunction. Recently, we provided evidence that OPN interacts with CD44 receptor, and induces myocyte apoptosis via the involvement of endoplasmic reticulum stress and mitochondrial death pathways. Here we tested the hypothesis that OPN induces oxidative stress in myocytes and the heart via the involvement of mitochondria and NADPH oxidase-4 (NOX-4). Treatment of adult rat ventricular myocytes (ARVMs) with OPN (20 nM) increased oxidative stress as analyzed by protein carbonylation, and intracellular reactive oxygen species (ROS) levels as analyzed by ROS detection kit and dichlorohydrofluorescein diacetate staining. Pretreatment with NAC (antioxidant), apocynin (NOX inhibitor), MnTBAP (superoxide dismutase mimetic), and mitochondrial KATP channel blockers (glibenclamide and 5-hydroxydecanoate) decreased OPN-stimulated ROS production, cytosolic cytochrome c levels, and apoptosis. OPN increased NOX-4 expression, while decreasing SOD-2 expression. OPN decreased mitochondrial membrane potential as measured by JC-1 staining, and induced mitochondrial abnormalities including swelling and reorganization of cristae as observed using transmission electron microscopy. OPN increased expression of BIK, a pro-apoptotic protein involved in reorganization of mitochondrial cristae. Expression of dominant-negative BIK decreased OPN-stimulated apoptosis. In vivo, OPN expression in cardiac myocyte-specific manner associated with increased protein carbonylation, and expression of NOX-4 and BIK. Thus, OPN induces oxidative stress via the involvement of mitochondria and NOX-4. It may affect mitochondrial morphology and integrity, at least in part, via the involvement of BIK.


Direct Z-scheme La1-xCexMnO3 catalyst for photothermal degradation of toluene.
A series of Ce-doped LaMnO3 (La1-xCexMnO3) were prepared and were tested for gaseous toluene oxidation in order to investigate the effect of cerium doping in LaMnO3 on activity under photothermal conditions. It was found that the activity and CO2 yield of the catalyst can be effectively increased when x = 0.25. A group of characterization is used to characterize the morphology, composition, and physical properties of the as-prepared catalysts. Results show that the Ce-doped LaMnO3 can form coexistence of La1-xCexMnO3 and CeO2, the reaction of CeO2/La1-xCexMnO3 under photothermal conditions follows the Mars-van Krevelen redox cycle mechanism, and the prepared CeO2/La1-xCexMnO3 can form a highly efficient Z-scheme heterojunction, which can enhance the electrons transfer speed of the catalyst. Moreover, in the photothermal catalytic degradation, lattice oxygen is the most important active substance, a small amount of cerium doping can increase the lattice oxygen content of perovskite and increase the activity of the reaction.


PTEN regulates lung endodermal morphogenesis through MEK/ERK pathway.
Pten is a multifunctional tumor suppressor. Deletions and mutations in the Pten gene have been associated with multiple forms of human cancers. Pten is a central regulator of several signaling pathways that influences multiple cellular functions. One such function is in cell motility and migration, although the precise mechanism remains unknown. In this study, we deleted Pten in the embryonic lung epithelium using Gata5-cre mice. Absence of Pten blocked branching morphogenesis and ERK and AKT phosphorylation at E12.5. In an explant model, Pten(Δ/Δ) mesenchyme-free embryonic lung endoderm failed to branch. Inhibition of budding in Pten(Δ/Δ) explants was associated with major changes in cell migration, while cell proliferation was not affected. We further examined the role of ERK and AKT in branching morphogenesis by conditional, endodermal-specific mutants which blocked ERK or AKT phosphorylation. MEK(DM/+); Gata5-cre (blocking of ERK phosphorylation) lung showed more severe phenotype in branching morphogenesis. The inhibition of budding was also associated with disruption of cell migration. Thus, the mechanisms by which Pten is required for early endodermal morphogenesis may involve ERK, but not AKT, mediated cell migration.


Variation in the course of vessels in the vicinity of the hepatic port in biliary atresia.
Among 114 patients with biliary atresia, the type of obstruction of the extrahepatic bile duct and the course of the hepatic artery, cystic artery, and portal vein were determined and analyzed from the view point of their mutual relationships and in comparison with postoperative bile excretion. As a result, the following findings characteristic of biliary atresia were obtained: (1) The course and location of the extrahepatic bile duct did not deviate greatly from normal conditions, excluding some exceptional cases, but the site of the origin of the cystic artery differed from that in normal cases. (2) The pattern of the course of the vessels varied among different types of obstruction of the extrahepatic bile duct. (3) There was a difference in postoperative bile excretion in relation to the type of obstruction of the extrahepatic bile duct, the course of the vessels, and their combinations.


Selective recovery of Ag(I) coordination anion from simulate nickel electrolyte using corn stalk based adsorbent modified by ammonia-thiosemicarbazide.
In nickel electrolyte, Ag(I) was present at trace level concentration (10-20 mg L(-1)) and existed in the form of AgCli(1-i) coordination anion, instead of Ag(+) positive ion usually in several sources. In the present study, TSC-NH3-OCS adsorbent based on natural corn stalk modified by ammonia (NH3)-thiosemicarbazide (TSC) was synthesized and characterized using some instrumental techniques. The TSC-NH3-OCS adsorbent could selectively adsorb Ag(I) as AgCl(i)(1-i) coordination anion from the Ag(I)-Cu(II)-Ni(II) simulate nickel electrolyte, especially in the case of the very high levels of Cu(II) and Ni(II), which significantly outperforms the commercial available resins. The adsorption mechanism was believed to be electrostatic interaction of the protonated bands of AgCl4(3-) with protonated thiol form of the thioamide units by FTIR and XPS analysis. The maximum adsorption capacity in the Ag(I) single and Ag(I)-Cu(II)-Ni(II) ternary system were obtained and calculated as 153.54 and 46.69 mg g(-1), respectively. The reasons that the maximum adsorption capacity of AgCl(i)(1-i) from the single and ternary system varied widely could be explained by adsorption kinetic and thermodynamic results. In addition, three successive sorption/desorption cycle runs from ternary system were performed which indicated that the TSC-NH3-OCS adsorbent has a good performance for recovery Ag(I) from simulate nickel electrolyte.


Diagnostic value of CD117 in differential diagnosis of acute leukemias.
C-kit receptor (CD117) and its ligand, stem cell factor, play a key role in normal hematopoiesis. It has been demonstrated that its expression extremely increases in leukemias with myeloid commitment. We analyzed findings on CD117 expression together with other myeloid related markers in 203 de novo acute leukemias, referred to Iranian immunophenotyping centers: Iranian Blood Transfusion Organization (IBTO) and Baghiatallah Hospital (BH). All cases were characterized based on the French American British cooperative group (FAB) and European Group for Immunological Classification of Leukemias (EGIL). The cases comprised of 111 acute myeloblastic leukemia (AML), 86 acute lymphoblastic leukemia (ALL), and 6 acute undifferentiated leukemia (AUL). CD117 was positive in 75 % of AML and 50 % of AUL, whereas none of the ALL cases was positive for this marker. Although CD117 was positive in 100 % of M5a cases, no M5b positive was found (p = 0.036). The calculated specificity for myeloid involvement was 100 % for CD117 and CD33, and 98 % for CD13 and CD15 (p < 0.001). The calculated sensitivity for myeloid involvement was 83, 76, 64, and 41 % for CD13, CD117, CD33, and CD15, respectively (p < 0.001). We concluded that CD117 expression is a specific and rather sensitive marker for differential diagnosis between AML and ALL, and except for M5 subtypes, it fails to determine FAB subtypes; lack of expression in M5 can identify M5b. Therefore, it should be included in the routine primary panel for diagnosis of acute leukemias.


