Decrease of rat-liver-T4-5'-deiodinase activity during chronical isoprenaline beta-action in vivo.
Pure adrenergic beta-action, brought about by long-term adrenaline + regitine application in rats, was able to increase liver T4-5'-deiodinase activity for 8 h (Nauman et al. 1984a). Long-term isoprenaline application without alpha-blocking yielded contrary results. One of the compensatory mechanism to be probably blamed could have been the very high endogenous adrenaline-levels (Porta et al. 1985). Simultaneous treatment with isoprenaline and alpha-methyltyrosinemethylester did not settle the problem since even then deiodinase activity was still drastically decreased. Two more components have been found which could very well be the reason for that "paradox beta-action" in vivo, namely very low glucose and insulin levels, both of which are known to influence deiodinase activity. In vivo--contrary to in vitro--it is seemingly not possible that catecholaminergic beta-action could increase the peripheral production of T3 unless general alpha-blocking took place.


Circulating tumour DNA reflects treatment response and clonal evolution in chronic lymphocytic leukaemia.
Several novel therapeutics are poised to change the natural history of chronic lymphocytic leukaemia (CLL) and the increasing use of these therapies has highlighted limitations of traditional disease monitoring methods. Here we demonstrate that circulating tumour DNA (ctDNA) is readily detectable in patients with CLL. Importantly, ctDNA does not simply mirror the genomic information contained within circulating malignant lymphocytes but instead parallels changes across different disease compartments following treatment with novel therapies. Serial ctDNA analysis allows clonal dynamics to be monitored over time and identifies the emergence of genomic changes associated with Richter's syndrome (RS). In addition to conventional disease monitoring, ctDNA provides a unique opportunity for non-invasive serial analysis of CLL for molecular disease monitoring.


Sacrificial Mechanical Bond is as Effective as a Sacrificial Covalent Bond in Increasing Cross-Linked Polymer Toughness.
Sacrificial chemical bonds have been used effectively to increase the toughness of elastomers because such bonds dissociate at forces significantly below the fracture limit of the primary load-bearing bonds, thereby dissipating local stress. This approach owes much of its success to the ability to adjust the threshold force at which the sacrificial bonds fail at the desired rate, for example, by selecting either covalent or noncovalent sacrificial bonds. Here, we report experimental and computational evidence that a mechanical bond, responsible for the structural integrity of a rotaxane or a catenane, increases the elastomer's fracture strain, stress, and energy as much as a covalent bond of comparable mechanochemical dissociation kinetics. We synthesized and studied 6 polyacrylates cross-linked by either difluorenylsuccinonitrile (DFSN), which is an established sacrificial mechanochromic moiety; a [2]rotaxane, whose stopper allows its wheel to dethread on the same subsecond time scale as DFSN dissociates when either is under tensile force of 1.5-2 nN; a structurally homologous [2]rotaxane with a much bulkier stopper that is stable at force >5.5 nN; similarly stoppered [3]rotaxanes containing DFSN in their axles; and a control polymer with aliphatic nonsacrificial cross-links. Our data suggest that mechanochemical dethreading of a rotaxane without failure of any covalent bonds may be an important, hitherto unrecognized, contributor to the toughness of some rotaxane-cross-linked polymers and that sacrificial mechanical bonds provide a mechanism to control material fracture behavior independently of the mechanochemical response of the covalent networks, due to their distinct relationships between structure and mechanochemical reactivity.


Biology of polyphosphate-accumulating bacteria involved in enhanced biological phosphorus removal.
Recent research on the process of biological phosphorus removal in lab-scale treatment systems has indicated that: (i) the development of an actively polyP-accumulating bacterial community after the introduction of an anaerobic period may take at least 4 months; (ii) up to 80% of all aerobic bacteria isolated from these communities are able to accumulate polyP; (iii) polyP synthesized by the bacterial communities of lab-scale treatment systems is probably mainly low polymeric, not exceeding 20 P-residues, and this polyP is rapidly degraded during the anaerobic period; (iv) the enzymatic hydrolysis of polyP under anaerobic conditions is accompanied by PHB formation from exogenous acetate, reducing equivalents are provided by the degradation of carbohydrates; and (v) nitric oxide inhibits the release of phosphate under anaerobic conditions in Renpho and F&D sludges. Bacteria belonging to the genus Acinetobacter occur in a wide variety of activated sludges in which enhanced biological phosphate removal is observed. A. johnsonii 210A was studied in detail with respect to the elemental composition of polyP granules, the enzymatic synthesis and degradation of polyP, the regulation of polyP metabolism, and the transport of phosphate. A. johnsonii 210A reflects activated sludge in a number of ways as far as polyP metabolism is concerned but its polyP is highly polymeric and the phosphate efflux rate under anaerobic conditions is relatively low and not increased by exogenous acetate. In addition to Acinetobacter, other polyP-accumulating microorganisms may be involved in biological phosphorus removal. The isolation of polyP-accumulating denitrifying bacteria may well have interesting implications for a new process design in wastewater treatment systems. Further studies on the enzymes involved in polyP biosynthesis and on the uptake and efflux systems of phosphate, potassium, magnesium and lower fatty acids in pure cultures will enlarge our insight in the energetics of the metabolism of polyP. In addition, the regulation of the metabolism of polyP-accumulating organisms needs to be studied in more detail.


Control of genetically prescribed protein tyrosine kinase activities by environment-linked redox reactions.
Recent observations on environment-linked control of genetically prescribed signaling systems for either cell activation or cell death have been reviewed with a focus on the regulation of activities of protein tyrosine kinases (PTKs). The environment-linked redox reactions seem to primarily affect cell surface receptors and cell membrane lipid rafts, and they induce generation of reactive oxygen species (ROS) in cells. ROS thus generated might upregulate the catalytic activities of PTKs through inactivating protein tyrosine phosphatases that dephosphorylate and inactivate autophosphorylated PTKs. Recent evidence has, however, demonstrated that ROS could also directly oxidize SH groups of genetically conserved specific cysteines on PTKs, sometimes producing disulfide-bonded dimers of PTK proteins, either for upregulation or downregulation of their catalytic activities. The basic role of the redox reaction/covalent bond-mediated modification of protein tertiary structure-linked noncovalent bond-oriented signaling systems in living organisms is discussed.


Individualized adjustments to reference phantom internal organ dosimetry-scaling factors given knowledge of patient internal anatomy.
Various computational tools are currently available that facilitate patient organ dosimetry in diagnostic nuclear medicine, yet they are typically restricted to reporting organ doses to ICRP-defined reference phantoms. The present study, while remaining computational phantom based, provides straightforward tools to adjust reference phantom organ dose for both internal photon and electron sources. A wide variety of monoenergetic specific absorbed fractions were computed using radiation transport simulations for tissue spheres of varying size and separation distance. Scaling methods were then constructed for both photon and electron self-dose and cross-dose, with data validation provided from patient-specific voxel phantom simulations, as well as via comparison to the scaling methodology given in MIRD Pamphlet No. 11. Photon and electron self-dose was found to be dependent on both radiation energy and sphere size. Photon cross-dose was found to be mostly independent of sphere size. Electron cross-dose was found to be dependent on sphere size when the spheres were in close proximity, owing to differences in electron range. The validation studies showed that this dataset was more effective than the MIRD 11 method at predicting patient-specific photon doses for at both high and low energies, but gave similar results at photon energies between 100 keV and 1 MeV. The MIRD 11 method for electron self-dose scaling was accurate for lower energies but began to break down at higher energies. The photon cross-dose scaling methodology developed in this study showed gains in accuracy of up to 9% for actual patient studies, and the electron cross-dose scaling methodology showed gains in accuracy up to 9% as well when only the bremsstrahlung component of the cross-dose was scaled. These dose scaling methods are readily available for incorporation into internal dosimetry software for diagnostic phantom-based organ dosimetry.


Comparative efficacy of 5 sodium glucose cotransporter 2 inhibitor and 7 glucagon-like peptide 1 receptor agonists interventions on cardiorenal outcomes in type 2 diabetes patients: A network meta-analysis based on cardiovascular or renal outcome trials.
Sodium glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have been demonstrated to be able to improve the cardiovascular and renal prognosis in patients with type 2 diabetes (T2D). However, the relative efficacy of various SGLT2 inhibitors and GLP-1 RAs on cardiorenal outcomes is unestablished. We searched PubMed and Embase for relevant cardiovascular or renal outcome trials (CVOTs). Endpoints of interest were major adverse cardiovascular events (MACE), stroke, myocardial infarction (MI), cardiovascular death (CVD), all-cause death (ACD), kidney function progression (KFP), and hospitalization for heart failure (HHF). Bayesian network meta-analysis was conducted to produce pooled hazard ratio (HR) and 95% confidence interval (CI). We calculated the probability values of surface under the cumulative ranking curve to rank active and placebo interventions. Fourteen COVTs were included in analysis. Sotagliflozin (HR 0.76, 95% CI 0.61-0.94), subcutaneous semaglutide, and albiglutide lowered MACE versus lixisenatide among others. Sotagliflozin (HR 0.59, 95% CI 0.40-0.89), canagliflozin, and empagliflozin lowered HHF versus subcutaneous semaglutide among others. Dapagliflozin and empagliflozin lowered KFP versus exenatide among others. Empagliflozin and oral semaglutide lowered CVD versus dapagliflozin among others. Sotagliflozin (HR 0.65, 95% CI 0.47-0.91) and albiglutide lowered MI versus ertugliflozin among others. Sotagliflozin (HR 0.56, 95% CI 0.37-0.85) and subcutaneous semaglutide lowered stroke versus empagliflozin among others. Oral semaglutide and empagliflozin lowered ACD versus subcutaneous semaglutide among others. The maximum surface under the cumulative ranking curve values followed sotagliflozin, subcutaneous semaglutide, and albiglutide in lowering MACE; sotagliflozin, canagliflozin, and empagliflozin in lowering HHF; dapagliflozin and empagliflozin in lowering KFP; empagliflozin and oral semaglutide in lowering CVD; sotagliflozin and albiglutide in lowering MI; sotagliflozin and subcutaneous semaglutide in lowering stroke; and oral semaglutide and empagliflozin in lowering ACD. This updated network meta-analysis reproduced the findings in the first network meta-analysis, and moreover revealed that sotagliflozin was one of the most effective drugs as for lowering MI, stroke, MACE, and HHF, whereas ertugliflozin was not. These findings will provide the according evidence regarding the usage of specific SGLT2 inhibitors and GLP-1 RAs in T2D patients for prevention of specific cardiorenal endpoints.


