Resistance to cutaneous leishmaniasis: acquired ability of the host to kill parasites at the site of infection.
The purpose of these studies was to follow the development of acquired resistance in experimental cutaneous leishmaniasis by measuring changes, against time, in the ability of mice infected with Leishmania tropica to inhibit the growth of a challenge inoculum of parasites. In addition, the development of T lymphocytes that mediate the acquired response was followed by adoptive immunization. It was found that acquired resistance developed rapidly and reached a maximum level at the time when the progressive multiplication of the parasites in the primary lesion stopped. Systemic immunity, however, as determined by the ability of splenic T cells to adoptively immunize normal recipients, did not develop fully until 4 weeks later. Acquired resistance is expressed systemically in the animal and probably nonspecifically, in that mice expressing resistance to a homologous challenge with L. tropica were also capable of destroying Listeria monocytogenes. These data, obtained from in vivo studies, are consistent with the hypothesis that the immunity which causes the destruction of L. tropica is mediated by T lymphocytes and expressed, nonspecifically, through macrophages.


Predictors of cross-clamp-induced intraoperative monitoring changes during carotid endarterectomy using both electroencephalography and somatosensory evoked potentials.
The efficacy of selective shunting during carotid endarterectomy (CEA) using intraoperative monitoring (IOM) for detection of cerebral ischemia is well established. There is mounting evidence that monitoring of both electroencephalography (EEG) and somatosensory evoked potentials (SSEPs) increases the sensitivity of cerebral ischemia detection. Predictors of cerebral ischemia requiring selective shunt placement using IOM of both EEG and SSEPs have not been previously identified. Consecutive patients who underwent CEA between January 1, 2000, and December 31, 2010, were retrospectively analyzed. Primary end points were IOM changes at any time during the operation or IOM changes with carotid cross-clamping. Risk factors assessed included demographics; baseline comorbidities; severity of ipsilateral and contralateral disease; symptomatic status; and use of statin, antiplatelet, and beta-blocker medications. Univariate and multivariate logistic regression was used for analysis. During the 11-year study period, a total of 758 patients underwent 804 CEAs (mean age, 70.6 ± 9.5 years; 59.8% male; 39.2% symptomatic) using IOM of both SSEPs and EEG for selective shunting guidance. Postoperative stroke rate was 1.37%; 27.1% of patients had significant SSEP or EEG changes, and 49.1% of these were clamp induced (within 5 minutes of cross-clamping). Of these patients, 83.2% received a shunt (11.4% overall). The most common reason that a shunt was not placed after cross-clamp-induced changes was that the changes resolved with further blood pressure elevation (8 of 17 patients). Clamp-induced IOM changes were predictive of postoperative stroke (odds ratio [OR], 5.5; P = .005). Risk factors for clamp-induced IOM changes were contralateral carotid occlusion (OR, 2.5; P = .01), symptomatic stenosis (OR, 1.8; P = .006), and diabetes (OR, 1.6; P = .03), whereas there was a trend toward increased risk with female sex (OR, 1.5; P = .08). Risk factors for any IOM change (clamp and nonclamp induced) were symptomatic carotid stenosis (OR, 1.8; P < .001), use of beta blockers (OR, 1.5; P = .03), and female sex (OR, 1.5; P = .02). Whereas some patients can be expected to experience IOM changes by monitoring of SSEPs and EEG, a much smaller percentage will receive a shunt. Contralateral carotid occlusion, symptomatic stenosis, diabetes, and female sex increase the risk of clamp-induced IOM changes and should be anticipated to need a shunt. Patients receiving beta blockers are likely to experience IOM changes during the operation that are not associated with clamping.


Soil fungal diversity in natural grasslands of the Tibetan Plateau: associations with plant diversity and productivity.
Previous studies have revealed inconsistent correlations between fungal diversity and plant diversity from local to global scales, and there is a lack of information about the diversity-diversity and productivity-diversity relationships for fungi in alpine regions. Here we investigated the internal relationships between soil fungal diversity, plant diversity and productivity across 60 grassland sites on the Tibetan Plateau, using Illumina sequencing of the internal transcribed spacer 2 (ITS2) region for fungal identification. Fungal alpha and beta diversities were best explained by plant alpha and beta diversities, respectively, when accounting for environmental drivers and geographic distance. The best ordinary least squares (OLS) multiple regression models, partial least squares regression (PLSR) and variation partitioning analysis (VPA) indicated that plant richness was positively correlated with fungal richness. However, no correlation between plant richness and fungal richness was evident for fungal functional guilds when analyzed individually. Plant productivity showed a weaker relationship to fungal diversity which was intercorrelated with other factors such as plant diversity, and was thus excluded as a main driver. Our study points to a predominant effect of plant diversity, along with other factors such as carbon : nitrogen (C : N) ratio, soil phosphorus and dissolved organic carbon, on soil fungal richness.


Blue-Shifted Green Fluorescent Protein Homologues Are Brighter than Enhanced Green Fluorescent Protein under Two-Photon Excitation.
Fluorescent proteins (FPs) are indispensable markers for two-photon imaging of live tissue, especially in the brains of small model organisms. The quantity of physiologically relevant data collected, however, is limited by heat-induced damage of the tissue due to the high intensities of the excitation laser. We seek to minimize this damage by developing FPs with improved brightness. Among FPs with the same chromophore structure, the spectral properties can vary widely due to differences in the local protein environment. Using a physical model that describes the spectra of FPs containing the anionic green FP (GFP) chromophore, we predict that those that are blue-shifted in one-photon absorption will have stronger peak two-photon absorption cross sections. Following this prediction, we present 12 blue-shifted GFP homologues and demonstrate that they are up to 2.5 times brighter than the commonly used enhanced GFP (EGFP).


The transfer of cephradine across the placenta.
The transfer of maternally administered cephradine (1 g given intravenously) to the fetal circulation and amniotic fluid was investigated in 2 pregnant patients undergoing fetoscopy. Cephradine was detected in fetal serum between 23 and 72 minutes after injection and was present in therapeutic concentrations. Fetal serum levels appeared to peak at approximately 40-50 min. Amniotic fluid levels were rising during the sampling period of 97 min. Cephradine is transferred across the placenta and appears to be a suitable antibiotic for use in selected obstetric patients when penetration of the fetal compartment is desirable.


Sporadic Creutzfeldt-Jacob Disease: An 8-Year Experience from a Single Center in Turkey.
Our aim was to conduct a retrospective review to demonstrate the clinical, radiological, and electrophysiological features of patients with sporadic Creutzfeldt-Jacob disease (sCJD). A total of 10 patients (5 female and 5 male, with a mean age of 45 years from a range of 40 to 67 years) out of 8.259 adult patients hospitalized from January 2000 to December 2008 were diagnosed with sCJD. Eight of the patients were diagnosed on the basis of clinical, radiological, electroencephalography (EEG), and cerebrospinal fluid (CSF) findings. Two other patients also had a pathological diagnosis. The most common signs and symptoms were behavioral disturbances, movement disorders, cognitive decline, myoclonus, psychosis, focal neurological deficit, and aphasia. Nine of the patients had periodic sharp wave discharges on EEG. Seven patients were positive for the 14.3.3 protein in the CSF. Five patients had pulvinar signs-a bilateral increased signal in the pulvinar thalami-on cranial magnetic resonance imaging. Eight patients were diagnosed with probable sCJD; two were diagnosed with definite sCJD. All of the patients died as a result of the disease within 24 months after the onset of symptoms. sCJD should be considered in the diagnosis of patients who present with rapidly progressive dementia. Clinical and radiological data appear to be sufficient for the diagnosis. However, detailed molecular examinations of the subtypes of the disease may be required for early diagnosis of cases given the wide spectra of CJD.


Dual Nanofriction Force Microscopy/Fluorescence Microscopy Imaging Reveals the Enhanced Force Sensitivity of Polydiacetylene by pH and NaCl.
Polydiacetylene (PDA) is a popular mechanochromic material often used in biosensing. The effect of its headgroup-headgroup interactions on thermochromism such as pH or salt concentration dependency has been extensively studied before; however, their effect on mechanochromism at the nanoscale is left unstudied. In this work, nanofriction force microscopy and fluorescence microscopy were combined to study the effect of pH and ionic strength on the polydiacetylene (PDA) force sensitivity at the nanoscale. We found that the increase in pH from 5.7 to 8.2 caused an 8-fold enhancement in force sensitivity. The elevation of NaCl concentration from 10 to 200 mM also made the PDA 5 times more force-sensitive. These results suggest that the PDA force sensitivity at the nanoscale can be conveniently enhanced by "pre-stimulation" with pH or ionic strength.


High-performance partially aligned semiconductive single-walled carbon nanotube transistors achieved with a parallel technique.
Single-walled carbon nanotubes (SWNTs) are widely thought to be a strong contender for next-generation printed electronic transistor materials. However, large-scale solution-based parallel assembly of SWNTs to obtain high-performance transistor devices is challenging. SWNTs have anisotropic properties and, although partial alignment of the nanotubes has been theoretically predicted to achieve optimum transistor device performance, thus far no parallel solution-based technique can achieve this. Herein a novel solution-based technique, the immersion-cum-shake method, is reported to achieve partially aligned SWNT networks using semiconductive (99% enriched) SWNTs (s-SWNTs). By immersing an aminosilane-treated wafer into a solution of nanotubes placed on a rotary shaker, the repetitive flow of the nanotube solution over the wafer surface during the deposition process orients the nanotubes toward the fluid flow direction. By adjusting the nanotube concentration in the solution, the nanotube density of the partially aligned network can be controlled; linear densities ranging from 5 to 45 SWNTs/μm are observed. Through control of the linear SWNT density and channel length, the optimum SWNT-based field-effect transistor devices achieve outstanding performance metrics (with an on/off ratio of ~3.2 × 10(4) and mobility 46.5 cm(2) /Vs). Atomic force microscopy shows that the partial alignment is uniform over an area of 20 × 20 mm(2) and confirms that the orientation of the nanotubes is mostly along the fluid flow direction, with a narrow orientation scatter characterized by a full width at half maximum (FWHM) of <15° for all but the densest film, which is 35°. This parallel process is large-scale applicable and exploits the anisotropic properties of the SWNTs, presenting a viable path forward for industrial adoption of SWNTs in printed, flexible, and large-area electronics.


