A simple kinetic parameter indicating the origin of the relaxations induced by point(-like) defects in metallic crystals and glasses.
Computer simulation shows that an increase of the volume V due to point defects in a simple metallic crystal (Al) and high entropy alloy (Fe20Ni20Cr20Co20Cu20) leads to a linear decrease of the shear modulus G. This diaelastic effect can be characterized by a single dimensionless parameter K = dln G/dln V. For dumbbell interstitials in single crystals K ≈ -30 while for vacancies the absolute K-value is smaller by an order of magnitude. In the polycrystalline state, K ≈ -20 but its the absolute value remains anyway 5-6 times larger than that for vacancies. The physical origin of this difference comes from the fact that dumbbell interstitials constitute elastic dipoles with highly mobile atoms in their nuclei and that is why produce much larger shear softening compared to vacancies. For simulated Al and high entropy alloy in the glassy state, K equals to -18 and -12, respectively. By the absolute magnitude, these values are by several times larger compared to the case of vacancies in the polycrystalline state of these materials. An analysis of the experimental data on isothermal relaxations of G as a function of V for six Zr-based metallic glasses tested at different temperatures shows that K is time independent and equals to ≈-43, similar to interstitials in single-crystals. It is concluded that K constitutes a important simple kinetic parameter indicating the origin of relaxations induced by point(-like) defects in the crystalline and glassy states.


Study of the single nucleotide polymorphism (SNP) at the palindromic sequence of hypersensitive site (HS)4 of the human beta-globin locus control region (LCR) in Indian population.
LCR, a genetic regulatory element, was examined in beta-thalassemia patients who do not show any mutation in the beta-globin genes. We sequenced LCR-HS2, HS3, and HS4 in samples from 16 such patients from the Indian population and found only one SNP A-G in the inverted repeat in HS4. A significant association was observed between the G allele and occurrence of beta-thalassemia by Fisher's exact test. The AG and GG genotypes showed higher relative risk as compared to the AA genotype. We also observed linkage disequilibrium between the A/G polymorphism and the AT-rich motif of the LCR HS2 region, suggesting that the G allele could be an evolutionarily new mutation in the study population.


Estimating the Environmental Costs of Africa's Massive "Development Corridors".
In sub-Saharan Africa, dozens of major "development corridors" have been proposed or are being created to increase agricultural production [1-4], mineral exports [5-7], and economic integration. The corridors involve large-scale expansion of infrastructure such as roads, railroads, pipelines, and port facilities and will open up extensive areas of land to new environmental pressures [1, 4, 8]. We assessed the potential environmental impacts of 33 planned or existing corridors that, if completed, would total over 53,000 km in length and crisscross much of the African continent. We mapped each corridor and estimated human occupancy (using the distribution of persistent night-lights) and environmental values (endangered and endemic vertebrates, plant diversity, critical habitats, carbon storage, and climate-regulation services) inside a 50-km-wide band overlaid onto each corridor. We also assessed the potential for each corridor to facilitate increases in agricultural production. The corridors varied considerably in their environmental values, and many were only sparsely populated. Because of marginal soils or climates, some corridors appear to have only modest agricultural potential. Collectively, the corridors would bisect over 400 existing protected areas and could degrade a further ~1,800 by promoting habitat disruption near or inside the reserves. We conclude that many of the development corridors will promote serious and largely irreversible environmental changes and should proceed only if rigorous mitigation and protection measures can be employed. Some planned corridors with high environmental values and limited agricultural benefits should possibly be cancelled altogether. VIDEO ABSTRACT.


SUMO: a multifaceted modifier of chromatin structure and function.
A major challenge in nuclear organization is the packaging of DNA into dynamic chromatin structures that can respond to changes in the transcriptional requirements of the cell. Posttranslational protein modifications, of histones and other chromatin-associated factors, are essential regulators of chromatin dynamics. In this Review, we summarize studies demonstrating that posttranslational modification of proteins by small ubiquitin-related modifiers (SUMOs) regulates chromatin structure and function at multiple levels and through a variety of mechanisms to influence gene expression and maintain genome integrity.


The significance for diagnosis and for surgical technique of multiple aneurysms of the same internal carotid artery.
A small series of five patients with more than one aneurysm on the same internal carotid artery is reported. The author believes that similar cases must have been observed by many neurosurgeons but can find no specific reference to the technical and diagnostic problems created by such lesions. Sometimes these lesions can be clipped separately, but when the aneurysms are contiguous it may be helpful to apply a clip with its jaws parallel to the long axis of the internal carotid artery. The author suggests that more case reports would help to advertise the relative frequency of such lesions and thereby should improve their management.


Four new Neotropical species of Eudicrana Loew (Diptera, Mycetophilidae, Sciophilinae) from the Colombian high Andean ecosystems, with comments on the genus.
Four new species of the sciophiline genus Eudicrana Loew are described for the Eastern and Central Andes of Colombia-Eudicrana silvaandina sp. nov., E. chingaza sp. nov., E. maculata sp. nov. and E. merizaldei. These are the first species of Eudicrana described from the extreme northern range of the Andes. The altitudinal distribution of these species in the paramos and high Andean forest ecosystems is restricted to 1750-3660 m a.s.l. and some other information on the environment is briefly discussed. A key for the Colombian species of Eudicrana is provided and a discussion is elaborated on the position of these species within the genus.