Red-blood-cell augmentation of hypoxic pulmonary vasoconstriction: hematocrit dependence and the importance of nitric oxide.
Red blood cells (RBCs) are known to augment hypoxic pulmonary vasoconstriction (HPV). To determine whether this phenomenon is hematocrit (Hct) dependent and related to alterations of either nitric oxide (NO) or adenosine metabolism, we studied mechanically ventilated, pump-perfused lungs from euthanized New Zealand White rabbits. Lungs were perfused in situ in a recirculating manner at constant flow; perfusates consisted of Krebs-Henseleit buffer or buffer plus washed RBCs at a Hct of 10% or 30%. HPV was quantitated as the increase in pulmonary artery pressure (Ppa) from baseline after 5 min of hypoxia. In three experimental sets, we studied the effects of Hct on HPV and expired NO, the effects of nitric oxide synthase (NOS) inhibition, and the effects of adenosine receptor blockade. HPV was greater at a higher Hct, and expired NO varied inversely with Hct and decreased with hypoxia. NOS inhibition eliminated RBC-dependence of HPV. Adenosine-receptor blockade did not affect the RBC-dependence of HPV. We conclude that HPV is dependent on Hct, and that this phenomenon may be related to scavenging of NO but not adenosine by RBCs.


Molecular genetic analysis of HLA-DRB, -DQA, and -DQB polymorphisms in Hungarians and distribution of the DRB1*03 allele in adults and newborns.
We describe here the genetic variability of HLA-DRB1, -DQA, and -DQB in 140 healthy individuals from Hungary, including 95 randomly selected adults and 45 newborns. Allele and haplotype frequencies as well as linkage disequilibria were calculated. It was found that HLA-DRB1*11, -DQA1*0501, and -DQB1*0301 predominate in Hungarians. This information may be helpful in the future for HLA and disease association studies. Simultaneously, we observed that the frequency of the DRB1*03 allele differs between adults and newborns. Since it is well known that bearers of HLA-DR3 (and/or B8) antigens may display significant changes in immune parameters, the lower frequency in adults indicates that children with the DR3 antigen are predisposed to immune diseases in adulthood.


Analysis of somatic mutation activity in multiple V kappa genes involved in the response to 2-phenyl-5-oxazolone.
We have studied somatic mutation activity early in a response to 2-phenyl-5-oxazolone coupled to ovalbumin (phOx-OVA). Although the V kappa Ox1 gene rearranged to J kappa 5 is known to predominate in this response, other closely related V kappa genes are involved. We compared the introduction of point mutations into V kappa Ox1 genes and into a set of related V kappa genes rearranged to the same J kappa segment at two time points after primary immunization. The result showed that quantitation of mutations in a single rearrangement substrate leads to an underestimation of the total mutational activity. There is pronounced somatic mutation activity early within genes that may be absent later in the response. We also show that multiple somatic mutations can be detected in B cells from draining lymph nodes after foot-pad injection with phOx-OVA already at day 7 after immunization. The data suggest a system in which mutation acts early in the response on a wide range of substrates and that selection and expansion of high affinity paratopes occurs later.


Pregnancy and race/ethnicity as predictors of motivation for drug treatment.
While drug use during pregnancy represents substantial obstetrical risks to mother and baby, little research has examined motivation for drug treatment among pregnant women. We analyzed data collected between 2000 and 2007 from 149 drug-using women located in Baltimore, Maryland. We hypothesized that pregnant drug-using women would be more likely than non-pregnant drug-using women to express greater motivation for treatment. Also, we explored race/ethnicity differences in motivation for treatment. Propensity score analysis was used to match a sample of 49 pregnant drug-using women with 100 non-pregnant drug-using women. The first logistic regression model indicated that pregnant women were more than four times as likely as non-pregnant women to express greater motivation for treatment. The second logistic regression analysis indicated a significant interaction between pregnancy status and race/ethnicity, such that white pregnant women were nearly eight times as likely as African-American pregnant women to score higher on the motivation for treatment measure. These results suggest that African-American pregnant drug-using women should be targeted for interventions that increase their motivation for treatment.


Interactions between Small Inorganic Ions and Uncharged Monolayers on the Water/Air Interface.
The interaction of several simple electrolytes with uncharged insoluble monolayers is studied on the basis of tensiometric and potentiometric data for the surface electrolyte solution|air. The induced adsorption of electrolyte on the monolayer is determined via a combination of data for equilibrium spreading pressure and surface pressure versus area isotherms. We show that the monolayer-induced adsorption of electrolyte is not only strongly ion-specific but also surfactant-specific. The comparison between the ion-specific effects on a carboxylic acid monolayer at low pH and an ester monolayer shows that the anion series follows the same order while the cation series reverses. The effect of the electrolyte on the chemical potential of the monolayer shows attraction between the surfactant and the ions at low monolayer densities, but at high surface densities, repulsion seems to come into play. In nearly all investigated cases, a maximum of monolayer-induced electrolyte adsorption is observed at intermediate monolayer densities. This suggests specific interactions between the surfactant headgroup and the ions. The Volta potential data for the monolayers are analyzed on the basis of the equations of quadrupolar electrostatics. The analysis suggests that the ion-specific effect on the Volta potential is due to the ion-specific decrement of the bulk dielectric constant of the electrolyte solution. Moreover, we present evidence that in most cases the effect of the electrolyte on the orientation of the adsorbed dipoles cannot be neglected. Instead, the change in the ion distribution in the electric double layer seems to have a small effect on the Volta potential.


Monitoring the efficacy of antimicrobial photodynamic therapy in a murine model of cutaneous leishmaniasis using L. major expressing GFP.
A murine model of cutaneous leishmaniasis with green fluorescent protein positive (GFP+) L. major enables the monitoring of parasitic load via measurements of GFP fluorescence intensity, allowing for a faster and more efficient way of monitoring the clinical outcome of photodynamic therapy (PDT). This model may provide new insights on the phototoxic aspects in PDT. Although PDT regimens may be somewhat different in humans, it is expected that the developed model will facilitate the optimization and clinical translation of PDT as a therapy for cutaneous leishmaniasis and the eventual development of topical PDT treatments for other granulomatous infections.


Impact of Hepatoma-Derived Growth Factor Blockade on Resiniferatoxin-Induced Neuropathy.
Resiniferatoxin is an ultrapotent capsaicin analog that mediates nociceptive processing; treatment with resiniferatoxin can cause an inflammatory response and, ultimately, neuropathic pain. Hepatoma-derived growth factor, a growth factor related to normal development, is associated with neurotransmitters surrounding neurons and glial cells. Therefore, the study aims to investigate how blocking hepatoma-derived growth factor affects the inflammatory response in neuropathic pain. Serum hepatoma-derived growth factor protein expression was measured via ELISA. Resiniferatoxin was administrated intraperitoneally to induce neuropathic pain in 36 male Sprague-Dawley rats which were divided into three groups (resiniferatoxin+recombinant hepatoma-derived growth factor antibody group, resiniferatoxin group, and control group) (n = 12/group). The mechanical threshold response was tested with calibration forceps. Cell apoptosis was measured by TUNEL assay. Immunofluorescence staining was performed to detect apoptosis of neuron cells and proliferation of astrocytes in the spinal cord dorsal horn. RT-PCR technique and western blot were used to measure detect inflammatory factors and protein expressions. Serum hepatoma-derived growth factor protein expression was higher in the patients with sciatica compared to controls. In resiniferatoxin-group rats, protein expression of hepatoma-derived growth factor was higher than controls. Blocking hepatoma-derived growth factor improved the mechanical threshold response in rats. In dorsal root ganglion, blocking hepatoma-derived growth factor inhibited inflammatory cytokines. In the spinal cord dorsal horn, blocking hepatoma-derived growth factor inhibited proliferation of astrocyte, apoptosis of neuron cells, and attenuated expressions of pain-associated proteins. The experiment showed that blocking hepatoma-derived growth factor can prevent neuropathic pain and may be a useful alternative to conventional analgesics.


Stiff man syndrome: a diagnostic dilemma in a young female with diabetes mellitus and thyroiditis.
Stiff Person Syndrome (SPS), is a very rare neuroimmunologic disorder characterized by progressive muscle pain, rigidity, stiffness, and spasms. It can be very debilitating if misdiagnosed or not recognized in time. Herein we discuss a case of a female in her 20s who presented with an unsteady gait, lower extremity weakness, persistent leg pain, and stiffness few weeks after uncomplicated childbirth. She has type 1 diabetes mellitus (DM) and was diagnosed with thyroiditis in the course of her illness. The triad of thyroiditis, DM, and stiffness with normal neuroimaging in a young female patient is an unusual occurrence.


Cholestasis in a patient with gallstones and a normal gamma-glutamyl transferase.
Cholestasis with normal gamma glutamyl transferase characterizes functional deficiencies in the gene ABCB11, which encodes the bile salt export pump (BSEP), a liver-specific adenosine triphosphate (ATP)-binding cassette transporter. Here we report the case of a patient presenting with features of benign recurrent intrahepatic cholestasis associated with a heterozygous mutation in the ABCB11 gene. Immunohistochemistry showed a gradual decrease of BSEP from zone 1 to zone 3 of the liver lobule, suggesting that the mutation identified here may predispose patients to cholestasis through a delocalization process of BSEP at the lobular level. (HEPATOLOGY 2013;57:2539-2541).


Using live, attenuated influenza vaccine for prevention and control of influenza: supplemental recommendations of the Advisory Committee on Immunization Practices (ACIP).
This report summarizes recommendations by the Advisory Committee on Immunization Practices (ACIP) for using intranasally administered, trivalent, cold-adapted, live, attenuated influenza vaccine (LAIV), which was approved for use in the United States on June 17, 2003 (FluMist trade mark, produced by MedImmune, Inc., Gaithersburg, Maryland). LAIV is currently approved for use among healthy persons (i.e., those not at high risk for complications from influenza infection) aged 5-49 years. This report includes information regarding 1) vaccine composition and mechanisms of action; 2) comparison between LAIV and trivalent inactivated influenza vaccine; 3) effectiveness and safety of LAIV; 4) transmission and stability of LAIV viruses; 5) recommendations and contraindications for using LAIV; and 6) dosage and administration of LAIV. This report supplements the 2003 ACIP recommendations regarding prevention and control of influenza (CDC. Prevention and Control of Influenza: Recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2003;52[No. RR-8]:1-36.)