Effect of Oat (Avena Sativa L.) Extract on Experimental Sciatic Nerve Injury in Rats.
Peripheral nerve disorders are the most common neurological problems; therefore, it is important to intervene to treat or stop the resulting side effects. This study aimed to investigate the effect of oat extract on experimental sciatic nerve injury in rats. Totally, 50 adult male rats were divided into five groups (n=10). Group 1 was exposed to sham condition, and group 2 was regarded as the control group (nerve injury without treatment). Moreover, groups 3-5 were subjected to sciatic nerve injury, and they received oral gavages of the oat extract (100, 200, and 400 mg/kg), respectively. Subsequently, 2 and 4 weeks later, the rats were euthanized for pathological evaluation of nerve repair. The results showed an increase in the formation of the perineurium and epineurium dose in the oat-treated groups (100, 200, and 400 mg/kg), compared to the control group after 2 weeks (P<0.05). Furthermore, the presence of inflammatory cells in the oat extract-treated groups (100, 200, and 400 mg/kg) decreased, compared to that in the control group after 2 weeks (P<0.05). In addition, the swelling of the axon significantly decreased in the oat extract-treated groups (200 and 400 mg/kg), compared to the control group (P<0.05). However, the axon dose-dependently increased in oat-treated groups (100, 200, and 400 mg/kg), compared to that in the control group after 4 weeks (P<0.05). These results suggest that oat extract has positive effects on sciatic nerve repair in rats.


Porous Poly(Ionic Liquid) Membranes as Efficient and Recyclable Absorbents for Heavy Metal Ions.
Heavy metal ion pollution has become a serious environmental problem. Herein, this study reports the synthesis of poly(ionic liquid) (PIL) membranes via in situ photo-crosslinking of vinyl imidazole with both hydrophilic and hydrophobic ionic liquid monomers. The resultant amphiphilic polymer membranes are porous and exhibit high absorption capacity of metal ions (including Hg2+ , Pb2+ , Cu2+ , Cd2+ , and Zn2+ ) in both high (1000 mg L-1 ) and low (10 mg L-1 ) concentration metal ion solutions. These metal ionic absorption membranes are easily regenerated in acid solution and can be reused without significant decreases of absorption capacity after many cycles. These PIL membranes may have potential applications as eco-friendly and safe heavy metal ion removal materials.


Microscopic decompression of the anterior upper cervical spine: a case of odontoid malunion to the atlas.
For the past 20 years, the transoral approach to the upper cervical spine has been utilized for odontoid fractures, the removal of an abnormal odontoid process, decompression of basilar impression, and biopsy or resection of nasopharyngeal or metastatic tumors. The effectiveness and safety of this procedure is well documented. Use of the surgical microscope adds to the efficiency and safety of the procedure. We are reporting a case of fusion of the odontoid base to the anterior arch of the atlas. To our knowledge, this entity has not been described previously. The spinal cord was protected by an initial posterior fusion of C-1, C-2, followed in 10 days by a tracheostomy and the transoral removal of the anterior C-1 arch and the abnormal dens. Because the medical history did not reveal a source of trauma, it is supposed that the patient had malunion of the odontoid process to C-2, with subsequent migration and fusion of the dens to the C-1 arch.


Characterization of monoclonal antibody 3G5 and utilization of this antibody to immobilize pancreatic islet cell gangliosides in a solid phase radioassay.
Monoclonal antibody 3G5, which was initially produced by immunization of mice with fetal rat brain, reacts specifically by indirect immunofluorescence with all cells of the pancreatic islets of human, rat, mouse, and bovine pancreas. This antibody reacts with the cell surface of isolated islet cells as well as the rat (RIN5F) insulinoma cell line. Antibody 3G5 reacts with islets, thyroid follicular cells, pituitary, and the adrenal medulla of a pattern similar to but distinct from those of antibody A2B5 and tetanus toxin, both of which react with complex gangliosides (sialic acid-containing glycosphingolipids). The antigen with which antibody 3G5 reacts also has the properties of ganglioside (neuraminidase sensitive, extracted into chloroform-methanol, partitioned into a methanol-water phase, soluble in water, and nondialyzable). Antibody 3G5, adsorbed to polyvinyl plates, can immobilize islet ganglioside micelles to which 125I-labeled 3G5, A2B5, and tetanus toxin all bind. The ability to immobilize micelles containing several complex gangliosides has led to a solid phase radioassay to detect antiganglioside antibodies. Monoclonal antibody 3G5 joins antibody A2B5 and tetanus toxin as markers for distinct complex gangliosides found on pancreatic islets and neurons.


Treatment Decisions for Babies with Trisomy 13 and 18.
Many babies with trisomy 13 and 18 die in the first year of life. Survivors all have severe cognitive impairment. There has been a debate among both professionals and parents about whether it is appropriate to provide life-sustaining interventions to babies with these serious conditions. On one side of the debate are those who argue that there is no point in providing invasive, painful, and expensive procedures when the only outcomes are either early death or survival with severe cognitive impairment. Others suggest that, although mortality is high and cognitive impairment universal, babies with these conditions have an acceptable quality of life. In this paper, we will discuss both points of view. We will review the ways in which these conditions are portrayed in pediatrics textbooks and on social media sites that offer support to parents. We will then suggest an appropriate way to deal with clinical decisions for babies with these trisomies.


Influence of the mother in the development of flavored-food preference in lambs.
The aim of the study was to determine the influence of the mother in the development of flavored-food preference in lambs. First, we demonstrated that lambs that ate flavored food in the presence of their mothers before weaning ate more of this food 1 month after weaning than lambs that ate flavored food with other ewes or lambs exposed to nonflavored food with their mothers. Second, lambs that could only see their mothers eating the flavored food and had access to the food's olfactory cues before weaning, showed similar preference for flavored food 1 month after weaning to lambs that ate the flavored food with their mothers. However, lambs that were separated from their mothers while their mothers consumed flavored food did not reveal a preference for it. Overall these results suggest that development of food preference in lambs depends mainly on observation of the mother, provided there is also access to olfactory cues characterizing the food.


The National Temporal Bone, Hearing, and Balance Pathology Resource Registry.
The National Temporal Bone, Hearing, and Balance Pathology Resource Registry has been established with funding provided by the National Institute on Deafness and Other Communication Disorders of the National Institutes of Health. The registry is meant to serve as a national resource for researchers and the public to stimulate and facilitate human otopathologic research. It will maintain a computerized database of currently active and inactive temporal bone and auditory brain-stem collections throughout the United States. In addition, it will encourage human temporal bone research by disseminating pertinent information, developing and fostering temporal bone professional educational activities, implementing a national temporal bone acquisition network, and encouraging investigative collaborations in the study of the human temporal bone and brain structures. It will also identify otopathologic collections at risk of being discarded or lost and will develop mechanisms and strategies to conserve them.


Survival of adults with primary malignant brain tumours in Europe; Results of the EUROCARE-5 study.
Primary malignant brain tumours are rare but represent a serious health burden due to their poor survival. This manuscript describes the survival of malignant brain tumours in adults diagnosed 2000-2007 in Europe. For this study we analysed patients archived in 86 European population-based cancer registries, followed up to 31st December 2008. Only primary malignant neuroepithelial brain tumours (with pathological confirmation) and primary malignant unspecified brain tumours without pathological confirmation were included. We estimated 1-year and 5-year relative survival (RS) weighted by age group and country. We also estimated country-specific and age-specific survival, together with survival differences between time periods (for 1999-2001, 2002-2004 and 2005-2007). Glioblastoma represents 49% of all brain tumours, followed by other/unspecified astrocytoma (18%), oligodendroglioma/oligoastrocytoma (9%), ependymoma (1.5%) and embryonal tumours (1%). Five-year RS was 20% for all tumours combined, but ranged from 58% for ependymoma to only 6% for glioblastoma and sharply decreased with increasing age. Differences between countries were relatively small, but generally RS in Ireland/United Kingdom (UK) and Eastern Europe was below the average. An increase in 1-year RS (up to 10-12%) was noted over time, being largest in Central and Northern Europe in patients between 45 and 74years of age. Despite an increase in 1-year RS in most European regions, the survival of primary malignant brain tumours is still poor. Disparities between countries were evident, being even larger at the end of the study period than at the beginning, suggesting differences in availability of the latest treatment modalities.


Where to from here?
Although this conceptual framework is easy to understand, the data requirements for the mathematical model that underpins the framework are complex and must be defined carefully. In our framework, simulations of the health system are used to provide needs-based estimates that are aimed at optimizing outcomes. This type of model builds on research conducted at the macro, meso, and micro levels in order to reflect the complexity of relationships in the health human resource process. The papers in this issue of the Journal provide insight into specific constructs of the model. At the macro level, Tomblin Murphy explores methodological challenges in HHRP research. She examines common assumptions and the validity of their use in modelling in all aspects of the proposed framework. Tourangeau and colleagues report on the impact of hospital nurse-staffing decisions on 30-day mortality rates. Their model adds to our knowledge of the relationships among the management, deployment, and utilization of nursing services and patient/population outcomes. Shamian and colleagues explore the relationship between hospital-level indicators of the work environment and aggregated indicators of health and well-being for registered nurses employed in acute-care hospitals in the province of Ontario. This paper contributes to our understanding of how management decisions regarding the work environment influence nurse outcomes. Manojlovich and Ketafian explore the conflict between the practice of nursing and the organizational structure of many hospitals. This study provides insight into the management aspects of how the work unit is organized and the process of care delivery. Zboril-Benson examines the reasons for nurse absenteeism in the province of Saskatchewan. Birch describes the need for the planning process to take into account demographic changes in both populations and provider groups. A major challenge in modelling health human resources is access to meaningful databases for planning purposes. Pringle describes a unique Ontario initiative currently underway to develop and validate a nurse-sensitive set of data that will be routinely collected and will enhance HHRP in that province. Since the science that underpins HHRP is complex and rapidly changing, few books have been written on the subject. Reflecting the dynamic nature of the science, Tomblin Murphy and Barrath provide an excellent review of "grey literature" and useful Web sites for those interested in HHRP.


ULTRASOUND-GUIDED SCIATIC POLITEAL NERVE BLOCK: A COMPARISON OF SEPARATE TIBIAL AND COMMON PERONEAL NERVE INJECTIONS VERSUS INJECTING PROXIMAL TO THE BIFURCATION.
Block of the sciatic nerve at the popliteal fossa can be performed using the ultrasound machine; it may be proximally or distally to the bifurcation of the sciatic nerve using lateral, medial, or posterior approaches. It is frequently used for surgeries below the knee specially the foot and ankle operations. This study compares one and two injections of the sciatic nerve in the popliteal fossa with ultrasound-guided block in foot or ankle surgeries. Forty patients received ultrasound-guided sciatic nerve block with the nerve stimulator, using the posterior approach. The patients were enrolled into two groups (20 patients each), group 1: received one injection at 2 cm cephalad to the bifurcation of the sciatic nerve, and group 2: received two injections caudate to the sciatic bifurcation; one for tibial nerve and the other for common peroneal nerve. All patients received 20 ml of levobupivacaine 0.5%. The block performance time, block efficacy, success rate, complications and patient's satisfaction were evaluated. Block the tibial and common peroneal nerves separately (two injections) distal to the point of bifurcation of the sciatic nerve has a significantly (P < 0.05) faster time to complete sensory block of tibial and common peroneal nerves compared to a pre-bifurcation sciatic nerve block (one injection). The complete motor block, block time performance, success rate and patient's satisfaction were not significantly different between groups (P > 0.05). The block of tibial and common peroneal nerves separately distal to the sciatic nerve bifurcation is superior to single injection block of sciatic nerve above the bifurcation in the popliteal fossa as regard complete sensory block time.