Antigenical alterations of hepatocyte membrane in rats after long-term administration of ethanol and carbon tetrachloride.
The presence of IgG over the hepatocyte's surfaces in ethanol- and/or carbon tetrachloride-pretreated rats was demonstrated as a very thin lineal fluorescent deposition around the membrane. The percentage of parenchymal IgG-positive liver cells ranged between 15 and 100% in all animals of treated groups. This suggests that ethanol may induce hepatic injury mediated by IgG autoantibodies which may be a response to an antigenical determinant present in hepatocytes altered by ethanol and/or carbon tetrachloride treatment.


Identification of intersubunit domain interactions within eukaryotic initiation factor (eIF) 2B, the nucleotide exchange factor for translation initiation.
In eukaryotic translation initiation, eIF2B is the guanine nucleotide exchange factor (GEF) required for reactivation of the G protein eIF2 between rounds of protein synthesis initiation. eIF2B is unusually complex with five subunits (α-ε) necessary for GEF activity and its control by phosphorylation of eIF2α. In addition, inherited mutations in eIF2B cause a fatal leukoencephalopathy. Here we describe experiments examining domains of eIF2Bγ and ε that both share sequence and predicted tertiary structure similarity with a family of phospho-hexose sugar nucleotide pyrophosphorylases. Firstly, using a genetic approach, we find no evidence to support a significant role for a potential nucleotide-binding region within the pyrophosphorylase-like domain (PLD) of eIF2Bε for nucleotide exchange. These findings are at odds with one mechanism for nucleotide exchange proposed previously. By using a series of constructs and a co-expression and precipitation strategy, we find that the eIF2Bε and -γ PLDs and a shared second domain predicted to form a left-handed β helix are all critical for interprotein interactions between eIF2B subunits necessary for eIF2B complex formation. We have identified extensive interactions between the PLDs and left-handed β helix domains that form the eIF2Bγε subcomplex and propose a model for domain interactions between eIF2B subunits.


Immunoproteomics: current technology and applications.
The varied landscape of the adaptive immune response is determined by the peptides presented by immune cells, derived from viral or microbial pathogens or cancerous cells. The study of immune biomarkers or antigens is not new and classical methods such as agglutination, enzyme-linked immunosorbent assay, or Western blotting have been used for many years to study the immune response to vaccination or disease. However, in many of these traditional techniques, protein or peptide identification has often been the bottleneck. Recent advances in genomics and proteomics, has led to many of the rapid advances in proteomics approaches. Immunoproteomics describes a rapidly growing collection of approaches that have the common goal of identifying and measuring antigenic peptides or proteins. This includes gel based, array based, mass spectrometry, DNA based, or in silico approaches. Immunoproteomics is yielding an understanding of disease and disease progression, vaccine candidates, and biomarkers. This review gives an overview of immunoproteomics and closely related technologies that are used to define the full set of antigens targeted by the immune system during disease.


Immunosuppression of the burned patient.
The burn patient is highly susceptible to infection due to the loss of the skin as a barrier to microorganisms. Immune defenses are activated in response to the burn injury; however, some of these defenses are altered. Neutrophil chemotaxis is compromised by decreased perfusion caused by hypovolemia and the formation of microthrombi. Chemotaxis and phagocytosis are dependent on complement components that are reduced in a large burn wound. Neutrophil intracellular killing power is reduced as oxygen delivery to the wound is decreased. Humoral immunity is altered with the drop in IgG levels. Cell-mediated immunity is depressed and T cell lymphocyte counts are deceased. Suppressor T cells are generated. Specific sources of infection for the burn patient include the patient's own bacterial flora; hospital personnel; respiratory equipment; and catheters, both urinary and intravascular. The best control for burn wound infection is the closure of the wound by early excision and grafting. When lack of donor sites prohibits this surgical therapy, control centers on the environment and wound care techniques. The selection of wound topical antibiotics on the basis of visual inspection and surface culturing assists in the prevention of burn wound sepsis. When wound sepsis does occur, systemic antibiotics are instituted. Although burn wound sepsis is an obvious cause of death for the burn patient, it is not the primary cause. Increasing sophistication in fluid resuscitation and in intensive care therapy has resulted in patients living beyond the initial insult and the following few days. Burn patient mortality is now associated with a syndrome presenting clinically as sepsis but without any identifiable septic source.(ABSTRACT TRUNCATED AT 250 WORDS)


Migration and mutation in stochastic models of gene frequency change. I. The island model.
Migration has in the past been introduced deterministically into stochastic gene frequency models. Migration at rate m then reduces the between-population variability by a factor of (1 - m)2 each generation. We show that with stochastic migration, whether of fixed or variable numbers of individuals, a positive term delta m is added to the variance. As a result of the delta m term, the equilibrium value of the between-population variability is increased compared to the corresponding value for deterministic migration by a factor of approximately (1 - m)-2 for small m. An equivalent result is derived for mutation, using the infinite allele model for a single population. We show in addition that these results may be derived much more simply by use of identity-by-descent probability methods, but only if a modified definition of the probability of identity-by-descent is used, involving the sampling with instead of without replacement of pairs of genes from the population.


Antenatal and Postnatal Care.
Optimal care during the antenatal and postnatal phases of the life cycle is a potentially positive determinant of health elsewhere in the continuum. A successful transition from the antenatal to the postnatal period requires early detection, optimal management, and prevention of disease; health promotion; birth preparedness; and complication readiness. Women, their babies, and families need appropriate evidence-based care based on their dignity and human rights before, during, and after birth. In this review, we present an overview of the components of antenatal and postnatal care needed to provide women a culturally sensitive and positive pregnancy and postnatal experience. The challenge of antenatal and postnatal care is determining their core components and underpinning them with evidence without overmedicalizing their practice.