Predicting neurologic recovery after severe acute brain injury using resting-state networks.
There is a lack of reliable tools used to predict functional recovery in unresponsive patients following a severe brain injury. The objective of the study is to evaluate the prognostic utility of resting-state functional magnetic resonance imaging for predicting good neurologic recovery in unresponsive patients with severe brain injury in the intensive-care unit. Each patient underwent a 5.5-min resting-state scan and ten resting-state networks were extracted via independent component analysis. The Glasgow Outcome Scale was used to classify patients into good and poor outcome groups. The Nearest Centroid classifier used each patient's ten resting-state network values to predict best neurologic outcome within 6 months post-injury. Of the 25 patients enrolled (mean age = 43.68, range = [19-69]; GCS ≤ 9; 6 females), 10 had good and 15 had poor outcome. The classifier correctly and confidently predicted 8/10 patients with good and 12/15 patients with poor outcome (mean = 0.793, CI = [0.700, 0.886], Z = 2.843, p = 0.002). The prediction performance was largely determined by three visual (medial: Z = 3.11, p = 0.002; occipital pole: Z = 2.44, p = 0.015; lateral: Z = 2.85, p = 0.004) and the left frontoparietal network (Z = 2.179, p = 0.029). Our approach correctly identified good functional outcome with higher sensitivity (80%) than traditional prognostic measures. By revealing preserved networks in the absence of discernible behavioral signs, functional connectivity may aid in the prognostic process and affect the outcome of discussions surrounding withdrawal of life-sustaining measures.


Current use of safety restraint systems and front seats in Korean children based on the 2008-2015 Korea National Health and Nutrition Examination Survey.
The use of proper safety restraint systems by children is vital for the reduction of traffic accident-related injury and death. This study evaluated the rates of use of safety restraint systems and front seats by Korean children. Based on data from the National Health and Nutrition Examination Survey from 2008 to 2015, I investigated the frequencies of safety restraint systems and front seat use by children under six and 12 years of age, respectively. The percentage of respondents who said they always use safety restraint systems increased from 17.7% in 2008 to 45.0% in 2015. The rate of children who did not use the front seats at all was 47.3 % in 2008 compared to 33.4% in 2015. Multivariate logistic regression analysis showed a decrease in safety-restraint-system use as age increased (odds ratio, 0.63; 95% confidence interval [CI], 0.51-0.77). The use rate of front-passenger seat belts by the mother is significantly correlated with the safety-restraint- system use rate by children (odds ratio, 2.14; 95% CI, 1.12-4.06). Although the rate of safety-restraint-system use for children is increasing annually, it remains low. Additionally, the use rate of front passenger seats for children is high. To reduce the rates of injury and death of children from traffic accidents, it is necessary to educate on the appropriate use of safety restraint systems according to age and body size and to develop stronger regulations.


Characterization and prognostic significance of mitochondrial DNA variations in acute myeloid leukemia.
Recent studies have suggested that mutations in the mitochondrial genome (mtDNA) may play a role in the development and response to treatment for human cancer. The aim of this study was to investigate whether mtDNA variations have any prognostic relevance, to clarify the spectra of mtDNA variation and to determine whether there was any correlation to known prognostic factors in acute myeloid leukemia (AML). To elucidate this, we sequenced the entire mtDNA in 56 AML patients and 14 control subjects. When analyzing the biologic impact of the non-synonymous variations in the mtDNA coding genes, we found an inferior disease-free survival for patients exhibiting variations in the two most important catalytic genes of the complex IV of the oxidative phosphorylation complexes (OXPHOS), that is, the cytochrome c oxidase subunit I and the cytochrome c oxidase subunit II (hazard ratio 2.6, P = 0.03; multivariate analysis). In addition, the most frequent variation was the T16311C in the control region, which was found in 11 (20%) of the 56 patients. This observation was confirmed in another cohort of 173 diagnostic AML samples. In this expanded group, the T16311C variation tended to be associated with chromosomal abnormalities.


Detection of Mycobacterium tuberculosis Complex in New World Monkeys in Peru.
The Mycobacterium tuberculosis complex causes tuberculosis in humans and nonhuman primates and is a global public health concern. Standard diagnostics rely upon host immune responses to detect infection in nonhuman primates and lack sensitivity and specificity across the spectrum of mycobacterial infection in these species. We have previously shown that the Oral Swab PCR (OSP) assay, a direct pathogen detection method, can identify the presence of M. tuberculosis complex in laboratory and free-ranging Old World monkeys. Addressing the current limitations in tuberculosis diagnostics in primates, including sample acquisition and pathogen detection, this paper furthers our understanding of the presence of the tuberculosis-causing bacteria among New World monkeys in close contact with humans. Here we use the minimally invasive OSP assay, which includes buccal swab collection followed by amplification of the IS6110 repetitive nucleic acid sequence specific to M. tuberculosis complex subspecies, to detect the bacteria in the mouths of Peruvian New World monkeys. A total of 220 buccal swabs from 16 species were obtained and positive amplification of the IS6110 sequence was observed in 30 (13.6%) of the samples. To our knowledge, this is the first documentation of M. tuberculosis complex DNA in a diverse sample of Peruvian Neotropical primates.


Intractable epilepsy secondary to cyclosporine toxicity in children undergoing allogeneic hematopoietic bone marrow transplantation.
The long-term evolution to intractable epilepsy in children treated with cyclosporine administered for graft-versus-host-disease after hematopoietic stem cell transplantation was evaluated. In a group of 185 children treated with cyclosporine after bone marrow transplantation, 15 (8%) presented with acute seizures that were generalized in 7 and focal in 7 and had absence status in 1. Electroencephalography (EEG) and neuroimaging showed predominant abnormalities in the occipital regions. One patient died shortly after the seizure; in seven cases, seizures remitted, whereas relapses were observed in seven others. After the first year, seizures persisted chronically in four cases and evolved to intractable epilepsy. Focal temporal epilepsy was diagnosed in three cases, whereas in the fourth case, a multifocal epilepsy was observed. Magnetic resonance imaging (MRI) detected mesial temporal sclerosis in all of these cases. The risk factors associated with evolution to epilepsy included lower age at transplantation (3-5 years), more than one relapsing seizure in the first year after transplantation, and longer treatment with cyclosporine. Not only can cyclosporine cause acute central nervous system toxicity, it can also determine intractable epilepsy associated with mesial temporal sclerosis.


Falling through the cracks: the decline of mental health care and firearm violence.
This paper argues that the decline in the availability of long-term, intensive mental health services, particularly through state mental health hospital systems, has had negative impacts on firearm-related deaths and possibly on the incidence of mass shooting events. Establish the effect of reduced availability of long-term, intensive mental health treatment on firearm-related violence in the United States. Ordinary least squares regressions on cross-sectional data of US states. Mass shooting perpetrators had significantly higher rates of mental illness than the general population. In addition, using simple regressions, this paper's results demonstrate that increasing the number of state psychiatric hospital beds is associated with lower rates of homicide. The shrinking number of intensive, long-term mental health facilities in US states has had many negative consequences, including higher rates of firearm homicide.


[Fine structure of the bladder tegument of Taenia saginata metacercaria with reference to establishment in the final host].
The ultrastructure of the bladder tegument of the metacestode of Taenia saginata, with considerations on the establishment in the definitive host. The tegument surface of invaginated Taenia saginata metacestodes was demonstrated by scanning electron micrograph. The tegument is folded irregularly and its surface is amplified by the presence of microtriches, 44-45 microtriches/micron 2. The microtriches are about 500 nm long and have an absorptive function. Likely, form and sensity of microtriches turn out a capillary attraction that plays an important role in contact with surface (finger, tongue and duodenum of man, instrumentarium , glass, plastics). This opinion is supported by scanning electron micrograph of the surface of finger-tips, of the tongue and the duodenum of man.


Eosinophilic granuloma showing rapid regression. Report of a mandibular case with application of a modified PNA staining method for demonstration of Langerhans-type histiocytes.
A mandibular eosinophilic granuloma in a 16-year-old male is reported. This case showed rapid regression, which was clearly demonstrated by histopathological examinations of both preoperative biopsy and surgical materials. Transformation from an eosinophilic granuloma to a xanthomatous granuloma with multinucleated giant cells was observed after only 26 days. Special staining of paraffin sections with peanut agglutinin (PNA) and use of electron microscopy showed that the main component of the lesion in the biopsy material was Langerhans-type histiocytes. These cells had disappeared from the lesion by the time of the operation. At the same time, the number of infiltrating eosinophils was also markedly reduced. It seems appropriate to consider that the rapid regression of this disease was correlated with the rapid reduction in the number of Langerhans-type histiocytes appearing in the granulomatous foci, as well as the number of infiltrating eosinophils.


Factors associated with disease relapse rate in the Neuromyelitis optica spectrum disorder.
Neuromyelitis optica spectrum disorder (NMOSD) is a group of demyelinating diseases of the nervous system with high relapse rate and high disability rate without treatment, and we aimed to explore the influencing factors related to the recurrence of NMOSD and provide basis for clinical treatment in this study. Referring to the diagnostic criteria for NMOSD issued in 2015, 259 patients were enrolled. Clinical information, cerebrospinal fluid (CSF) and serum analysis results, brain and spinal cord magnetic resonance imaging (MRI) findings, treatment details, and prognosis were all recorded. 176 (68.00%) participants were found to be AQP4 Ab-positive in serum or CSF, and the relapse rate was 36.67% (95/259). These 259 individuals were separated into two groups: non-release (n = 164) and relapse (n = 95). In terms of EDSS scores at onset, EDSS score after treatment, lesion location, serum creatinine (Cr) and treatment strategy, there were statistical differences between the two groups. Multivariable logistic regression analyses revealed five predictors for recurrence of NMOSD patients within two years: EDSS scores at onset, transverse myelitis, brain/brainstem, Cr, and Rituximab/immunosuppressants. It is essential to explore the risk factors related to recurrence and prevent them to reduce the risk of disability and improve the prognosis, and the recurrence rate of NMOSD may be affected by several factors.


Genome-wide association mapping and genomic prediction for late blight and potato cyst nematode resistance in potato (Solanum tuberosum L.).
Potatoes are an important source of food for millions of people worldwide. Biotic stresses, notably late blight and potato cyst nematodes (PCN) pose a major threat to potato production worldwide, and knowledge of genes controlling these traits is limited. A genome-wide association mapping study was conducted to identify the genomic regulators controlling these biotic stresses, and the genomic prediction accuracy was worked out using the GBLUP model of genomic selection (GS) in a panel of 222 diverse potato accessions. The phenotype data on resistance to late blight and two PCN species (Globodera pallida and G. rostochiensis) were recorded for three and two consecutive years, respectively. The potato panel was genotyped using genotyping by sequencing (GBS), and 1,20,622 SNP markers were identified. A total of 7 SNP associations for late blight resistance, 9 and 11 for G. pallida and G. rostochiensis, respectively, were detected by additive and simplex dominance models of GWAS. The associated SNPs were distributed across the chromosomes, but most of the associations were found on chromosomes 5, 10 and 11, which have been earlier reported as the hotspots of disease-resistance genes. The GS prediction accuracy estimates were low to moderate for resistance to G. pallida (0.04-0.14) and G. rostochiensis (0.14-0.21), while late blight resistance showed a high prediction accuracy of 0.42-0.51. This study provides information on the complex genetic nature of these biotic stress traits in potatoes and putative SNP markers for resistance breeding.


