Mobility in Older Adults Receiving Maintenance Hemodialysis: A Qualitative Study.
For older adults, maintaining mobility is a major priority, especially for those with advanced chronic diseases like kidney failure. However, our understanding of the factors affecting mobility in older adults receiving maintenance hemodialysis is limited. Descriptive qualitative study. Using purposive sampling, we recruited (1) persons aged≥60 years receiving maintenance hemodialysis; and (2) care partners (≥18 years) providing regular support to an older adult receiving hemodialysis. During a single in-person home visit, we assessed mobility using the Short Physical Performance Battery (SPPB) and conducted individual one-on-one interviews regarding important personal factors related to mobility. Descriptive statistics were used for demographic and SPPB data. Transcripts underwent thematic coding, informed by the International Classification of Function framework of mobility. We used conceptual content analysis to inductively extract themes and subthemes. We enrolled 31 older adults receiving hemodialysis (42% female, 68% Black) with a mean age of 73±8 years and mean dialysis vintage of 4.6±3.5 years; their mean SPPB score was 3.6±2.8 points. Among 12 care partners (75% female, 33% Black), the mean age was 54±16 years and mean SPPB score was 10.1±2.4 points. Major themes extracted were (1) mobility represents independence; (2) mobility is precarious; (3) limitations in mobility cause distress; (4) sources of encouragement and motivation are critical; and (5) adaptability is key. Modest sample from single geographic area. For older adults receiving hemodialysis, mobility is severely limited and is often precarious in nature, causing distress. Older adults receiving hemodialysis and their care partners have identified sources of encouragement and motivation for mobility, and cite an adaptable mindset as important. Future studies should conceptualize mobility as a variable condition and build on this outlook of adaptability in the development of interventions.


Steroid-Enriched Fraction of Achyranthes bidentata Protects Amyloid β Peptide 1-40-Induced Cognitive Dysfunction and Neuroinflammation in Rats.
The roots of Achyranthes bidentata Blume (AB) is commonly used in the treatment of osteoporosis and dementia in traditional Chinese medicine. Pharmacological reports evidenced that AB possessed anti-osteoarthritis effects. However, there is little literature about the anti-dementia activities of AB. The present study was designed to prepare steroid-enriched fraction of AB (ABS) and investigate whether ABS can protect from cognitive dysfunction and neuroinflammation against Aβ 1-40-induced Alzheimer's disease (AD) model in rats. ABS only contained 135.11 ± 4.28 mg of ecdysterone per gram. ABS (50 mg/kg) reversed the dysfunction of exploratory activity and memory function on plus-maze and Morris water maze caused by Aβ 1-40 in rats. ABS (50 mg/kg) also decreased amyloid deposition, neurofibrillary tangle, neural damage, activated astrocyte, and microglial caused by Aβ 1-40. Furthermore, ABS reversed the phenomenon of neural oxidative damage and neuroinflammation, including the higher levels of MDA and cytokines, and the lower activities of antioxidant enzymes and GSH levels caused by Aβ 1-40 in rat cortex and hippocampus. Finally, ABS restored the activation of ERK pathway and decreased NF-κB phosphorylation and translocation altered by Aβ 1-40. ABS alone (50 mg/kg) promoted cognitive function, activated brain antioxidant defense system, and decreased brain TNF-α levels in sham group. Therefore, ABS has the cognition-promoting and antidementia potential. Steroids especial ecdysterone are major active components of AB. The action mechanism is due to decreasing oxidative stress and neuroinflammation through modulating ERK pathway, NF-κB phosphorylation, and translocation in Aβ 1-40-induced AD rat model.


Novel biomarker-based model for the prediction of sorafenib response and overall survival in advanced hepatocellular carcinoma: a prospective cohort study.
Prediction of the outcome of sorafenib therapy using biomarkers is an unmet clinical need in patients with advanced hepatocellular carcinoma (HCC). The aim was to develop and validate a biomarker-based model for predicting sorafenib response and overall survival (OS). This prospective cohort study included 124 consecutive HCC patients (44 with disease control, 80 with progression) with Child-Pugh class A liver function, who received sorafenib. Potential serum biomarkers (namely, hepatocyte growth factor [HGF], fibroblast growth factor [FGF], vascular endothelial growth factor receptor-1, CD117, and angiopoietin-2) were tested. After identifying independent predictors of tumor response, a risk scoring system for predicting OS was developed and 3-fold internal validation was conducted. A risk scoring system was developed with six covariates: etiology, platelet count, Barcelona Clinic Liver Cancer stage, protein induced by vitamin K absence-II, HGF, and FGF. When patients were stratified into low-risk (score ≤ 5), intermediate-risk (score 6), and high-risk (score ≥ 7) groups, the model provided good discriminant functions on tumor response (concordance [c]-index, 0.884) and 12-month survival (area under the curve [AUC], 0.825). The median OS was 19.0, 11.2, and 6.1 months in the low-, intermediate-, and high-risk group, respectively (P < 0.001). In internal validation, the model maintained good discriminant functions on tumor response (c-index, 0.825) and 12-month survival (AUC, 0.803), and good calibration functions (all P > 0.05 between expected and observed values). This new model including serum FGF and HGF showed good performance in predicting the response to sorafenib and survival in patients with advanced HCC.


Influence of Organic Chemicals on Water Molecule Bridges in Soil Organic Matter of a Sapric Histosol.
Water molecules in soil organic matter (SOM) can form clusters bridging neighboring molecular segments (water molecule bridges, WaMBs). WaMBs are hypothesized to enhance the physical entrapment of organic chemicals and to control the rigidity of the SOM supramolecular structure. However, the understanding of WaMBs dynamics in SOM is still limited. We investigated the relation between WaMBs stability and the physicochemical properties of their environment by treating a sapric histosol with various solvents and organic chemicals. On the basis of predictions from molecular modeling, we hypothesized that the stability of WaMBs, measured by differential scanning calorimetry, increases with the decreasing ability of a chemical to interact with water molecules of the WaMBs. The interaction ability between WaMBs and the chemicals was characterized by linear solvation energy relationships. The WaMBs stability in solvent-treated samples was found to decrease with increasing ability of a solvent to undergo H-donor/acceptor interactions. Spiking with an organic chemical stabilized (naphthalene) or destabilized (phenol) the WaMBs. The WaMBs stability and matrix rigidity were generally reduced strongly and quickly when hydrophilic chemicals entered the soil. The physicochemical aging following this destabilization is slow but leads to successive WaMBs stabilization and matrix stiffening.


[Complex endovascular repairs of the aortic arch.]
Thoracic endovascular aneurysm repair (TEVAR) of the aortic arch has started to spread in recent years. We present our initial experience with TEVAR involving supra-aortic branches using parallel and branched grafts. Parallel grafts are typically used in emergency cases. In the case of Z0 proximal fixation, we can perform a combined hybrid surgery with Z1 debranching and securing of the innominate artery with chimney graft, which can also be used instead of Z0 debranching when the patient is unfit for sternotomy. In the case of TEVAR with planned Z2 position with inadvertent covering of the left common carotid artery, we can perform chimney conversion to rapidly recover the circulation of the left common carotid artery (LCCA). Instead of prior revascularization of the left subclavian artery, chimney graft can be used to recover the lumen, in the case of left upper limb ischemia after Z2 TEVAR. Exclusion of penetrating aortic ulcers located in the lesser curvature can be facilitated by use of a custom-made graft, where a scallop is placed around the origin of the supra-aortic vessel, thus increasing the length of the proximal neck. For elective interventions, custom-made branching grafts can be allowed to save all three branches with Z0 fixation. Technical success was obtained in all cases. Orv Hetil. 2023; 164(11): 426-431.


Polyethylene glycol-poly(ε-benzyloxycarbonyl-l-lysine)-conjugated VEGF siRNA for antiangiogenic gene therapy in hepatocellular carcinoma.
A polyethylene glycol-poly(ε-benzyloxycarbonyl-l-lysine) (PEG-SS-PLL) block copolymer based on a disulfide-linked, novel biodegradable catiomer bearing a PEG-sheddable shell was developed to avoid "PEG dilemma" in nanoparticle intracellular tracking of PEG-PLL where PEG was nondegradable. However, PEG-SS-PLL catiomers have not been used to deliver small interfering VEGF RNA (siVEGF) in antiangiogenesis gene therapy. In this study, we aimed to investigate whether this novel biodegradable catiomer can deliver siVEGF into cancer cells and at the same time have an antitumor effect in a xenograft mouse model. It was found that PEG-SS-PLL efficiently delivered siVEGF with negligible cytotoxicity, and significantly decreased the expression of VEGF at both the messenger-RNA and protein levels both in vitro and in vivo, and thus tumor growth was inhibited. Our findings demonstrated that PEG-SS-PLL/siVEGF could potentially be applied to antiangiogenesis gene therapy for hepatocellular carcinoma.


Circulating plasma exosomal long non-coding RNAs LINC00265, LINC00467, UCA1, and SNHG1 as biomarkers for diagnosis and treatment monitoring of acute myeloid leukemia.
Exosomal long non-coding RNAs (lncRNAs) have emerged as a cell-free biomarker for clinical evaluation of cancers. However, the potential clinical applications of exosomal lncRNAs in acute myeloid leukemia (AML) remain unclear. Herein, we attempted to identify plasma exosomal lncRNAs as prospective biomarkers for AML. In this study, plasma exosomes were first successfully extracted from AML patients and healthy donors (HD). Subsequently, the downregulated plasma exosomal lncRNAs (LINC00265, LINC00467, and UCA1) and the upregulated plasma exosomal lncRNA (SNHG1) were identified in AML patients (n=65) compared to HD (n=20). Notably, individual exosomal LINC00265, LINC00467, UCA1, or SNHG1 had a capability for discriminating AML patients from HD, and their combination displayed better efficiency. Furthermore, exosomal LINC00265 and LINC00467 were increased expressed in patients achieving complete remission after chemotherapy. Importantly, there was upregulation of exosomal LINC00265 and downregulation of exosomal SNHG1 upon allogeneic hematopoietic stem cell transplantation. Additionally, these lncRNAs were high stability in plasma exosomes. Exosomal LINC00265, LINC00467, UCA1, and SNHG1 may act as promising cell-free biomarkers for AML diagnosis and treatment monitoring and provide a new frontier of liquid biopsy for this type of cancer.