[The ecological cause of the higher accumulation of 90Sr and 137Cs in the food of northern inhabitants].
The higher accumulation of 90Sr and 137Cs in the trophic chains of North inhabitants was analysed. The specific of the higher accumulation is caused by one-sided trend of the typical for North the biotical and abiotical factors.


[Hemodynamics in patients suffering from hyperkinetic cardiac syndromes and in normal persons under psychological stress before and after treatment with propranolol (author's transl)].
In patients with hyperkinetic heart syndrome we found at rest a higher heart rate, a higher stroke volume and a higher cardiac output than in normal volunteers. Therefore blood pressure is high although peripheral resistance is lower than in normals. Similar circulatory differences were found under conditions of mental stress. After beta-adrenergic blockade with 15 mg Propranolol heart rate and cardiac output decrease, whereas peripheral resistance increases. Mean blood pressure thus remains unchanged. Even after beta-adrenergic blockade circulatory differences between normals and patients with hyperkinetic heart syndrome are seen. The possible causes of these differences are discussed.


Migrant health in Italy: a better health status difficult to maintain-country of origin and assimilation effects studied from the Italian risk factor surveillance data.
Many studies on migrant health have focused on aspects of morbidity and mortality, but very few approach the relevant issues of migrants' health considering behavioral risk factors. Previous studies have often been limited methodologically because of sample size or lack of information on migrant country of origin. Information about risk factors is fundamental to direct any intervention, particularly with regard to non-communicable diseases that are leading causes of death and disease. Thus, the main focus of our analysis is the influence of country of origin and the assimilation process. Utilizing a surveillance system that has been collecting over 30,000 interviews a year in Italy since 2008, we have studied migrants' attitudes and behaviors by country of origin and by length of stay. Given 6 years of observation, we have obtained and analyzed 228,201 interviews of which over 9000 were migrants. While migrants overall present similar conditions to native-born Italians, major differences appear when country of origin or length of stay is considered. Subgroups of migrants present substantially different behaviors, some much better than native-born Italians, some worse. However, integration processes generally produce a convergence towards the behavioral prevalence observed for native-born Italians. Health programs should consider the diversity of the growing migrant population: data and analyses are needed to support appropriate policies. Many migrants' subgroups arrive with healthier behaviors than those of their adopted country. However, they are likely to have a less favorable social position in their destination countries that could lead to a change towards less healthy behaviors. Interventions capable of identifying this tendency could produce significant better health for this important part of the future (multicultural) populations.


PDZ proteins bind, cluster, and synaptically colocalize with Eph receptors and their ephrin ligands.
Localizing cell surface receptors to specific subcellular positions can be critical for their proper functioning, as most notably demonstrated at neuronal synapses. PDZ proteins apparently play critical roles in such protein localizations. Receptor tyrosine kinases have not been previously shown to interact with PDZ proteins in vertebrates. We report that Eph receptors and their membrane-linked ligands all contain PDZ recognition motifs and can bind and be clustered by PDZ proteins. In addition, we find that Eph receptors and ligands colocalize with PDZ proteins at synapses. Thus, PDZ proteins may play critical roles in localizing vertebrate receptor tyrosine kinases and/or their ligands and may be particularly important for Eph function in guidance or patterning or at the synapse.


Bladder cancer-induced skeletal muscle wasting: disclosing the role of mitochondria plasticity.
Loss of skeletal muscle is a serious consequence of cancer as it leads to weakness and increased risk of death. To better understand the interplay between urothelial carcinoma and skeletal muscle wasting, cancer-induced catabolic profile and its relationship with muscle mitochondria dynamics were evaluated using a rat model of chemically induced urothelial carcinogenesis by the administration of N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN). The histologic signs of non-muscle-invasive bladder tumors observed in BBN animals were related to 17% loss of body weight and high serum levels of IL-1β, TNF-α, TWEAK, C-reactive protein, myostatin and lactate and high urinary MMPs activities, suggesting a catabolic phenotype underlying urothelial carcinoma. The 12% loss of gastrocnemius mass was related to mitochondrial dysfunction, manifested by decreased activity of respiratory chain complexes due to, at least partially, the impairment of protein quality control (PQC) systems involving the mitochondrial proteases paraplegin and Lon. This was paralleled by the accumulation of oxidatively modified mitochondrial proteins. In overall, our data emphasize the relevance of studying the regulation of PQC systems in cancer cachexia aiming to identify therapeutic targets to counteract muscle wasting.


Retrograde axonal transport of a wheat germ agglutinin-horseradish peroxidase conjugate in Aplysia californica.
To begin examining retrograde transport in a single invertebrate neuron we have used wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP), 18 h after the conjugate was injected extracellularly into the neuropil of the buccal ganglion of Aplysia, HRP reaction product could be detected cytochemically in putative lysosomes, cisternae and vesicles near Golgi in the giant metacerebral neuron (GCN) of the cerebral ganglion. Appearance of reaction product in the cell body was blocked by ligating GCN's axon and was inhibited by colchicine.


Radial bimetallic structures via wire arc directed energy deposition-based additive manufacturing.
Bimetallic wire arc additive manufacturing (AM) has traditionally been limited to depositions characterized by single planar interfaces. This study demonstrates a more complex radial interface concept, with in situ mechanical interlocking and as-built properties suggesting a prestressed compressive effect. A 308 L stainless core is surrounded by a mild steel casing, incrementally maintaining the interface throughout the Z-direction. A small difference in the thermal expansion coefficient between these steels creates residual stresses at their interface. X-ray diffraction analysis confirms phase purity and microstructural characterization reveals columnar grain growth independent of layer transitions. Hardness values are consistent with thermal dissipation characteristics, and the compressive strength of the bimetallic structures shows a 33% to 42% improvement over monolithic controls. Our results demonstrate that biomimetic radial bimetallic variation is feasible with improved mechanical response over monolithic compositions, providing a basis for advanced structural design and implementation using arc-based metal AM.


[Partnership relaxation].
Therapeutic relaxations, as psycho-corporal practices, weave the body-mind links. The relaxation partnership, a structured and flexible approach, is inspired by the same principle, by specifically remodeling the relational positions and postures of professionals and users. It responds to precise indications and contraindications and is proposed to the patient in an individual or group approach.


High-performance liquid chromatographic investigations on the time-dependent reaction of cis-Pt(NH3)2Cl2, Pt(en)Cl2 and Pt(pn)Cl2 with RNA fragments.
The reaction of three platinum compounds, Pt(NH3)2Cl2, Pt(en)Cl2 and Pt(pn)Cl2 with nucleic acid fragments (Ade, Gua; GpG, GpA and ApA), both reactants (1:1, 1 X 10(-2) M; 1 X 10(-3) M) being dissolved in water, has been studied. UV measurements have been used to characterize the products. Kinetics and adduct formation in the nucleoside-Pt compound system were studied by reversed-phase high-performance liquid chromatography [gradient 0-30% methanol in 30 min, ammonium acetate buffer (0.1 M) at pH 4.25] at fixed intervals of time and the product formation was examined by measuring the peak heights. After 10 h, the reaction was complete for guanosine and showed a steady state for adenosine. The increasing lipophilicity in the sequence of the platinum compounds resulted in a shift to longer retention times.