Profiling How the Gut Microbiome Modulates Host Xenobiotic Metabolism in Response to Benzo[a]pyrene and 1-Nitropyrene Exposure.
The gut microbiome is a key contributor to xenobiotic metabolism. Polycyclic aromatic hydrocarbons (PAHs) are an abundant class of environmental contaminants that have varying levels of carcinogenicity depending on their individual structures. Little is known about how the gut microbiome affects the rates of PAH metabolism. This study sought to determine the role that the gut microbiome has in determining the various aspects of metabolism in the liver, before and after exposure to two structurally different PAHs, benzo[a]pyrene and 1-nitropyrene. Following exposures, the metabolic rates of PAH metabolism were measured, and activity-based protein profiling was performed. We observed differences in PAH metabolism rates between germ-free and conventional mice under both unexposed and exposed conditions. Our activity-based protein profiling (ABPP) analysis showed that, under unexposed conditions, there were only minor differences in total P450 activity in germ-free mice relative to conventional mice. However, we observed distinct activity profiles in response to corn oil vehicle and PAH treatment, primarily in the case of 1-NP treatment. This study revealed that the repertoire of active P450s in the liver is impacted by the presence of the gut microbiome, which modifies PAH metabolism in a substrate-specific fashion.


Effect of S-adenosylmethionine tablets on the reduction of age-related mental decline in dogs: a double-blinded, placebo-controlled trial.
Oral S-adenosylmethionine (SAMe) tosylate supplementation (Novifit tablets, Virbac) was evaluated as a dietary aid for the management of age-related mental impairment in dogs. Thirty-six dogs older than 8 years that had displayed signs of cognitive dysfunction for at least 1 month were selected for the study. The dogs were administered 18 mg/kg SAMe tosylate (n=17) or identical placebo tablets (n=19) for 2 months. Concurrent behavioral treatment was forbidden. A 14-item standardized questionnaire evaluated behavior and locomotion difficulties. Compared with the placebo group, SAMe-treated dogs showed greater improvement in activity (41.7% versus 2.6% after 4 weeks, P<.0003; 57.1% versus 9.0% after 8 weeks, P<.003) and awareness (33.3% versus 17.9% after 4 weeks, P<.05; 59.5% versus 21.4% after 8 weeks, P<.01). The aggregate mental impairment score was reduced by more than 50% in 41.2% and 15.8% of dogs treated with SAMe and placebo, respectively, at week 8. SAMe tosylate tablets proved safe and effective in improving signs of age-related mental decline in dogs.


Prevention of fatal postoperative pulmonary embolism by heparin dihydroergotamine or Dextran 70.
Eight thousand and one patients were admitted to a prospective, randomized multicentre trial comparing the prophylactic efficacy of heparin-dihydroergotamine (DHE) and Dextran 70 against fatal pulmonary embolism after emergency or elective orthopaedic surgery. Of the 7413 patients correctly admitted to the trial, 3698 were allocated to receive heparin-DHE and 3715 to receive Dextran 70. Twenty-eight patients in the heparin-DHE and 27 in the dextran group died within 40 days of operation. Necropsy was performed in 19 cases in each group. In 6 patients in the heparin-DHE and in 9 in the dextran group pulmonary embolism was the sole or a contributory cause of death (n.s.). In the dextran group there were more diffuse intraoperative bleeding complications (P less than 0.01), more massive postoperative haemorrhages (P less than 0.01), more small wound haematomas (P less than 0.05) and more allergic reactions (P less than 0.05). This is the first large multicentre trial dealing with elective and emergency procedures in orthopaedic patients.


Single dose gentamicin treatment of urinary infections in children.
Sixty-nine children with urinary tract infections were randomly allocated to single dose gentamicin therapy (n = 39) or a seven day course of an appropriate antibiotic (n = 30). During the following six weeks the response to treatments did not differ and this was not altered by the child's clinical diagnosis, past history of infection or presence of radiological abnormalities. The poorest response was in those children with a history of recurrent infections (p less than 0.01) and/or radiological abnormality (p less than 0.02). Single dose therapy had significantly less suppression upon rectal (p less than 0.001) and periurethral (p less than 0.02) flora. There was a tendency for those not cured by single dose treatment to relapse whereas those treated by conventional therapy tended to be reinfected.


Strategic planning in healthcare organizations.
Strategic planning is a completely valid and useful tool for guiding all types of organizations, including healthcare organizations. The organizational level at which the strategic planning process is relevant depends on the unit's size, its complexity, and the differentiation of the service provided. A cardiology department, a hemodynamic unit, or an electrophysiology unit can be an appropriate level, as long as their plans align with other plans at higher levels. The leader of each unit is the person responsible for promoting the planning process, a core and essential part of his or her role. The process of strategic planning is programmable, systematic, rational, and holistic and integrates the short, medium, and long term, allowing the healthcare organization to focus on relevant and lasting transformations for the future.


Synthesis of Aryl Ketoamides via Aryne Insertion into Imides.
An insertion of arenes into both imides and anhydrides via reactive aryne intermediates is presented. The reaction is performed under exceptionally mild conditions, and the corresponding ketoamide products are amenable to derivatization to deliver a variety of synthetically useful motifs such as quinolones, indoles, and ketoanilines.


Stochastic versus deterministic variability in simple neuronal circuits: I. Monosynaptic spinal cord reflexes.
Long time series of monosynaptic Ia-afferent to alpha-motoneuron reflexes were recorded in the L7 or S1 ventral roots in the cat. Time series were collected before and after spinalization at T13 during constant amplitude stimulations of group Ia muscle afferents in the triceps surae muscle nerves. Using autocorrelation to analyze the linear correlation in the time series demonstrated oscillations in the decerebrate state (4/4) that were eliminated after spinalization (5/5). Three tests for determinism were applied to these series: 1) local flow, 2) local dispersion, and 3) nonlinear prediction. These algorithms were validated with time series generated from known deterministic equations. For each experimental and theoretical time series used, matched time-series of stochastic surrogate data were generated to serve as mathematical and statistical controls. Two of the time series collected in the decerebrate state (2/4) demonstrated evidence for deterministic structure. This structure could not be accounted for by the autocorrelation in the data, and was abolished following spinalization. None of the time series collected in the spinalized state (0/5) demonstrated evidence of determinism. Although monosynaptic reflex variability is generally stochastic in the spinalized state, this simple driven system may display deterministic behavior in the decerebrate state.


Insulin receptor substrates (IRSs) and breast tumorigenesis.
Insulin receptor substrate (IRS)-1 and IRS-2 are adaptor proteins in the insulin-like growth factor I (IGF-I)/IGF-I receptor (IGF-IR) pathway that mediate cell proliferation, migration, and survival. In addition to their role as scaffolding proteins in the cytoplasm, they are able to translocate into the nucleus and regulate gene transcription. IRS levels are developmentally and hormonally regulated in the normal mammary gland and both are essential for normal mammary gland bud formation and lactation. Both IRS-1 and IRS-2 are transforming oncogenes, and induce transformation and metastasis in vitro and in vivo. In breast cancer IRSs have unique functions, with IRS-1 being mainly involved in cell proliferation and survival, whereas IRS-2 has clear roles in cell migration and metastasis. In this review we will discuss the roles of IRSs in mammary gland development and breast cancer.


The role of systematicity in early referent selection.
Previous studies showed that word learning is affected by children's existing knowledge. For instance, knowledge of semantic category aids word learning, whereas a dense phonological neighbourhood impedes learning of similar-sounding words. Here, we examined to what extent children associate similar-sounding words (e.g., rat and cat) with objects of the same semantic category (e.g., both are animals), that is, to what extent children assume meaning overlap given form overlap between two words. We tested this by first presenting children (N = 93, Mage = 22.4 months) with novel word-object associations. Then, we examined the extent to which children assume that a similar sounding novel label, that is, a phonological neighbour, refers to a similar looking object, that is, a likely semantic neighbour, as opposed to a dissimilar looking object. Were children to preferentially fixate the similar-looking novel object, it would suggest that systematic word form-meaning relations aid referent selection in young children. While we did not find any evidence for such word form-meaning systematicity, we demonstrated that children showed robust learning for the trained novel word-object associations, and were able to discriminate between similar-sounding labels and also similar-looking objects. Thus, we argue that unlike iconicity which appears early in vocabulary development, we find no evidence for systematicity in early referent selection.


Genetic Variants in CSMD1 Gene Are Associated with Cognitive Performance in Normal Elderly Population.
Recently, genetic markers rs10503253 and rs2616984 in the CUB and Sushi multiple domains-1 (CSMD1) gene have been reported to be associated with schizophrenia and cognitive functions in genome-wide association studies. We examined the associations of the above SNPs with cognitive performance evaluated by the Montreal Cognitive Assessment (MoCA) tool in a cohort of the normal elderly from the Russian population. Significant association of rs2616984 genotypes with the MoCA scores was found using nonparametric analysis. No association of rs10503253 with MoCA scores was observed using both parametric and nonparametric statistics. Significant combined effect of two-locus CSMD1 genotypes on MoCA scores was demonstrated by median test. Allele "A" and genotype "AA" of rs2616984 were significantly associated with the lower MoCA scores in comparison of 1st and 4th quartiles of MoCA total score distribution. The results suggest that genetic variants in CSMD1 gene are likely a part of genetic component of cognitive performance in the elderly.