Changes in retail tobacco product sales and market share among retail payroll establishments in the U.S. Economic Census between 1997 and 2017.
The tobacco industry spends the vast majority of their marketing and promotional budget at retail outlets. However, few studies have used publicly available data to examine trends in the number and types of retail establishments where tobacco products are sold. Using the U.S. Economic Census for 1997, 2002, 2007, 2012 and 2017 (the latest year), we examined the number, type, and sales of payroll establishments selling tobacco products. Nine store types accounted for 94% - 99% of tobacco product sales between 1997 and 2017. Gas/convenience stores had the greatest market share (33% - 49% of tobacco sales). The number of warehouse clubs selling tobacco quadrupled; however, market share only increased from 9.6% to 10.3%. Supermarkets experienced the largest decrease in percent of stores selling tobacco. Pharmacy tobacco sales increased in 2012 then decreased in 2017; per store sales volume more than doubled between 1997 and 2012. Online shopping accounted for less than 1% of the market share between 1997 and 2012, but rose to 6.3% in 2017. Between 1997 and 2017, consumers shifted where they purchased tobacco products. Declining tobacco sales in supermarkets is a promising trend for consumers seeking healthy food without exposure to tobacco product marketing; however, the consistently large number of tobacco retailers, and thus widespread tobacco availability, is concerning. Consumer tobacco purchase changes over time support the case for point-of-sale policies that affect different retail types, including pharmacy bans, to reduce tobacco retailer density. Additionally, the rapid shift to online tobacco purchasing in 2017 identifies a new target for enhanced regulation and enforcement.


Physicians and futile care: using ethics committees to slow the momentum.
Given the history of the medical profession's diffident attitude toward patients' rights and its reliance on well-meaning paternalism, the notion that doctors should determine futility and limit access to specific interventions must be carefully scrutinized. Indeed, the emergence of two other themes in health policy and ethics, in particular the living will/power of attorney initative on the one hand and the open discussion of rationing care in Oregon on the other, tends to undermine the key rationales for physician control over futile care. Careful review of all three trends suggests that we ought to brake the momentum in favor of physician determination of futility of care and that ethics committees can be the vehicle to address this goal.


Virological Response to Conventional Interferon Therapy Combined with Ribavirin against Various HCV Genotypes in Khyber Pakhtunkhwa, Pakistan.
Response to antiviral therapy has been linked to different genotypes and this impacts on clinical management. Data on general responses to standard interferon (IFN) against HCV infection exists but little is known regarding HCV genotype specific responses. Therefore, we attempted to determine genotype specific responses of chronic HCV patients, having different HCV genotypes, to standard IFN and ribavirin combination therapy administered for a period of six months in Kybher Pakhtunkhwa province of Pakistan. HCV genotype was determined for all serum samples. Each patient received standard IFN combination therapy with ribavirin administered at dose of 3 MIU three times a week and 800-1200 mg/ day, respectively, for a period of six months. After completion of this therapy, PCR was performed for all course completed subjects. Out of total 51 selected patients the most abundant genotypes were 3a (49.0%) and 1a (21.6%) followed by 3b (9.8%), 1b (7.84%), 2a (7.84%) and untypable (3.94%). Moast responsive genotypes were 2a followed by 3a, with end of treatment responses of 77.7%, and 72.2%. Responses for 3b, 1b and untypable were 66.7%, 33.3% and 0%, respectively. IFN response is efficient in case of 2a and 3a genotypes while in case of untypable genotypes, further categorization is required to know about genomic sequences and to adopt some new regimes against these genotypes.


Use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis for rapid confirmation of Burkholderia pseudomallei in septicemic melioidosis.
Burkholderia pseudomallei was quickly identified from blood cultures collected from septicemic patients by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis using an in-house reference library. This procedure reduced the time to definitive identification by more than 24 hours. This analysis is a useful addition to laboratory methods for early recognition of septicemic melioidosis in non-endemic settings.


Refractory Thrombocytopenia with Multilineage Dysplasia: A Rare Type of Myelodysplastic Syndrome.
Thrombocytopenia may be the presenting cytopenia of myelodysplastic syndrome (MDS) and is named as refractory thrombocytopenia (RT) and categorized in the refractory cytopenia with multilineage dysplasia (RCMD) group according to the recent World Health Organization (WHO) classification of the acute leukemias and MDS. Abnormal cytogenetics can be found in 60% to 80% of patients with MDS. Most common cytogenetic abnormalities include monosomy 5, 5q-, monosomy 7, trisomy 8, deletion 20q and loss of X or Y chromosome. Here we report clinical features and outcomes of nine patients with RT. Cytogenetic abnormalities were detected in seven. Among two patients who have a normal karyotype at diagnosis, one of them transformed to acute myeloid leukemia (AML). During a median follow-up of 29 months, two patients died of hemorrhagia and one of AML. The features and prognosis of patients with RT needs to be determined by larger series.


Galactose-Containing Polymer-DOX Conjugates for Targeting Drug Delivery.
A novel multifunctional drug delivery system was fabricated by conjugating galactose-based polymer, methoxy-poly(ethylene glycol)-block-poly(6-O-methacryloyl-D-galactopyranose) (mPEG-b-PMAGP) with doxorubicin (DOX) via an acid-labile carbamate linkage. The mPEG-b-PMAGP-co-DOX nanoparticles were spherical in shape, and the diameter determined by dynamic light scattering (DLS) was 54.84 ± 0.58 nm, larger than that characterized by transmission electron microscopy (TEM). The in vitro drug release profiles were studied, and the release of DOX from the nanoparticles was pH-responsive. The cellular uptake behavior of free-DOX and mPEG-b-PMAGP-co-DOX nanoparticles by asialoglycoprotein (ASGP) receptor-positive cancer cell line (HepG2) and ASGP receptor-negative cancer cell lines (MCF-7 and A549 cells) was evaluated by confocal laser scanning microscopy (CLSM) and flow cytometry (FCM), respectively. The mPEG-b-PMAGP-co-DOX nanoparticles which contain galactose functional groups exhibited higher cellular uptake behavior via ASGP receptor-mediated endocytosis in HepG2 cells than in other two cancer cells. The in vitro cytotoxicity assay manifested that the mPEG-b-PMAGP-co-DOX nanoparticles exhibited higher anticancer efficacy against HepG2 cells than MCF-7 cells. These results indicated that the multifunctional mPEG-b-PMAGP-co-DOX nanoparticles possessing pH-responsible and hepatoma-targeting function have great potential to be used as a targeting drug delivery system for hepatoma therapy.


Protection of islet cells from inflammatory cell death in vitro.
Islet cells cocultured with activated macrophages are lysed within 15 h in vitro. We showed previously that nitric oxide generated by macrophages is a major mediator of islet cell death. We have now probed several pathways to interfere with the chain of events leading to islet cell death. Scavenging of extracellular oxygen radicals by superoxide dismutase and catalase did not improve islet cell survival. Scavenging of extra- and intracellular oxygen radicals by two potent substances, citiolone and dimethyl-thiourea, also did not reduce islet cell lysis, while a lipid-soluble scavenger, probucol, provided partial protection. These findings argue against a synergistic action of nitric oxide and oxygen radicals in islet cell toxicity. The inhibition of poly(ADP-ribose)polymerase by 3-aminobenzamide significantly improved islet cell survival. Selective inhibitors of cyclooxygenase, such as indomethacin or acetylsalicylic acid, did not improve islet cell survival. Full protection was seen in the presence of NDGA, an inhibitor of lipoxygenase, and partial suppression was caused by BW755c, an inhibitor of both lipoxygenase and cyclooxygenase. We conclude that inflammatory islet cell death caused by activated macrophages involves the activation of arachidonic acid metabolism and of poly(ADP-ribose)polymerase, but that scavenging of oxygen free radicals provides little protection from lysis.


Overcoming healthcare workers vaccine refusal--competition between egoism and altruism.
Vaccination reduces the risk of becoming infected with and transmitting pathogens. The role of healthcare workers (HCWs) in controlling and limiting nosocomial infections has been stressed repeatedly. This has also been recognised at a political level, leading the European Council of Ministers in 2009 to encourage coverage of 75% seasonal influenza vaccine in HCWs. Although there are policies, recommendations and well-tolerated vaccines, still many HCWs refuse to get vaccinated. This article uses literature from psychology and behavioural economics to understand vaccination decisions and the specific situation of HCWs. HCWs are expected to be highly motivated to protect others. However, their individual vaccination decisions follow the same principles (of weighting individual risks) as everyone else's vaccination decisions. This will lead to decisional conflict in a typical social dilemma situation, in which individual interests are at odds with collective interests. Failure to get vaccinated may be the result. If we understand the motivations and mechanisms of HCWs' vaccine refusal, interventions and campaigns may be designed more effectively. Strategies to increase HCWs' vaccine uptake should be directed towards correcting skewed risk perceptions and activating pro-social motivation in HCWs.


Surface Activity and Ca2+-Dependent Aggregation Property of Lichenysin Produced by Bacillus licheniformis NBRC 104464.
Bacillus licheniformis NBRC 104464 produces a cyclic lipopeptide different from surfactin. After we performed liquid chromatography fractionation and purification, we used structural analyses to identify the cyclic lipopeptide as lichenysin. Surface tension measurements of lichenysin sodium salt in water yielded a critical micelle concentration (CMC) of 1.0×10-5 M. The surface tension at the CMC was 28.9 mN/m. Comparative analysis of Ca2+-influenced micellar aggregation of lichenysin and surfactin revealed that the formation rate of the lichenysin-Ca2+ complex aggregate remained low up to a [Ca2+]/[lichenysin] molar ratio of 80, whereas the surfactin-Ca2+ complex formed micellar aggregates at the same molar ratio. Further excessive addition of Ca2+ to the micellar solution of lichenysin induced higher turbidity than surfactin.


Inherited levels of A and B types of monoamine oxidase activity.
In establishing the role of inherited variations in levels of monoamine oxidase (MAO) activity in neuropsychiatric diseases, it is important to measure levels of both A and B types of activity as they appear to be under separate genetic control. Levels of A and B types of activity can be evaluated in fibroblasts and platelets, respectively. A number of genes could be involved in determining levels of activity, including those coding for the catalytic and noncatalytic subunits of the enzyme, as well as those coding for enzymes involved in covalent attachment of the flavin cofactor, other processing steps, degradation of MAO, and lipid metabolism. Different genes may be critical in controlling activity levels in various cell types depending on differential expression of the genome. In order to establish the molecular basis of variation in activity, techniques should be employed to assess the structure and conformation of the enzyme, as well as the number of enzyme molecules and their interaction with other cellular components. Only by understanding the genetic and environmental factors controlling levels of A and B types of MAO activity can we hope to evaluate and manipulate the role of MAO in human neurophysiology.