[Transplantation of a kidney harvested laparoscopically from a related living donor].
Transplantation of kidney grafts harvested in living donors has demonstrated better results than grafts harvested from brain dead donors. Recently, laparoscopic live donor nephrectomy has been introduced to reduce the live procurement morbidity. In 1997, we performed two laparoscopic live donor nephrectomy and we report the first case of this program in this paper.


Impact of Mercaptopurine Metabolites on Disease Outcome in the AIEOP-BFM ALL 2009 Protocol for Acute Lymphoblastic Leukemia.
In the maintenance phase of Associazione Italiana di Ematologia e Oncologia Pediatrica (AIEOP)- Berlin-Frankfurt-Muenster (BFM) acute lymphoblastic leukemia (ALL) 2009 protocol, mercaptopurine (MP) is given at the planned dose of 50 mg/m2 /day; however, dose adjustments are routinely performed to target patients' white blood cells to the optimal range of 2,000-3,000 cells/μL. Pediatric patients with ALL (n = 290, age: median (1st-3rd quartile): 4.8 (3.0-8.1) years; boys: 56.9%) were enrolled mainly in 4 medium-large Italian pediatric hospitals; 14.1% of patients relapsed after a median (1st-3rd quartile) follow-up time of 4.43 (3.82-5.46) years from maintenance beginning. MP metabolites (thionucleotide (TGN) and methyl-derivatives (MMPN)) were measured in the erythrocytes of 387 blood samples of 200 patients by high performance liquid chromatography with ultraviolet detection. Single-nucleotide polymorphisms (SNPs; (rs1800462, rs1800460, and rs1142345 in TPMT gene, rs116855232 in NUDT15, rs1127354, rs7270101, rs6051702 in ITPA, and rs2413739 in PACSIN2) were characterized by Taqman SNP genotyping assays. Cox proportional hazard models did not show an impact of TGN levels and variability on relapse. In contrast, after multivariate analysis, relapse hazard ratio (HR) increased in children with ALL of the intermediate risk arm compared with those in standard risk arm (3.44, 95% confidence interval (CI), 1.31-9.05, P = 0.012), and in carriers of the PACSIN2 rs2413739 T allele compared with those with the CC genotype (heterozygotes CT: HR, 2.32, 95% CI, 0.90-5.97, P = 0.081; and homozygous TT: HR, 4.14, 95% CI, 1.54-11.11, P = 0.005). Future studies are needed to confirm the lack of impact of TGN levels and variability on relapse in the AIEOP-BFM ALL trials, and to clarify the mechanism of PACSIN2 rs2413739 on outcome.


The effects of three polysaccharides on the gelation properties of myofibrillar protein: Phase behaviour and moisture stability.
The effects of three polysaccharides on the textural properties and microstructure of myofibrillar protein (MP) gels were studied. The gel strength and rheological properties of composite MP gels were significantly improved with insoluble dietary fibre (DF) and modified starch (MS) addition, while konjac glucomannan (KG) had limited effects at 1% addition. The SEM images indicated that moisture extrusion formed moisture channels and deteriorated the aggregation of MP gel networks during the thermal process. The polysaccharides stabilized moisture and reduced the appearance of moisture channels in the gel network, thereby promoting the formation of compact and integral gel networks. The MP-polysaccharide mixture is a thermally incompatible system and presented two main forms after the thermal process: 1) the "trapped" structure and 2) the "interpenetrated" structure. In the "trapped" structure, the MP was the dominant structure of the composite gel network. In the "interpenetrated" structure, the continuous polysaccharide hydrogel substantially hindered the aggregation of MP gel networks. Principal component analysis showed that the phase behaviour and moisture stability of polysaccharides significantly influenced the textural quality and microstructure of composite MP gelation. The study indicated that polysaccharides that contribute to moisture stability and form a "trapped structure" (phase behaviour) are ideal fat replacements for improving composite gel properties, especially DF.


The pancreas-specific form of secretory pathway calcium ATPase 2 regulates multiple pathways involved in calcium homeostasis.
Acinar cell exocytosis requires spatiotemporal Ca2+ signals regulated through endoplasmic reticulum (ER) stores, Ca2+ATPases, and store-operated Ca2+ entry (SOCE). The secretory pathway Ca2+ATPase 2 (SPCA2) interacts with Orai1, which is involved in SOCE and store independent Ca2+ entry (SICE). However, in the pancreas, only a C-terminally truncated form of SPCA2 (termed SPAC2C) exists. The goal of this study was to determine if SPCA2C effects Ca2+ homeostasis in a similar fashion to the full-length SPCA2. Using epitope-tagged SPCA2C (SPCA2CFLAG) expressed in HEK293A cells and Fura2 imaging, cytosolic [Ca2+] was examined during SICE, SOCE and secretagogue-stimulated signaling. Exogenous SPCA2C expression increased resting cytosolic [Ca2+], Ca2+ release in response to carbachol, ER Ca2+ stores, and store-mediated and independent Ca2+ influx. Co-IP detected Orai1-SPCA2C interaction, which was altered by co-expression of STIM1. Importantly, SPCA2C's effects on store-mediated Ca2+ entry were independent of Orai1. These findings indicate SPCA2C influences Ca2+ homeostasis through multiple mechanisms, some of which are independent of Orai1, suggesting novel and possibly cell-specific Ca2+ regulation.


Autohydrolysis and organosolv process for recovery of hemicelluloses, phenolic compounds and lignin from grape stalks.
A combination of two environment-friend processes for hemicelluloses and lignin recovery from red grape stalks were investigated: an autohydrolysis pretreatment at 180°C for 30 min followed by a non-catalysed ethanol organosolv step at 180°C for 90 min. Hemicelluloses were precipitated by ethanol addition to autohydrolysis liquor, while lignin was tentatively precipitated by acidification of liquors from both the processes. Results suggest that stalks hemicelluloses can be easily hydrolysed requiring a milder treatment to reduce sugar degradation, while the organosolv process did not give a consistent delignification. Autohydrolysis allowed a recovery of 2% (on stalks d.m.) of total phenols in the liquor. Organosolv liquor had a higher concentration of phenols (corresponding to 0.72% of stalks d.m.) which almost completely precipitated with lignin.


Olfactory discrimination of structurally related molecules: receptor cell responses to camphoraceous odorants.
Electrophysiological investigations of the selective sensitivity of receptor cells have shown that odorants could be distributed into groups according to the profiles of responses that they elicited from a population of receptor cells. As the concept of odorant group plays an important role in the understanding of olfactory coding, an attempt was made to investigate in detail the group properties of a number of structurally and qualitatively related molecules: 1,8 cineole, DL-camphor, borneol, iso-borneol, adamantane, fenchone, fenchyl alcohol, 3,3,5-tri-methyl cyclohexanone, camphene, 1,1,2,2-tetra-bromoethane. These odorants, along with several other representatives of other odorant groups, were utilized to stimulate a set of 71 individually recorded receptor cells. Factor analysis of electrophysiological data demonstrated that the grouping of odorants with camphor could be predicted on the basis of the shape and size of the molecules. The analysis also showed that even a clearly defined odorant group such as the camphor group is not likely to be determined by a single type of receptor site.