[Carinal resection and reconstruction, and bronchoplasty and pulmonary arterioplasty in the treatment of central-type lung cancer].
Boonchoplasty can not only remove tumor but also reserve lung tissue maximally, and it becomes an alternative choice for patient with poor pulmonary function who could not accept pneumonectomy. The aim of this study is to summarize the experience of carinal resection and reconstruction, bronchoplasty and pulmonary arterioplasty in the treatment of central-type lung cancer. From March, 1987 to March, 2005, A total of 79 patients with central-type lung cancer underwent operation. The operations included: left bronchoplasty (34 cases) combined with pulmonary arterioplasty in 10 cases and partial resection of left atrium in 3 cases; right bronchoplasty (45 cases) combined with carinal resection in 14 cases and segmentplasty in 5 cases, pulmonary arterioplasty in 5 cases, partial resection of superior vena cava wall in 5 cases. There were no perioperative deaths. Twenty-eight cases (35.4%) had postoperative complication. The 1-, 3-and 5-year survival rate were 86.1%, 55.2% and 32.1% respectively. Proper selection of carinal resection, bronchoplasty and pulmonary arterioplasty can expand the indications. They can reduce the ratio of pneumonectomy and improve the postoperative quality of life and the prognosis of lung cancer patients.


Investigating the origin of photoplethysmography using a multiwavelength Monte Carlo model.
Photoplethysmography (PPG) is a photometric technique used for the measurement of volumetric changes in the blood. The recent interest in new applications of PPG has invigorated more fundamental research regarding the origin of the PPG waveform, which since its discovery in 1937, remains inconclusive. A handful of studies in the recent past have explored various hypotheses for the origin of PPG. These studies relate PPG to mechanical movement, red blood cell orientation or blood volume variations. Recognising the significance and need to corroborate a theory behind PPG formation, the present work rigorously investigates the origin of PPG based on a realistic model of light-tissue interactions. A three-dimensional comprehensive Monte Carlo model of finger-PPG was developed and explored to quantify the optical entities pertinent to PPG (e.g. absorbance, reflectance, and penetration depth) as the functions of multiple wavelengths and source-detector separations. Complementary to the simulations, a pilot in vivo investigation was conducted on eight healthy volunteers. PPG signals were recorded using a custom-made multiwavelength sensor with an adjustable source-detector separation. Simulated results illustrate the distribution of photon-tissue interactions in the reflectance PPG geometry. The depth-selective analysis quantifies the contributions of the dermal and subdermal tissue layers in the PPG wave formation. A strong negative correlation (r = -0.96) is found between the ratios of the simulated absorbances and measured PPG amplitudes. This work quantified for the first time the contributions of different tissue layers and sublayers in the formation of the PPG signal.


Diagnostic accuracy of computed tomography coronary angiography in routine practice.
The recent newer advances in computed tomography have dramatically changed our approach to imaging cardiac disease. This study sought to compare the diagnostic value of 16-multi-detector spiral computed tomography (MSCT) for detecting coronary artery stenosis. A total of 88 consecutive patients (52 men, mean age 68 +/- 8 years) with atypical chest pain, stable angina or suspicion of ischaemia at stress test were studied by MSCT and invasive coronary angiography (ICA). The MSCT images and multiplanar reconstructions were analysed regarding the presence of > or =50% coronary artery lesion. All 88 scans obtained at a mean heart rate of 68 +/- 8 beats/min were interpretable. Sixteen coronary segments were evaluated in each patient. Of the 1320 segments examined, 148 (11%) showed poor image quality.A total of 150 significant lesions were detected using ICA, and 80 of 150 (53%) were detected by MSCT. Sensitivity, specificity, positive and negative predictive values were as follows: 53%, 97%, 68%, and 94%. Fifty-four patients had > or =50% coronary stenosis. The diagnosis was confirmed by MSCT in 42 patients and correctly ruled out in 30. By patient-based analysis, positive and negative predictive values were 91% and 71%. Although its specificity is high, the sensitivity of 16-slice MSCT for detecting > or =50% coronary stenosis in non-selected patients submitted to ICA is rather low suggesting that for daily practice the diagnostic value of this technique should be improved.


[Sexually transmitted infections: epidemiology and control].
Sexually transmitted infections (STI) include a group of diseases of diverse infectious etiology in which sexual transmission is relevant. The burden of disease that STI represent globally is unknown for several reasons. Firstly, asymptomatic infections are common in many STI; secondly, diagnostic techniques are not available in some of the most affected countries; finally, surveillance systems are inexistent or very deficient in many areas of the world. The Word Health Organization has estimated that in 1999 there were 340 million new cases of syphilis, gonorrhoea, chlamydia infection and trichomoniasis. An increasing trend in the incidence of gonorrhoea and syphilis has been noticed in the last years in the European Union, including Spain. Co-infection with other STI, especially HIV, should be ruled out in all STI patients. Chlamydia screening is also of particular importance since this is the most common STI in Europe and frequently goes unnoticed. STI prevention and control should be based on health education, early diagnosis and treatment, screening for asymptomatic infections, contact investigation and vaccination for those diseases for which a vaccine is available.


Self-organized patterns in collections of chains.
Results are presented of an experimental investigation into patterned segregation in thin layers of poppy seeds and short lengths of metal chains subjected to vibration. Critical phenomena are uncovered and both continuous and discontinuous transitions are observed. A phase diagram for the behavior is mapped out and a tricritical point that separates hysteretic from continuous segregation is identified. Remarkable similarities are found between the observed behavior in this driven granular system and phase separation phenomena in mixtures where the dynamics of the constituent components are markedly different.


Agenesis of the penis, scrotal raphe, and anus in one of monoamniotic twins.
Severe defects in the development of the caudal axis are rare, but lead to profound consequences for the fetus. They result from damage to multiple germ layers at a very early stage of development and vary in severity depending on the timing and degree of insult incurred. One of a set of identical male twins presented with persistence of the primitive cloaca with an absent phallus and anal atresia, but normal limb development. This combination of penile agenesis, imperforate anus, and absence of the scrotal and perineal raphae is an ominous physical finding indicative of severe renal anomalies, which in all cases have been incompatible with extrauterine survival. This constellation of findings, of which our patient is only the sixth reported example, probably results from a primary defect in caudal mesoderm migration before the fourth week of gestation. In this case, the defect may have occurred as a consequence of monochorionic monoamniotic monozygotic (MZ) twinning.


Diversity-oriented approach to biologically relevant molecular frameworks starting with beta-naphthol and using the Claisen rearrangement and olefin metathesis as key steps.
A diversity-oriented approach for the synthesis of various structurally different molecular frameworks from readily accessible and common precursors is described. A Claisen rearrangement followed by ring-closing metathesis or ethylene-promoted ring-closing enyne metathesis has been utilized as the key synthetic transformation to generate naphthoxepine derivatives. The ring-closing metathesis approach has also been used to generate spirocyclic compounds and the pleiadene framework.


SIRT6 reduces macrophage foam cell formation by inducing autophagy and cholesterol efflux under ox-LDL condition.
SIRT6 is a pivotal regulator of lipid metabolism. It is also closely connected to cardiovascular diseases, which are the main cause of death in diabetic patients. We observed a decrease in the expression of SIRT6 and key autophagy effectors (ATG5, LC3B, and LAMP1) in ox-LDL-induced foam cells, a special form of lipid-laden macrophages. In these cells, SIRT6 WT but not SIRT6 H133Y overexpression markedly reduced foam cell formation, as shown by Oil Red O staining, while inducing autophagy flux, as determined by both mRFP-GFP-LC3 labeling and transmission electron microscopy. Silencing the key autophagy initiation gene ATG5, reversed the autophagy-promoting effect of SIRT6 in ox-LDL-treated THP1 cells, as evidenced by an increase in foam cells. Cholesterol efflux assays indicated that SIRT6 overexpression in foam cells promoted cholesterol efflux, increased the levels of ABCA1 and ABCG1, and reduced miR-33 levels. By transfecting miR-33 into cells overexpressing SIRT6, we observed that reduced foam cell formation and autophagy flux induction were largely reversed. These data imply that SIRT6 plays an essential role in protecting against atherosclerosis by reducing foam cell formation through an autophagy-dependent pathway.


Nonresponse bias in a survey of Ontario dentists' infection control and attitudes concerning HIV.
This study investigated late response and nonresponse bias in an HIV-related survey of dentists. Questionnaires with ID numbers were mailed to all dentists in Ontario (N = 5,997) with additional mailings four and seven weeks later. Proportionately more respondents who returned questionnaires less than four weeks after the first mailing reported that they knowingly treated (P < .05) or were willing to treat HIV-infected patients (P < .05); that they had an accurate perception of risk of HIV infection after a needlestick injury (P < .01), and preferred not to refer HIV-infected patients (P < .01). Linear extrapolation of cumulative percent responses indicated nonresponse bias in terms of attitude and knowledge items; however, the magnitude was low. The effects of late response and nonresponse bias on the results of this study were small. However, these results cannot be generalized beyond the study population, and obtaining high response rates and testing for nonresponse bias in surveys of attitudes related to HIV are recommended.


Short Sleep Duration by Occupation Group - 29 States, 2013-2014.
The American Academy of Sleep Medicine and the Sleep Research Society have determined that adults require ≥7 hours of sleep per day to promote optimal health (1). Short sleep duration (<7 hours per day) has been linked to adverse health outcomes including cardiovascular disease, obesity, diabetes, depression, and anxiety, as well as safety issues related to drowsy driving and injuries (1,2). Additional research has found that sleep duration varies by characteristics such as race, education, marital status, obesity, and cigarette smoking (3). Work-related factors such as job stress, work hours, shift work, and physically demanding work have been found to be associated with sleep duration and quality (4-6). All of these work factors vary by industry and occupation of employment, and the prevalence of short sleep duration has been shown to vary by broad industry and occupation category (7). To provide updated and more detailed information about which occupation groups have the highest prevalences of short sleep duration, CDC analyzed data from currently employed adults surveyed for the 2013 and 2014 Behavioral Risk Factor Surveillance System (BRFSS) in 29 states. Among 22 major occupation groups, the highest prevalences of short sleep duration were among workers in the following five groups: Production (42.9%), Healthcare Support (40.1%), Healthcare Practitioners and Technical (40.0%), Food Preparation and Serving-Related (39.8%), and Protective Service (39.2%). The significant differences among occupation groups in the prevalence of short sleep duration suggest that work-related factors should be further evaluated as they might relate to sleep.