Dynamics of DNA binding of replication initiation proteins during de novo formation of pre-replicative complexes in Xenopus egg extracts.
We investigated the dynamics of DNA binding of replication initiation proteins during formation of the pre-replicative complex (pre-RC) on plasmids in Xenopus egg extracts. The pre-RC was efficiently formed on plasmids at 23 degrees C, with one or a few origin recognition complex (ORC) molecules and approximately 10-20 mini-chromosome maintenance 2 (MCM2) molecules loaded onto each plasmid. Although geminin inhibited MCM loading, MCM interacted weakly but stoichiometrically with the plasmid in an ORC-dependent manner, even in the presence of geminin (with approximately 10 MCM2 molecules per plasmid). Interestingly, DNA binding of ORC, CDC6, and CDT1 was significantly stabilized in the presence of geminin, under which conditions approximately 10-20 molecules each of ORC and CDC6 were bound. Moreover, a similarly stable ORC-CDC6-CDT1 complex rapidly formed on DNA at lower temperature (0 degrees C) without geminin, with approximately 10-20 molecules each of ORC and CDC6 bound to the plasmid, but almost no binding of MCM. However, upon shifting the temperature to 23 degrees C, most ORC, CDC6, and CDT1 molecules were displaced from the DNA, leaving about one ORC molecule on the plasmid, whereas approximately 10 MCM2 molecules were loaded onto each plasmid. Furthermore, it was possible to load MCM onto DNA when the isolated ORC-CDC6-CDT1-DNA complex was mixed with purified MCM proteins. These results suggest that an ORC-CDC6-CDT1 complex pre-formed on DNA is directly involved in MCM loading and imply that each DNA-bound ORC molecule loads only one or a few MCM2-7 complexes during metazoan pre-RC formation.


Catanionic aggregates formed from drugs and lauric or capric acids enable prolonged release from gels.
The aim of this study was to add to the range of charged surfactants that can be used to form catanionic aggregates with oppositely charged surface active drug substances; and to apply these aggregates to prolong drug release from gels. The surfactants used in this study, lauric and capric acids are of natural origin-unlike traditionally used, synthetic, surfactants. The mixtures of drug substances and oppositely charged surfactants were studied visually and with cryogenic transmission electron microscopy. Drug release from gels was studied with a modified USP paddle method. This study shows that lauric and capric acids are as, or even more, active in forming catanionic aggregates than traditionally used surfactants such as sodium dodecyl sulfate. It is shown that the length of the hydrophobic part of the surfactant plays an important role in the formation of pharmaceutically interesting catanionic aggregates. As seen in previous studies, using catanionic vesicles prolongs the drug release from gels and decreases the apparent diffusion coefficient by a factor of 10-50, compared to a gel containing only drug substance.


An in vivo humanized model to study homing and sequestration of Plasmodium falciparum transmission stages in the bone marrow.
Recent evidence suggests that the bone marrow (BM) plays a key role in the diffusion of P. falciparum malaria by providing a "niche" for the maturation of the parasite gametocytes, responsible for human-to-mosquito transmission. Suitable humanized in vivo models to study the mechanisms of the interplay between the parasite and the human BM components are still missing. We report a novel experimental system based on the infusion of immature P. falciparum gametocytes into immunocompromised mice carrying chimeric ectopic ossicles whose stromal and bone compartments derive from human osteoprogenitor cells. We demonstrate that immature gametocytes home within minutes to the ossicles and reach the extravascular regions, where they are retained in contact with different human BM stromal cell types. Our model represents a powerful tool to study BM function and the interplay essential for parasite transmission in P. falciparum malaria and can be extended to study other infections in which the human BM plays a role.


Synthesis and molecular docking of 1,2,3-triazole-based sulfonamides as aromatase inhibitors.
A series of 1,4-disubstituted-1,2,3-triazoles (13-35) containing sulfonamide moiety were synthesized and evaluated for their aromatase inhibitory effects. Most triazoles with open-chain sulfonamide showed significant aromatase inhibitory activity (IC50=1.3-9.4μM). Interestingly, the meta analog of triazole-benzene-sulfonamide (34) bearing 6,7-dimethoxy substituents on the isoquinoline ring displayed the most potent aromatase inhibitory activity (IC50=0.2μM) without affecting normal cell. Molecular docking of these triazoles against aromatase revealed that the compounds could snugly occupy the active site of the enzyme through hydrophobic, π-π stacking, and hydrogen bonding interactions. The potent compound 34 was able to form hydrogen bonds with Met374 and Ser478 which were suggested to be the essential residues for the promising inhibition. The study provides compound 34 as a potential lead molecule of anti-aromatase agent for further development.


Desamino-D-arginine vasopressin in childhood nocturnal enuresis.
The effect of desamino-D-arginine vasopressin was investigated in a double-blind study of 37 children more than 9 years old with nocturnal enuresis resistant to conventional therapy. A significant reduction of wet nights was observed but as soon as the medication was stopped the children reverted to earlier bedwetting habits.


DNA-repair deficiencies do not affect intercalator-induced cytotoxicity or DNA scission in human cells.
The ability of the DNA intercalator m-AMSA to produce protein-associated DNA-strand breaks in normal, xeroderma pigmentosum and ataxia-telangiectasia fibroblasts was compared with m-AMSA uptake and cytotoxicity. No differences were detected between the cytotoxicity and DNA breakage produced by this antineoplastic acridine derivative among these three human cell lines. Uptake studies confirmed that no actual increased sensitivity was being masked by decreased intracellular drug. m-AMSA appears to be unique in its ability to produce breaks in cellular DNA that are not associated with an enhanced sensitivity in repair-deficient cells. Intercalator-induced, protein-associated DNA breaks are probably the result of a novel cellular response which differs from that which is abnormal in xeroderma pigmentosum or ataxia-telangiectasia cells.