OPA3, mutated in 3-methylglutaconic aciduria type III, encodes two transcripts targeted primarily to mitochondria.
3-Methylglutaconic aciduria type III (3-MGCA type III), caused by recessive mutations in the 2-exon gene OPA3, is characterized by early-onset bilateral optic atrophy, later-onset extrapyramidal dysfunction, and increased urinary excretion of 3-methylglutaconic acid and 3-methylglutaric acid. Here we report the identification of a novel third OPA3 coding exon, the apparent product of a segmental duplication event, resulting in two gene transcripts, OPA3A and OPA3B. OPA3A deficiency (as in optic atrophy type 3) causes up-regulation of OPA3B. OPA3 protein function remains unknown, but it contains a putative mitochondrial leader sequence, mitochondrial sorting signal and a peroxisomal sorting signal. Our green fluorescent protein tagged OPA3 expression studies found its localization to be predominantly mitochondrial. These findings thus place the cellular metabolic defect of 3-MGCA type III in the mitochondrion rather than the peroxisome and implicate loss of OPA3A rather than gain of OPA3B in disease etiology.


[Magnetic resonance cholangiopancreatography: an advanced technique in the diagnosis of biliopancreatic diseases (the first experience in Panama)].
We evaluated the biliopancreatic pathology by a non invasive method of Choloangiqgraphy by Magnetc Resonance (the first experience in Panamá). We correlated the method with the retrograde cholangiopancreatography, the surgical findings and the clinical evolution. Our conclusion is that the non invasive method allows us to have confidence in the findings for the biliopancreatic pathology.


Purification of the colony-stimulating factor 1 receptor and demonstration of its tyrosine kinase activity.
Colony-stimulating factor 1 (CSF-1) regulates the survival, proliferation, and differentiation of mononuclear phagocytes. The CSF-1 receptor was purified from cell membranes of the J774.2 mouse macrophage cell line by solubilization with Triton X-100, CSF-1 affinity chromatography, and gel filtration. The purified receptor is a protein or glycoprotein of 165 kDa comprising a single polypeptide chain that is not covalently associated, either as a homopolymer, or with any other protein. CSF-1 stimulated autophosphorylation of the purified receptor in tyrosine residues. Casein but not histone was shown to act as a substrate for the tyrosine protein kinase activity of purified receptor.


Serotonin regulation of T-cell subpopulations and of macrophage accessory function.
The role of serotonin as an immune modulator was investigated by measuring the functional competence of T cells from control mice versus from mice whose intracellular stores of serotonin had been depleted by pretreatment with p-chlorophenylalanine (PCPA). While the proportions of splenic CD4+ and CD8+ T cells isolated from control and PCPA-treated mice were similar, the level of expression of the alpha-chain interleukin-2 receptor (IL-2R) was reduced on splenic CD4+ cells but not on CD8+ cells. Culture with the T-cell mitogen concanavalin A (Con A) failed to induce expression of the IL-2R on either CD4+ or CD8+ cells of PCPA-treated mice, although IL-2R was induced on control cells. The proliferative response to Con A by these spleen cells from PCPA-treated mice was also reduced compared to that by control spleen cells. Both expression of IL-2R and proliferation in response to Con A by spleen cells from serotonin-depleted mice were increased or completely restored by supplementation of the cultures with serotonin. Studies to identify the mechanisms for the reduction in T-cell activation when serotonin levels were reduced implicated a defect in the capacity of macrophages from PCPA-treated mice to provide accessory help for T-cell activation. Splenic macrophages from control mice were able to restore the blastogenic capability of lymphocytes from PCPA-treated mice, although macrophages from PCPA-treated mice were unable to support normal lymphocyte blastogenesis unless the cultures were supplemented with serotonin. These results show the requirement of autologous serotonin for optimal T-cell activation and suggest the importance of serotonin in macrophage accessory function for T-cell activation.


Lateral and Vertical Two-Dimensional Layered Topological Insulator Heterostructures.
The heterostructured configuration between two-dimensional (2D) semiconductor materials has enabled the engineering of the band gap and the design of novel devices. So far, the synthesis of single-component topological insulator (TI) 2D materials such as Bi2Se3, Bi2Te3, and Sb2Te3 has been achieved through vapor phase growth and molecular beam epitaxy; however, the spatial controlled fabrication of 2D lateral heterostructures in these systems has not been demonstrated yet. Here, we report an in situ two-step synthesis process to form TI lateral heterostructures. Scanning transmission electron microscopy and energy-dispersive X-ray mapping results show the successful spatial control of chemical composition in these as-prepared heterostructures. The edge-induced growth mechanism is revealed by the ex situ atomic force microscope measurements. Electrical transport studies demonstrate the existence of p-n junctions in Bi2Te3/Sb2Te3 heterostructures.


Colloidal particles with complex microstructures via phase separation in swelled polymer microspheres.
Polymer microparticles with complex microstructures, including cut spheres, bowl-like particles, hollow spheres with holes and porous hollow spheres, were prepared via phase separation in polymer microspheres. The incorporation of sulfonic acid groups is crucial, and the resulting microparticles are in sharp contrast to those prepared from regular polystyrene microspheres.


Glucocorticoid regulation of the inflammatory response to injury.
During the first half of the 20th century, physiologists were interested in the adrenal glands primarily because adrenalectomized animals failed to survive even mild degrees of systemic stress. It eventually became clear that hormones secreted by the adrenal cortex were critical for survival and, in this context, adrenal cortical hormones were widely considered to support or stimulate important responses to stress or injury. With the purification and manufacture of adrenal cortical hormones in the 1930s and 1940s, clinicians suddenly discovered the potent anti-inflammatory actions of glucocorticoids (GCs). This dramatic, and unexpected, discovery has dominated clinical and laboratory research into GC actions throughout the second half of the 20th century. More recent research is again reporting GC-induced stimulatory effects on a variety of inflammatory response components. These effects are usually observed at low GC concentrations, close to concentrations that are observed in vivo during basal, unstimulated states. For example, GC-mediated stimulation has been reported for the hepatic acute-phase response, for cytokine secretion, expression of cytokine/chemokine receptors, and for the pro-inflammatory mediator, macrophage migration inhibition factor. It seems clear that the long-held clinical view that GCs act solely as anti-inflammatory agents needs to be re-assessed. Varying doses of GCs do not lead simply to varying degrees of inflammation suppression, but rather GCs can exert a full range of effects from permissive to stimulatory to suppressive.


Anion-Redox Mechanism of MoO(S2)2(2,2'-bipyridine) for Electrocatalytic Hydrogen Production.
Redox processes of molybdenum-sulfide (Mo-S) compounds are important in the function of materials for various applications from electrocatalysts for the hydrogen evolution reaction (HER) to cathode materials for batteries. Our group has recently described a series of Mo-S molecular HER catalysts based on a MoO(S2)2L2 structural motif. Herein, reductive pathways of MoO(S2)2bpy (Mo-bpy) (bpy = 2,2'-bipyridine) are presented from both experimental and theoretical studies. We tracked chemical reduction of Mo-bpy with UV-vis spectroscopy using sodium napthalenide (NaNpth) as the reducing agent and found that Mo-bpy undergoes anionic persulfide reduction to form the tetragonal Mo(VI) complex [MoOS3]2-. We also identified silver mercury amalgam as an inert working electrode (WE) for spectroectrochemical (SEC) studies. UV-vis spectra in the presence of trifluoroacetic acid with an applied potential confirmed that Mo-bpy maintains its structure during catalytic cycling. Finally, theoretical catalytic reaction pathways were explored, revealing that Mo=O may function as a proton relay. This finding together with the observed anion reduction as the redox center is of broad interest for amorphous Mo-S (a-MoSx) electrocatalytic materials and anion-redox chalcogel battery materials.


A feline thymocyte antigen defined by a monoclonal antibody (FT2) identifies a subpopulation of non-helper cells capable of specific cytotoxicity.
A monoclonal antibody, FT2 (IgG1 kappa) prepared against cat thymocytes, was found to be reactive with an antigenic determinant expressed by approximately 76% of thymocytes, 15% of blood mononuclear cells, 14% of splenocytes, and 1% of bone marrow cells. The FT2-reactive determinant was not expressed on B cells, macrophages, granulocytes, or erythrocytes. Both FT2+ and FT2- populations of peripheral blood mononuclear cells were capable of proliferative responses to the T cell mitogens Con A and PHA. When splenocytes were sensitized to the lymphoblastoid cell line, 79p90, cytotoxic T cells were found in the FT2+ population and were absent from the FT2- population. Conversely, the FT2- population contained the helper T cell activity required for pokeweed mitogen-induced B cell differentiation. Under nonreducing conditions, the FT2 antigen had an apparent m.w. of 71,000. When reduced, subunits of 31,000 and 38,000 apparent m.w. were observed. The data suggest that the FT2 antibody identifies the feline analog of the human T8/Leu-2, murine Ly-2 molecules expressed by cytotoxic/suppressor T cells.


The Effects of Talus Control Foot Orthoses in Children with Flexible Flatfoot.
A talus control foot orthosis (TCFO) combines an inverted rigid foot orthosis (RFO) with a broad upright portion that rises well above the navicular to cover and protect the talonavicular joint. We sought to identify the therapeutic effect of TCFOs in children with flexible flatfoot. Flexible flatfoot was diagnosed in 40 children when either of the feet had greater than 4° valgus of resting calcaneal stance position (RCSP) angle and one of the radiographic indicators was greater than 30° in anteroposterior talocalcaneal angles, 45° in lateral talocalcaneal angles, and 4° in lateral talometatarsal angles and less than 10° of calcaneal pitch in barefoot radiographs. Of 40 children with flexible flatfoot, 20 were fitted with a pair of RFOs and 20 with TCFOs, randomly. Follow-up clinical and radiographic measurements were completed 12 months later. All of the radiographic indicators changed toward the corrective direction in both groups. There were significant improvements in calcaneal pitch and RCSP in both groups (P < .05). In the TCFO group, the anteroposterior talocalcaneal angle and the RCSP showed statistically significant improvement compared with the RFO group. In this study, the TCFO was more effective than the RFO at treating children with flexible flatfoot.