Lupane-type triterpenoids from Microtropis fokienensis and Perrottetia arisanensis and the apoptotic effect of 28-hydroxy-3-oxo-lup-20(29)-en-30-al.
Seven new lupane triterpenoids were isolated from bioactive methanol extracts of Microtropis fokienensis (1- 4) and Perrottetia arisanensis (4-7), along with 18 known compounds. The structures of the new compounds were elucidated on the basis of spectroscopic data analysis. All triterpenoids were evaluated for their in vitro cytotoxicity toward seven human cancer cell lines. Compound 8 (28-hydroxy-3-oxo-lup-20(29)-en-30-al) was among the most cytotoxic substances obtained and was found to induce apoptosis of human leukemia HL60 cells and mediate cleavage of PARP and up-regulation of Bax proteins.


The population structure of Rose rosette virus in the USA.
Rose rosette virus (RRV) (genus Emaravirus) is the causal agent of the homonymous disease, the most destructive malady of roses in the USA. Although the importance of the disease is recognized, little sequence information and no full genomes are available for RRV, a multi-segmented RNA virus. To better understand the population structure of the virus we implemented a Hi-Plex PCR amplicon high-throughput sequencing approach to sequence all 7 segments and to quantify polymorphisms in 91 RRV isolates collected from 16 states in the USA. Analysis revealed insertion/deletion (indel) polymorphisms primarily in the 5' and 3' non-coding, but also within coding regions, including some resulting in changes of protein length. Phylogenetic analysis showed little geographical structuring, suggesting that topography does not have a strong influence on virus evolution. Overall, the virus populations were homogeneous, possibly because of regular movement of plants, the recent emergence of RRV and/or because the virus is under strong purification selection to preserve its integrity and biological functions.


Mapping Functionally Important Residues in the Na+/Dicarboxylate Cotransporter, NaDC1.
Transporters from the SLC13 family couple the transport of two to four Na+ ions with a di- or tricarboxylate, such as succinate or citrate. We have previously modeled mammalian members of the SLC13 family, including the Na+/dicarboxylate cotransporter NaDC1 (SLC13A2), based on a structure of the bacterial homologue VcINDY in an inward-facing conformation with one sodium ion bound at the Na1 site. In the study presented here, we modeled the outward-facing conformation of rabbit and human NaDC1 (rbNaDC1 and hNaDC1, respectively) using an outward-facing model of VcINDY as a template and identified residues in or near the putative Na2 and Na3 cation binding sites. Guided by the structural models in both conformations, we performed site-directed mutagenesis in rbNaDC1 for residues proposed to be in the Na+ or substrate binding sites. Cysteine substitution of T474 in the predicted Na2 binding site results in an inactive protein. The M539C mutant has a low apparent affinity for both sodium and lithium cations, suggesting that M539 may form part of the putative Na3 binding site. The Y432C and T86C mutants have increased Km values for succinate, supporting their proposed location in the outward-facing substrate binding site. In addition, cysteine labeling by MTSEA-biotin shows that Y432C is accessible from the outside of the cell, and the accessibility changes in the presence or absence of Na+. The results of this study improve our understanding of substrate and ion recognition in the mammalian members of the SLC13 family and provide a framework for developing conformationally specific inhibitors against these transporters.


Antibody-induced movement of protozoan surface membrane antigens.
Direct and indirect immunofluorescence techniques were used to study the effects of host antibodies on surface membrane antigens of viable Leishmania parasites in vitro. Antisera to L. enriettii and L. tropica caused surface membrane antigens of these parasites to aggregate, move toward the poles of the parasite, and to eventually disappear. This sequence did not occur at low temperature or in the presence of some metabolic inhibitors. Antigen subsequently reappeared on the parasite membrane. These phenomena appear to be similar to those described in mammalian cells. Antibodies may therefore effect an alteration in the surface membrane structure of living protozoan parasites.


Racial heterogeneity of IgA1 hinge-region O-glycoforms in patients with IgA nephropathy.
Galactose (Gal)-deficient IgA1 (Gd-IgA1) is involved in IgA nephropathy (IgAN) pathogenesis. To reflect racial differences in clinical characteristics, we assessed disease- and race-specific heterogeneity in the O-glycosylation of the IgA1 hinge region (HR). We determined serum Gd-IgA1 levels in Caucasians (healthy controls [HCs], n = 31; IgAN patients, n = 63) and Asians (HCs, n = 20; IgAN patients, n = 60) and analyzed profiles of serum IgA1 HR O-glycoforms. Elevated serum Gd-IgA1 levels and reduced number of Gal residues per HR were observed in Caucasians. Reduced number of N-acetylgalactosamine (GalNAc) residues per HR and elevated relative abundance of IgA1 with three HR O-glycans were common features in IgAN patients; these features were associated with elevated blood pressure and reduced renal function. We speculate that the mechanisms underlying the reduced GalNAc content in IgA1 HR may be relevant to IgAN pathogenesis.


A multi-domain trust management model for supporting RFID applications of IoT.
The use of RFID technology in complex and distributed environments often leads to a multi-domain RFID system, in which trust establishment among entities from heterogeneous domains without past interaction or prior agreed policy, is a challenge. The current trust management mechanisms in the literature do not meet the specific requirements in multi-domain RFID systems. Therefore, this paper analyzes the special challenges on trust management in multi-domain RFID systems, and identifies the implications and the requirements of the challenges on the solutions to the trust management of multi-domain RFID systems. A multi-domain trust management model is proposed, which provides a hierarchical trust management framework include a diversity of trust evaluation and establishment approaches. The simulation results and analysis show that the proposed method has excellent ability to deal with the trust relationships, better security, and higher accuracy rate.


What keeps me up at night.
The lessons of COVID-19 must be heeded if the world is to be prepared for the next emergent pathogen with pandemic potential.


Psychological variables and Wechsler Adult Intelligence Scale-IV performance.
The MMPI-2 and WAIS-IV are commonly used together in neuropsychological evaluations yet little is known about their interrelationships. This study explored the potential influence of psychological factors on WAIS-IV performance in a sample of 180 predominantly male veteran referrals that underwent a comprehensive neuropsychological examination in a VA Medical Center. Exclusionary criteria included failed performance validity testing and self-report distortion on the MMPI-2. A Principal Components Analysis was performed on the 15 MMPI-2 content scales, yielding three broader higher-order psychological dimensions: Internalized Emotional Dysfunction (IED), Externalized Emotional Dysfunction (EED), and Fear. Level of IED was not related to performance on the WAIS-IV Full Scale IQ or its four indexes: (Verbal Comprehension, Perceptual Reasoning, Working Memory, and Processing Speed). EED was not related to WAIS-IV performance. Level of Fear, which encompasses health preoccupations (HEA) and distorted perceptions (BIZ), was significantly related to WAIS-IV Full Scale IQ and Verbal Comprehension. These results challenge the common use of high scores on the MMPI-2 IED measures (chiefly depression and anxiety) to explain deficient WAIS-IV performance. In addition, they provide impetus for further investigation of the relation between verbal intelligence and Fear.


[Efficacy of 3-dimensional conformal hypofractionated single high-dose radiotherapy combined with transcatheter arterial chemoembolization for portal vein tumor thrombus in patients with hepatocellular carcinoma].
Hepatocellular carcinoma (HCC) often results in portal vein tumor thrombus (PVTT), and the prognosis of the patients is extremely poor. It has been reported that some oversea scholars achieved fine therapeutic effects in treatment of this disease by 3-dimensional conformal radiation therapy (3DCRT) in fractionated conventional dose. The aim of this study was to evaluate the efficacy of 3-dimensional conformal hypofractionated single high-dose radiotherapy combined with transcatheter arterial chemoembolization (TACE) for portal vein tumor thrombus in patients with hepatocellular carcinoma. From May 1998 to December 2000, 35 patients with unresectable HCC complicated with PVTT were treated with 3-dimensional conformal hypofractionated single high-dose radiotherapy and TACE. According to the volume of the tumors, radiotherapy was performed at an exposure of 4-8 Gy/time, 3 times/week, 48-60 Gy, 8-12 times, 3.0-3.5 weeks. The objective responses were analyzed and the survival rates were assessed from the date of the beginning of treatment using the Kaplan-Meier method. The Cox proportional hazards model was used to analyze the prognostic factors. The objective response was 71.4%. The overall survival rates were 59.3%, 31.6%, and 26.6% at 1, 2, 3 years, respectively, with a median survival time of 11 months. Cox proportional hazards model analysis showed that Child-Pugh class was the most important prognostic factors for the survival probability of the patients. Radiation-induced liver disease (RILD) and gastrointestinal bleeding were the most common treatment-related complications. 3-Dimensional conformal hypofractionated single high-dose radiotherapy combined with TACE is an effective and feasible approach to treat PVTT in unresectabe HCC patients. Child-Pugh class was identified as a predictor for PVTT in unresectabe HCC patients.


Macrophage polarization in tissue fibrosis.
Fibrosis can occur in all major organs with relentless progress, ultimately leading to organ failure and potentially death. Unfortunately, current clinical treatments cannot prevent or reverse tissue fibrosis. Thus, new and effective antifibrotic therapeutics are urgently needed. In recent years, a growing body of research shows that macrophages are involved in fibrosis. Macrophages are highly heterogeneous, polarizing into different phenotypes. Some studies have found that regulating macrophage polarization can inhibit the development of inflammation and cancer. However, the exact mechanism of macrophage polarization in different tissue fibrosis has not been fully elucidated. This review will discuss the major signaling pathways relevant to macrophage-driven fibrosis and profibrotic macrophage polarization, the role of macrophage polarization in fibrosis of lung, kidney, liver, skin, and heart, potential therapeutics targets, and investigational drugs currently in development, and hopefully, provide a useful review for the future treatment of fibrosis.