Influence of dietary macronutrient composition on adiposity and cellularity of different fat depots in Wistar rats.
The aim of this study was to investigate the role of dietary macronutrient content on adiposity parameters and adipocyte hypertrophy/hyperplasia in subcutaneous and visceral fat depots from Wistar rats using combined histological and computational approaches. For this purpose, male Wistar rats were distributed into 4 groups and were assigned to different nutritional interventions: Control group (chow diet); high-fat group, HF (60% E from fat); high-fat-sucrose group, HFS (45% E from fat and 17% from sucrose); and high-sucrose group, HS (42% E from sucrose). At day 35, rats were sacrificed, blood was collected, tissues were weighed and fragments of different fat depots were kept for histological analyses with the new softwareAdiposoft. Rats fed with HF, HFS and HS diets increased significantly body weight and total body fat against Control rats, being metabolic impairments more pronounced on HS rats than in the other groups. Cellularity analyses usingAdiposoft revealed that retroperitoneal adipose tissue is histologically different than mesenteric and subcutaneous ones, in relation to bigger adipocytes. The subcutaneous fat pad was the most sensitive to the diet, presenting adipocyte hypertrophy induced by HF diet and adipocyte hyperplasia induced by HS diet. The mesenteric fat pad had a similar but attenuated response in comparison to the subcutaneous adipose tissue, while retroperitoneal fat pad only presented adipocyte hyperplasia induced by the HS diet intake after 35 days of intervention. These findings provide new insights into the role of macronutrients in the development of hyperplastic obesity, which is characterized by the severity of the clinical features. Finally, a new tool for analyzing histological adipose samples is presented.


Microsatellite marker-based genetic analysis of relatedness between commercial and heritage turkeys (Meleagris gallopavo).
The turkey is second only to the chicken in importance as an agriculturally important poultry species. Unlike the chicken, however, genetic studies of the turkey continue to be limited. For example, to date, many genomic investigations have been conducted to characterize genetic relationships between commercial (CO) and non-CO chicken breeds, whereas the nature of the genetic relatedness between CO and heritage turkeys remains unknown. The objective of the current research was to use microsatellites to analyze the genetic relatedness between CO and heritage domestic turkeys including Narragansett, Bourbon Red, Blue Slate, Spanish Black, and Royal Palm. Primer pairs specific for 10 previously described turkey microsatellite markers were used. The phylogenetic analysis showed that the Blue Slate, Bourbon Red, and Narragansett were genetically closely related to the CO strain, with a Nei distance of 0.30, and the Royal Palm and Spanish Black were the least related to the CO strain, with Nei distances of 0.41 and 0.40, respectively. The present work provides a foundation for the basis of using heritage turkeys to genetically improve CO populations by introgression.


Long-Term Follow-Up of UCLP Patients: Surgical and Orthodontic Burden of Care During Growth and Final Orthognathic Surgery Need.
The goal of this study was to evaluate the craniofacial morphology at 5 and 10 years of age and at the completion of growth, the need for final orthognathic surgery, and the orthodontic burden in a sample of patients with unilateral cleft lip and palate consecutively treated by the same surgeon with the same two-step protocol. A sample of 62 adult patients with unilateral cleft lip and palate was retrospectively collected (mean age, 17.5 years). Lateral cephalograms at three time points were traced. The need for orthognathic surgery was assessed, subdividing the sample into an orthognathic surgery group and nonorthognathic surgery group. Time and modality of orthodontic treatment were recorded. Cephalometric values related to maxillary growth (SNA, SNAns) and maxillomandibular relation (ANB, NAPg) were significantly different between the two groups already at 5 and 10 years of age. All patients presenting an ANB smaller than 2° at 5 years needed a Le Fort I osteotomy. Mandibular protrusion (SNB, SNPg) was not different at 5 and 10 years, but was different at the completion of growth. Patients with the same initial maxillomandibular relation did not show better growth when subjected to earlier or longer orthodontic treatment. Patients needing final jaw surgery had a more severe skeletal discrepancy during early childhood. The ANB angle at 5 years allowed doctors to identify 45% of the need for orthognathic surgery. The final craniofacial pattern does not seem to change significantly with early or prolonged orthodontic treatment.


Asiatic acid ameliorates dextran sulfate sodium-induced murine experimental colitis via suppressing mitochondria-mediated NLRP3 inflammasome activation.
In the present study, the effect of asiatic acid, a natural triterpenoid compound, on murine experimental colitis induced by dextran sulfate sodium (DSS) and its possible mechanism were examined in vivo and vitro. Oral administration of asiatic acid dose-dependently attenuated the loss of body weight and shortening of colon length induced by DSS. The disease activity index, histopathologic scores of musco and myeloperoxidase activity were also significantly reduced by asiatic acid treatment. Protein and mRNA levels of DSS-induced pro-inflammatory cytokines in colon, including TNF-α, IL-1β, IL-6 and IFN-γ, were markedly suppressed by asiatic acid. At the same time, decreased activation of caspase-1 in peritoneal macrophages was detected in asiatic acid-treated mice, which suggested that the NLRP3 inflammasome activation was suppressed. In addition, we also found that asiatic acid dose-dependently inhibited IL-1β secretion, caspase-1 activation as well as inflammasome assembling in vitro. Furthermore, the mechanism of asiatic acid was related to the inhibition of mitochondrial reactive oxygen species generation and prevention of mitochondrial membrane potential collapse. Taken together, our results demonstrate the ability of asiatic acid to inhibit NLRP3 inflammasome activation and its potential usage in the treatment of inflammatory bowel diseases.


The Ethics and Politics of Human Experimentation, by Paul M. McNeill.
...McNeill's book raises some very important questions about the ways in which a society comes to terms with the fact that the practice of medicine is more closely linked with experimentation than ever before. That often puts the doctor-patient relation into a new setting. We have registered our objection to McNeill's tendency to see that relationship, where experimentation is involved, in an adversarial form: there are, we must repeat, more than two sides to this argument, and the medical scientist's commitment is not only to truth at any cost any more than the medical practitioner's is to treatment in all circumstances. Objections do not mean that we cannot learn from this book: on the contrary they may help us to sharpen our perceptions of what should happen. Fair-mindedness would suggest that failure to fulfill expectations is nothing like as widespread or for that matter incurable as McNeill's polemical tone might lead us to believe. When McNeill ceases to be the prosecuting counsel the true worth of his comments will become more apparent.


Origin of spontaneous rhythmicity in smooth muscle.
Rhythmic electrical activity is a feature of most smooth muscles but the mechanical consequences can vary from regular rapid phasic contractions to sustained contracture. For many years it was thought that spontaneous electrical activity originated in smooth muscle cells but recently it has become apparent that there are specialized pacemaker cells in many organs that are morphologically and functionally distinct from smooth muscle and that the former cells are the source of spontaneous electrical activity. Such a pacemaker function is well documented for the ICC of the gastrointestinal tract but evidence is accumulating that ICC-like cells play a similar role in other types of smooth muscle. We have recently shown that there are specialized pacemaking cells in the rabbit urethra which are spontaneously active when freshly isolated, readily distinguishable from smooth muscle cells under bright field illumination and relatively easy to study using patch-clamp and confocal imaging techniques. Recent results suggest that calcium oscillations in isolated rabbit urethral interstitial cells are initiated by calcium release from ryanodine sensitive intracellular stores, that oscillation frequency is very sensitive to the external calcium concentration and that conversion of the primary oscillation to a propagated calcium wave depends upon IP3-induced calcium release.


The effect of echothiophate on the biphasic response of rabbit ocular pressure to dipivefrin.
A time-course study was performed on the intraocular pressure response of pigmented rabbit eyes. Dipivefrin administration produced in initial hypertensive phase lasting less than two hours followed by a prolonged hypotensive phase. Echothiophate iodide therapy produced a more pronounced and prolonged hypertensive response; there was no hypotensive phase. Administration of echothiophate plus dipivefrin resulted in a hypertensive phase similar to that from echothiophate alone; as previously reported, this combination was not followed by a hypotensive phase. The alpha-blocker phentolamine mesylate prevented the echothiophate-induced hypertension. When dipivefrin was administered with echothiophate plus phentolamine, there was an immediate hypotensive effect. It was concluded that the hypertensive effect of echothiophate in pigmented rabbit eyes may mask the hypotensive action of dipivefrin. This, rather than an echothiophate-induced inhibition of esterases, may explain why combination therapy with these drugs seemed ineffective.


Establishment and characterization of a human adenoid cystic carcinoma cell line forming colonies cultured in collagen gel and transplantable in nude mice.
We established a new cell line (ACCNS) from human adenoid cystic carcinoma (AdCC) of the maxilla, using tissue culture techniques and it has been successfully subcultured for more than 100 passages during 2 years. The population doubling time was approximately 39.2 h on a plastic dish. In type I collagen gel culture, the cells formed spherical colonies by day 7 after seeding. The colonies showed tubular and solid structures, and eosinophilic material stained with mucicarmine was revealed in the inner space. Immunohistochemically, ACCNS cells demonstrated expressions of keratin, alpha-smooth muscle actin, vimentin and S-100 protein, similar to those of original AdCC. These findings indicate that ACCNS cells possess the characteristics of AdCC. In addition, inoculation of 4.0x10(6) cells into nude mice developed tumors that were histologically confirmed as undifferentiated carcinoma. Therefore, ACCNS is the first AdCC cell line with tumorigenicity in nude mice. Based on these results, ACCNS provides a useful culture model of AdCC to analyze the biological characteristics and behavior of this tumor.


Shotgun proteomic analysis of mulberry dwarf phytoplasma.
Mulberry dwarf (MD), which is caused by phytoplasma, is one of the most serious infectious diseases of mulberry. Phytoplasmas have been associated with diseases in several hundred plant species. The inability to culture phytoplasmas in vitro has hindered their characterization at the molecular level. Though the complete genomes of two phytoplasmas have been published, little information has been obtained about the proteome of phytoplasma. Therefore, the proteomic information of phytoplasmas would be useful to elucidate the functional mechanisms of phytoplasma in many biological processes. MD phytoplasmas, which belong to the 16SrI-B subgroup based on the 16S DNA analysis, were purified from infected tissues using a combination of differential centrifugation and density gradient centrifugation. The expressed proteome of phytoplasma was surveyed by one-dimensional SDS-PAGE and nanocapillary liquid chromatography-tandem mass spectrometry. A total of 209 phytoplasma proteins were unambiguously assigned, including the proteins with the functions of amino acid biosynthesis, cell envelope, cellular processes, energy metabolism, nucleosides and nucleotide metabolism, replication, transcription, translation, transport and binding as well as the proteins with other functions. In addition to these known function proteins, 63 proteins were annotated as hypothetical or conserved hypothetical proteins. Taken together, a total of 209 phytoplasma proteins have been experimentally verified, representing the most extensive survey of any phytoplasma proteome to date. This study provided a valuable dataset of phytoplasma proteins, and a better understanding of the energy metabolism and virulence mechanisms of MD phytoplasma.