Evaluation of cardiovascular biomarkers and histopathological alterations in cattle naturally infected by Babesia bigemina.
Hemolytic anemia and secondary hypoxia are characteristics of naturally occurring Babesia bigemina infection in cattle. The anemic phase comes with cardiovascular insufficiency due to hypoxia-induced system dysfunction; but to date there is no description of cardiac damage in the infected animals. Therefore, this study was undertaken to investigate hematological parameters, biomarkers of cardiac function and D-dimer in 13 cattle infected with B. bigemina which were unresponsive to standard treatment. The animals were necropsied and the cardiac tissue was examined for histopathologic alterations. A significant parasitemia burden-dependent increase in the cardiac biomarkers and D-dimer level were recorded in the infected cattle compared to the control animals. Thrombocytes count was also significantly lower in the infected animals than the control. Both macroscopic and microscopic hemorrhage, mononuclear infiltrates, and myocardial necrosis were the evident histopathologic findings. These findings suggest that B. bigemina infection can potentially induce cardiac dysfunction in cattle. Furthermore, mechanistic studies should be conducted to understand the mechanisms beyond cardiac complications.


[A new method of gatheing ecological data on the common buzzard (Buteo buteo) and on the field mouse (Microtus arvalis)].
In treeless regions the common buzzard uses the towers of electric overhead transmission lines (110-150 kV) for roosting. The streams of excrement bring about flash-overs which can be registered according to date and time of day. These records provide information as to diurnal and annual rhythms, as wells as to the relationships existing between topographical and climatic factors and the population density of the birds.Ninety per cent of the animals leave the roosting place between 42 minutes before and 11 minutes after sunrise. An increase of one unit in cloud density leads to a mean delay of about 2.8 minutes in departure. Excretion during the night exhibits a definite periodical variation. The relationship between population numbers in winter and summer can be measured quantitatively. Regressions for the influence of climatic factors on fluctuations of population density are given. The population dynamics of the field mouse is reflected in the frequency variations of the flash-overs set off by the excrement of the buzzards.


Lymph node metastasis density and growth pattern as independent prognostic factors in advanced esophageal squamous cell carcinoma.
Esophageal cancer is one of the leading types of cancer, and it is a particularly deadly form of malignancy. TNM classification is the most common staging system, but it has been reported that prognosis is not reflected adequately by this classification. The purpose of this study was to clarify independent prognostic factors in esophageal squamous cell carcinoma (ESCC), a dominant type of esophageal cancer in Japan, to broaden the staging system to improve its predictive value. Thus staging could be expanded to make the prognosis a valuable clinical tool, and to improve knowledge of the biological traits of advanced ESCC. The present study included 121 patients with advanced ESCC (stage II to IVA) treated by esophagectomy between 1990 and 2003 at the Kitasato University Higashi Hospital. Univariate prognostic analysis of the disease-specific survival revealed that TNM stage (p < 0.0001), lymph node metastasis density over 10% (ND10; p < 0.0001), R-category (p = 0.003), intramural metastasis within the esophagus (IM; p = 0.009), growth pattern (p = 0.01), and size of tumor (p = 0.02) were significantly associated with a poor outcome in advanced ESCC. Multivariate analysis confirmed that growth pattern (p = 0.02, HR = 3.1) and ND10 (p = 0.02, HR = 2.0) were finally remnant prognostic factors independent of TNM stage. Growth pattern was prominent in stage II, whereas ND10 was directly proportional to stage progression and characteristics to stage IV disease. Interestingly, ND20, the most malignant phenotype of ESCC, was the only prognostic determinant, even in stage IV disease. From the present study, we concluded that progression of lymph node density is characteristic of a life-threatening phenotype of advanced ESCC, and it should be employed as a therapeutic target to improve patient survival. Growth pattern is an alternative target characteristic of less advanced ESCC. Both of these parameters may be applied as useful clinical tools in the management of patients with advanced esophageal cancer.


Illegal Trade in Protected Sharks: The Case of Artisanal Whale Shark Meat Fisheries in Java, Indonesia.
Illegal, unreported, and unregulated fishing, including that of sharks, poses a significant threat to marine ecosystems and individual species. I use data from the media, tourists, and artisan fishermen to gain insight into the trade in the world's largest fish, the whale shark (Rhincodon typus). I focus on the Indonesian island of Java where, along its south coast, whale sharks are landed and butchered on the beach in view of hundreds of people and local media. Whale sharks are typically caught in fishing nets and dragged alongside boats to the shallows, where they are butchered. The meat and oil (valued at ~USD 2000 per shark) are sold and distributed within the community. I document 58 landings of mainly immature whale sharks (2002-2022). Artisanal fishermen see the landing of whale sharks as a fortuitous event, but the species is protected, and Indonesia is a signatory to various international agreements that preclude the fishing of whale sharks. It is imperative for the conservation of whale sharks that the various parties in Indonesia adhere better to their own rules and regulations protecting this species.


Correction to: Szabolcs Fekete, Imre Molnár (Eds.): Software-assisted method development in high performance liquid chromatography.
The reviewer would like to call the reader's attention to the fact that due to a typing error there was a mistake in the description of chapter 5 in the section "Contents". The correct text is.