How to help depressed older people living in residential care: a multifaceted shared-care intervention for late-life depression.
To describe a population-based, multifaceted shared-care intervention for late-life depression in residential care as a new model of geriatric practice, to outline its development and implementation, and to describe the lessons learned during the implementation process. A large continuing-care retirement community in Sydney, Australia, providing three levels of care (independent living units, assisted-living complexes, and nursing homes). The intervention was implemented for the entire non-nursing home population (residents in independent and assisted living: N = 1,466) of the facility and their health care providers. Of the 1,036 residents whowere eligible and agreed to be interviewed, 281 (27.1%) were classified as depressed according to the Geriatric Depression Scale. INTERVENTION DESCRIPTION: The intervention included: (a) multidisciplinary collaboration between primary care physicians, facility health care providers, and the local psychogeriatric service; (b) training for primary care physicians and other facility health care providers about detecting and managing depression; and (c) depression-related health education/promotion programs for residents. The intervention was widely accepted by residents and their health care providers, and was sustained and enhanced by the facility after the completion of the study. It is possible to implement and sustain a multifaceted shared-care intervention for late-life depression in a residential care facility where local psychogeriatric services are scarce, staff-to-resident ratios are low, and the needs of depressed residents are substantial.


How noise and language proficiency influence speech recognition by individual non-native listeners.
This study investigated how speech recognition in noise is affected by language proficiency for individual non-native speakers. The recognition of English and Chinese sentences was measured as a function of the signal-to-noise ratio (SNR) in sixty native Chinese speakers who never lived in an English-speaking environment. The recognition score for speech in quiet (which varied from 15%-92%) was found to be uncorrelated with speech recognition threshold (SRTQ/2), i.e. the SNR at which the recognition score drops to 50% of the recognition score in quiet. This result demonstrates separable contributions of language proficiency and auditory processing to speech recognition in noise.


The social and family dynamics behind the uptake of cataract surgery: findings from Kilimanjaro region, Tanzania.
To describe and understand better the barriers that elderly cataract patients in Kilimanjaro region (Tanzania) experience at the family level in order to access surgery. A phenomenological study carried out in the catchment area of a teaching hospital in Kilimanjaro Region. 60 semi-structured interviews were conducted with patients and ex-cataract patients. The perceived need for sight and for surgery appears partly socially constructed at the family level. It was found that women were less likely to express a need for sight for fear of being seen as a burden. Furthermore, young heads of family are more inclined to support old men than old women. The consensus is that asking children for help can be difficult. Going for cataract surgery must be seen as a social process where elderly patients might have to wait or negotiate support for weeks, months, or even years. Eye programmes must promote the benefits of cataract surgery to all family members, not just to the patient. A changing social climate, changing expectations of vision, and evolving cost sharing systems will have significant, sometimes contradictory, impacts on use of eye care services. Strategies for reaching those without access to financial resources need to be strengthened.


[Genetic polymorphisms in X-ray repair cross-complementing gene 1 and susceptibility to papillary thyroid carcinoma].
To study the association of polymorphisms in the X-ray repair cross-complementing gene 1 (XRCC1) and papillary thyroid carcinoma (PTC). A hospital based, matched case-control study was carried out. The polymorphisms in XRCC1 for 105 pairs of cases with PTC and controls were identified by PCR-RFLP. The frequencies of Arg/Arg, Arg/Trp and Trp/Trp genotypes at XRCC1 Arg194Trp site were 47.6%, 49.5% and 2.9% among cases compared to 45.7%, 48.6% and 5.7% among controls. There was no statistically significant difference between the two groups (chi(2) = 1.07, P = 0.59). The frequencies of Arg/Arg, Arg/Gln and Gln/Gln genotypes at XRCC1 Arg399Gln site were 46.7%, 41.9% and 11.4% among cases, while 54.2%, 42.9% and 2.9% among controls respectively. There was statistically significant difference between the two groups (chi(2) = 6.40, P = 0.04). Individuals with Gln/Gln genotype had a 3.65-fold increased risk of developing PTC compared to Arg/Arg genotype (OR = 4.65, 95% CI: 1.24 - 17.45). The multivariate conditional logistic regression analysis showed that the XRCC1 Arg399Gln polymorphism, negative life events and X-irradiation history were associated with PTC, with odds ratios of 2.71 (95% CI: 1.22 - 6.05), 5.34 (95% CI: 1.40 - 20.38) and 0.38 (95% CI: 0.12 - 0.72) respectively. However, XRCC1 Arg194Trp polymorphism, drinking tea, fruit and economic levels did not show statistically significant associations with PTC. The Gln/Gln genotype at XRCC1 Arg399Gln site and negative life events significantly increased while X-irradiation history decreased the risk of developing PTC.


Profile of rhBMP-2 release from collagen minipellet and induction of ectopic bone formation.
For a cylindrical controlled-release formulation using collagen as a carrier, called the minipellet (MP), which contains rhBMP-2, the relationship between the diameter of MPs and rhBMP-2 release profiles was investigated, and its effect in inducing bone formation was evaluated. Samples with three different diameters were tested for each of the following formulations: MP without additives, MP with 10% (w/w) glutamic acid (Glu) and 20% (w/w) alanine (Ala), and MP with 20% (w/w) Glu and 20% (w/w) Ala. The results of the in vitro release test and the amount of rhBMP-2 remaining in the MPs after subcutaneous implantation into mice were compared among different samples. It was found that the addition of Glu accelerated release of rhBMP-2 effectively. Release was accelerated as the diameter of MP became smaller and the amount of Glu added increased. The amount of calcium formed in 3 weeks after subcutaneous implantation into mice was dose-dependent. The amount of calcium formed per unit rhBMP-2 dose tended to increase as the diameter of MP became smaller and the amount of Glu added became greater; calcification was thus associated with release rate. These results indicate that MPs with smaller diameters induce bone formation more efficiently. For use in the treatment of fracture, etc., MP is considered to be a suitable dosage form, which can be administered noninvasively.


Multifocal avascular necrosis after short-term high-dose steroid therapy. A report of three cases.
Avascular necrosis of bone is a well-recognised phenomenon in patients on long-term steroid therapy, especially after renal transplantation. There are only four cases reported in the literature of multifocal avascular necrosis after short-term high-dose steroid therapy, and three additional cases are reported in this paper. All the hips have needed reconstructive surgery within two and a half years of the onset of symptoms; in one patient, however, this has been prevented by other medical problems. In two of the three patients reported in this paper the shoulders also were affected; eventually they became pain-free but movement was restricted. Short-term high-dose steroid therapy has only recently been recognised as a cause of avascular necrosis and attempts should be made to prevent the incidence increasing.


DNA polymorphism of HLA class II genes in pauciarticular juvenile rheumatoid arthritis.
We investigated the DNA restriction fragment length polymorphism (RFLP) of the major histocompatibility complex (MHC) class II genes: HLA-DRB, -DQA, -DQB, DPA, and -DPB in 54 patients with pauciarticular juvenile rheumatoid arthritis (PJRA) and in healthy Danes. The frequencies of DNA fragments associated with the following HLA class II genes were increased in PJRA when compared to normal controls: DRB1*08 (DRw8) (35.2% vs 10.3%, RR = 4.6, p less than 10(-3), DRB3*01/02/03 (DRw52) (76.3% vs 48.1%, RR 3.5, p less than 10(-3)), DQA1*0401 (41.0% vs 7.4%, RR = 7.9, p less than 10(-3)), DQA1*0501 (55.6% vs 29.7%, RR = 3.0, p less than 10(-2), DQB1*0301 (DQw7) (46.2% vs 17.5%, RR = 4.0; p less than 10(-2)), DPA1*0201 (44.2% vs 7.9%, RR = 8.7, p less than 10(-5)), and DPB1*02 (DPw2) (40.7% vs 7.1%, RR = 8.5, p less than 10(-6)). The frequency of DRB1*11 was not significantly increased. The frequencies of DNA fragments associated with the following HLA class II genes were decreased in PJRA although not statistically significantly so after 'correction' of p values: DRB1*04 (14.8% vs 40.2%, RR = 0.27; p less than 10(-3)), DRB1*07 (0% vs 25.9%, RR = 0.04, p less than 10(-3)), DRB4*0101 (DRw53) (25.9% vs 53.6%, RR = 0.31, p less than 10(-3)), DQA1*0102 (11.6% vs 36.0%, RR = 0.25, p less than 10(-4)), and DQA1*0201 (2.6% vs 34.2%, RR = 0.05, p less than 10(-2)).(ABSTRACT TRUNCATED AT 250 WORDS)


DS86760016, a Leucyl-tRNA Synthetase Inhibitor with Activity against Pseudomonas aeruginosa.
DS86760016 is a new leucyl-tRNA-synthetase inhibitor at the preclinical development stage. DS86760016 showed potent activity against extended-spectrum multidrug-resistant Pseudomonas aeruginosa isolated from clinical samples and in vitro biofilms. In a murine catheter-associated urinary tract infection model, DS86760016 treatment resulted in significant eradication of P. aeruginosa from the kidney, bladder, and catheter without developing drug resistance. Our data suggest that DS86760016 has the potential to act as a new drug for the treatment of Pseudomonas infections.


Growth hormone and cortisol responses to psychological stress: comparison of normal and neurotic subjects.
The mirror drawing test (MDT) was performed to induce acute psychological stress in 9 normal controls and 10 neurotic subjects. Plasma growth hormone (GH) and cortisol were determined serially before, during, and after the test. In controls the MDT caused no significant change in plasma GH level, while in neurotics plasma GH increased progressively following the test. The increase of cortisol also tended to be greater in neurotics as a group, but there was considerable overlap in individual responses. The maximum increments of GH in neurotics correlated inversely with those of cortisol. The results indicate: 1) effective psychological coping mechanisms operate in normal man to keep the hormonal response minimum. 2) GH response is a more adequate indicator than cortisol response to psychological stress in neurotics. 3) GH and cortisol may have different psychological correlates in neurotics.


Formulation, characterisation and antibacterial activity of lemon myrtle and anise myrtle essential oil in water nanoemulsion.
This study focussed on the formulation, characterisation of lemon myrtle (LM) and anise myrtle (AM) essential oil (EO) in water nanoemulsion and their antibacterial activity. The required hydrophilic lipophilic balance (rHLB) value of LM EO and AM EO was 14 and 12, respectively. The Central Composite Rotatable Design (CCRD) model produces the smallest droplet size and polydispersity index (PDI) for LMEO (d ≈ 16.07 nm; PDI ≈ 0.209) and AMEO (d ≈ 30.23 nm; PDI ≈ 0.216) at 1% EO and 10% surfactant mixture (Smix) ratio using ultrasonication for 5 min. Whereas, increased in EO, decrease in Smix concentrations and ultrasonication time produces higher droplet size of nanoemulsions. LMEO (LM-15, LM-17) nanoemulsions was clear and transparent compared to AMEO (AM-15, AM-17). All the selected nanoemulsions showed good stability at 4, 25 and 40 °C during storage, except LM-15 at 40 °C. LMEO nanoemulsion showed enhanced antibacterial activity compared to LMEO alone (P < 0.05).