Differences in the Spectrum of Anti-Citrullinated Protein Antibody Fine Specificities Between Malaysian and Swedish Patients With Rheumatoid Arthritis: Implications for Disease Pathogenesis.
Antibodies to the citrullinated protein antigens (ACPAs) are important in the diagnosis and pathogenesis of rheumatoid arthritis (RA). However, the prevalence of ACPAs with different fine specificities in different populations is unclear. This study sought to examine the fine specificity of the antibody responses toward citrullinated proteins in RA patients from Malaysia, an area where genetic and environmental determinants of RA are different from those in more frequently studied cohorts of Caucasian subjects. A multiplex analytic microarray system was used to analyze the occurrence of antibodies to 10 different citrullinated peptides (filaggrin [fil307-324], vimentin [Vim2-17, Vim60-75], fibrinogen [Fibα563-583, Fibα580-600, Fibβ36-52, Fibβ62-81a, Fibβ62-81b], enolase [Eno5-21], and type II collagen [CitCII355-378]) in serum samples from 4,089 RA patients (1,231 Malaysian and 2,858 Swedish) and 827 healthy control subjects (249 Malaysian and 578 Swedish). The positive reaction threshold for each peptide was set separately for each population based on a specificity of 98%. Distinct differences in the frequencies of 5 ACPA fine specificities (Vim60-75, Vim2-17, Fibβ62-81b, Eno5-21, and CitCII355-378) were found between the Malaysian and Swedish RA populations, despite a nearly identical percentage of patients in each population who were positive for anti-cyclic citrullinated peptide 2 antibodies. In Malaysian RA patients compared with Swedish RA patients, the frequencies of antibodies to Vim60-75 (54% versus 44%, corrected P [Pcorr ] = 1.06 × 10-8 ) and CitCII355-378 (17% versus 13%, Pcorr = 0.02) were significantly higher, while the frequencies of antibodies to Vim2-17 (25% versus 32%, Pcorr = 1.91 × 10-4 ), Fibβ62-81b (15% versus 30%, Pcorr = 2.47 × 10-22 ), and Eno5-21 (23% versus 50%, Pcorr = 3.64 × 10-57 ) were significantly lower. Serum ACPA fine specificities differ between RA patients in different populations, although the total proportions of individuals positive for ACPAs are similar. Differing patterns of ACPA fine specificity could be attributed to variations in genetic and/or environmental factors.


Biological and clinical features of non-Hodgkin's lymphoma in the elderly.
The incidence of non-Hodgkin's lymphomas (NHLs) in elderly people has increased in recent years because the world population is getting older. The aim of this study was to compare the biological and clinical features in patients diagnosed with NHLs younger and older than 65 years, and the possible influence of age on the choice of optimal therapeutic approach. We retrospectively evaluated 193 patients with NHLs: 111 (68%) were <65 years and 82 (42%) ≥65 years. The following parameters were analysed: age, gender, clinical stage, International Prognostic Index (IPI), histological type, presence of B symptoms, disease localization, presence of bulky mass, Karnofsky performance status (PS), comorbidities, blood counts, liver and renal function and serum LDH. Elderly patients had statistically more frequent indolent NHLs (p=0.036), IPI 3 and 4 (p<0.0001), presence of comorbidities (p<0.001), and less frequent presence of bulky disease (p7equals;0.043). Response to therapy was different in the 2 age groups: 29% of patients ≥65 years achieved complete remission (CR) in contrast to 71% of patients <65 years (p<0.001). The most frequent cause of death was disease progression (PD) (86% of younger patients and 71% of elderly patients (p7equals;0.150). Older patients died more frequently because of comorbidities compared younger ones (21 and 107percnt;, respectively; p=0.250), and had more complications of therapy (8.1 and 47percnt;, respectively (p=0.320). Overall survival (OS) was shorter in older patients in all lymphoma types: indolent lymphoma (36 vs. 17 months), aggressive (22 vs. 20 months) and very aggressive (14 vs. 1 months). Multivariate analysis showed that parameters for shorter survival in the elderly were Karnofsky PS <60, increased serum LDH and treatment toxicity. In elderly NHLs patients, treatment response and survival are significantly poorer. Since older patients mostly died of PD, they should be treated with standard regimens and best supportive measures.


Tools for assessing child and adolescent stunting: Lookup tables, growth charts and a novel appropriate-technology "MEIRU" wallchart - a diagnostic accuracy study.
Stunting affects 149 million children worldwide and is a form of chronic malnutrition defined by low height-for-age. Surveys and intervention programmes depend on effective assessment and identification of affected individuals. Gold standard assessment is based on height-for-age Z-score (HAZ): HAZ <-2 defines stunting; HAZ <-3 defines severe stunting. However, a major problem for field-based programmes is that Z-scores can be time-intensive and challenging to calculate. We thus developed a novel wallchart that we have coined 'MEIRU wallchart' to easily and accurately identify stunted children and adolescents. Our study aim was to evaluate its performance and acceptability against other methods used in current clinical/field practice. We undertook a non-interventional diagnostic accuracy study in Malawi. We recruited 244 participants aged 8-19 years and determined each individual's stunting status using, in varying order: the MEIRU wallchart, traditional lookup tables, and traditional growth charts. All were compared against 'gold standard' HAZ, calculated using AnthroPlus WHO software. Local community healthcare workers performed all the assessments. The wallchart method was strongly preferred by both participants and staff. It had an overall accuracy of 95.5%(kappa = 0.91) and was faster than lookup tables by an average of 62.5%(41.4sec; p<0.001) per measurement. Lookup tables and growth charts had overall agreements of 59.4%(kappa = 0.36) and 61.9%(kappa = 0.31) respectively. At the HAZ-2 cut-off, the wallchart had a sensitivity of 97.6%(95%CI: 91.5-99.7) and specificity of 96.3%(95%CI: 92.1-98.6). We conclude that the MEIRU wallchart performs well and is acceptable for screening and identification of stunted children/adolescents by community-level health workers. It fulfils key criteria that justify a role in future screening programmes: easy to perform and interpret; acceptable; accurate; sensitive and specific. Potential future uses include: conducting rapid stunting prevalence surveys; identifying affected individuals for interventions. Current field methods, lookup tables and growth charts performed poorly and should be used with caution.


Efficacy of Ethinylestradiol Re-challenge for Metastatic Castration-resistant Prostate Cancer.
There has recently been renewed interest in the use of estrogens as a treatment strategy for castration-resistant prostate cancer (CRPC). The purpose of this study was to evaluate the feasibility and efficacy of ethinylestradiol re-challenge (re-EE) in the management of CRPC. Patients with metastatic CRPC who received re-EE after disease progression on prior EE and other therapy were retrospectively reviewed for prostate-specific antigen (PSA) response, PSA progression-free survival (P-PFS) and adverse events. Thirty-six re-EE treatments were performed for 20 patients. PSA response to the initial EE treatment was observed in 14 (70%) patients. PSA response to re-EE was 33.3% in 36 re-EE treatments. The median P-PFS for patients treated with initial and re-EE was 7 months and 4 months, respectively. Interestingly, PSA response to re-EE was observed even in non-responders to initial EE, and those treated with multiple re-EE. No patients developed cardiovascular or thromboembolic events. Re-EE may be safely repeated several times and can lead to a prolonged disease control in selected patients. Re-challenge with EE appears to be a reasonable option worth considering for patients with metastatic CRPC.


Breaking the Dogma of Aldolase Specificity: Simple Aliphatic Ketones and Aldehydes are Nucleophiles for Fructose-6-phosphate Aldolase.
d-Fructose-6-phosphate aldolase (FSA) was probed for extended nucleophile promiscuity by using a series of fluorogenic substrates to reveal retro-aldol activity. Four nucleophiles ethanal, propanone, butanone, and cyclopentanone were subsequently confirmed to be non-natural substrates in the synthesis direction using the wild-type enzyme and its D6H variant. This exceptional widening of the nucleophile substrate scope offers a rapid entry, in good yields and high stereoselectivity, to less oxygenated alkyl ketones and aldehydes, which was hitherto impossible.


Structural characterization of peptide-mediated inhibition of Porphyromonas gingivalis biofilm formation.
Porphyromonas gingivalis is a periodontal pathogen whose primary niche is the anaerobic environment of subgingival dental plaque, but initial colonization of the oral cavity is likely to occur on supragingival surfaces that already support robust biofilm communities. Our studies have shown that P. gingivalis adheres to Streptococcus gordonii through interaction of the minor fimbrial antigen Mfa1 with a specific region of the streptococcal SspB polypeptide (residues 1167 to 1193) designated BAR. We show that a synthetic peptide comprising the BAR sequence potently inhibits P. gingivalis adherence to S. gordonii (50% inhibitory concentration = 1.3 microM) and prevents the development of P. gingivalis biofilms. However, a retroinverso peptide that possessed the same side chain topology as that of BAR was inactive, suggesting that interactions of Mfa1 with the peptide backbone of BAR are important for binding. A conformationally constrained analog of BAR inhibited P. gingivalis adherence and biofilm formation but at a lower specific activity than that of BAR. Therefore, to further define the structural features of the Mfa1-BAR interaction, we functionally screened combinatorial libraries of BAR in which active site residues (Asn1182, Thr1184, and Val1185) were replaced with each of the 19 common amino acids. Peptides containing positively charged amino acids at position 1182 or hydrophobic residues at position 1185 bound P. gingivalis more efficiently than did control peptides containing Asn and Val at these positions, suggesting that electrostatic and hydrophobic interactions may contribute to Mfa1-SspB binding. In contrast, replacement of Pro or Gly at these positions was detrimental to adherence, suggesting that perturbation of the BAR secondary structure influences activity. The net effect of substitutions for Thr1184 was less pronounced either positively or negatively than that at the other sites. These results define physicochemical characteristics of the interacting interface of Mfa1 and SspB and suggest that peptides or peptidomimetics with greater specific inhibitory activity than that of BAR can be developed. These compounds may represent potential therapeutics that target some of the first molecular interactions that allow P. gingivalis to colonize the oral cavity.


Juvenile periodontitis: healing following autogenous iliac marrow graft, long-term evaluation.
A case of juvenile periodontitis treated by autogenous bone grafting is reported. The patient, an 18-year-old female, presented with periodontal lesions around the incisors and the first lower left molar. The first molar was severely affected with bone defects at the mesial aspect and in the furcation region and, for this reason, was selected for grafting. Minced fragments of bone with its marrow, obtained from the patient's iliac crest, were implanted into the diseased periodontium. 1 year after treatment, clinical and radiological inspection revealed the presence of bone. This bone completely filled the furcation area of the tooth but only partially the mesial aspect. There was, also, significant bone fill in the supracrestal region.


Prevalence of gallstone disease in a general population of Okinawa, Japan.
A total of 2,584 healthy residents in the Yaeyama District of Okinawa, Japan, were investigated in 1984 to determine the prevalence of gallstone disease and its associated factors. Diagnosis of gallstone disease was assessed by real-time ultrasonography. For participants over 20 years of age, obesity index and serum levels of total cholesterol and triglycerides were measured. Overall prevalence of gallstone disease was 3.2%. Prevalence increased with age from 0% under 19 years of age to 11.4% over 70 years of age and was higher in females (4.0%) than in males (2.5%). The results of the logistic regression analysis indicated that age and fatty liver were significant predictors of gallstone disease. The results of the automatic interaction detector analysis indicated that age and fatty liver were strong factors associated with gallstone disease and that prevalence was highest in females over age 50 with fatty liver.