Colonic micropapillary carcinoma, a recently recognized subtype associated with histological adverse factors: clinicopathological analysis of 15 cases.
Micropapillary carcinoma (MPC) is regarded as an aggressive variant of adenocarcinoma in any location. The reported proportion of a micropapillary carcinoma component in an entire tumour ranges from 5 to 95% and only one case of pure MPC has been reported. To date, approximately 130 cases of MPC in the colorectum have been reported, but it is likely that this small number is to some extent due to under-reporting because this pattern is not well recognized by the general pathologist. All previous studies have combined colonic and rectal primary tumours and most have only analysed patients with clinical Stages I or II. We analysed 15 cases of MPC of the colon alone, diagnosed in our institution, and compared them with 105 conventional carcinomas of the colon. An MPC component was present in 10% of all colonic carcinomas. These tumours presented at a median age of 56 years, and all were of American Joint Committee on Cancer Stages III and IV. Subserosal tissue invasion was present in every case, 60% had more than four positive lymph nodes, 60% were accompanied by poorly differentiated conventional carcinoma, 40% had had an incomplete resection and a third demonstrated lymphovascular invasion. Despite these adverse prognostic factors, tumours containing MPC showed the same survival, stage by stage, as conventional adenocarcinoma in multivariate analysis, although 3-year survival (81.7%vs 87.3%, P=0.035) was worse on univariate analysis. The histopathologist should be aware of the possibility of MPC. Three-year survival is worse than in patients with conventional colonic carcinomas in Stage III.


Salvage re-irradiation for recurrent high-grade glioma and comparison to bevacizumab alone.
While salvage re-irradiation is often used for recurrent high-grade glioma (HGG), there have been few comparisons between various re-radiation dose/fractionation schedules or with bevacizumab alone. We analyzed patients with recurrent HGG who received re-irradiation at Dana-Farber Cancer Institute and Brigham and Women's Hospital from 2010 to 2014 (n = 67), as well as those who received bevacizumab alone (n = 177). Cox proportional hazards modeling was used to examine factors associated with overall survival (OS). Propensity score modeling was used to compare survival after re-irradiation vs. bevacizumab alone. Median time from initial diagnosis to re-irradiation was 31.4 months. The most common re-irradiation dose/fractionations used were 6 Gy × 5 (36%), 3.5 Gy × 10 (21%), 2.67 Gy × 15 (15%), and 18-20 Gy × 1 (15%). No early or late toxicities >grade 2 were observed. Median PFS and OS after re-irradiation were 4.8 and 10.7 months, respectively. Number of progressions prior to re-irradiation (adjusted hazard ratio [AHR] 1.6; 95% CI, 1.1-2.3; p = .007), and recurrence in a new brain location (vs. local-only; AHR 7.4; 95% CI, 2.4-23.1; p < .001) were associated with OS; dose/fractionation was not. Compared with bevacizumab alone, re-irradiated patients had a non-significant increase in OS (HR 0.80; 95% CI, 0.53-1.23; P = .31). Among patients with a local-only recurrence, there was a trend towards longer median OS after re-irradiation compared to bevacizumab alone (12.4 vs. 8.0 months; p = .12). Survival after re-irradiation for recurrent HGG appears independent of dose/fractionation and compares favorably with bevacizumab alone.


Quality assessment of U.S. marketplace vancomycin for injection products using high-resolution liquid chromatography-mass spectrometry and potency assays.
In response to a published concern about the potency and quality of generic vancomycin products, the United States Food and Drug Administration investigated a small sampling of the vancomycin products available in North America with regard to purity, content, and potency. To facilitate identification of impurities, a new liquid chromatography method was developed using high-resolution mass spectrometry in addition to diode array detection to characterize impurities in several commercial products. Furthermore, a microbiological assay was utilized to link the analytical profiles with an in vitro potency. All products tested met the quality specifications outlined in the United States Pharmacopeia (USP) (vancomycin hydrochloride for injection monograph) for impurities and potency (USP, Vancomycin hydrochloride for injection. United States Pharmacopeia and National Formulary, vol USP 34-NF 29, 2011).


Titanium: the mystery metal of implant dentistry. Dental materials aspects.
A number of important points concerning titanium and its alloys have been discussed. They are summarized as follows. Ti and its alloys, particularly the alpha-beta alloys, possess mechanical properties that make them ideal implant materials. Ti and its alloys oxidize readily in air. This surface oxide is extremely stable in the physiologic environment of the body. The stability and inertness of this surface oxide layer acts to protect Ti from corrosive breakdown when used in the body. The elimination of surface irregularities and contaminants is important when preparing a metal for implantation. Titanium can be coupled with equally passive metals in the body without causing galvanic corrosion.


Follicular variant of thyroid papillary carcinoma: a clinicopathologic study of six cases.
The clinicopathologic features of six cases of a peculiar variant of differentiated carcinoma of the thyroid composed of follicles with or without solid areas and having a characteristics ground-glass appearance of the nuclei were studied and compared with those of conventional papillary and follicular carcinomas. This variant resembled papillary carcinoma in its biologic behavior and all morphologic features with the exception that papillae were not present. The term "papillary carcinoma, follicular variant" is proposed for this tumor type in order to emphasize its close biologic relationship with the conventional papillary carcinoma.


An exploration of the characteristics of post-traumatic stress disorder in reserve forces deployed during Desert Storm.
Post-traumatic stress disorder (PTSD), previously defined in Vietnam War veterans, was described in 251 Desert Storm reservists. The Mississippi Scale, Revised, was used with a brief demographic profile to survey Army, Marine, and Air Force personnel who had been deployed to Saudi Arabia. Age, sex, marital status, race, rank, duty, length of deployment, and branch of service were not found to be significantly related to PTSD symptoms. However, those surveyed within 3 to 6 months of homecoming reported significantly greater symptoms than those surveyed after 6 months. Five percent of subjects were found to have clinically diagnostic levels of PTSD symptoms 6 months after homecoming. Individuals who expressed difficulty discussing their experiences with more than one person also showed significantly higher PTSD scores. These findings indicate that readjustment reactions were prevalent during the first 6 months and that PTSD could be identified in 5% of the Desert Storm veterans.


A new method to estimate left ventricular circumferential midwall systolic function by standard echocardiography: Concordance between models and validation by speckle tracking.
Assessment of left ventricular circumferential (LVcirc) systolic function by standard echocardiography can be performed by estimating midwall fractional shortening (mFS) and stress-corrected mFS (ScmFS). Their determination is based on spherical or cylindrical LV geometric models, which often yield discrepant values. We developed a new model based on a more realistic truncated ellipsoid (TE) LV shape, and explored the concordance between models among hypertensive patients. We also compared the relationships of different mFS and ScmFS estimates with indexes of LVcirc systolic strain. In 364 hypertensive subjects, mFS was determined using the spherical (mFSspher), cylindrical (mFScyl), and TE model (mFSTE). Corresponding values of ScmFSspher, ScmFScyl, and ScmFSTE were obtained. Global circumferential strain (GCS) and systolic strain rate (GCSR) were also measured by speckle tracking. The three models showed poor concordance for the estimation of mFS, with average differences ranging between 11% and 30% and wide limits of agreement. Similar results were found for ScmFS, where reclassification rates for the identification of abnormal LVcirc systolic function ranged between 18% and 29%. When tested against strain indexes, mFSTE and ScmFSTE showed the best correlations (R=0.81 and R=0.51, p<0.0001 for both) with GCS and GCSR. Multivariable analysis confirmed that mFSTE and ScmFSTE showed the strongest independent associations with LVcirc strain measures. Substantial discrepancies in LVcirc midwall systolic indexes exist between different models, supporting the need of model-specific normative data. The use of the TE model might provide indexes that show the best associations with established strain measures of LVcirc systolic function.