Agonist-induced modulation of agonist binding to alpha 1-adrenoceptors in bovine aorta.
Prolonged exposure of tissues to hormone agonists results in a subsequent reduction in the sensitivity of the tissue through a process known as desensitization. The desensitization response, either homologous or heterologous, has been shown to be correlated with receptor phosphorylation. Recently we have provided evidence that protein kinase C, when activated by a phorbol ester, regulates alpha 1-adrenoceptor coupling to a G-protein. In the present study, the effects of epinephrine (10 microM) pretreatment on the binding behavior of the alpha 1-adrenoceptor were determined from radioligand binding assays at 25 degrees and 2 degrees C. Pretreatment of tissues with epinephrine for 25 min moderately decreased [3H]prazosin binding by 12% (Bmax 121.5 fmol/mg) in comparison to control (139.3 fmol/mg) with no change in its affinity. The second consequence of desensitization by epinephrine is a decrease in the affinity of agonist binding to alpha 1-adrenoceptors associated with uncoupling of the receptors from the G-protein. In control membranes, at 25 degrees C, epinephrine defined two different affinity states of the receptor, viz. high affinity (KDH 16.5 nM, % RH 21) and low affinity (KDL 710 nM, % RL 79). The high affinity state formed at 25 degrees C is stabilized by forming a ternary complex with a G-protein. Addition of guanylylimidodiphosphate (Gpp(NH)p) reduced the stability of this complex resulting in a loss of high affinity sites in control membranes. On the other hand, epinephrine treated membranes exhibited only a single class of low affinity agonist binding (KDH 659 nM) and further, Gpp(NH)p had no significant effect on binding.(ABSTRACT TRUNCATED AT 250 WORDS)


Boosting innate immunity: development and validation of a cell-based screening assay to identify LL-37 inducers.
Innate immunity, the front line of our defence against pathogens, relies, to a great extent, on the production of antimicrobial peptides (AMPs). These peptides exhibit antimicrobial activity and immunomodulatory properties. In humans, AMPs include the defensins (α- and β-families) and the cathelicidin, LL-37. Bacterial resistance against antibiotics is a growing concern, and novel antimicrobial strategies are needed urgently. Hence, the concept of strengthening immune defences against infectious microbes by inducing AMP expression may represent novel or complementary pharmaceutical interventions in the treatment or prevention of infections. We have developed and validated a robust cell-based reporter assay for LL-37 expression, which serves as a marker for a healthy epithelial barrier. This reporter assay can be a powerful tool for high-throughput screenings. We first employed our assay to screen a panel of histone deacetylase inhibitors and derivatives, and then the Prestwick Chemical Library of Food and Drug Administration-approved compounds. After hit confirmation and independent validation in the parental cell line we identified five novel inducers of LL-37. This reporter assay will help to identify novel drug candidates for the treatment and prevention of infections. Importantly, the pattern of hits obtained may suggest cellular pathways and key mediators involved in the regulation of AMP expression.


Mitral valve annuloplasty with Carpentier-Edwards physio ring: mid-term results.
The mid-term results of mitral valve repair with the Carpentier-Edwards Physio annuloplasty ring were assessed in 97 consecutive patients in a single tertiary-referral cardiothoracic surgical center. The mean follow-up time was 3.9 years (range, 1 month to 8.9 years). Most patients were in functional class II and III before the operation. Ejection fraction was < 40% in 8 patients. Causes of mitral regurgitation included degenerative disease (66%), infective endocarditis (13.4%), rheumatic disease (10.3%), and ischemic heart disease (9.3%). Thirty-day mortality was 2.1%. Actuarial survival and freedom from re-operation at 8 years were 91% and 90.8%, respectively. The only significant risk factor for re-operation was residual mitral regurgitation. Four patients suffered thromboembolic complications, giving an overall event-free survival of 93% +/- 3.7% during the follow-up period. The Carpentier-Edwards Physio ring provides safe and effective repair of mitral regurgitation on mid-term follow-up.


Comparison of media and sampling locations for isolation of Listeria monocytogenes in queso fresco cheese.
Listeriosis associated with Hispanic-style soft cheese is an ongoing public health concern. Although rapid detection methods based on molecular and immunological technologies have been applied successfully for detecting Listeria monocytogenes in foods, obtaining isolates of the pathogen is a critical procedure for epidemiologic studies and regulatory analysis. Oxford agar, a medium recommended by the U.S. Food and Drug Administration Bacteriological Analytical Manual (BAM) to isolate L. monocytogenes from cheese, is unable to differentiate L. monocytogenes from other Listeria species. Hence, two selective isolation media, L. monocytogenes blood agar (LMBA) and Rapid 'L. mono agar (RLMA), were compared with Oxford agar for isolating L. monocytogenes from cheese. Queso fresco cheese was inoculated at 10(0) or 10(1) CFU/g with a five-strain mixture of L. monocytogenes or with the five-strain L. monocytogenes mixture and Listeria innocua. Cheese samples were stored at 21, 12, and 4 degrees C and Listeria counts were determined at 3, 7, and 10 days; 7, 10, 14, 21 days; and 2, 4, 8, and 12 weeks postinoculation, respectively. Surface and interior cheese samples as well as liquid exudate produced during storage were assayed individually to determine differences in Listeria contamination at different sampling locations. L. monocytogenes was more easily differentiated from L. innocua on RLMA than LMBA and Oxford agar. Similar L. monocytogenes counts (ca. 10(4) CFU/g) were obtained on the last sampling day on the surface and interior of cheese samples (P > 0.05) for all storage temperatures and both initial inoculation levels, but smaller cell numbers were detected in the exudate produced during storage. In addition, simultaneous inoculation of L. innocua with L. monocytogenes did not affect the final L. monocytogenes counts in the cheese. The amount of exudate released from the cheese and decrease of pH correlated with storage temperature. More exudate was produced and a greater decrease of pH occurred at 21 degrees C than at 12 or 4 degrees C. Our results indicate that RLMA is a suitable medium for isolating L. monocytogenes from queso fresco cheese. Higher counts of L. monocytogenes were obtained from surface and interior samples of cheese than from the exudate of the cheese during storage. In addition, pH may be a useful indicator of improperly stored queso fresco cheese.


Evaluating drug absorption after oral administration. Some problems and some solutions.
Quantitative assessment of drug absorption remains a difficult task, because the multiple-compartment disposition of a drug may not be obvious after oral administration (the problem of the vanishing exponential) and the macroconstants are indistinguishable. For these reasons, proper analysis of the drug absorption based on the apparent behavior of oral data without intravenous reference curve rarely provides absorption information useful for in vivo - in vitro correlations. When intravenous reference curve is available, compartment model used for analysis of the oral data should be corresponding to the iv data such as the Loo - Riegelman method. The model independent statistical moments method is one of the preferable alternatives because of its ease of computation and its potentially smaller error, if absorption can be assumed to be first-order.


Mechanisms of hormonal regulation of hepatic glucose metabolism.
Acute hormonal regulation of liver carbohydrate metabolism mainly involves changes in the cytosolic levels of cAMP and Ca2+. Epinephrine, acting through beta 2-adrenergic receptors, and glucagon activate adenylate cyclase in the liver plasma membrane through a mechanism involving a guanine nucleotide-binding protein that is stimulatory to the enzyme. The resulting accumulation of cAMP leads to activation of cAMP-dependent protein kinase, which, in turn, phosphorylates many intracellular enzymes involved in the regulation of glycogen metabolism, gluconeogenesis, and glycolysis. These are (1) phosphorylase b kinase, which is activated and, in turn, phosphorylates and activates phosphorylase, the rate-limiting enzyme for glycogen breakdown; (2) glycogen synthase, which is inactivated and is rate-controlling for glycogen synthesis; (3) pyruvate kinase, which is inactivated and is an important regulatory enzyme for glycolysis; and (4) the 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase bifunctional enzyme, phosphorylation of which leads to decreased formation of fructose 2,6-P2, which is an activator of 6-phosphofructo-1-kinase and an inhibitor of fructose 1,6-bisphosphatase, both of which are important regulatory enzymes for glycolysis and gluconeogenesis. In addition to rapid effects of glucagon and beta-adrenergic agonists to increase hepatic glucose output by stimulating glycogenolysis and gluconeogenesis and inhibiting glycogen synthesis and glycolysis, these agents produce longer-term stimulatory effects on gluconeogenesis through altered synthesis of certain enzymes of gluconeogenesis/glycolysis and amino acid metabolism. For example, P-enolpyruvate carboxykinase is induced through an effect at the level of transcription mediated by cAMP-dependent protein kinase. Tyrosine amino-transferase, serine dehydratase, tryptophan oxygenase, and glucokinase are also regulated by cAMP, in part at the level of specific messenger RNA synthesis. The sympathetic nervous system and its neurohumoral agonists epinephrine and norepinephrine also rapidly alter hepatic glycogen metabolism and gluconeogenesis acting through alpha 1-adrenergic receptors. The primary response to these agonists is the phosphodiesterase-mediated breakdown of the plasma membrane polyphosphoinositide phosphatidylinositol 4,5-P2 to inositol 1,4,5-P3 and 1,2-diacylglycerol. This involves a guanine nucleotide-binding protein that is different from those involved in the regulation of adenylate cyclase. Inositol 1,4,5-P3 acts as an intracellular messenger for Ca2+ mobilization by releasing Ca2+ from the endoplasmic reticulum.(ABSTRACT TRUNCATED AT 400 WORDS)


Fast transmission CT for determining attenuation maps using a collimated line source, rotatable air-copper-lead attenuators and fan-beam collimation.
We describe a technique using a line source and a rotatable air-copper-lead assembly to acquire gamma transmission computed tomographic (TCT) data for determining attenuation maps to compensate SPECT emission scans. The technique minimizes problems associated with discriminating 99mTc transmission and 201Tl emission photons and requires only a modest increase in total study time. A 99mTc line source and a stacked foil ("multislat") collimator are placed near the focal line of a fan-beam collimator (114 cm focal length) mounted on one detector of a triple-camera SPECT system. We acquired TCT data of plastic rod and anthropomorphic thorax phantoms to investigate the capability of the line source and rotatable air-copper-lead attenuators to determine attenuation maps. The data were acquired with and without 5.4 MBq (145 microCi) of 201Tl placed in the myocardial chamber of the thorax phantom. Phantoms also were scanned using a curved transmission slab source mounted to a parallel-hole collimator. Fan-beam TCT images have improved resolution compared with parallel-beam TCT images. Two patient scans also were performed to evaluate the clinical usefulness of fan-beam TCT. The rotatable air-copper-lead attenuator method eliminates contamination of emission data by transmission photons and reduces spill-over of emission data into the transmission energy window for some cases. Results show the feasibility of using fast, sequential or interlaced transmission scans of a line source within a rotatable air-copper-lead attenuator assembly to obtain accurate attenuation maps for SPECT attenuation compensation.