Recommendations for culturally safe clinical kidney care for First Nations Australians: a guideline summary.
First Nations Australians display remarkable strength and resilience despite the intergenerational impacts of ongoing colonisation. The continuing disadvantage is evident in the higher incidence, prevalence, morbidity and mortality of chronic kidney disease (CKD) among First Nations Australians. Nationwide community consultation (Kidney Health Australia, Yarning Kidneys, and Lowitja Institute, Catching Some Air) identified priority issues for guideline development. These guidelines uniquely prioritised the knowledge of the community, alongside relevant evidence using an adapted GRADE Evidence to Decision framework to develop specific recommendations for the management of CKD among First Nations Australians. These guidelines explicitly state that health systems have to measure, monitor and evaluate institutional racism and link it to cultural safety training, as well as increase community and family involvement in clinical care and equitable transport and accommodation. The guidelines recommend earlier CKD screening criteria (age ≥ 18 years) and referral to specialists services with earlier criteria of kidney function (eg, estimated glomerular filtration rate [eGFR], ≤ 45 mL/min/1.73 m2 , and a sustained decrease in eGFR, > 10 mL/min/1.73 m2 per year) compared with the general population. Our recommendations prioritise health care service delivery changes to address institutional racism and ensure meaningful cultural safety training. Earlier detection of CKD and referral to nephrologists for First Nations Australians has been recommended to ensure timely implementation to preserve kidney function given the excess burden of disease. Finally, the importance of community with the recognition of involvement in all aspects and stages of treatment together with increased access to care on Country, particularly in rural and remote locations, including dialysis services.


Increasing RN Perceived Competency With Substance Use Disorder Patients.
Although behavioral health and substance use disorder patients visit hospitals in significant numbers, nurses are often ill-prepared to care for them. The purpose of this quasi-experimental preclass-postclass design was to determine the effects of an educational intervention on the perceived competency of 57 nurses who care for patients with behavioral and substance abuse disorders. The nurses who chose to participate were asked to respond to a demographic questionnaire and a survey designed to measure perceived competency. Survey data were analyzed to determine whether any differences (alpha = .05) existed between participants' attitudes and knowledge preclass and postclass. Immediately following the educational intervention, a statistically significant increase was found in perceived competency related to self-confidence, attitudes, communication, and knowledge of resource availability among participating nurses. Nurses working in acute care hospitals, particularly those without addiction and psychiatric services, may benefit from continuing education on this important topic. J Contin Nurs Educ. 2017;48(4):175-183.


Managing early ejaculation: what does the future hold?
Recent attention in the field of male sexual dysfunction has focused on erectile dysfunction. However, premature ejaculation (PE) is an extremely common condition that warrants clinical study and exploration of pharmacologic treatments. Until recently, PE was thought to be a behavioral problem for which the best remedy was a learned control technique. However, some drugs currently on the market, including sildenafil and the selective serotonin reuptake inhibitors, appear to have efficacy in the treatment of PE. More research is needed before FDA approval of such agents for this indication, but more and better options for men with PE are anticipated as attention to ejaculatory disorders grows and, hopefully, the associated stigma decreases.


The feasibility of a telephone-based weight loss intervention in rural Ohio: A pilot study.
Weight loss through lifestyle modification can produce health benefits and may reduce cancer risk. The goal of this study was to examine the feasibility of and adherence to a 15-week telephone-based weight loss intervention in rural Ohio, an area with high rates of obesity. This pilot 2-arm randomized controlled study was designed for rural Ohio residents who were overweight or obese. Eligible participants were 2:1 randomly assigned to either a 15-week weight loss intervention group or active control group. The weight loss intervention group received weekly telephone sessions to improve healthy diet and increase physical activity. The active control group received education brochures with information on physical activity and dietary guidelines. Feasibility was defined as at least 80% of participants completing the follow-up surveys, and acceptable adherence was defined as the percentage of participants in the weight loss group who attend ≥75% of weekly telephone sessions. A total of 423 individuals entered the online screening survey, 215 (50.8%) completed the survey, and 98 (45.6%) of those were eligible. Forty eligible individuals were enrolled and randomly assigned to the weight loss group (n = 27) or active control group (n = 13). The average age of the weight loss group was 49 (SD = 10) years, and 89% were female. The average age of the active control group was 51 (SD = 9) years, and 92% were female. Feasibility was demonstrated: 90% of participants completed the online follow-up surveys at 15-weeks. Among participants in the weight loss group, 22 out of 27 (81.5%) completed the 15-week intervention, the average number of sessions attended was 9.7 (64.9%). Adherence to the intervention was rated as acceptable among almost half of the group (48.1%). Feasibility of a 15-week telephone-based weight loss study among rural residents with overweight/obesity were determined. A future study will test this intervention for weight loss efficacy.


Medicolegal issues arising when pacemaker and implantable cardioverter defibrillator devices are deactivated in terminally ill patients.
The number of patients receiving pacemakers and implantable cardioverter defibrillator (ICD) devices continues to increase dramatically. In this paper, the issue of when it is appropriate to deactivate these devices if the patient becomes terminally ill and the medicolegal implications of this action are examined. This appears to constitute a withdrawal of treatment. However, the issue has never come before the courts and therefore no medicolegal guidance exists on the point. This paper highlights a lack of knowledge among health-care staff regarding switching off electromechanical devices in terminally ill patients. We propose some guidance and recommendations for dealing with this issue when it arises in practice, and highlight some important differences between pacemakers and ICDs that will influence decision-making. Conclusions are expressed regarding how this issue should be dealt with in the postmortem setting and in the antemortem setting, where the issue of capacity and consent will influence decisions regarding deactivating these devices.


Patterns of abnormal pudendal nerve function that are associated with postpartum fecal incontinence.
The purpose of this study was to assess patterns of abnormal pudendal nerve function in women who complain of postpartum fecal incontinence. During a 12-month period, a cohort of 83 women underwent neurophysiologic assessment as part of an evaluation of fecal incontinence after vaginal delivery. Pudendal nerve assessment consisted of the measurement of the clitoral-anal reflex and quantitative electromyography of the external anal sphincter. Endoanal ultrasound examination and anal manometry were also performed in each patient. Thirty of 83 women (38%) with fecal incontinence were found to have abnormal neurophysiologic condition, among whom four identifiable patterns of abnormality emerged. Five women (17%) had evidence of pudendal nerve demylenation with a prolonged sensory threshold of the clitoral-anal reflex (>5.2 mA), although electromyography studies were normal. Eight women (27%) had abnormal electromyography results that were consistent with axonal neuropathy with or without reinervation, in whom the clitoral-anal reflex was normal. Thirteen women (43%) demonstrated a mixed demyelinating and axonal pudendal neuropathy, with evidence of reinervation. Four women (13%) had abnormal patterns of neurophysiologic condition that was not attributable directly to past obstetric trauma but to coincident medical problems. Four abnormal patterns of pudendal nerve function may be identified, three of which (demyelinating, axonal, and mixed demyelinating/axonal) can be attributed to specific past obstetric events, although a fourth radicular pattern is due to coincident medical or orthopedic problems. Assessment of pudendal nerve function is important in women with postpartum fecal incontinence because particular patterns of abnormality correlate with different symptoms and can influence treatment options.


Tuning of mid-infrared absorption through phonon-plasmon-polariton hybridization in a graphene/hBN/graphene nanodisk array.
In this paper, we utilize a heterostructured graphene/hBN/graphene nanodisk array to implement an electrically tunable absorber in and out of the Reststrahlen band (RSB) region of hBN. Tuning of phonon-type resonance absorption in the RSB region is achieved through phonon-plasmon-polariton hybridization. The hybrid phonon mode enabled a 290 nm shift of the resonant wavelength, and the sensitivity of absorption peak to the electrical control is 362.5 nm/eV. Simultaneously, the nearly perfect absorption is obtained in the condition of high chemical potential of graphene. Moreover, the plasmon polaritons are strongly modified by phonon polaritons of hBN, so the FWHM of absorption peaks out of the RSB region reduce to 45-49 nm, and the maximum Q of absorption reaches 220.44 at EF=0.65 eV, which is paving a way toward coherent emission at the atmospheric transparent band. Importantly, graphene-assisted hyperbolic phonon polaritons of hBN will enable future phonon devices with high optical performance and wide tunability.


Crystals from cocoons of Malacosoma neustria testacea.
The crystalline material covering the cocoon of Malacosoma neustria testacea (Lasiocampidae, Lepidoptera) was analyzed physically and chemically. The mean component was identified as calcium oxalate monohydrate, and the crystals were found to be whewellite in form.


Corticotropin-releasing factor antagonist attenuates stress-induced inhibition of seasonal ovarian recrudescence in the lizard Mabuya carinata.
Whether administration of the corticotropin-releasing factor (CRF) antagonist alpha-helical CRF(9-41) (hCRF) prevents stress response of the ovary, the oviduct, the adrenals, and the spleen was studied in the lizard Mabuya carinata. Stressors (handling, chasing, and noise) applied randomly, five times a day, for 1 month to lizards during the recrudescence phase of the ovarian cycle caused a significant increase in mean nuclear diameter of the adrenal cortical cells and a significant reduction in mean number of islands of white pulp in the spleen. These results, albeit indirectly, indicated an activation of the adrenal gland and immune suppression. There was a significant decrease in the mean relative weight of the ovary and the oviduct and in the mean number of oocytes and the primordial follicles compared to those of controls. Furthermore, vitellogenic follicles were absent in the ovary of lizards exposed to stressors in contrast to their presence in controls. However, administration of hCRF to the lizards exposed to stressors (stress + hCRF) resulted in vitellogenesis and follicular growth. The mean relative weight of the ovary and the oviduct and the mean number of oocytes and the primordial follicles in stress + hCRF-treated lizards were significantly higher than those in the lizards exposed to stressors, whereas they did not significantly differ from those of controls. The results indicate that hCRF attenuates stress-induced inhibition of ovarian follicular and oviductal development in M. carinata. To the best of our knowledge, this is the first report revealing that CRF antagonist can prevent ovarian stress response in lower vertebrates.


Seminar on adult mortality and orphanhood in the past: five Latin American cases.
This report concerns a seminar on adult mortality and orphanhood in the past in Latin America that was held in San Jose, Costa Rica, December 12-14, 1984. The first part describes five historical studies presented at the seminar concerning Mexico, Chile, Peru, Brazil, and Argentina. "The second part of this article is an explanation of the calculation involved in a life table derived from information on the incidence of orphanhood according to the age of newly married couples on their marriage."