Clinical implications of drug-induced liver injury in early-phase oncology clinical trials.
Data on drug-induced liver injury (DILI) and acute liver failure (ALF) in modern phase 1 oncology trials are limited, specifically with respect to the incidence and resolution of DILI and the safety of drug rechallenge. This study reviewed all patients who were recruited to phase 1 oncology trials between 2013 and 2017 at Memorial Sloan Kettering Cancer Center. Clinicopathologic data were extracted to characterize DILI, and attribution was assessed on the basis of data prospectively generated during the studies. Logistic regression models were used to explore factors related to DILI and DILI recurrence after drug rechallenge. Among 1670 cases recruited to 85 phase 1 trials, 81 (4.9%) developed DILI. The rate of DILI occurrence was similar for patients in immune-based trials and patients in targeted therapy trials (5.0% vs 4.9%), as was the median time to DILI (5.5 vs 6.5 weeks; P = .48). Two patients (0.12%) met the criteria of Hy's law, although none developed ALF. The DILI resolved in 96% of the patients. Pretreatment factors were not predictive for DILI development. Thirty-six of the 81 patients underwent a drug rechallenge, and 28% of these patients developed DILI recurrence. Peak alanine aminotransferase during the initial DILI was associated with DILI recurrence (odds ratio, 1.04; 95% confidence interval, 1.0-1.09; P = .035). In modern phase 1 oncology trials, DILI is uncommon, may occur at any time, and often resolves with supportive measures. Rechallenging after DILI is feasible; however, the high rate of DILI recurrence suggests that clinicians should consider the severity of the DILI episode and treatment alternatives.


Age-related respiratory responses to substance P in normal sheep.
The in vivo effects of substance P (SP) on respiratory parameters in four different age groups of sheep were examined. Intravenous SP (10(-8) to 5 x 10(-6) mol kg-1 bodyweight) caused a dose-dependent reduction in dynamic compliance and increase in respiratory resistance in all four groups. The bronchoconstrictor response was age-related, with the greatest response occurring in the youngest age group (four to six months). In the oldest group (over four years) there was minimal bronchomotor response to SP, but a dose-dependent apnoea was present. These findings indicate that there is an age-related alteration in the respiratory response to SP in sheep.


Purification and characterization of chicken ovalbumin upstream promoter transcription factor from HeLa cells.
A transcription factor which binds to the chicken ovalbumin upstream promoter (COUP) sequence spanning between -70 and -90 is required for efficient transcription of the ovalbumin gene. This COUP transcription factor has been purified approximately 200,000-fold by a combination of conventional column and sequence-specific DNA affinity column chromatography. A few polypeptides were identified in the purified preparation on sodium dodecyl sulfate gel. Upon renaturation, all the major polypeptides in the molecular size range between 43 and 53 kDa bound specifically to the COUP sequence. Furthermore, at least one of the renatured polypeptides in the region of 43-45 kDa retained transcriptional activity. The binding of the COUP transcription factor to the ovalbumin promoter cannot be competed by DNA fragments which contain the CCAAT box promoter sequence. Since the COUP and CCAAT binding proteins can be separated on an S300 column, they are distinct molecules. Using band-shifting assays and 3' and 5' deletion mutants and oligonucleotide mutants, the sequence important for binding was mapped.


Performance of feedlot lambs fed palm kernel cake-based diets.
Fifty-four castrated male lambs with an average body weight of 23 ± 0.35 kg were randomly assigned to five treatments that consisted of different levels of palm kernel cake in the diet (0.0, 7.5, 15.0, 22.5, and 30.0 % on a DM basis) in order to evaluate the effects on intake, digestibility, empty body weight, and body gain composition. The intakes of dry matter, organic matter, crude protein, and non-fiber carbohydrates (NFC) presented with a decreasing linear effect. However, the intakes of EE and NDF presented with increased linear results as the palm kernel cake was added to the concentrate. There was a quadratic effect for the digestibility coefficient of all nutrients, except for NFC. The palm kernel cake had a decreasing linear effect on final body weight, empty body weight, and the average daily gain of the animals that were fed increased levels of palm kernel cake. The inclusion of palm kernel cake as a partial substitute for concentrate decreases the intake of the majority of nutrients, except for EE and NDF, and consequently, causes deleterious effects on the nutrient digestibility and performance of lambs that are fed a 50:50 roughage/concentrate ratio.


Planning hybrid intensity modulated radiation therapy for whole-breast irradiation.
To test tangential and not-tangential hybrid intensity modulated radiation therapy (IMRT) for whole-breast irradiation. Seventy-eight (36 right-, 42 left-) breast patients were randomly selected. Hybrid IMRT was performed by direct aperture optimization. A semiautomated method for planning hybrid IMRT was implemented using Pinnacle scripts. A plan optimization volume (POV), defined as the portion of the planning target volume covered by the open beams, was used as the target objective during inverse planning. Treatment goals were to prescribe a minimum dose of 47.5 Gy to greater than 90% of the POV and to minimize the POV and/or normal tissue receiving a dose greater than 107%. When treatment goals were not achieved by using a 4-field technique (2 conventional open plus 2 IMRT tangents), a 6-field technique was applied, adding 2 non tangential (anterior-oblique) IMRT beams. Using scripts, manual procedures were minimized (choice of optimal beam angle, setting monitor units for open tangentials, and POV definition). Treatment goals were achieved by using the 4-field technique in 61 of 78 (78%) patients. The 6-field technique was applied in the remaining 17 of 78 (22%) patients, allowing for significantly better achievement of goals, at the expense of an increase of low-dose (∼5 Gy) distribution in the contralateral tissue, heart, and lungs but with no significant increase of higher doses (∼20 Gy) in heart and lungs. The mean monitor unit contribution to IMRT beams was significantly greater (18.7% vs 9.9%) in the group of patients who required 6-field procedure. Because hybrid IMRT can be performed semiautomatically, it can be planned for a large number of patients with little impact on human or departmental resources, promoting it as the standard practice for whole-breast irradiation.


Micro-tensile bond strength of adhesives bonded to Class-I cavity-bottom dentin after thermo-cycling.
A widely used artificial aging methodology is thermo-cycling. The ISO TR 11450 standard (1994) recommends 500 cycles in water between 5 and 55 degrees C. Recent literature revealed that more cycles are needed to mimic long-term bonding effectiveness. Furthermore, the artificial aging effect induced by thermo-cycling is not clearly established. Two underlying mechanisms can be advanced: (1) hot water may accelerate hydrolysis and elution of interface components and (2) repetitive contraction/expansion stress can be generated. The purpose of this study was to evaluate the relative contribution of both chemical (hydrolysis and elution of interface components) and mechanical (repetitive contraction/expansion stress) degradation pathways on the thermo-cycling-induced artificial aging of dentin-adhesive interfaces at the bottom of class-I cavities. The micro-tensile bond strength (muTBS) of contemporary adhesives (a three-step etch and rinse, a two-step and a one-step self-etch adhesive) bonded to class-I cavity-bottom dentin was determined after 20,000 cycles as well as after 20 days of water storage (control). Restored class-I cavities (repetitive contraction/expansion stress) as well as prepared micro-specimens (diffusion-dependent hydrolysis and elution) were subjected to the thermo-cycling regimen. Thermo-cycling did not enhance chemical or mechanical degradation of the bonds produced by a two-step self-etch and a three-step etch and rinse adhesive to dentin. The one-step self-etch adhesive tested was, however, not able to withstand polymerization shrinkage stress, nor thermo-cycling, when applied in class-I cavities. Thermo-cycling results in combined contraction/expansion stress and accelerated chemical degradation. However, the relative contribution of each is strongly dependent on the specific test set-up and the adhesive used.