Daylight photodynamic therapy with methyl aminolaevulinate in patients with actinic keratoses: a preliminary experience in Southern Italy.
Daylight photodynamic therapy (D-PDT) is a novel modality of PDT in which the activation of the topical photosensitizer is mediated by the exposure to daylight instead of artificial light sources without the need of preliminary occlusion. This simplified modality has been found to be well tolerated. We report our experience with D-PDT in patients with actinic keratoses (AK). The data relative to 53 patients consecutively treated for AK with a single session of D-PDT using methyl aminolaevulinate cream were retrospectively reviewed. Most patients had grade I and/or II AK on the face and/or the scalp. Some patients had additional cutaneous lesions, including non-melanoma skin cancers, in the AK-associated field, that were simultaneously treated with D-PDT. At 3 months, a complete response (AK number=0) was achieved by 54.7% of patients, and the lesion clearance rate was 82.7%. Treatment was more effective in thinner lesions, with complete clearance involving 93% of grade I AK. At 6-9 months after treatment, response was maintained in 85.7% of the lesions previously cleared, and 72.4% of the initial complete responders did not relapse. No relevant effect of D-PDT was instead observed on senile lentigo, nodular basal cell carcinoma and squamous cell carcinoma, whereas a complete response was seen in 7 of the 9 superficial basal cell carcinomas treated. Local skin reactions mostly consisted in slight erythema. Mild symptoms (burning and tingling sensations) were reported by 12 patients. These preliminary results support the favorable efficacy and tolerability profile of D-PDT, which seems to be an interesting, valid, and convenient therapeutic option for AK, and possibly also for superficial basal cell carcinomas.


Lactogenic hormone and cell type-specific control of the whey acidic protein gene promoter in transfected mouse cells.
The whey acidic protein (WAP) is a major milk protein. It is abundantly expressed in mammary epithelial cells, and its gene is controlled by lactogenic hormones. The identification of regulatory cis-acting sequences of the mouse WAP gene was so far dependent on the analysis of transgenic animals. We report here the possibility of analyzing regulatory sequences by gene transfer experiments using the lactogenic hormone-dependent mammary epithelial cell line HC11. A WAP-chloramphenicol acetyltransferase construct containing 2.5 kilobases of the 5'-flanking sequence of the WAP gene was stably transfected into HC11 cells. High chloramphenicol acetyltransferase activity was induced in pools of transfected cells cultured in the presence of the lactogenic hormones glucocorticoid, PRL, and insulin. A lower induction was observed by glucocorticoid hormone alone. PRL by itself was not able to induce the WAP gene promoter above the level observed in the absence of lactogenic hormones. A time course of hormone induction showed a weak initial response with a steady increase over at least 4 days of hormone treatment. Induction was not observable in the mammary epithelial cell line NOG-8 and NIH3T3 fibroblasts, despite the presence of functional glucocorticoid receptor in these cells. This indicates the requirement for a cell type-specific transcription factor present in the mammary epithelial cell line HC11, but not in NOG-8 epithelial cells or NIH3T3 fibroblasts.(ABSTRACT TRUNCATED AT 250 WORDS)


European position paper on polypharmacy and fall-risk-increasing drugs recommendations in the World Guidelines for Falls Prevention and Management: implications and implementation.
Falls prevention and management in older adults is a critical global challenge. One of the key risk factors for falls is the use of certain medications. Therefore, to prevent medication-related falls, the following is recommended in the recent World Guidelines for Falls Prevention and Management: (1) assess for fall history and the risk of falls before prescribing potential fall-risk-increasing drugs (FRIDs), (2) use a validated, structured screening and assessment tool to identify FRIDs when performing a medication review, (3) include medication review and appropriate deprescribing of FRIDs as a part of the multifactorial falls prevention intervention, and (4) in long-term care residents, if multifactorial intervention cannot be conducted due to limited resources, the falls prevention strategy should still always include deprescribing of FRIDs.In the present statement paper, the working group on medication-related falls of the World Guidelines for Falls Prevention and Management, in collaboration with the European Geriatric Medicine Society (EuGMS) Task and Finish group on FRIDs, outlines its position on how to implement and execute these recommendations in clinical practice.Preferably, the medication review should be conducted as part of a comprehensive geriatric assessment to produce a personalized and patient-centered assessment. Furthermore, the major pitfall of the published intervention studies so far is the suboptimal implementation of medication review and deprescribing. For the future, it is important to focus on gaining which elements determine successful implementation and apply the concepts of implementation science to decrease the gap between research and practice.


Induction of thymidine phosphorylase activity and enhancement of capecitabine efficacy by taxol/taxotere in human cancer xenografts.
Thymidine phosphorylase (dThdPase) is an essential enzyme for the activation of the cytostatics capecitabine (N(4)-pentyloxycarbonyl-5'-deoxy-5-fluorocytidine) and its intermediate metabolite [5'-deoxy-5-fluorouridine (5'-dFUrd)] to 5-fluorouracil in tumors. We have tried to identify the best partners of capecitabine in combination therapy, such as dThdPase up-regulators, which may enhance the efficacy of this compound. Among various cytostatics studied with the WiDr human colon cancer xenograft model, Taxol, Taxotere, and mitomycin C greatly increased levels of human dThdPase in tumors, and cyclophosphamide slightly increased the enzyme level. These cytostatics simultaneously increased the levels of human tumor necrosis factor alpha (TNFalpha), which is an up-regulator of dThdPase. In cultures of the WiDr cells, however, Taxol did not up-regulate TNFalpha to a detectable level and only slightly enhanced levels of dThdPase. These results suggest that Taxol might indirectly elevate TNFalpha in tumor cells, which in turn up-regulated dThdPase in the tumor cells in the WiDr cancer xenograft. In the combination therapy, the efficacy of Taxol and Taxotere with either capecitabine or 5'-dFUrd was more than just additive. In contrast, Taxol and either 5-fluorouracil or UFT (a mixture of tegafur and uracil) in combination showed only additive activity. Taxol and Taxotere might enhance the efficacy of capecitabine and 5'-dFUrd, probably by modulating dThdPase activity in tumor tissues.


Screening of hepatoprotective effect of a herbal mixture against CCl4 induced hepatotoxicity in Swiss albino mice.
The hepatoprotective potential of a herbal mixture was evaluated against CCl4 induced liver injury in Swiss albino mice. Liv 52, a commercially available polyherbal hepatoprotective drug was evaluated for comparison. The potential toxicity of the above herbal hepatoprotective agents was also compared. It was observed that there was a reduction in the enzyme biomarkers (Aspartate and Alanine Transaminase) of liver injury in the herbal mixture treated groups, which was similar to the reduction initiated by Liv 52. An increase in glutathione was observed in the herbal mixture treated groups and it was assumed that the herbal mixture protects the liver by virtue of its antioxidant nature along with high regeneration initiation potential. From the study it is also concluded that the herbal mixture is safer than Liv 52.


On the role of unmutated antigens in tumor rejection in mice with unperturbed T-cell repertoires.
We investigate here whether P1A, which was the first CTL-recognized and unmutated tumor antigen to be identified, is a tumor rejection antigen for J558 plasmacytoma in mice with an unperturbed T-cell repertoire. We show that although transgenic mice expressing P1A in the thymus have almost complete deletion of P1A-reactive T cells, they reject the B7-1-transfected J558 at a rate comparable with wild-type mice. Thus, P1A is not a necessary tumor rejection antigen for the J558 tumor cells. On the other hand, if anti-P1A CTL response is sufficient for tumor rejection, tumor cells must lose the antigenic epitope to evade CTL destruction. To test this, we analyze whether tumor cells escaping J558-B7 immune spleen cells harbor mutations in the P1A epitope. We find that although the spleen contained a high proportion of P1A-reactive T cells, the recurrent tumor cells have no mutation in the P1A antigenic epitope and remain susceptible to lysis by P1CTL. Thus, the antigen-bearing tumor cells can evade immune destruction in the presence of a high number of P1A-reactive T cells. Taken together, our results demonstrate that in mice with a normal TCR repertoire, substantial numbers of P1A-reactive T cells are neither necessary nor sufficient for tumor rejection and raise interesting questions regarding the significance of T-cell response against unmutated tumor antigens.


Intestinal absorption of pallidifloside D are limited by P-glycoprotein in mice.
1. Pallidifloside D, a saponin glycoside constituent from the total saponins of Smilax riparia, had been proved to be very effective in hyperuricemic control. But it is poorly bioavailable after oral administration. Here, we determined the role of P-glycoprotein (P-gp) in the intestinal absorption of Pallidifloside D. 2. We found that Pallidifloside D significantly stimulated P-gp ATPase activity in vitro ATPase assay with a small EC50 value of 0.46 μM. 3. In the single-pass perfused mouse intestine model, the absorption of Pallidifloside D was not favored in the small intestine (duodenum, jejunum and ileum) with a P*w value of 0.35-0.78. By contrast, this compound was well-absorbed in the colon with a P*w value of 1.23. The P-gp inhibitors cyclosporine significantly enhanced Pallidifloside D absorption in all four intestinal segments (duodenum, jejunum, ileum and colon) and the fold change ranged from 5.5 to 15.3. Pharmacokinetic study revealed that cyclosporine increased the systemic exposure of Pallidifloside D by a 2.5-fold after oral administration. 4. These results suggest that P-gp-mediated efflux is a limiting factor for intestinal absorption of Pallidifloside D in mice.


Neuroendocrine tumor imaging with 68Ga-DOTA-NOC: physiologic and benign variants.
Imaging with (68)Ga-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-octreotide analogs has become an important modality in patients with neuroendocrine tumors (NETs). In addition to high uptake in NET lesions, prominent physiologic radiotracer activity has been reported in the pituitary gland, pancreas, adrenal glands, liver, and spleen, and faint activity has been reported in the thyroid and gastrointestinal tract. This article describes previously unknown sites of 68Ga-DOTA-1-NaI3-octreotide (NOC) uptake unrelated to NETs. One hundred eighty-two patients (96 female and 86 male patients; age range, 4-89 years) with documented (n=156) or suspected (n=26) NETs underwent 207 68Ga-DOTA-NOC PET/CT studies. Studies were retrospectively reviewed for the presence, intensity, and localization of foci of increased uptake that were further correlated with findings on additional imaging studies and clinical follow-up for a period of 4-32 months. Uptake of 68Ga-DOTA-NOC not identified as NET or known physiologic activity was detected in 297 sites with confirmation in 149 of 207 studies (72%). The most common location of non-NET-related 68Ga-DOTA-NOC-avid sites was in small lymph nodes, followed by prostate, uterus, breasts, lungs, brown fat, musculoskeletal system, and other sites, including oropharynx, pineal body, thymus, aortic plaque, genitalia, surgical bed, and subcutaneous granuloma. Intensity of uptake in non-NET-related 68Ga-DOTA-NOC-avid sites ranged in maximum standardized uptake value from 0.8 to 10.5. Previously unreported benign sites of 68Ga-DOTA-NOC uptake were found in the majority of studies, suggesting the presence of somatostatin receptors in physiologic variants or processes with no evidence of tumor. Knowledge of increased tracer uptake in non-NET-related sites is important for accurate interpretation and for avoiding potential pitfalls of 68Ga-DOTA-NOC PET/CT.