Immunologic localization of alpha- and beta-endorphins and beta-lipotropin in corticotropic cells of the normal and anencephalic fetal pituitaries.
The use of antibodies to alpha-(17--39) ACTH, beta-LPH, and alpha- and beta-endorphins has enabled the detection of immunoreactive cells as early as the eight week of fetal life. Immunoreactive cells are located in the anterior and intermediate lobes of the pituitary gland in normal human fetuses. The same cells reacted with different antisera used in the present study. No immunoreactive cells were observed in the posterior lobe. The specificity of the immunocytological reaction has been controlled. In seven anencephalic fetuses, the presence of immunoreactive cells suggests that ACTH and beta-LPH can originate from a common precursor and are synthesized independent of the hypothalamus.


The composition of the incubation medium influences the sensitivity of mitochondrial permeability transition to cyclosporin A.
The aim of this work was to study permeability transition, and the influence of the composition of the incubation medium, on the inhibitory action of cyclosporin A. It was found that cyclosporin inhibited the opening of a nonspecific pore, as induced by the uncoupler carbonyl cyanide m-chlorophenylhydrazone, provided K+ was present in the incubation medium, but failed to do so if mitochondria are incubated in sucrose or Na+-based medium. It was also found that the sensitivity of mitochondria to the uncoupler depended on the incubation mixture, being more sensitive when sucrose was the osmotic support. Matrix Ca2+ release, large amplitude swelling, and drop in transmembrane electric gradient revealed permeability transition. The titration of membrane thiol groups shows them to be increased in mitochondria incubated in sucrose medium, in comparison with the values found in mitochondria incubated in KCl or NaCl medium. Our proposal is that the incubation in sucrose medium propitiated a conformational change of membrane proteins in such a way that cyclosporin was unable to bind to its target site.


Stabilized lipid film based biosensor for atenolol.
This work reports a technique for the stabilization after storage in air of a lipid film based biosensor for atenolol. Microporous filters composed of glass fibers (nominal pore sizes 0.7 and 1.0 microm) were used as supports for the formation and stabilization of these devices. The lipid film is formed on the filter by polymerization prior to its use. Methacrylic acid was the functional monomer, ethylene glycol dimethacrylate was the crosslinker and 2,2'-azobis-(2-methylpropionitrile) was the initiator. The method for preparation of stabilized lipid film biosensor is studied throughout this work. The response towards atenolol of these stabilized lipid membrane biosensor, for repetitive use, composed of phosphatidylcholine was compared with planar freely suspended bilayer lipid membranes (BLMs). The stabilized lipid membranes provided similar artificial ion gating events as BLMs in the form of transient signals and can function for repetitive uses after storage in air. This will allow the practical use of the techniques for chemical sensing based on lipid films and commercialization of these devices.


l-Leucylglycylglycine.
In the title compound, C10H19N3O4, the N- and C-termini are protonated and ionized, respectively, and the mol-ecule forms a zwitterion. The main chain is in a folded form. In the crystal, the N-terminal -NH3 (+) group hydrogen bonds to three C-terminal -COO groups and one carbonyl O atom, forming a three-dimensional network. In addition, an N-H⋯O hydrogen bond between the amide groups of the middle glycine residue and a C-H⋯O inter-action continue along the a-axis direction. The side chains of the leucyl residues form a hydro-phobic region along the a axis.


Influence of temperature on secretion and functionality of lupin seed γ-conglutin.
Basic 7S globulins, a group of proteins commonly found in legumes, undergo the intriguing phenomenon of release from the seeds into hot water. γ-Conglutin is a representative of this group of proteins found in lupin seeds. The physiological significance and the molecular mechanism of the selective release of γ-conglutin from lupin seeds remain unknown. Therefore, the presented study aimed to determine changes in the functionality of this protein in response to the high temperature occurring during lupin seed incubation. It was confirmed that the main protein fraction released from the seeds during high-temperature incubation was γ-conglutin. The incubation condition favours the occurrence of this protein in a monomeric form, and the temperature used corresponds to its midpoint unfolding temperature. Subsequent analysis carried out on the γ-conglutin monomer revealed changes in its functionality after heat shock. The thermally treated protein shows a considerable increase in its interaction strength with flavonoids. Moreover, the inhibitory activity against glycoside hydrolases was enhanced when γ-conglutin monomer was exposed to specific temperatures. The results of the present study provide a potential explanation of the physiological relevance of γ-conglutin and shed new light on a possible mechanism of its activation upon specific heat treatment. This knowledge will help characterise homologous proteins, which are commonly found in other legumes and undergo a similar heat-induced secretion phenomenon. © 2021 Society of Chemical Industry.


Developing an electrochemical deoxyribonucleic acid (DNA) biosensor on the basis of human interleukine-2 gene using an electroactive label.
Development of an electrochemical DNA biosensor based on a human interleukine-2 (IL-2) gene probe, using a pencil graphite electrode (PGE) as transducer and methylene blue (MB) as electroactive label is described. The sensor relies on the immobilization of a 20-mer single stranded oligonucleotide probe (hIL-2) related to the IL-2 gene on the electrode. The hybridization between the probe and its complementary sequence (chIL-2) as the target was studied by square wave voltammetry (SWV) of MB accumulated on the PGE. In this approach the extent of hybridization is evaluated on the basis of the difference between SWV signals of MB accumulated on the probe-PGE and MB accumulated on the probe-target-PGE. Some hybridization experiments with non-complementary oligonucleotides were carried out to assess whether the suggested DNA sensor responds selectively to the target. Some experimental variables affecting the performance of the biosensor including: polishing of PGE, its electrochemical activation conditions (i.e., activation potential and activation time) and probe immobilization conditions on the electrodes (i.e., immobilization potential and time) were investigated and the optimum values of 1.80 V and 300 s for PGE activation, and -0.5 V and 400s for the probe immobilization on the electrode were suggested.