Clinical microsystems, Part 3. Transformation of two hospitals using microsystem, mesosystem, and macrosystem strategies.
Two hospitals-a large, urban academic medical center and a rural, community hospital-have each chosen a similar microsystem-based approach to improvement, customizing the engagement of the micro-, meso-, and macrosystems and the improvement targets on the basis of an understanding of the local context. CINCINNATI CHILDREN'S HOSPITAL MEDICAL CENTER (CCHMC): Since 2004, strategic changes have been developed to support microsystems and their leaders through (1) ongoing improvement training for all macro-, meso-, and microsystem leaders; (2) financial support for physicians who are serving as co-leaders of clinical microsystems; (3) increased emphasis on aligning academic pursuits with improvement work at the clinical front lines; (4) microsystem leaders' continuous access to unit-level data through the organization's intranet; and (5) encouragement of unit leaders to share outcomes data with families. CDH has moved from near closure to a survival-turnaround focus, significant engagement in quality and finally, a complete reframing of a quality focus in 2004. Since then, it has deployed the clinical microsystems approach in one pilot care unit (West 2, a medical surgery unit), broadened it to two, then six more, and is now spreading it organizationwide. In "2+2 Charters," interdisciplinary teams address two strategic goals set by senior leadership and two goals set by frontline microsystem leaders and staff CCHMC and CDH have had a clear focus on developing alignment, capability, and accountability to fuse together the work at all levels of the hospital, unifying the macrosystem with the mesosystem and microsystem. Their improvement experience suggests tips and actions at all levels of the organization that could be adapted with specific context knowledge by others.


Paratesticular dermoid cyst in 6-month-old infant.
We describe a 6-month-old male infant with a dermoid cyst of the left paratesticular region. To our knowledge, this represents the youngest patient reported with this rare benign teratoma. We advocate enucleation for this particular type of teratoma based on referenced histopathological criteria.


Continuing professional development (CPD) training needs assessment for medical laboratory professionals in Ethiopia.
Continuing professional development (CPD) is required for health workers in practice to update knowledge and skills regularly to match the changing complexity of healthcare needs. The objective of this study was to identify the training needs of Medical Laboratory professionals in Ethiopia. A total of 457 medical laboratory professionals from five regions and two city administrations were involved in the study. Data were collected from August 02 to 21, 2021 with structured self-administered online tool with five-point Likert scale. The tool had consent, demography, cross-cutting issues, and main activity area specific to medical laboratory. Majority of the participants were male (80.1%). Participants from Amhara region 110 (24.1%) were the largest groups in the survey followed by Oromia 105 (23%) and Addis Ababa 101 (22.1%). The study participants comprised 54.7% with a bachelor's degree, 31.3% with a diploma (associate degree), and 14% with a master's degree. The participants had varying years of service, ranging from less than one year to over 10 years of experience. Most of the participants work as generalists (24.1%) followed by working in microbiology (17.5%) and parasitology (16%). The majority (96.9%) were working in a public sector or training institutions and the rest were employed in the private sector. Our study showed that the three most important topics selected for training in the cross-cutting health issues were health and emerging technology, computer skills and medico-legal issues. Topics under microbiology, clinical chemistry and molecular diagnostics were selected as the most preferred technical areas for training. Participants have also selected priority topics under research skill and pathophysiology. When the laboratory specific issues were regrouped based on areas of application as technical competence, research skill and pathophysiology, thirteen topics under technical competence, four topics under research skill and three topics under pathophysiology were picked as priority areas. In conclusion, our study identified that CPD programs should focus on topics that address technical competence in microbiology, clinical chemistry and molecular diagnostics. Additionally competencies in research skill and updating knowledge in pathophysiology should also receive due attention in designing trainings.


Is there alteration in aortic stiffness in Leber hereditary optic neuropathy?
Leber hereditary optic neuropathy (LHON) is recognized as the most common cause of isolated blindness in young men. The current study was designed to test whether LHON as a mitochondrial disease is associated with vascular functional alterations characterized by aortic elastic properties during echocardiography. A total of 19 patients with typical features of LHON aged 42+/-13 years (10 males) were included. Their results were compared to 19 age- and gender-matched healthy controls. Aortic stiffness index was calculated from the echocardiographically derived aortic diameters and the clinical blood pressure data. In this patient population, the point mutation was present in 3460G>A position in five cases, in 11778G>A position in five cases, and in 14484T>C position in nine patients. Diastolic aortic diameter (26.0+/-2.5 mm vs 28.4+/-4.1 mm, p<0.05) and aortic stiffness index (5.1+/-2.6 vs 12.0+/-7.9, p<0.05) were significantly increased in LHON patients compared to controls. Aortic stiffness can be increased in LHON disease, but further studies are warranted to confirm these findings in a larger LHON patient population with a more reliable method focusing on the pathophysiologic background.


Walking into the unknown: a 'step down' PCR-based technique leading to the direct sequence analysis of flanking genomic DNA.
We describe a novel and efficient PCR-based technique for walking into unknown flanking genomic DNA without recourse to protracted laborious library screening for overlapping sequences. This two component 'hot start' and 'step down' PCR method uses 6x1 microg of genomic DNA (ca 20kb in length) restricted with six different endonucleases and ligated to adaptors with the inclusion of two further restriction enzymes to prevent self-ligation. This allowed us to walk, in a single step, up to 6kb into flanking DNA and gave sufficient PCR products for up to 200 different walking experiments. This technology enabled us to clone and characterize the previously elusive 5' sequence of the barley powdery mildew chitin synthase gene, BgChs2, which includes a myosin motor-like sequence fused to a type V chitin synthase gene.


The experience of facilitation in reflective groups: a phenomenological study.
The use of facilitation in all areas of nursing has increased in the last decade. There is little research related to the process of facilitation. In order to evaluate facilitation as an aspect of practice, an exploratory study was conducted to clarify the meaning of facilitation as used in practice. A phenomenological approach allowed identification of the meaning of facilitation from the lived experiences of practitioners who have implemented facilitation. Open interviews (conversations) were used to elicit relevant experiences from three nurse teachers who were engaged in the facilitation of reflective groups. The data collected were analysed using Collaizi's method of phenomenological data analysis. Having considered the findings of the study in the light of literature available related to facilitation, the implications for practice within nurse education are explored.


Fluoranthene and phenantrene, two predominant PAHs in heat-prepared food, do not influence the frequency of micronucleated mouse erythrocytes induced by other PAHs.
Polycyclic aromatic hydrocarbons (PAHs) occur in complex mixtures present in the human environment. Because of the carcinogenic properties of some of these PAHs, they raise concerns regarding health and food safety. Because the occurrence of benzo[a]pyrene, chrysene, benz[a]anthracene, and benzo[b]fluoranthene (PAH4) are considered markers for other genotoxic PAHs in foodstuffs, the European Union has put a maximum level of PAH4 in some foodstuffs. Fluoranthene (Flu) and phenanthrene (Phe), two other PAHs, are not classified as genotoxic and are abundant at rather high concentrations in food. Inasmuch as PAH4, Flu, and Phe are metabolized by the same cytochrome P450 pathway system, it is important to clarify whether Phe and Flu influence the genotoxicity of PAH4. We have analyzed the genotoxic response of Phe and Flu, separately and together, as well as in combination with different low doses of PAH4. In all experiments we used the flow cytometer-based micronucleus test in vivo. Phe and Flu, when administered separately, did not show any dose-related effect on the frequency of micronucleated polychromatic erythrocytes (fMNPCE). Nor did a mixture of Phe and Flu change the fMNPCEs. Phe and Flu did not significantly change the fMNPCE of PAH4-exposed FVB and BALB/c mice.