Dynamic-template-directed multiscale assembly for large-area coating of highly-aligned conjugated polymer thin films.
Solution processable semiconducting polymers have been under intense investigations due to their diverse applications from printed electronics to biomedical devices. However, controlling the macromolecular assembly across length scales during solution coating remains a key challenge, largely due to the disparity in timescales of polymer assembly and high-throughput printing/coating. Herein we propose the concept of dynamic templating to expedite polymer nucleation and the ensuing assembly process, inspired by biomineralization templates capable of surface reconfiguration. Molecular dynamic simulations reveal that surface reconfigurability is key to promoting template-polymer interactions, thereby lowering polymer nucleation barrier. Employing ionic-liquid-based dynamic template during meniscus-guided coating results in highly aligned, highly crystalline donor-acceptor polymer thin films over large area (>1 cm2) and promoted charge transport along both the polymer backbone and the π-π stacking direction in field-effect transistors. We further demonstrate that the charge transport anisotropy can be reversed by tuning the degree of polymer backbone alignment.


Catalytic mechanism in cyclic voltammetry at disc electrodes: an analytical solution.
The theory of cyclic voltammetry at disc electrodes and microelectrodes is developed for a system where the electroactive reactant is regenerated in solution using a catalyst. This catalytic process is of wide importance, not least in chemical sensing, and it can be characterized by the resulting peak current which is always larger than that of a simple electrochemical reaction; in contrast the reverse peak is always relatively diminished in size. From the theoretical point of view, the problem involves a complex physical situation with two-dimensional mass transport and non-uniform surface gradients. Because of this complexity, hitherto the treatment of this problem has been tackled mainly by means of numerical methods and so no analytical expression was available for the transient response of the catalytic mechanism in cyclic voltammetry when disc electrodes, the most popular practical geometry, are used. In this work, this gap is filled by presenting an analytical solution for the application of any sequence of potential pulses and, in particular, for cyclic voltammetry. The induction principle is applied to demonstrate mathematically that the superposition principle applies whatever the geometry of the electrode, which enabled us to obtain an analytical equation valid whatever the electrode size and the kinetics of the catalytic reaction. The theoretical results obtained are applied to the experimental study of the electrocatalytic Fenton reaction, determining the rate constant of the reduction of hydrogen peroxide by iron(II).


Theoretical and experimental examination of near-field acoustic levitation.
A planar object can be levitated stably close to a piston sound source by making use of acoustic radiation pressure. This phenomenon is called near-field acoustic levitation [Y. Hashimoto et al., J. Acoust. Soc. Am. 100, 2057-2061 (1996)]. In the present article, the levitation distance is predicted theoretically by numerically solving basic equations in a compressible viscous fluid subject to the appropriate initial and boundary conditions. Additionally, experiments are carried out using a 19.5-kHz piston source with a 40-mm aperture and various aluminum disks of different sizes. The measured levitation distance agrees well with the theory, which is different from a conventional theory, and the levitation distance is not inversely proportional to the square root of the surface density of the levitated disk in a strict sense.


Exploring the role of locomotor sensitization in the circadian food entrainment pathway.
Food entrainment is the internal mechanism whereby the phase and period of circadian clock genes comes under the control of daily scheduled food availability. Food entrainment allows the body to efficiently realign the internal timing of behavioral and physiological functions such that they anticipate food intake. Food entrainment can occur with or without caloric restriction, as seen with daily schedules of restricted feeding (RF) or restricted treat (RT) that restrict food or treat intake to a single feeding time. However, the extent of clock gene control is more pronounced with caloric restriction, highlighting the role of energy balance in regulating clock genes. Recent studies have implicated dopamine (DA) to be involved in food entrainment and caloric restriction is known to affect dopaminergic pathways to enhance locomotor activity. Since food entrainment results in the development of a distinct behavioral component, called food anticipatory activity (FAA), we examined the role of locomotor sensitization (LS) in food entrainment by 1) observing whether amphetamine (AMPH) sensitization results in enhanced locomotor output of FAA and 2) measuring LS of circadian and non-circadian feeding paradigms to an acute injection of AMPH (AMPH cross-sensitization). Unexpectedly, AMPH sensitization did not show enhancement of FAA. On the contrary, LS did develop with sufficient exposure to RF. LS was present after 2 weeks of RF, but not after 1, 3 or 7 days into RF. When food was returned and rats regain their original body weight at 10-15 days post-RF, LS remained present. LS did not develop to RT, nor to feedings of a non-circadian schedule, e.g. variable restricted feeding (VRF) or variable RT (VRT). Further, when RF was timed to the dark period, LS was observed only when tested at night; RF timed to the light period resulted in LS that was present during day and night. Taken together our results show that LS develops with food entrainment to RF, an effect that is dependent on the chronicity and circadian phase of RF but independent of body weight. Given that LS involves reorganization of DA-regulated motor circuitry, our work provides indirect support for the role of DA in the food entrainment pathway of RF. The findings also suggest differences in neuronal pathways involved in LS from AMPH sensitization and LS from RF.


Impact of Spanish-language information sessions on Spanish-speaking patients seeking bariatric surgery.
Bariatric centers frequently provide preoperative educational programs to inform patients about the risks and benefits of weight loss surgery. However, most programs are conducted in English, which may create barriers to effective treatment and access to care for non-English speaking populations. To address this concern, we instituted a comprehensive Spanish-language education program consisting of preoperative information and group nutrition classes conducted entirely in, and supported with Spanish-language materials. The primary aim was to examine the effect of this intervention on Spanish-speaking patients' decision to undergo surgery in a pilot study. University Hospital/Community Health Center, United States. Three cohorts of patients seeking bariatric surgery between January 1, 2011 and March 31, 2012 were identified: 1) primary English speakers attending English-language programs ("English-English"); 2) primary Spanish speakers attending Spanish-language programs ("Spanish-Spanish"); and 3) primary Spanish speakers attending English-speaking programs with the assistance of a Spanish-to-English translator ("Spanish-English"). 26% of the English-English cohort ultimately underwent surgery compared with only 12% of the Spanish-Spanish cohort (P = .009). Compared with the English-English group, time to surgery was 35 days longer for the Spanish-Spanish and 185 days longer for the Spanish-English group (both P< .001). Spanish-speaking patients were less likely to undergo bariatric surgery regardless of the language in which educational sessions are provided. For those choosing surgery, providing Spanish-language sessions can shorten time to surgery. A barrier to effective obesity treatment may exist for Spanish speakers, which may be only partially overcome by providing support in Spanish.


An extension of the rigorous base-unit oriented description of nucleic acid structures.
Our proposed description for DNA base/base-pair structures (1), though rigorous, does not satisfy some of the requirements as established at the Cambridge Workshop (2). Here, we propose a revised description for base/base-unit structures of nucleic acids. This new description is as rigorous and satisfies all the requirements (2). Following the original approach, the moment-of-inertia frame is still the choice of the internal coordinate system for a base/base-unit. The revised description has the minimum number of parameters (i.e., six parameters per rigid body) in the set. Besides regular Watson-Crick type of helices (e.g., A-DNA, A-RNA, B-DNA, Z-DNA, etc.), the revised description also works for non-Watson-Crick, multiple stranded molecules (e.g., triplex, quadruplex, etc.) as well as parallel stranded molecules.


Impact of a modified data capture period on Liu comorbidity index scores in Medicare enrollees initiating chronic dialysis.
The Liu Comorbidity Index uses the United States Renal Data System (USRDS) to quantify comorbidity in chronic dialysis patients, capturing baseline comorbidities from days 91 through 270 after dialysis initiation. The 270 day survival requirement results in sample size reductions and potential survivor bias. An earlier and shorter time-frame for data capture could be beneficial, if sufficiently similar comorbidity information could be ascertained. USRDS data were used in a retrospective observational study of 70,114 Medicare- and Medicaid-eligible persons who initiated chronic dialysis during the years 2000-2005. The Liu index was modified by changing the baseline comorbidity capture period to days 1-90 after dialysis initiation for persons continuously enrolled in Medicare. The scores resulting from the original and the modified comorbidity indices were compared, and the impact on sample size was calculated. The original Liu comorbidity index could be calculated for 75% of the sample, but the remaining 25% did not survive to 270 days. Among 52,937 individuals for whom both scores could be calculated, the mean scores for the original and the modified index were 7.4 ± 4.0 and 6.4 ± 3.6 points, respectively, on a 24-point scale. The most commonly calculated difference between scores was zero, occurring in 44% of patients. Greater comorbidity was found in those who died before 270 days. A modified version of the Liu comorbidity index captures the majority of comorbidity in persons who are Medicare-enrolled at the time of chronic dialysis initiation. This modification reduces sample size losses and facilitates inclusion of a sicker portion of the population in whom early mortality is common.


Role of protriptyline and acetazolamide in the sleep apnea/hypopnea syndrome.
The role of drug therapy in the treatment of the sleep apnea/hypopnea syndrome is unclear. In a randomised, double-blind, placebo-controlled study, we investigated the value of 14-day therapy with protriptyline (20 mg daily) or acetazolamide (250 mg 4 times per day) on symptoms and on the frequency of apneas, hypopneas, arousals, and 4% desaturations in 10 patients with obstructive sleep apnea/hypopnea syndrome. Overall, protriptyline did not have a significant effect either on symptoms or on any of the above polysomnographic criteria. Acetazolamide reduced the apnea/hypopnea frequency [placebo 50 +/- 26 (SD); acetazolamide 26 +/- 20/h of sleep, p less than 0.03] and tended to decrease the frequency of 4% desaturations (placebo 29 +/- 20; acetazolamide 19 +/- 16/h of sleep, p = 0.06). Despite these physiological improvements, acetazolamide did not significantly improve symptoms and paraesthesiae were common. Contrary to earlier studies, we conclude that protriptyline may have a limited role in the treatment of the sleep apnea syndrome. The reason why acetazolamide produced a physiological, but not a symptomatic, response requires further investigation.