Enhanced root-to-shoot translocation of cadmium in the hyperaccumulating ecotype of Sedum alfredii.
Sedum alfredii (Crasulaceae) is the only known Cd-hyperaccumulating species that are not in the Brassica family; the mechanism of Cd hyperaccumulation in this plant is, however, little understood. Here, a combination of radioactive techniques, metabolic inhibitors, and fluorescence imaging was used to contrast Cd uptake and translocation between a hyperaccumulating ecotype (HE) and a non-hyperaccumulating ecotype (NHE) of S. alfredii. The K(m) of (109)Cd influx into roots was similar in both ecotypes, while the V(max) was 2-fold higher in the HE. Significant inhibition of Cd uptake by low temperature or metabolic inhibitors was observed in the HE, whereas the effect was less pronounced in the NHE. (109)Cd influx into roots was also significantly decreased by high Ca in both ecotypes. The rate of root-to-shoot translocation of (109)Cd in the HE was >10 times higher when compared with the NHE, and shoots of the HE accumulated dramatically higher (109)Cd concentrations those of the NHE. The addition of the metabolic inhibitor carbonyl cyanide m-chlorophenylhydrazone (CCCP) resulted in a significant reduction in Cd contents in the shoots of the HE, and in the roots of the NHE. Cd was distributed preferentially to the root cylinder of the HE but not the NHE, and there was a 3-5 times higher Cd concentration in xylem sap of the HE in contrast to the NHE. These results illustrate that a greatly enhanced rate of root-to-shoot translocation, possibly as a result of enhanced xylem loading, rather than differences in the rate of root uptake, was the pivotal process expressed in the Cd hyperaccumulator HE S. alfredii.


Antiretroviral nonadherence and condomless sex in the HIV Outpatient Study, USA, 2007-2014.
Effective antiretroviral therapy (ART) reduces plasma HIV RNA viral load (VL) to undetectable levels and its effectiveness depends on consistent adherence. Consistent adherence and use of safe sex practices may substantially decrease the risk of HIV transmission. We sought to explore the potential association between self-reported nonadherence to ART and engaging in unsafe sexual practices capable of transmitting HIV. Using clinical and audio computer-assisted self-interview data from the prospective HIV Outpatient Study from 2007 to 2014, we assessed the frequency of self-reported ART nonadherence during the three days prior to the survey among HIV-infected persons in care and factors associated with self-reported ART nonadherence. Of 1729 patients included in this analysis (median age = 48 years, 74.3% men who have sex with men), 17% were nonadherent, 15% had a detectable VL, and 42% reported condomless anal or vaginal sex in the past six months. In multivariable analysis, self-reported nonadherence was independently associated with younger age (adjusted odds ratio [aOR] 0.8 per additional ten years, [95% CI] 0.7-1.0), non-Hispanic black race/ethnicity (aOR 1.9; 95% CI 1.4-2.6 versus white), public health insurance (aOR 1.6, 95% CI 1.2-2.3 compared with private), survey date in 2011-2014 versus 2007-2010 (aOR 0.7, 95% CI 0.5-0.9), CD4 cell count ≥ 500 versus < 200 cells/mm3 (aOR 0.3, 95% CI 0.2-0.5), greater number of ART regimen doses (aOR 1.6, 95% CI 1.3-2.2), and binge drinking (aOR 1.4, 95% CI, 1.1-1.9). In this analysis, self-reported nonadherence was not associated with engaging in condomless sex.


The relationship between gastrointestinal motility and gastric dilatation-volvulus in dogs.
Gastric dilatation-volvulus (GDV) is a devastating disease that most commonly affects large and giant-breed dogs. Though a number of risk factors have been associated with the development of GDV, the etiology of GDV remains unclear. Abnormal gastric motility patterns and delayed gastric emptying have been previously described in dogs following GDV. Work evaluating the effects of gastropexy procedures and changes to gastric motility after experimental GDV has not found the same changes as those found in dogs with naturally occurring GDV. Although the role of abnormal gastric motility in dogs with GDV will need to be clarified with additional research, such study is likely to be facilitated by improved access to and development of noninvasive measurement techniques for the evaluation of gastric emptying and other motility parameters. In particular, the availability of Food and Drug Administration-approved wireless motility devices for the evaluation of gastrointestinal motility is particularly promising in the study of GDV and other functional gastrointestinal diseases of large and giant-breed dogs.


Communicating about cancer through Facebook: a qualitative analysis of a breast cancer awareness page.
Social media channels are increasingly being used for health communication and promotion. Social networking sites such as Facebook have become popular platforms for organizations to communicate health messages and encourage user participation around health topics. While the evaluation of social media's effectiveness in health promotion is beginning to emerge in the literature, few studies have examined actual interactions and user behaviors on Facebook Pages hosted by health organizations. The authors present a qualitative case study of a popular Facebook Page from a nonprofit organization devoted to raising awareness about breast cancer. With the goal of identifying the functions and uses of the Page, our study analyzes the content of Wall posts during Breast Cancer Awareness Month, October 2010. Common themes and characteristics are identified, including open mic communication, scarcity of health information, the commodification of breast cancer, unpredictable locations of conversation, and the use of gendered images and language. The findings have potential implications for health promotion efforts using social media platforms.


Systemic radiotherapy with monoclonal antibodies. An experimental study with human neuroblastoma xenografts in nude mice.
In this experimental study, feasibility and efficiency of systemic radiotherapy with the I-131 labelled monoclonal antibody BW575/9 (radioimmunotherapy) are investigated using human SK-N-SH neuroblastoma transplanted into nude mice. Series of six nude mice were treated with intravenous application of 400 microCi (group 1), 700 microCi (group 2) of the I-131 labelled and of the unlabelled MAb (group 3). An untreated group (group 4) served as control. Tumors of group (3) and (4) showed an identical growth. In group (1), tumor growth was arrested for seven days. In group (2), the tumor showed complete regression after eight days which lasted for 55 days. Thereafter, the tumor started to regrow. This growth characteristics are correlated with the doses achieved in the tumor using a medical internal radiation dose (MIRD) formulation. The biodistribution data necessary for MIRD calculation were obtained by previously performed experiments with the I-125 labelled MAb. The doses assessed in the tumor turned out to be five to ten times greater than those in normal tissues (liver, bone, etc.) These results confirm feasibility, selectivity and efficiency of radioimmunotherapy in the above described model. Moreover, this in vivo model seems suitable for further investigations concerning fundamental issues of radioimmunotherapy.


Bioactivity of naringin and related mechanisms.
Naringin is a flavonoid compound, which can be used to treat or prevent various diseases, such as obesity, heart disease, diabetes, and metabolic syndrome. The medicinal value of naringin is mainly reflected in its antioxidant and anti-inflammatory functions, and it has a protective effect on pathophysiology. Furthermore, naringin has shown potential to become an alternative as traditional anti-inflammatory drug, because it exerts less side effects than chemically synthesized compounds. In this paper, we are reviewing the specific molecular mechanisms of anti-inflammatory and antioxidant properties of naringin. We analyze and discuss the primary role of naringin in the treatment of diseases such as acute and chronic liver injury, lung injury, bowel disease, and neurodegenerative diseases. Besides, the bactericidal effect of naringin is also reviewed.


Immunological aspects of herpetic stromal keratitis.
Herpetic stromal keratitis (HSK) is an immune reaction related to herpes simplex virus (HSV) corneal infection, and has many important immunological aspects. CD4(+) T lymphocytes, especially Th1 cells, are the principal mediators for HSK. In addition, neutrophils and antigen-presenting cells play vital roles in HSK. CD8(+) T lymphocytes, B cells, and natural killer cells all participate in the pathogenesis of HSK under certain circumstances. Many molecules are involved in the pathogenesis of HSK. Th1 cytokines such as interleukin 2 (IL-2), IL-12 and interferon gamma, and inflammatory cytokines such as IL-1alpha and IL-6 are especially important ones. Among various chemokines that take part in HSK, MIP-1alpha is one of the most important aggravating factors. Vaccination therapy against HSK has been developed; glycoprotein D is a particularly promising candidate. However, the possibility of HSK exacerbation due to vaccination is the final problem to be solved before vaccination can be clinically applied to HSK. Molecular mimicry theory and bystander activation theory are the two new autoimmune theories that have been advocated. Since genuine autoimmune HSK without HSV growth can hardly be the case in clinical practice, some part of these new theories remains controversial. In the future, better understanding of the pathogenesis of HSK is essential to resolve the paradox between suppressing the immune reaction to avoid corneal scarring and preventing viral proliferation.


Opioid stewardship training during the transition to residency to prepare medical students to recognize and treat opioid use disorder.
Background: With a drastic shortage of addiction medicine specialists-and an ever-growing number of patients with opioid use disorder (OUD)-there is a dire need for more clinicians to feel confident in prevention and management of OUD and obtain a DEA-X waiver to prescribe medications to treat OUD. Here we determine if it is feasible to certify 4th year medical students with DEA-X waiver training as a component of the PROUD (Prevent and Reduce Opioid Use Disorder) curriculum, and if PROUD enhanced preparedness for medical students to manage OUD as interns. Methods: We implemented a sequential mixed-methods IRB approved study to assess feasibility (completing all required components of DEA-X waiver training) and impact of PROUD (measured by knowledge growth, enhancement for residency, and utilization of training during internship). Students completed 11 hours of required OUD training. Quantitative data included pre-/post- knowledge and curriculum satisfaction assessments as well as long-term impact with follow up survey as interns. Qualitative data was collected by survey and semi-structured focus groups. Results: All 120 graduating medical students completed the required components of the curriculum. Knowledge improved on the Provider Clinical Support Services (12.9-17.3, p < 0.0001) and Brief Opioid Overdose Knowledge assessments (10.15-10.81, p < 0.0001). Course satisfaction was high: 90% recommended online modules; 85% recommended training overall. Six qualitative themes emerged: (1) curriculum content was practical, (2) online modules allowed flexibility, (3) in-person seminars ensured authenticity, (4) timing at the transition to residency was optimal, (5) curriculum enhanced awareness and confidence, and (6) training was applicable to future careers. At 3 months, 60% reported using their training during internship; 64% felt more prepared to treat OUD than peers. Conclusions: PROUD trained 4th year medical students in opioid stewardship. As interns, students felt ready to serve as change agents to prevent, diagnose, and treat OUD.


Smallpox vaccination revisited. Some observations on the biology of vaccinia.
Sixty-two volunteers were studied to determine their local cutaneous, serologic, and virologic reactions to smallpox revaccination. Of 55 subjects available for examination, 45 (82%) had major cutaneous reactions. Subjects over 30 years old were more likely to have a major reaction. An increase in complement-fixing antibody titer was found in 74% of revaccinees with a major reaction. An increase in complement-fixing antibody titer was found in 74% of revaccinees with a major cutaneous reaction and is felt to be the best serologic indicator revaccination did not yield vaccinia virus. Cultures of the vaccination site demonstrated the virus to be present for a mean of 7.8 days (range 0--18 days) which coincided with separation correlate with antibody response. However, subjects vaccinated more than 3 years previously and subjects with major skin reactions shed vaccinia virus for longer periods than those vaccinated less than 3 years previously or who had equivocal reactions.