Safety and Efficacy of Glass Membrane Pumping Emulsification Device in Transarterial Chemoembolization for Hepatocellular Carcinoma: First Clinical Outcomes.
Novel glass membrane pumping emulsification devices (GMDs) enable the formation of a high-percentage water-in-oil emulsion with homogeneous and stable droplets. Although GMDs are expected to improve therapeutic effects in transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC), clinical outcomes are not yet available. A total of 26 patients with unresectable HCC who underwent TACE using a GMD were analyzed retrospectively. Ethiodized oil was mixed with epirubicin solution using a GMD. The emulsion was injected into the tumor-feeding artery, followed by embolization. The median size of HCCs was 28 (range=15-60) mm, and 15 nodules were solitary. Overall treatment effects were complete response in 18 cases (90%) and partial response in two (10%). The local recurrence rate at 6 months was 24.2%. No major complication was observed except for grade 4 elevations of liver enzymes in one case. TACE using a GMD is effective and safe in clinical practice.


The utility of an erythroblast scoring system and gender-independent short tandem repeat (STR) analysis for the detection of aneuploid fetal cells in maternal blood.
The aim of this study was to determine whether fetal nucleated red blood cells (NRBCs) could be distinguished from maternal cells in peripheral blood using an erythroblast scoring system based on the unique morphological and hemoglobin staining characteristics of this cell type. Presumptive fetal NRBCs were further analyzed for the presence of paternally inherited DNA polymorphisms to prove fetal origin. NRBCs were isolated by density gradient separation, CD15/45 depletion, and gamma hemoglobin positive selection from peripheral blood of nine women following termination of pregnancy for trisomy 21 (n=4), 18 (n=1), 13 (n=2), and other genetic abnormalities (n=2). Candidate fetal NRBCs, based on four discrete morphological and hemoglobin staining criteria, were then subjected to fluorescent PCR (polymerase chain reaction) amplification of chromosome 21 (D21S1411, D21S11) and chromosome 18 (D18S535) short tandem repeat (STR) DNA polymorphisms. In all cases, candidate fetal NRBCs were accurately identified on the basis of morphologic and hemoglobin staining characteristics and confirmed to be fetal in origin based on the presence of shared and nonshared polymorphic DNA alleles when compared to DNA isolated from maternal cells. Using the erythroblast scoring system and subsequent analysis of inherited DNA polymorphisms, we were able to distinguish fetal NRBCs from maternal cells and prove fetal origin independent of gender. These results suggest that this novel combined approach to fetal cell isolation and genetic analysis is a promising method for noninvasive prenatal diagnostic applications.


When protein-based biomineralization meets hydrothermal synthesis: the nanostructures of the as-prepared materials are independent of the protein types.
Proteins were proved to be type-independent templates for the biomineralization of iron ions into hematite mesocrystals with tunable structures and morphologies under hydrothemal conditions. Our finding could pave the way for the synthesis of mesocrystals with controlled stuctures and morphologies using templates of low-cost proteins.


The ability of bifunctional and monofunctional pyrrole compounds to induce sister-chromatid exchange (SCE) in human lymphocytes and mutations in Salmonella typhimurium.
The ability to induce sister-chromatid exchange (SCE) in human lymphocytes and mutations in Salmonella typhimurium has been assessed for 4 pyrrole compounds. Three of the compounds, 2,3-bishydroxymethyl-1-methylpyrrole (BHMP), 2-hydroxymethyl-1-methylpyrrole (2HMP) and 3-hydroxymethyl-1-methylpyrrole (3HMP) are synthetic pyrrolic alcohols; the fourth compound, dehydroretronecine (DHR) is a metabolite of several naturally occurring pyrrolizidine alkaloids. The activity of these compounds was compared with that of mitomycin C (MMC) and decarbamoyl mitomycin C (DCMMC), chemicals related structurally to the pyrrole compounds. All 6 compounds caused an increase in the numbers of SCEs. Whereas the bifunctional pyrroles, DHR and BHMP, and the mitomycins, MMC and DCMMC, increased levels of SCEs by 8-12 times control levels, the monofunctional pyrroles gave increases of only 2 times. Three of the 4 pyrrole compounds (DHR, BHMP and 3HMP) induced mutations in the Salmonella typhimurium base substitution strain TA92, the fourth (2HMP) was not found to be mutagenic in any of the 8 strains used. The mitomycins induced mutations in the frameshift strain TA94 in addition to the base substitution strain TA92, with DCMMC always more mutagenic and less cytotoxic than MMC. All bifunctional compounds induced more mutations and were less cytotoxic in strains containing an efficient excision-repair system. With the pyrrole compounds numbers of SCEs and mutations were only increased when using chemical concentrations significantly higher than those required for the mitomycins: more than twice as high to produce significant numbers of SCEs and more than 100 times as high to produce equal numbers of mutations.


Self-reported physical activity levels during a segmented school day in a large multiethnic sample of high school students.
The school day provides youth several opportunistic time periods to be active. How active youth are during these time periods or whether they engage in physical activity across multiple time periods is not well established. A cross-sectional sample of 12-18-year-old students (n=3471) were recruited from low socioeconomic status high schools within South Auckland, New Zealand. Participants reported their physical activity during lunchtime, morning recess, and after school, as well as their level of active transportation to and from school. For each physical activity opportunity participants were dichotomised as being either "more active" or "less active". Height, weight, and waist circumference measurements were also collected for each participant. Data were analysed using binary logistic regression to understand demographic associations and with kappa coefficient calculations to examine level of association in participation levels between different time periods. The percentage of students considered 'more active' depended on the physical activity variable of interest (after-school, 56.3%; active transportation, 58.1%; morning recess, 26.4%; lunchtime recess, 32.4%). Only 11.1% of participants were classified as 'more active' across all four physical activity opportunities. Substantial agreement (kappa=.68) was only observed in participation levels at lunchtime and morning recess. At-risk groups for lower physical activity were female students, senior students, and students of Asian/Other descent. During a school day multiple opportunistic time periods exist for youth to be active, yet a large proportion of students are not as active as they could be with few youth engaging in physical activity across various segments of the school day.


Partial purification from human serum of a specific binding protein for human growth hormone.
Following the recent identification and characterization of a highly specific binding protein(s) for human growth hormone (hGH) in human sera, we now report our initial studies on its purification. Outdated blood blank serum was first fractionated by ammonium sulphate precipitation. The majority of the binding activity appeared in the 30-45% saturation fraction, which was then applied in sequence to an hGH-affinity column, to strong anion exchange (SAX) chromatography (a Mono Q column 0.01-0.2 M phosphate gradient), to a TSK phenyl hydrophobic interaction column (HIC) (0.75-0 M sulphate gradient in 0.1 M phosphate) and finally to a second SAX step. By Scatchard analysis the final product was purified approximately 16,500-fold compared to serum with an overall recovery of 5%. The binding affinity (Ka) of the purified material was approximately 0.4 X 10(9) M-1, very similar to that of whole serum (approximately 0.5 X 10(9) M-1). On silver-stained, sodium dodecyl sulphate-polyacrylamide gels, the final SAX product yielded a major doublet, under reduced conditions, of molecular weights (MW) 55,000 and 59,000. Although it is not known whether one or both of these bands might have hGH binding activity, the MW 59,000 band is very similar in size to one (MW 60,000) of two specific binding proteins observed by covalent crosslinking techniques. These data indicate that the specific hGH binding activity of human serum can be substantially purified and that it appears to exist in at least two forms. Further studies are required to determine the biochemical and physiological relationship, if any, between the two forms.