Haemodynamic responses to specific renin-angiotensin inhibitors in hypertension and congestive heart failure. A review.
The renin-angiotensin system is an important regulator of vascular resistance in many patients with hypertension and congestive heart failure. To quantitatively evaluate this contribution requires correlation of markers of the renin-angiotensin system with haemodynamic parameters, notably blood pressure, cardiac output, and calculated systemic vascular resistance. In addition, to determine ventricular loading properties, assessment of cardiac filling pressures is also required. The availability of specific pharmacological inhibitors of the renin-angiotensin system greatly enhances such correlation, as the haemodynamic consequence of blocking the renin-angiotensin system can then more fully identify its contribution. In the last decade, highly specific pharmacological inhibitors have become available to serve such a purpose. Renin inhibitory peptides, and renin-specific antibodies can block the rate-limiting step of the renin-angiotensin cascade: namely, the cleavage of 4 amino acids from the angiotensinogen substrate by renin. However, this method of blockade is still at the early stages of investigation. More readily available are converting enzyme inhibitors which block the formation of angiotensin II, the potent vasoconstrictor which mediates increased systemic vascular resistance, and angiotensin II analogues which compete with endogenous angiotensin II for vascular and adrenal receptors. Although hypertension and chronic congestive heart failure are clinically distinct entities in many respects, their common bond is the fact that both pathological mechanisms are mediated by an increase of systemic vascular resistance. The implications of blocking the resulting vasoconstriction in both entities are therefore quite similar. This review summarises our present knowledge of the contribution of the renin-angiotensin system to the vasoconstriction of hypertension and congestive heart failure, and also summarises the haemodynamic consequences of such inhibition. The implications of the response to these specific pharmacological probes, as well as their limitations, are discussed. Their importance rests not only in their therapeutic application, but also in their contribution as probes for pathophysiological mechanisms of vasoconstriction in cardiovascular disease.


The phagocytosis stimulating peptide tuftsin: further look into structure-function relationships.
Sixteen new analogs of the phagocytosis-stimulating peptide tuftsin have been synthesized. The biological activities of these synthetic peptides, in which either the C-terminal or both C- and N-terminals are chemically altered, were evaluated by studying their effects on the phagocytosis of heat-killed yeasts and on the reduction of the dye nitroblue tetrazolium by normal human polymorphonuclear leukocytes. The results demonstrate that the integrity of the guanidine side chain of arginine at position four of tuftsin is crucial for maximal activity. Modification, even in side chain length, of the guanidine leads to decreasing activity. Preservation of the positive charge of position four of tuftsin yields analogs possessing considerable activity. Simultaneous alterations of both C- and N-terminal results in diminishing activities. The results of this study are discussed in relation to the structural features of tuftsin. It appears that interaction between the carboxyl of Arg4 and the amino group of Thr1 which would indicate a specific conformation such as a 4 leads to 1 beta-turn are not favored.


Effects of malachite green (MG) and its major metabolite, leucomalachite green (LMG), in two human cell lines.
Malachite green (MG) is still illegally used as a fungicide in aquaculture. In fish it is absorbed and metabolised to its major reduced metabolite, leucomalachite green (LMG). This latter represents the main residue found in fish tissues and may persist for several months. Since MG, suspected to act as a tumour promoter in vitro and in vivo, might be also present as a residue in fish, the present study was undertaken to ascertain the in vitro toxicity of both compounds in two human tumour cell lines (Caco-2 and HEp-2). After 24h incubation with MG, significant decreases of cell viability, measured by neutral red uptake (NRU) or total protein content (TPC) as well as proliferation capability (colony-forming ability, CFA) were noticed in HEp-2 cells; the mean IC(50) value was about 2 microM. As regards the differentiated Caco-2 cells, MG caused a dose-related significant cytotoxicity, measured either by MTT test, the LDH leakage or NRU, with a mean IC(50) value of about 15 microM. By contrast, LMG disclosed, in both cell lines, a lower cytotoxicity compared to MG. These results also show that HEp-2 cells are more sensitive than intestinal cells to the toxic action of both compounds.


Kick proficiency and skill adaptability increase from an Australian football small-sided game intervention.
This investigation is the first to explore the effect of a 4 week small-sided game (SSG) and traditional training intervention on player kick proficiency and player adaptability in Australian football. Twenty-two amateur Australian football players (mean ± SD; age 22.3 ± 2.46; height 182.4 ± 5.25; weight 82.1 ± 6.10; years playing senior amateur football 3.86 ± 3.09) were randomly selected into either a traditional training group (n = 11) or a SSG group (n = 11). Traditional training involved activities where skills were generally executed in isolation and with minimal contact (e.g., kicking lane drill or possession football). The SSG training group participated in 5v6 competitive games on varied shaped areas (approximately 272 m2 per player) and changing constraints (e.g., game tempo, game rules). All players participated in the team training sessions; however, the SSG group participated in a 4 × 3min training protocol, with 60 seconds recovery, in the last 20-min of the session. The SSG group participated in these alternative sessions twice a week for 4 weeks. Results indicated only the SSG enhanced their kick proficiency (17%) and were found to be more adaptable. The intervention group executed more kicks over longer distances (i.e., 20-40 m), made quicker decisions (e.g., executing more kicks in < 1s), applied more pressure to the opposition when they were executing a skill and were more likely to "take the game on" by decreasing the amount of times a skill was executed from a stationary position. The results of this study can be used by coaches when designing and implementing training programs as different training strategies will elicit different player behavioral adaptations.