Theoretical Studies of the Gas-Phase Reactions of S-Methyl Methanesulfinothioate (Dimethyl Thiosulfinate) with OH and Cl Radicals: Reaction Mechanisms, Energetics, and Kinetics.
The mechanisms, energetics, and kinetics of the gas-phase reactions of terrestrial plant-derived dimethyl thiosulfinate (DMTS) with the atmospheric oxidants OH and Cl radicals were investigated using high-level ab initio calculations. The results show that the addition of OH and Cl radicals to the sulfinyl [-S(═O)] of DMTS, followed by S(═O)-S single bond cleavage to form methanesulfinic acid + CH3S• and methanesulfinyl chloride + CH3S•, respectively, are the more dominant reactions. The barrier heights for the reactions with OH and Cl radicals were found to be -5.6 and -12.7 kcal/mol relative to the energies of the starting reactants, respectively, when computed at the CCSD(T)/aug-cc-pVTZ//M06-2X/6-311++G(3df,3pd) level of theory. The rate constants for all possible pathways of DMTS + •OH/•Cl reactions were investigated using the MESMER kinetics code over the temperature range between 200 and 300 K. The calculated global rate constants for the DMTS + •OH and DMTS + •Cl reactions at 300 K were found to be 1.42 × 10-11 and 3.72 × 10-11 cm3 molecule-1 s-1, respectively. In addition, the thermochemistry of all possible paths and branching ratios was determined. The atmospheric chemistry implications of the DMTS + •OH/•Cl reactions are discussed.


[A variety of mediastinal bronchogenic cyst: the broncho-alveolar cyst].
Congenital bronchogenic cysts are usually located in the mediastinum or develop as intrapulmonary cysts. Gross examination of excised bronchogenic cysts shows them to be unilocular; histologically, these lesions are characterized by the presence of respiratory-type pseudostratified epithelium as well as small islands of cartilage and seromucinous glands. We report a case of a mediastinal bronchogenic cyst having pulmonary parenchyma within the cyst wall. The rarity of our case, the pathological and clinical features and the embryological development of bronchogenic cysts are briefly discussed.


Zein based magnesium oxide nanoparticles: Assessment of antimicrobial activity for dental implications.
MgO nanoparticles have been recently discovered as an antibacterial, however, they limited by property degradation due to agglomeration. The addition of a coating agent, such as a zein polymer, is effective in preventing agglomeration without affecting nanosized properties. The aim of this study was to assess the antimicrobial property of MgO nanoparticles when coated with a zein polymer against several oral bacteria and fungi. This was done by utilizing various assessment techniques. The ultimate aim is to use these nanoparticles in dental preparations. The antimicrobial activity of zein-coated MgO nanoparticles at different concentrations of 0.5, 1 and 2% were tested against four different microorganisms: Staphylococcus aureus, Streptococcus mutans and Enterococcus faecalis (gram positive bacteria), and Candida albicans (as oral fungus). Two different techniques were utilized: the Kirby-Bauer test, and a modified direct contact test. The results indicated that the antibacterial effect of 1% or 2% zein-coated MgO nanowires were statistically significant (p<0.05) against the four organisms studied: S. mutans, S. aureus, E. faecalis and C. albicans. Zein-coated MgO nanoparticles are a new human friendly and potent antimicrobial agent that can be incorporated in the formulation of a variety of new dental materials and products that should provide improvements in dental care and oral health.


[Need for occupational and environmental allergology in occupational health - the 45th Japanese society of Occupational and Environmental Allergy Annual Meeting 2014 in Fukuoka].
The 45th Japanese Society of Occupational and Environmental Allergy (OEA) Annual Meeting 2014 was held in Fukuoka city in conjunction with a technical course for occupational health physicians to learn occupational and environmental diseases more deeply. Allergic reaction due to low concentrations of chemical and biological materials is important in toxicological diseases due to highly concentrated chemical materials in the field of occupational and environmental medicine. In this paper we describe the activities of the OEA, which was established in 1970 and has completely cured patients with severe occupational asthma, such as the regional Konjac asthma in Gunma prefecture and Sea Squirt asthma in Hiroshima prefecture. Regard for the occupational environment will prevent the onset and/or exacerbation of allergic occupational disease in individual employees with allergy. Occupational cancer of the bile duct and asbestosis are also current, serious issues that should be resolved as soon as possible. It is desirable for the occupational health physician to have a large stock of knowledge about toxicological and allergic diseases in various occupational settings to maintain the health and safety of workers.


Involvement of calpain in osteoclastic bone resorption.
There is increasing evidence that calpain contributes to the reorganization of the cytoskeleton in the integrin-mediated signaling pathway. Osteoclastic bone resorption requires cell-matrix contact, an event mediated by integrin alphavbeta3, and subsequent cytoskeletal reorganization to form characteristic membrane domains such as the sealing zone and ruffled border. In this study, therefore, we investigated whether calpain is involved in osteoclastic bone resorption. Membrane-permeable calpain inhibitors suppress the resorption activity of human osteoclasts, but an impermeable inhibitor does not. Upon the attachment of osteoclasts to bone, micro-calpain is translocated from the cytosolic to the cytoskeletal fraction and is autolytically activated. Both the activation of micro-calpain and the formation of actin-rings, the cytoskeletal structures essential for bone resorption, are inhibited by membrane-permeable calpain inhibitors. The activated micro-calpain in osteoclasts selectively cleaves talin, which links the matrix-recognizing integrin to the actin cytoskeleton. These findings suggest that calpain is a regulator of the bone resorption activity of osteoclasts through reorganization of the cytoskeleton related to actin-ring formation.


Ethanol prevents oxidant-induced mitochondrial permeability transition pore opening in cardiac cells.
The purpose of this study was to determine if ethanol prevents the mitochondrial permeability transition pore (mPTP) opening via glycogen synthase kinase 3beta (GSK-3beta). Cardiac H9c2 cells were exposed to ethanol (10-1000 microM) for 20 min. GSK-3beta activity was determined by measuring its phosphorylation at Ser(9). Mitochondrial membrane potential (DeltaPsi(m)) was assessed by imaging (confocal microscopy) H9c2 cells loaded with tetramethylrhodamine ethyl ester (TMRE). To activate GSK-3beta, cells were transfected with constitutively active GSK-3beta (GSK-3beta-S9A-HA) mutant plasmid. Treatment of cardiac cells with low doses of ethanol (10-500 microM) significantly enhanced GSK-3beta phosphorylation, indicating that ethanol can inactivate GSK-3beta in H9c2 cells. The effect of ethanol on GSK-3beta activity was reversed by the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 and ethanol could enhance Akt phosphorylation, implying that the PI3K/Akt pathway accounts for the action of ethanol. Ethanol prevented oxidant (H(2)O(2))-induced loss DeltaPsi(m), an effect that was reversed by LY294002, indicating that ethanol can modulate the mPTP opening caused by oxidant stress through the PI3K/Akt pathway. Ethanol failed to preserve DeltaPsi(m) in cells transfected with the constitutively active GSK-3beta (GSK-3beta-S9A-HA) mutant, suggesting that ethanol prevents the mPTP opening by inactivating GSK-3beta. These data suggest that ethanol prevents the mPTP opening through inactivation of GSK-3beta. The PI3K/Akt signaling pathway is responsible for inactivation of GSK-3beta by ethanol.


[Fractures of the clavicle: classification, diagnosis, therapy].
Clavicular fracture is one of the most frequent skeletal lesions. In most cases the median third of the clavicula is affected (this is due to the peculiar biomechanical structure). Accompanying lesions and complications of clavicular fractures are rare. A total of 13 x-ray diagnostic techniques are described for clavicular fractures. X-ray film should, as a matter of principle, always be taken in two planes. Definitely the major part of clavicular fractures are treated conservatively (rucksack dressing), whereas surgery is reserved for few and strictly defined indications.


Baseline peripheral blood mononuclear cell (PBMC) transcriptomics before ustekinumab treatment is linked with Crohn Disease clinical response at 1 year.
Ustekinumab (Stelara), a monoclonal antibody to the p40 subunit of interleukin-12 and interleukin-23, is used for Crohn Disease (CD), and the documented clinical remission rate after one year was observed in about 50% of patients. We aimed to identify predictors for a clinical response using peripheral blood obtained from CD patients just before ustekinumab treatment initiation. RNA extraction from peripheral blood mononuclear cells (PBMC) was followed by mRNA paired-end sequencing. Differential gene expression was performed using DESeq2. We processed samples from 36 adults with CD (13 males, 36%) obtained at baseline before starting ustekinumab treatment. 22/36 (61%) were defined as responders and 14/36 (39%) as non-responders after one year based on Physician Global Assessment (PGA). Differential gene expression between responders (n=22) and non-responders (n=14) did not show a gene expression signature that passed false discovery rate (FDR) correction. However, the analyses identified 68 genes, including CXCL1/2/3, that were induced in non-responders vs. responders with p<0.05 and fold change above 1.5. Functional annotation enrichments of these 68 genes using ToppGene indicated enrichment for cytokine activity (FDR=1.98E-05), CXCR chemokine receptor binding (FDR=2.11E-05), Interleukin-10 signaling (FDR=5.03E-07), Genes encoding secreted soluble factors (FDR=1.73E-05), and Myeloid Dendritic cells (FDR=1.80E-08). No substantial differences were found in PBMC transcriptomics between responders and non-responders. However, among the non-responders, we noted an increased inflammatory response enriched for pathways linked with cytokine activity and chemokine receptor binding, and innate myeloid signature. A larger cohort is required to validate and further explore these findings.


Activation of the aryl hydrocarbon receptor by methyl yellow and related congeners: structure-activity relationships in halogenated derivatives.
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates the biological action of many environmental compounds. Methyl yellow (4-dimethylaminoazobenzene; MY) is a principal azo-dye, and structurally related compounds were subjected to analysis of structure-activity relationships as AhR ligands by using a yeast AhR signaling assay. The effects of halogen-substitution among 23 halogenated MYs on the AhR ligand activity can be summarized as follows: enhancement by halogen-substitution at the ortho-position (2'- and 6'-position), and reduction by substitution at the para-position (4'-position). The greatest enhancement of the ligand activity was observed in 2',6'-dichlorinated MY (13.5-fold of MY), and its AhR ligand activity was very close to that of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the present assay system. In the study of compounds structurally related to MY, benzanilide (BA) showed almost the same AhR ligand activity as azobenzene and trans-stilbene. Furthermore, 4'-chlorobenzanilide, in which the length of the molecule is similar to that of MY, enhanced the AhR ligand activity by ortho(2')-chlorine-substitution, and the AhR ligand activity of 2',4'-dichlorobenzanilide was similar to that of 2'-chloro-MY. These results suggest that the amide bond is equivalent to the -N=N- or -CH=CH- double bond for recognition as the ligand by AhR in 1,2-diphenyl-1,2-ene derivatives.