In vitro and in vivo anti-inflammatory activities of high molecular weight sulfated polysaccharide; containing fucose separated from Sargassum horneri: Short communication.
Recent studies on crude and pure compounds from Sargassum horneri have shown promising bioactive properties. However, anti-inflammatory potentials of fucose-rich sulfated polysaccharides from S. horneri have not yet been discovered. In the present study, we evaluated the in vitro and in vivo anti-inflammatory activities of four polysaccharide fractions separated from membrane filters according to their molecular weights (<5kDa (f1), 5-10kDa (f2), 10-30kDa (f3), and >30kDa (f4)). According to the results, F4 fraction inhibited the lipopolysaccharides (LPS)-induced nitric oxide (NO) (IC50=87.12μg/mL) and prostaglandin E2 production as well as pro-inflammatory cytokine production in RAW 264.7 cells through down-regulating nuclear factor-κB signaling cascade. According to the results, f4 has a potential to down-regulate LPS-induced toxicity, cell death and NO production levels in LPS-induced in vivo zebrafish embryo model. These results suggest that f4 fraction has the potential to develop functional materials or drugs to treat inflammatory diseases.


Formation of superoxide anion on aerial oxidation of Cu(II)-porphyrinogen in the synthesis of tetrakis(cyclohexyl)porphyrinogenCu(III) anion.
Tetraethylammonium-tetrakis(cyclohexyl)porphyrinogenCu(II) (1) is spontaneously oxidized by aerial oxygen to the corresponding Cu(III) (2) species, producing 1 equiv of O2(-). Steric crowding of the peripheral hydrogens in 1 prevented any direct Cu-O2 bond formation in the oxidation process, which suggests an outer-sphere electron transfer reaction.


Field Report: Medical Response to Super Typhoon Haiyan.
This report describes the experience and observations during a humanitarian medical response 10 days after landfall of Typhoon Haiyan in the Leyte Island region of the Philippines. Loss of availability of local health care providers was observed to affect the ability of the local community to provide for immediate, post-event medical relief.


Patient Selection, Techniques, and Complication Mitigation for Epicardial Ventricular Tachycardia Ablation.
Percutaneous epicardial ventricular tachycardia ablation can decrease implanted cardioverter defibrillator shocks and hospitalizations; proper patient selection and procedural technique are imperative to maximize the benefit-risk ratio. The best candidates for epicardial ventricular tachycardia will depend on history of prior ablation, type of cardiomyopathy, and specific electrocardiogram and cardiac imaging findings. Complications include hemopericardium, hemoperitoneum, coronary vessel injury, and phrenic nerve injury. Modern epicardial mapping techniques provide new understandings of the 3-dimensional nature of reentrant ventricular tachycardia circuits across cardiomyopathy etiologies. Where epicardial access is not feasible, alternative techniques to reach epicardial ventricular tachycardia sources may be necessary.


Increased levels of IgA antibodies to cytokeratin-18 and epidermal keratin in rheumatoid arthritis.
To investigate whether levels of antibodies to cytokeratin-18 (CK-18) and epidermal keratin (EPK) were raised in patients with rheumatoid arthritis (RA). We measured antibodies to CK-18 and EPK in patients with RA and in patients with osteoarthritis (OA), as well as in normal control subjects by means of an enzyme-linked immunosorbent assay. IgA antibodies to both CK-18 and EPK were significantly increased in patients with RA compared with the controls and with patients with OA (P < 0.0001). No difference was noted in the levels of IgG or IgM antibodies to CK-18 or EPK between controls and patients with OA or RA. Raised levels of IgA autoantibody to CK-18 and EPK may reflect damage to cytokeratin-containing cells (e.g., in synovial endothelium) and could be a useful disease marker in RA.


Different Malabsorptive Obesity Surgery Interventions Result in Distinct Postprandial Amino Acid Metabolomic Signatures.
Biliopancreatic diversion with duodenal switch (BPD-DS) is an effective weight loss surgical procedure. Yet, BPD-DS is technically difficult to perform and carries a higher risk of nutrient deficiencies as compared with other surgical interventions. Single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) is a modified BPD-DS procedure conceived with the aim of decreasing the technical complexity, while retaining the weight loss efficiency. Whether the two surgical procedures diverge in nutrient absorption rates and malnutrition risk is still matter of debate. Our aim was to determine if postprandial nutrient absorption rates are different in patients subjected to BPD-DS or SADI-S for weight loss. Plasma amino acid metabolomic profiling during mixed-meal tolerance test (MMTT) was performed in subjects (N = 18) submitted to BPD-DS (n = 9) or SADI-S (n = 9) 1.6 ± 0.1 years earlier. Patients submitted to SADI-S or BPD-DS presented distinct postprandial metabolomic profiles. Postprandial excursions of total and essential amino acids-leucine, isoleucine, and valine-were higher after SADI-S as compared with BPD-DS. Our study demonstrates that a simplified malabsorptive bariatric surgery procedure SADI-S results in greater essential branched-chain amino acid absorption when compared with the classical BPD-DS intervention. These findings suggest that SADI-S can potentially lower lifetime risk of postoperative protein malnutrition, as well as have a positive impact on systemic metabolism and glucose homeostasis.


Trends in systemic sclerosis and systemic sclerosis-related pulmonary arterial hypertension mortality in the USA.
There are limited data nationwide on the burden of systemic sclerosis (SSc)-related mortality. We aimed to determine recent trends in SSc and SSc-related pulmonary arterial hypertension (PAH) mortality overall and across population subgroups. Using death certificate data from the National Center for Health Statistics, we computed the age-adjusted mortality rates of SSc and SSc-SSc-PAH, a lethal prevailing complication, across demographic groups, geographic regions and comorbid cardiorespiratory conditions, and used Joinpoint regression analysis to calculate the average annual percentage change (APC) in mortality. From 2003 to 2016, 25 175 death records contained a code for SSc. Decedents were predominantly female (81%) and white (73%), with an average age of 66±14 years. The age-adjusted mortality rate decreased by 3% per year from 6.6 in 2003 to 4.3 per 1 000 000 population in 2016. Also, a decreasing trend was found when SSc was stratified by age, sex, race and geographic region. The prevalence of PAH was 23%. The odds of PAH were highest in female and black decedents, and in decedents with concomitant pulmonary embolism, cardiomyopathy and interstitial lung disease (ILD). SSc-PAH mortality remained stable from 2003 to 2008 then decreased by 3% per year from 2008 to 2016. In decedents with SSc-PAH, among all concomitant comorbidities, the mortality rate associated with ILD had the highest increase (average APC 6%, 95% CI 2%-10%). The mortality rate from SSc decreased from 2003 to 2016. Decreases in mortality rates were similar across demographic groups and geographic regions. SSc-PAH-related mortality remained stable. The death rate for SSc-ILD and concomitant PAH increased during this period.