[15]aneN4S: synthesis, thermodynamic studies and potential applications in chelation therapy.
The purpose of this work was to synthesize and characterize the thiatetraaza macrocycle 1-thia-4,7,10,13-tetraazacyclopentadecane ([15]aneN4S). Its acid-base behaviour was studied by potentiometry at 25 °C and ionic strength 0.10 M in KNO3. The protonation sequence of this ligand was investigated by 1H-NMR titration that also allowed the determination of protonation constants in D2O. Binding studies of [15]aneN4S with Mn2+, Fe2+, Co2+, Ni2+, Cu2+, Zn2+, Cd2+, Hg2+ and Pb2+ metal ions were further performed under the same experimental conditions. The results demonstrated that this compound has a higher selectivity and thermodynamic stability for Hg2+ and Cu2+, followed by Ni2+. The UV-visible-near IR spectroscopies and magnetic moment data for the Co(II) and Ni(II) complexes indicated a tetragonal distorted coordination geometry for both metal centres. The value of magnetic moment and the X-band EPR spectra of the Cu(II) complex are consistent with a distorted square pyramidal geometry.


Comparative quantitative prevalence of Mycobacteria and functionally abundant nidA, nahAc, and nagAc dioxygenase genes in coal tar contaminated sediments.
The Chattanooga Creek Superfund site is heavily contaminated with metals, pesticides, and coal tar with sediments exhibiting high concentrations of polycyclic aromatic hydrocarbons (PAHs). High molecular weight PAHs are of concern because of their toxicity and recalcitrance in the environment; as such, there is great interest in microbes, such as fast-growing Mycobacterium spp., capable of degradation of these compounds. Real-time quantitative PCR assays were developed targeting multiple dioxygenase genes to assess the ecology and functional diversity of PAH-degrading communities. These assays target the Mycobacterium nidA, beta-proteobacteria nagAc, and gamma-proteobacteria nahAc with the specific goal of testing the hypothesis that Mycobacteria catabolic genes are enriched and may be functionally associated with high molecular weight PAH biodegradation in Chattanooga Creek. Dioxygenase gene abundances were quantitatively compared to naphthalene and pyrene mineralization, and temporal and spatial PAH concentrations. nidA abundances ranged from 5.69 x 10(4) to 4.92 x 10(6) copies per gram sediment; nagAc from 2.42 x 10(3) to 1.21 x 10(7), and nahAc from below detection to 4.01 x 10(6) copies per gram sediment. There was a significantly greater abundance of nidA and nagAc at sites with the greatest concentrations of PAHs. In addition, nidA and nagAc were significantly positively correlated (r = 0.76), indicating a coexistence of organisms carrying these genes. A positive relationship was also observed between nidA and nagAc and pyrene mineralization indicating that these genes serve as biomarkers for pyrene degradation. A 16S rDNA clone library of fast-growing Mycobacteria indicated that the population is very diverse and likely plays an important role in attenuation of high molecular weight PAHs from Chattanooga Creek.


Assessment of nasal functions and their relationship with cholesteatoma formation in patients with unilateral chronic otitis media.
To evaluate the nasal functions of patients with unilateral chronic otitis media using rhinomanometry, comparing chronic otitis media sides with healthy sides, chronic otitis media patients with cholesteatoma and without cholesteatoma, and patients with healthy individuals. This prospective study included 102 patients with unilateral chronic otitis media (48 with and 54 without cholesteatoma). The control group comprised 40 individuals without any ear or nasal pathologies. All patients underwent active anterior rhinomanometry to measure nasal airway resistance and a saccharin test to measure mucociliary transport times. There were no significant differences in nasal airway resistance and mucociliary transport time between the chronic otitis media sides and unaffected sides in the 102 patients (p = 0.72 and p = 0.28, respectively), between the non-suppurative chronic otitis media patients (without cholesteatoma) and chronic otitis media with cholesteatoma patients (p > 0.05), or between the study and control groups (p > 0.05). The present study, with a larger sample size compared to previously published literature, supports the conclusion that unilateral nasal obstruction is unlikely to lead to chronic otitis media on the same side. The results also suggest that nasal functions do not contribute to the development of cholesteatoma.


Residential detoxification: essential for marginalised, severely alcohol- and drug-dependent individuals.
In an era of health care rationalisation, residential detoxification services catering for drug- and alcohol-dependent homeless people are being closed. The principal findings of a recent evaluation of a non-medicated residential detoxification service are presented. The aims were to describe the characteristics of residents, their experience of admission, rates of withdrawal completion, referral patterns, staff and key informant perceptions of the service and its role within the wider treatment system. A process evaluation was utilised incorporating interviews with residents (n = 80) and key informants (n = 13); a survey of all service staff (n = 10); and demographic and clinical data for all residents (n = 392) admitted over one calendar year. Results. Residents were heavily substance-dependent and marginalised, with many exhibiting substantial mental and physical health impairments. Polydrug use and frequent prior engagement with drug and alcohol services were common. The majority completed withdrawal and were referred to further treatment. Residents who presented for heroin and other opiate withdrawal were more likely than other residents to leave before completing treatment (odds ratio 2.47, 95% confidence interval 1.48 - 4.15). Information from key informants, service staff and residents converged in underscoring the important role performed by the service. Out-patient detoxification for homeless and severely drug- and alcohol-dependent populations is unrealistic. For this group, access to residential detoxification is vital as it provides an environment where potentially serious medical and psychological complications can be managed. There continues to be a clear role for supervised withdrawal in such a setting.


[Quality of life in medicine--origins, main concepts and directions of change].
Assessment of the quality of life depends not only health, but also on many other factors, which together make up the everyday life of the individual, including: independence, relationship to the environment, personal beliefs, attitudes and religion. The illness process, irrespective of its stage or magnitude, influences the life of the patient, very often leading to a break down in organisation and limiting his/her ability to fulfill his/her roles and social functions. In consequence, a lowering of living standards results. For many years, health was measured in very narrow terms and in a negative sense. Deviations from normal health were measured, with no attempt to find indicators of good health. The aim of this paper is to present the origins and main concepts underlying the notion of quality of life, which developed first within the social sciences, and since the 1970s has been recognised within medicine. The approach demonstrates a different perspective for understanding a sick person, not merely from the biological point of view, but also taking into account aspects of psychological social and spiritual functioning. Introduction of the concept of quality of life is determined by the fact that the aim of therapeutic interventions ought to be not only reducing the symptoms of an illness, but also providing an improvement in the sick person's functioning, thus leading to an improvement in his/her quality of life.


Analyses of surface membrane carbohydrates in parasitic flagellates of the order kinetoplastida using lectins.
Crithidia fasciculata, Leishmania donovani, Leishmania major, Leishmania mexicana amazonensis, Leishmania tropica, Leishmania tarentolae, Trypanosoma sp. from Formosan bats (Tb), Trypanosoma lewisi, Trypanosoma musculi, and different strains of Trypanosoma cruzi (Tc) were cultivated at 27 degrees C in a liquid culture medium. Flagellates harvested from log phase culture were analyzed for their lectin agglutinating characteristics with concanavalin A (Con A), Peanut agglutinin, Ricinus communis agglutinin 120, soybean agglutinin (SBA), Ulex europeus agglutinin (UEA) and wheat germ agglutinin (WGA). Results indicated that all these flagellates might have D-galactose and methyl- alpha-D-manopyranoside on their surface. The presence of L-Fucose, which complexes specifically with UEA, could not be demonstrated on the surface of these flagellates. Results from quantitative comparison of surface molecules of Tb and the Tulahuen strain of Tc suggested that Tb may have more WGA-binding molecules while Tc may have more ConA-binding molecules. Pretreatment of the flagellates with 0.05% trypsin at 37 degrees C for 30 minutes caused some reduction of agglutination titers. Cell agglutination with lectins was completely inhibited or reversed in the presence of the specific lectin-binding monosaccharides.


Deletion of p21 (WAF-1/Cip1) does not induce systemic autoimmunity in female BXSB mice.
Cell cycle, apoptosis, and replicative senescence are all influenced by the cyclin-dependent kinase inhibitor, p21. It was previously reported that deletion of p21 in 129/Sv x C57BL/6 mixed genetic background mice induced a severe lupus-like disease, almost exclusively in females. However, we did not confirm this finding in an independently derived stock of 129/Sv x C57BL/6 p21(-/-) mice. To further address this discrepancy, we examined the effects of p21 deletion in BXSB female mice that develop late-life, mild lupus-like disease. Survival, polyclonal Igs, anti-chromatin Abs, and kidney histopathology in these mice were unremarkable and identical to wild-type littermates for up to 14 mo of age. We conclude that p21 deficiency does not promote autoimmunity even in females of a predisposed strain. The findings indicate that the use of mixed background 129/Sv x C57BL/6 mice to study effects of gene deletions in systemic autoimmunity may be confounded by the genetic heterogeneity of this cross. We suggest that studies addressing gene deletion effects in systemic autoimmunity should use sufficiently backcrossed mice to attain genetic homogeneity, include wild-type littermate controls, and preferentially use congenic inbred strains with late-life lupus predisposition to emulate the polygenic nature of this disease.


Common Factors' Role in Accredited MFT Training Programs.
Common factors proponents discuss the benefits and methods of including common factors in marriage and family therapy (MFT) training; yet there are no empirical investigations of how common factors are incorporated into MFT curricula. The purpose of this study was to obtain a baseline understanding of common factors' role in MFT training. Thirty-one directors of COAMFTE- and CACREP-accredited MFT training programs responded to a survey about the inclusion of common factors in their training program, as well as the benefits, challenges, and students' reactions to common factors training. Findings show that common factors are regularly included in MFT training programs and have garnered largely positive responses. Additional results are discussed regarding the implications of common factors in MFT training.


Retention of eyeblink conditioning in periweanling and adult rats.
Eyeblink conditioning is a well-established model for studying the developmental neurobiology of associative learning and memory, though nothing is known regarding developmental differences in retention between periweanling and adult rats. The present study examined retention of eyeblink conditioning in periweanling (postnatal day 24 at the start of training) and adult rats 1, 7, or 28 days after acquisition. Retention was assessed by (1) a conditional stimulus (CS)-alone test session followed by (2) CS-unconditional stimulus (US) reacquisition tests. Conditional response (CR) levels at acquisition were comparable in most respects between ages, and robust CR levels were present at the start of retention tests for both ages in the 1 day group, with CR percentages at block 1 of reacquisition higher in periweanlings relative to adults. At the 7 day retention test there was a trend toward significance for higher CR percentages at the CS-alone test in adults relative to periweanlings, though there were no age differences at reacquisition testing. When testing occurred 28 days after acquisition, however, periweanlings showed fewer CRs relative to adults during reacquisition despite low CR levels in both ages throughout the CS-alone test. Furthermore, periweanlings in the 28 day group required more trials at reacquisition than all other groups to exceed CR levels from their first acquisition session. These findings are consistent with rapid forgetting in the young commonly referred to as "infantile amnesia." The well-characterized eyeblink preparation may be useful for future studies investigating neural mechanisms responsible for rapid forgetting in developing animals.