Rate of Insulin Dimer Dissociation: Interplay between Memory Effects and Higher Dimensionality.
We calculate the rate of dissociation of an insulin dimer into two monomers in water. The rate of this complex reaction is determined by multiple factors that are elucidated. By employing advanced sampling techniques, we first obtain the reaction free energy surface for the dimer dissociation as a function of two order parameters, namely, the distance between the center-of-mass of two monomers (R) and the number of cross-contacts (Q) among the backbone Cα atoms of two monomers. We then construct an orthogonal 2D reaction energy surface by introducing the reaction coordinate X to denote the minimum energy pathway and a conjugate coordinate Y that spans the orthogonal direction. The free energy landscape is rugged with multiple maxima and minima. We calculate the rate by employing not only the non-Markovian multidimensional rate theory but also several other theoretical approaches. The necessary reaction frequencies and the frictions are calculated from the time correlation function formalism. Our best estimate of the rate is 0.4 μs-1. Our study reveals interesting opposite influences of dimensionality and memory in determining the rate constant of the reaction. We gain interesting insights into the dimer dissociation process by looking directly at the trajectories obtained from molecular dynamics simulation.


Spectral, structural, and electrochemical properties of ruthenium porphyrin diaryl and aryl(alkoxycarbonyl) carbene complexes: influence of carbene substituents, porphyrin substituents, and trans-axial ligands.
A wide variety of ruthenium porphyrin carbene complexes, including [Ru(tpfpp)(CR(1)R(2))] (CR(1)R(2) = C(p-C(6)H(4)Cl)(2) 1 b, C(p-C(6)H(4)Me)(2) 1 c, C(p-C(6)H(4)OMe)(2) 1 d, C(CO(2)Me)(2) 1 e, C(p-C(6)H(4)NO(2))CO(2)Me 1 f, C(p-C(6)H(4)OMe)CO(2)Me 1 g, C(CH==CHPh)CO(2)CH(2)(CH==CH)(2)CH(3) 1 h), [Ru(por)(CPh(2))] (por=tdcpp 2 a, 4-Br-tpp 2 b, 4-Cl-tpp 2 c, 4-F-tpp 2 d, tpp 2 e, ttp 2 f, 4-MeO-tpp 2 g, tmp 2 h, 3,4,5-MeO-tpp 2 i), [Ru(por)[C(Ph)CO(2)Et]] (por=tdcpp 2 j, tmp 2 k), [Ru(tpfpp)(CPh(2))(L)] (L = MeOH 3 a, EtSH 3 b, Et(2)S 3 c, MeIm 3 d, OPPh(3) 3 e, py 3 f), and [Ru(tpfpp)[C(Ph)CO(2)R](MeOH)] (R = CH(2)CH==CH(2) 4 a, Me 4 b, Et 4 c), were prepared from the reactions of [Ru(por)(CO)] with diazo compounds N(2)CR(1)R(2) in dichloromethane and, for 3 and 4, by further treatment with reagents L. A similar reaction of [Os(tpfpp)(CO)] with N(2)CPh(2) in dichloromethane followed by treatment with MeIm gave [Os(tpfpp)(CPh(2))(MeIm)] (3 d-Os). All these complexes were characterized by (1)H NMR, (13)C NMR, and UV/Vis spectroscopy, mass spectrometry, and elemental analyses. X-ray crystal structure determinations of 1 d, 2 a,i, 3 a, b, d, e, 4 a-c, and 3 d-Os revealed Ru==C distances of 1.806(3)-1.876(3) A and an Os==C distance of 1.902(3) A. The structure of 1 d in the solid state features a unique "bridging" carbene ligand, which results in the formation of a one-dimensional coordination polymer. Cyclic voltammograms of 1 a-c, g, 2 a-d, g-k, 3 b-d, 4 a, b, and 3 d-Os show a reversible oxidation couple with E(1/2) values in the range of 0.06-0.65 V (vs Cp(2)Fe(+/0)) that is attributable to a metal-centered oxidation. The influence of carbene substituents, porphyrin substituents, and trans-ligands on the Ru==C bond was examined through comparison of the chemical shifts of the pyrrolic protons in the porphyrin macrocycles ((1)H NMR) and the M==C carbon atoms ((13)C NMR), the potentials of the metal-centered oxidation couples, and the Ru==C distances among the various ruthenium porphyrin carbene complexes. A direct comparison among iron, ruthenium, and osmium porphyrin carbene complexes is made.


Employer-sponsored health insurance for chiropractic services.
The use of chiropractors has increased substantially in recent years, and there is growing scientific evidence on the effectiveness of chiropractic treatment for common low back ailments. Despite the increased acceptance of chiropractic care, little is known about the prevalence of chiropractic coverage in employer health plans and the nature of such benefits when they are provided. This article reports on the extent and composition of chiropractic insurance among workers with employer-sponsored health insurance in 1993. The prevalence of the benefits in employer plans was examined, as was the extent to which plans are in compliance with state mandated benefits in this area. The authors also examined what the actual benefits consist of and how they compare with those for physician office visits and physical therapy.


LAR Downregulation Protects the Astrocytic U251 and Cocultured SH-SY5Y Cells in a Rotenone-Induced Parkinson's Disease Cell Model.
Leukocyte common antigen-related protein tyrosine phosphatase (LAR) is a member of the protein tyrosine phosphatase family that serves as a key regulator of cellular survival. It is also involved in neurodevelopment and brain disorders. This study was designed to investigate the role of LAR in a cell-based model of Parkinson's disease (PD) in which U251 and SH-SY5Y cells were used as models of astrocytes and dopaminergic neurons, respectively. Cell viability, cell death, cell morphology, protein phosphorylation and expression, ATP levels, reactive oxygen species (ROS) generation, and mitochondrial membrane potential were analyzed in the wild-type (WT) and heterozygous LAR-knockout astrocytoma U251 cells to assess the cell state, signal transduction, and mitochondrial function. LAR downregulation showed a protective effect in rotenone-exposed U251 cells by increasing cell viability, reducing cell mortality, and restoring appropriate cellular morphology. LAR downregulation enhanced IGF-1R phosphorylation and downstream signal transduction as evidenced by increases in the Akt and GSK-3β phosphorylation, as well as the upregulation of NRF2 and HO-1. The downregulation of LAR also augmented DJ-1 levels in these cells. The enhanced Akt and GSK-3β phosphorylation contributed to a reduced Bax/Bcl2 ratio and suppressed apoptosis after rotenone exposure. Heterozygous LAR-knockout U251 cells exhibited higher mitochondrial function evidenced by increased mitochondrial membrane potential, ATP contents, and reduced ROS production compared to the WT cells following rotenone exposure. Further studies showed that the astrocytic protection mediated by the heterozygous knockout of LAR was associated with the activation of Akt. A specific Akt inhibitor, MK2206, reduced the cell viability, Akt and GSK3β phosphorylation, and HO-1 and NRF2 expression in U251 cells exposed to rotenone. Astrocytes provide structural and metabolic support to maintain neuronal health. Astrocytic glial cell-derived neurotrophic factor (GDNF) production is vital for dopaminergic neuron survival. Heterozygous LAR-knockout U251 cells produced higher amounts of GDNF than the WT cells. The SH-SY5Y cells cocultured with heterozygous LAR-knockout U251 cells exhibited greater viability than that of cells cocultured with WT U251 cells in response to rotenone. Together, these findings demonstrate that the heterozygous knockout of LAR in astrocytes can play a key role in protecting both astrocytic cells and cocultured neurons in a rotenone-induced cell-based model of PD. This neuroprotective effect is attributable to the augmentation of IGF1R-Akt-GDNF signaling and the maintenance of astrocytic mitochondrial function.


Golden Glittering Biocomposite Fibers from Poly(lactic acid) and Nanosilver-Coated Titanium Dioxide with Unique Properties; Antimicrobial, Photocatalytic, and Ion-Sensing Properties.
Golden glittering biocomposite fibers from poly(lactic acid) (PLA) and nanosilver-coated titanium dioxide (Ag/TiO2) were successfully prepared via a melt spinning process. Various contents of 10% Ag/TiO2/PLA masterbatch were diluted with PLA in concentrations of 5, 10, 15, 20, 25, and 30 phr, respectively. The physical, mechanical, thermal, and antibacterial properties of the obtained fibers were investigated. The results indicated that the glittering biocomposite fiber had a light, yellow-gold color and a slightly rough surface. Tenacity and elongation at break of the glittering biocomposite fibers were lower than those of the pristine PLA fiber. The thermal properties of the glittering composite fibers also decreased with increasing masterbatch content. The PLA/PEG-10 biocomposite fiber with good spinnability and mechanical properties was suitably used for preparing the golden glittering composite fabric by the knitting process. Moreover, the golden glittering biocomposite fabrics exhibited antibacterial activity against certain microbes, for example, Staphylococcus aureus, Bacillus subtilis, and Candida albicans. The prepared fabric has significant potential for use in eco-friendly textile products and antibacterial fabrics. Besides, our novel textiles showed not only the photocatalytic property needed to degrade organic dyes such as methylene blue in water but also the ion-sensing property for mercury(II) ions by changing the textile color from yellow to colorless.


Living donor adult liver transplantation: a longitudinal study of the donor's quality of life.
We report the results of a prospective, longitudinal quality of life survey on our adult right lobe (RL) liver donors. A total of 47 donors were enrolled; a standard SF-36 form and 43 questions developed by our team were completed before donation, at 1 week, and 1, 3, 6 and 12 months after donation. There were no donor deaths. Twenty-nine complications occurred in 16 patients. Major complication rate was 12.8%. Employment status and personal finances were identified as major stressors. All donors who wished to return to work did so by 1 year (mean 3.4 months). Individuals reported between 0 dollars and 25,000 dollars in losses (wages, travel, lodging, etc.). Relationships with recipients and other family members were not altered significantly. Anticipated pain (predonation) was greater than actual pain reported. Donors indicated satisfaction with the donation process regardless of recipient outcome. Physical complaints were significant at 1 week and 1 month, but returned to baseline. Donor mental health remained stable. In conclusion, RL donors found the experience to be a positive one throughout the first postdonation year. The study identified areas (finances, employment and expected recipient outcomes) to be stressed as future donors are evaluated.