Placental delayed villous maturation is associated with fetal congenital heart disease.
The placenta is crucial for the overall development and lifelong health of the fetus. Abnormal placental development and function occur in pregnancies with fetal congenital heart disease. However, studies that use standardized diagnostic criteria and incorporate control populations are lacking. This limits the generalizability of current research and the ability to determine the specific placental abnormalities associated with congenital heart disease. This study applied consensus statement guidelines (known as the Amsterdam criteria) for placental pathology interpretation to compare the frequency and pattern of abnormalities in pregnancies with fetal congenital heart disease to demographically matched control pregnancies and evaluate for differences in placental abnormalities by cardiac physiology. A single-center retrospective cohort study was conducted from January 2013 to June 2019. Infants with a prenatal diagnosis of moderate-severe congenital heart disease who were born at ≥37 weeks of gestation were included. A control group born at ≥37 weeks of gestation but without fetal congenital heart disease or other major pregnancy complications was matched to the congenital heart disease group on maternal race and ethnicity and infant sex. Using the Amsterdam criteria, placental pathology findings were categorized as delayed villous maturation, maternal vascular malperfusion, fetal vascular malperfusion, and inflammatory lesions. The frequency of placental abnormalities was compared between groups, and logistic regression was performed to evaluate the association of clinical and sociodemographic factors with delayed villous maturation, maternal vascular malperfusion, and fetal vascular malperfusion. There were 194 pregnancies with fetal congenital heart disease and 105 controls included, of whom 83% in the congenital heart disease group and 82% in the control group were of non-Hispanic White race and ethnicity. Compared with controls, pregnancies with fetal congenital heart disease had higher rates of delayed villous maturation (6% vs 19%; P<.001) and maternal vascular malperfusion (19% vs 34%; P=.007) but not fetal vascular malperfusion (6% vs 10%; P=.23). Infants with congenital heart disease with 2-ventricle anatomy displayed the highest odds of delayed villous maturation compared with controls (odds ratio, 5.5; 95% confidence interval, 2.2-15.7; P<.01). Maternal vascular malperfusion was 2.2 times higher (P=.02) for infants with 2-ventricle anatomy and 2.9 times higher (P=.02) for infants with single-ventricle physiology with pulmonic obstruction. Within the congenital heart disease group, delayed villous maturation was associated with higher maternal body mass index, polyhydramnios, larger infant birth head circumference, and infant respiratory support in the delivery room, whereas maternal vascular malperfusion was associated with oligohydramnios. In multivariable models adjusting for cardiac diagnosis, associations of delayed villous maturation persisted for infant birth head circumference (odds ratio, 1.2; 95% confidence interval, 1.0-1.5; P=.02) and infant respiratory support in the delivery room (odds ratio, 3.0; 95% confidence interval, 1.3-6.5; P=.007). Pregnancies with fetal congenital heart disease displayed higher rates of delayed villous maturation and maternal vascular malperfusion than controls, suggesting that placental maldevelopment may relate to maternal factors. Future investigations are needed to determine the association of these abnormalities with postnatal infant outcomes.


Serotonin is released from isolated leech ganglia by potassium-induced depolarization.
1. The quantities of serotonin that are released from isolated leech ganglia in vitro were measured with the sensitive neurochemical techniques of HPLC-EC. 2. Segmental ganglia were exposed to elevated concentrations of potassium that depolarize leech serotonin-containing neurons by approximately 35 mV per decade. 3. Each segmental ganglion released on average 0.20 pmol of serotonin during 10 min of incubation in a solution containing 64 mM K+. 4. The rate of serotonin release increased nearly four-fold to 0.74 pmol/10 min when ganglia were incubated in 120 mM K+. 5. The rates of ganglionic serotonin release in 120 mM K+ were quantitatively similar in these three, experimentally important species of leeches: Hirudo medicinalis, Macrobdella decora and Haementeria ghilianii. 6. Ionic substitution experiments with the divalent cations Mg2+ and Co2+ indicated that the release of serotonin from leech ganglia is mediated by a Ca2+ dependent process. 7. The serotonin-uptake blockers, imipramine and chlorimipramine, did not increase the amount of serotonin released in elevated potassium. 8. Vitally staining the identified serotonin-containing neurons with Neutral Red dye did not reduce the quantity of serotonin that was released from the ganglia in elevated potassium. 9. This study demonstrates the capacity of leech ganglia to release the neurochemical serotonin, and the rates of transmitter release increase with the degree of depolarization of serotonin-containing neurons.


Calcium signaling in skeletal muscle development, maintenance and regeneration.
Skeletal muscle-specific stem cells are pivotal for tissue development and regeneration. Muscle plasticity, inherent in these processes, is also essential for daily life activities. Great advances and efforts have been made in understanding the function of the skeletal muscle-dedicated stem cells, called muscle satellite cells, and the specific signaling mechanisms that activate them for recruitment in the repair of the injured muscle. Elucidating these signaling mechanisms may contribute to devising therapies for muscular injury or disease. Here we review the studies that have contributed to our understanding of how calcium signaling regulates skeletal muscle development, homeostasis and regeneration, with a focus on the calcium dynamics and calcium-dependent effectors that participate in these processes.