Healing the schism: medicine and public health in Pakistan.
The relationship between medicine and public health has a long and complex co-evolution. In developing countries where the health needs are greatest and resources are few, this relationship is of critical importance. This paper provides a case study of the development of the relationship between medical and public health at the Aga Khan University (AKU), a leading educational institution in Pakistan, which was founded with a vision of reuniting medicine and public health. Rapid growth and development have led to successful medicine and public health programs, but have fallen short in creating the synergies needed to address the population health problems of the country. In a twenty-five year history of strong growth and development, the AKU has recreated the schism that marked US institutional development in the 20th century, despite strategic consideration to address population health in the design of the University. We recommend the creation of public health schools that focus on leadership to renew an emphasis on unifying health concepts and actions following successful examples to bring medicine and public health together.


Primary diffuse large B-cell lymphoma of the dura with skull and scalp involvement: A case report and brief review of the literature.
Primary dural lymphoma (PDL) refers to a lymphoma with epidural or subdural involvement and is a rare subtype of primary central nervous system lymphoma. Diffuse large B-cell lymphoma (DLBCL) presenting as PDL is extremely rare. The present study reports a case of PDL with skull and scalp involvement in a 56-year-old man. Magnetic resonance imaging (MRI) revealed that the tumor was located under the right parietal inner plate and was attached to the dura mater. Following contrast-enhanced MRI, markedly enhanced tumor signals were observed, and mild homogeneous enhancement was observed in the diploë and soft tissues under the scalp, near the parietal bone. Under general anesthesia, the patient underwent craniotomy and tumor resection. The postoperative pathological diagnosis was DLBCL. Tumors were additionally identified inside the skull and subcutaneous tissues. The patient was administered chemotherapy postoperatively, and the prognosis subsequent to the 4-year follow-up was favorable. Primary malignant lymphoma should be considered in the differential diagnosis of scalp masses and meningeal lesions. Early diagnosis and individualized treatment is closely associated with a favorable outcome.


Endogenous bioactive peptides as potential biomarkers for atherosclerotic coronary heart disease.
Cardiovascular disease is the leading cause of death worldwide, with high medical costs and rates of disability. It is therefore important to evaluate the use of cardiovascular biomarkers in the early diagnosis of coronary artery disease (CAD). We have screened a variety of recently identified bioactive peptides candidates in anticipation that they would allow detection of atherosclerotic CAD. Especially, we have focused on novel anti-atherogenic peptides as indicators and negative risk factors for CAD. In vitro, in vivo and clinical studies indicated that human adiponectin, heregulin-β(1), glucagon-like peptide-1 (GLP-1), and salusin-α, peptides of 244, 71, 30, and 28 amino acids, respectively, attenuate the development and progression of atherosclerotic lesions by suppressing macrophage foam cell formation via down-regulation of acyl-coenzyme A: cholesterol acyltransferase-1. Circulating levels of these peptides in the blood are significantly decreased in patients with CAD compared to patients without CAD. Receiver operating characteristic analyses showed that salusin-α is a more useful biomarker, with better sensitivity and specificity, compared with the others for detecting CAD. Therefore, salusin-α, heregulin-β(1), adiponectin, and/or GLP-1, alone or in various combinations, may be useful as biomarkers for atherosclerotic CAD.


Practical asymmetric preparation of azetidine-2-carboxylic acid.
[reaction: see text] Facile and straightforward syntheses of both enantiomers of azetidine-2-carboxylic acid are described. The syntheses depart from inexpensive chemicals and allow for the production, in five to six steps, of practical quantities of each enantiomer. Synthetic highlights include the construction of the azetidine ring using an intramolecular alkylation and the use of optically active alpha-methylbenzylamine as chiral auxiliary.


A20 protects endothelial cells from TNF-, Fas-, and NK-mediated cell death by inhibiting caspase 8 activation.
A20 is a stress response gene in endothelial cells (ECs). A20 serves a dual cytoprotective function, protecting from tumor necrosis factor (TNF)-mediated apoptosis and inhibiting inflammation via blockade of the transcription factor nuclear factor-kappaB (NF-kappaB). In this study, we evaluated the molecular basis of the cytoprotective function of A20 in EC cultures and questioned whether its protective effect extends beyond TNF to other apoptotic and necrotic stimuli. Our data demonstrate that A20 targets the TNF apoptotic pathway by inhibiting proteolytic cleavage of apical caspases 8 and 2, executioner caspases 3 and 6, Bid cleavage, and release of cytochrome c, thus preserving mitochondrion integrity. A20 also protects from Fas/CD95 and significantly blunts natural killer cell-mediated EC apoptosis by inhibiting caspase 8 activation. In addition to protecting ECs from apoptotic stimuli, A20 safeguards ECs from complement-mediated necrosis. These data demonstrate, for the first time, that the cytoprotective effect of A20 in ECs is not limited to TNF-triggered apoptosis. Rather, A20 affords broad EC protective functions by effectively shutting down cell death pathways initiated by inflammatory and immune offenders.


Syndromes from segmental vibration and nerve entrapment: observations on case definitions for carpal tunnel syndrome.
The purpose of this paper is to assess the overlap and stability of two different case definitions of carpal tunnel syndrome CTS. The analysis considers the association between different case definitions and objective tests (sensory nerve conduction velocities, SNCVs and vibrotactile perception thresholds, TTS), and the natural history of CTS, in the context of two vibration-exposed cohorts. Clinical CTS cases were defined in two ways: (1) by the study physician using fixed criteria, and; (2) by questionnaire and hand diagram. SNCV in median and ulnar nerves was measured for digital, transpalmar, and transcarpal segments, and conventionally as from wrist-digit. Skin temperature was assessed as a point measurement by thermistor and regionally by thermal imaging. VTTs were determined at the bilateral fingertips of the third and fifth digits using a tactometer meeting the requirements of ISO 13091-1 (ISO 2001). The subjects were cohorts of shipyard workers in 2001 and 2004, and dental hygienists in 2002 and 2004. Results are reported for 214 shipyard workers in 2001 and 135 in 2004, and for 94 dental hygienists in 2002 and 66 in 2004. In 2001, 50% of shipyard workers were diagnosed as CTS cases by at least one of the diagnostic schemes, but only 20% were positive by both criteria. Among study physician diagnosed cases, 64% were CTS negative in 2001, 76% were negative in 2004, 13% were positive in both years, 22% became negative after being positive, and 11% became positive after being negative. For only study physician diagnosed CTS did VTTs differ between cases differ and non-cases in digit 3; there was no such distinction in digit 5. The dental hygienists had little CTS. Clinical case definitions of CTS based on diagrams and self-assessment, and clinical evaluation have limited overlap. Combining clinical criteria to create a more narrow or specific case definition of CTS does not appear to predict SNCV. The natural history of CTS suggests a protean disorder with considerable flux in case status over time.


The Fatty Acid Profile Analysis of Cyperus laxus Used for Phytoremediation of Soils from Aged Oil Spill-Impacted Sites Revealed That This Is a C18:3 Plant Species.
The effect of recalcitrant hydrocarbons on the fatty acid profile from leaf, basal corm, and roots of Cyperus laxus plants cultivated in greenhouse phytoremediation systems of soils from aged oil spill-impacted sites containing from 16 to 340 g/Kg total hydrocarbons (THC) was assessed to investigate if this is a C18:3 species and if the hydrocarbon removal during the phytoremediation process has a relationship with the fatty acid profile of this plant. The fatty acid profile was specific to each vegetative organ and was strongly affected by the hydrocarbons level in the impacted sites. Leaf extracts of plants from uncontaminated soil produced palmitic acid (C16), octadecanoic acid (C18:0), unsaturated oleic acids (C18:1-C18:3), and unsaturated eichosanoic (C20:2-C20:3) acids with a noticeable absence of the unsaturated hexadecatrienoic acid (C16:3); this finding demonstrates, for the first time, that C. laxus is a C18:3 plant. In plants from the phytoremediation systems, the total fatty acid contents in the leaf and the corm were negatively affected by the hydrocarbons presence; however, the effect was positive in root. Interestingly, under contaminated conditions, unusual fatty acids such as odd numbered carbons (C15, C17, C21, and C23) and uncommon unsaturated chains (C20:3n6 and C20:4) were produced together with a remarkable quantity of C22:2 and C24:0 chains in the corm and the leaf. These results demonstrate that weathered hydrocarbons may drastically affect the lipidic composition of C. laxus at the fatty acid level, suggesting that this species adjusts the cover lipid composition in its vegetative organs, mainly in roots, in response to the weathered hydrocarbon presence and uptake during the phytoremediation process.


[Chronic endophthalmitis caused by Propionibacterium acnes in a pseudophakic patient].
This paper reports the case of a chronic endophthalmitis with hypopion produced by propionibacterium acnes (p. a.) in a patient operated on for cataract and implanted with a posterior chamber intraocular lens. This granulomatous uveitis appeared 8 days after surgery and did not heal with a systemic corticoid-antibiotics treatment. The diagnosis was obtained by vitreous analysis. The responsibility of p. a. must be always searched in case of chronic endophthalmitis in pseudophakic patients: a specific treatment has to be used.


Poor efficacy of the phosphorylated high-molecular-weight neurofilament heavy subunit serum level, a biomarker of axonal damage, as a marker of chemotherapy-induced peripheral neuropathy.
The phosphorylated form of the high-molecular-weight neurofilament heavy subunit (pNF-H) is a major structural protein in axons. The pNF-H level is elevated in the serum of certain patients with central nervous disorders, including chemotherapy-induced cognitive impairment. The present study was conducted to elucidate the potential role of pNF-H as a marker of chemotherapy-induced peripheral neuropathy (CIPN). A total of 71 patients with early breast cancer in various stages of treatment (following 1, 3 or 7 cycles of chemotherapy, or a previous history of breast cancer chemotherapy) were assessed with a self-administered PainDETECT questionnaire [pain location, pain intensity on an 11-point numeric rating scale (NRS), and various pain qualities] and a single serum pNF-H measurement. Patients were divided into two groups based on the presence or absence of bilateral symmetric pain in the distal portions of the extremities [CIPN(+) or CIPN(-)]. The χ2 and Mann-Whitney tests were used for statistical analyses. Among the participants, only 8 patients complained of CIPN. Their pain intensity was 3.5±1.9 (mean ± standard deviation) compared with 1.5±1.8 in the CIPN(-) group (P<0.01). The NRS of numbness in the CIPN(+) group was significantly higher (2.4±1.4) than that of the CIPN(-) group (1.0±1.0). Increased pNF-H levels were observed in 37.5% of the CIPN(+) patients and in 23.8% of CIPN(-) patients (P=0.40). In conclusion, CIPN is observed in the most distal portions of the peripheral nerves that are composed of dendrites but not axons. Although serum pNF-H is a biomarker of axonal damage, it is not useful as a marker of CIPN.


Prevalence of EGFR Mutations in Lung Cancer in Uruguayan Population.
Incorporation of molecular analysis of the epidermal growth factor receptor (EGFR) gene into routine clinical practice represents a milestone for personalized therapy of the non-small-cell lung cancer (NSCLC). However, the genetic testing of EGFR mutations has not yet become a routine clinical practice in developing countries. In view of different prevalence of such mutations among different ethnicities and geographic regions, as well as the limited existing data from Latin America, our aim was to study the frequency of major types of activating mutations of the EGFR gene in NSCLC patients from Uruguay. We examined EGFR mutations in exons 18 through 21 in 289 NSCLC Uruguayan patients by PCR-direct sequencing. EGFR mutations were detected in 53 of the 289 (18.3%) patients, more frequently in women (23.4%) than in men (14.5%). The distribution by exon was similar to that generally reported in the literature. This first epidemiological study of EGFR mutations in Uruguay reveals a wide spectrum of mutations and an overall prevalence of 18.3%. The background ethnic structure of the Uruguayan population could play an important role in explaining our findings.


The Healthy School Canteen programme: a promising intervention to make the school food environment healthier.
The environment can exert a strong influence on people's food decisions. In order to facilitate students to make more healthy food choices and to develop healthy eating habits, it is important that the school food environment is healthy. The Healthy School Canteen programme of The Netherlands Nutrition Centre is an intervention that helps schools to make their cafeteria's offering healthier. A descriptive study was conducted by an independent research agency to survey the perceptions, experiences, and opinions of users of the programme (school directors, parents, students, and health professionals). Results show that directors and students of participating schools perceive their cafeteria's offering to be healthier after implementing the programme than prior to implementation. Next, further important results of the study are highlighted and relations with other projects, caveats, and practical recommendations are discussed. It is concluded that the Healthy School Canteen programme is a promising intervention to change the school food environment but that further research is needed to ultimately establish its effectiveness. Also, it will be a challenge to motivate all schools to enroll in the programme in order to achieve the goal of the Dutch Government of all Dutch school cafeterias being healthy by 2015.


A Neural Network-Based Identification of Developmentally Competent or Incompetent Mouse Fully-Grown Oocytes.
Infertility clinics would benefit from the ability to select developmentally competent vs. incompetent oocytes using non-invasive procedures, thus improving the overall pregnancy outcome. We recently developed a classification method based on microscopic live observations of mouse oocytes during their in vitro maturation from the germinal vesicle (GV) to the metaphase II stage, followed by the analysis of the cytoplasmic movements occurring during this time-lapse period. Here, we present detailed protocols of this procedure. Oocytes are isolated from fully-grown antral follicles and cultured for 15 h inside a microscope equipped for time-lapse analysis at 37 °C and 5% CO2. Pictures are taken at 8 min intervals. The images are analyzed using the Particle Image Velocimetry (PIV) method that calculates, for each oocyte, the profile of Cytoplasmic Movement Velocities (CMVs) occurring throughout the culture period. Finally, the CMVs of each single oocyte are fed through a mathematical classification tool (Feed-forward Artificial Neural Network, FANN), which predicts the probability of a gamete to be developmentally competent or incompetent with an accuracy of 91.03%. This protocol, set up for the mouse, could now be tested on oocytes of other species, including humans.


Near haploid cell line in lymphoid blast crisis of Ph1-positive chronic myeloid leukemia.
This report describes a case of lymphoid blast crisis of a chronic myelocytic leukemia with the occurrence of a double chromosomal population carrying a Philadelphia chromosome. Fifty-five % of the cells have 28 chromosomes, and 36% show the exact duplicate of the near haploid chromosome complement. The similarities between this near haploid cell line and those previously reported, as well as the presence of such clones in acute lymphoblastic leukemia, are discussed. In the leukemic lymphoblasts, the association of the Philadelphia chromosomes with a near haploid karyotype described so far in acute lymphoblastic leukemia provides further support for the concept of a pluripotent Philadelphia chromosome-positive stem cell common to both lymphoid and myeloid lines.


IDH1 mutation promotes lung cancer cell proliferation through methylation of Fibulin-5.
Mutation in isocitrate dehydrogenase (IDH) leads to an aberrant function of the enzyme, leading to the production of hydroxyglutarate, as well as changes in cellular metabolism, DNA methylation and histone modification. Previous studies uncovered mutations in IDH1 in several malignancies, with the most frequent mutation being IDH1 R132H. It has been demonstrated that IDH1 expression is induced in non-small-cell lung cancer (NSCLC). However, the contribution of IDH1 mutation in the malignant transformation and development of NSCLC is unclear. In our study, we show that IDH1 R132H enhanced the migration and proliferation of NSCLC cells. Moreover, IDH1 R132H was a crucial modulator of 2-hydroxyglutarate, whose production from cells with IDH1 mutation promoted the binding of DNA-methyltransferase 1 (DNMT1) to the Fibulin-5 promoter, leading to its methylation. As a result, Fibulin-5 silencing in cells with IDH1 mutation enhanced the migration and proliferation of NSCLC cells. We show that the IDH1 mutation was present in tissues sampled from patients with NSCLC, which was reversely linked to Fibulin-5 expression. In this study, we suggest an innovative model for IDH1 R132H/Fibulin-5 pathway, which could throw light upon the activity of IDH1 R132H in NSCLC.


Understanding Robust Adaptation Dynamics of Gene Regulatory Network.
Robust adaptation is a critical attribute for gene regulatory network (GRN), understanding the relationship between adaptation and the GRN topology, and corresponding parameters is a challenging issue. The work in this paper includes: first, seven constraint multiobjective optimization algorithms are used to find sufficient solutions to get more reliable statistic rules. Meanwhile, the algorithms are compared to facilitate the future algorithm selection; second, a fuzzy c-mean algorithm is used to analyze solutions and to classify the solutions into different groups; third, the histogram analysis for all satisfactory solutions shows the preferred parameter range, i.e., parameter motif. The contributions of this paper includes: 1) Two new adaptation indices i.e., peak time and settle down time, are proposed for the first time to give more accurate description of the robust adaptation. Our conclusion is that some solutions even with satisfactory sensitivity and precision are not practically of robust adaptation because of too long time needed. 2) The relationship between topology, parameter set, and robust adaptation of GRN is discovered in the sense of both preferred topology and parameter motif. Our conclusion is that the robust adaptation depends more on the GRN topology than the model parameter set in two feasible topologies.


[Secretion of the salivary glands of the medicinal leech Hirudo medicinalis inhibits ADP-induced aggregation of human platelets and platelet adhesion to a collagen-coated surface].
As was earlier demonstrated, secretion of medical leech exhibits high antithrombin activity of hirudin and inhibits contact activation of factor XII. Attempts were made to investigate the effects of the leech secretion on (i) the ADP-induced aggregation of platelets in suspension, registered by photometry according to Born, and (ii) platelet adhesion to the calf skin collagen-coated surface measured by scanning electron microscopy. The following results were obtained: 1) the secretion at doses of 0.13 vol % and 0.75 vol % inhibits the ADP-induced aggregation of gel-filtered human platelets by 50 and 97%, respectively; 2) the secretion inhibits the total adhesion and initial attachment of the gel-filtered platelets to the collagen substrate by 60-70% (dose 0.1-1.0 vol %) and 87-88% (dose 10 vol %); 3) platelet spreading on the collagen substrate and adhesion of the platelets from suspension to the upper surface of the spread platelets are inhibited by the secretion as well, but these effects are not statistically significant. The data obtained suggest that the secretion contains components which inhibit both the coagulating and platelet-vascular wall pathways of hemostasis.


Alcohol-related problems, drug use, and male intimate partner violence severity among US couples.
Particularly for women, level of intimate partner violence (IPV) severity is associated with risk of injury. Previous research suggests that male drinking problems and drug use are key risk factors. Few studies, however, have examined the associations between male and female alcohol problems and drug use and risk of moderate and severe male IPV in general household population samples. A multiethnic sample of 1615 married and cohabiting couples was obtained from the 1995 National Study of Couples, a cross-sectional study on alcohol and IPV. We assessed the contribution of past year male and female alcohol-related problems (i.e., drinking consequences and alcohol-dependence symptoms) and illicit drug use to the risk of moderate and severe male IPV. A series of generalized multinomial logit models, with adjustment for sociodemographic and psychosocial covariates, was constructed to assess these associations. Female and male alcohol-related problems and female drug use, were associated with increased risk of moderate and severe male IPV. Contrary to our expectation, male drug use was not associated with elevated risk for either type of male IPV. Compared with couples residing in low-unemployment neighborhoods, couples residing in high-unemployment neighborhoods were at greater risk for severe, but not moderate, male IPV. Alcohol-related problems among men and women and drug use among women, appear to be important correlates of male IPV severity among couples in the general population. These findings can aid in IPV screening efforts, the formulation of prevention strategies, and help inform batterer and victim treatment programs.


Complement levels and leucocyte phagocytosis in newborn babies.
Newborn babies face higher risk of infection than adults, but the immunological basis of this observation is yet to be fully explained particularly in babies of different gestations and birth weights. Sixty-two (62) adults, 55 full-term babies, 18 low birth weight babies and 44 normal birth weight babies were considered for the study. B-lymphocytes and T-lymphocytes were enumerated by EAC-rosette and E-rosette respectively. Leucocyte migration and intracellular killing were assessed by percentage migration index (%M.I), percentage Candidacidal index (%C.I) and bacterial stimulated nitroblue tetrazolium (NBT) dye reduction index (%NBT) respectively. Also, serum levels of C3 and C5 were measured by single radial immuno-diffusion method. Percentage T cell, C3, C5, %NBT and %C.I were lowest in low birth weight babies but % B cell was lowest in full term babies while normal birth babies had least %M.I. The present study suggests that gestational age and birth weight affect different aspects of immune response.