[Effect of Epidural Volume Extension on Combined Spinal-anesthesia of Parturients in Women Undergoing Cesarean Delivery].
To evaluate the blocking characteristics of epidural volume extension on combined spinal-anesthesia of parturients undergoing cesarean delivery. Eighty parturients were randomly allocated to one of four groups, receiving 0, 5, 10 or 15 mL normal saline, respectively, through epidural catheter at a rate of 0.5 mL/s (n = 20 in each group) after combined spinal-anesthesia with 11 mg intrathecally isobaric bupivacaine. Peak sensory block height, time for sensory block to sixth thoracicdermatome level, time for highest modified Bromage motor score, time for sensory regression to tenth thoracicdermatome level, and motor block recovery to Modified Bromage 0 were recorded. The groups with 10 mL and 15 mL epidural extension had a higher level of peak sensory and shorter time for the sensory block to sixth thoracicdermatome level compared with the control group (P< 0.05). There were no significant group differences in the time for sensory regression to tenth thoracicdermatome level (P > 0.05). The saline epidural extension groups had significant shorter time for highest modified Bromage motor score and motor block recovery to Modified Bromage 0 compared with the control group (P < 0.05). The use of phenylephrine was significantly higher in the 15 mL treatment group (P < 0.05). 10 mL of epidural saline volume extension is optimal for combined spinal-epidural anaesthesia of parturients undergoing caesarean delivery.


Computational Search for Two-Dimensional MX2 Semiconductors with Possible High Electron Mobility at Room Temperature.
Neither of the two typical two-dimensional materials, graphene and single layer MoS 2 , are good enough for developing semiconductor logical devices. We calculated the electron mobility of 14 two-dimensional semiconductors with composition of MX 2 , where M (=Mo, W, Sn, Hf, Zr and Pt) are transition metals, and Xs are S, Se and Te. We approximated the electron phonon scattering matrix by deformation potentials, within which long wave longitudinal acoustical and optical phonon scatterings were included. Piezoelectric scattering in the compounds without inversion symmetry is also taken into account. We found that out of the 14 compounds, WS 2 , PtS 2 and PtSe 2 are promising for logical devices regarding the possible high electron mobility and finite band gap. Especially, the phonon limited electron mobility in PtSe 2 reaches about 4000 cm 2 ·V - 1 ·s - 1 at room temperature, which is the highest among the compounds with an indirect bandgap of about 1.25 eV under the local density approximation. Our results can be the first guide for experiments to synthesize better two-dimensional materials for future semiconductor devices.


Immune Reconstitution Bone Loss Exacerbates Bone Degeneration Due to Natural Aging in a Mouse Model.
Immune reconstitution bone loss (IRBL) is a common side-effect of antiretroviral therapy (ART) in people with human immunodeficiency virus (PWH). Immune reconstitution bone loss acts through CD4+ T-cell/immune reconstitution-induced inflammation and is independent of antiviral regimen. Immune reconstitution bone loss may contribute to the high rate of bone fracture in PWH, a cause of significant morbidity and mortality. Although IRBL is transient, it remains unclear whether bone recovers, or whether it is permanently denuded and further compounds bone loss associated with natural aging. We used a validated IRBL mouse model involving T-cell reconstitution of immunocompromised mice. Mice underwent cross-sectional bone phenotyping of femur and/or vertebrae between 6 and 20 months of age by microcomputed tomography (µCT) and quantitative bone histomorphometry. CD4+ T cells were purified at 20 months to quantify osteoclastogenic/inflammatory cytokine expression. Although cortical IRBL in young animals recovered with time, trabecular bone loss was permanent and exacerbated skeletal decline associated with natural aging. At 20 months of age, reconstituted CD4+ T cells express enhanced osteoclastogenic cytokines including RANKL, interleukin (IL)-1β, IL-17A, and tumor necrosis factor-α, consistent with elevated osteoclast numbers. Immune reconstitution bone loss in the trabecular compartment is permanent and further exacerbates bone loss due to natural aging. If validated in humans, interventions to limit IRBL may be important to prevent fractures in aging PWH.


Annulation of β-Enaminonitriles with Alkynes via RhIII-Catalyzed C-H Activation: Direct Access to Highly Substituted 1-Naphthylamines and Naphtho[1,8- bc]pyridines.
A Cp*RhIII-catalyzed oxidative annulation of β-enaminonitriles with alkynes was reported to achieve selective synthesis of polysubstituted 1-naphthylamines and naphtho[1,8- bc]pyridines via multiple C-H activations. Assisted by a naphthylamine NH2 group, 1-naphthylamines were also readily cyclized to produce naphtho[1,8- bc]pyridines. In addition, the obtained naphtho[1,8- bc]pyridine derivatives exhibit intense fluorescence in the solid state.


Effects of gentrification on health status after Hurricane Katrina.
Despite substantial debate about the impacts of gentrification on cities, neighborhoods, and their residents, there is limited evidence to demonstrate the implications of gentrification for health. We examine the impacts of gentrification on several health measures using a unique individual-level longitudinal data set. We employ data from the Resilience in Survivors of Hurricane Katrina (RISK) project, a study of low-income parents, predominantly non-Hispanic Black single mothers, who participated in a New Orleans-based study before and after Hurricane Katrina. After Katrina, all participants were displaced, at least temporarily, from New Orleans, and had little or no control over neighborhood placement immediately following the storm. This near-random displacement after Katrina created a natural experiment. We employ a quasi-experimental intent to treat design to assess the causal effects of gentrification on health in the RISK population. We do not find evidence of significant main effects of being displaced to a gentrified neighborhood on BMI, self-rated health, or psychological distress. The analysis employs a quasi-experimental design and has several additional unique features--homogeneous population, limited selection bias, and longitudinal data collection-- that improve our ability to draw causal conclusions about the relationship between gentrification and health. However, the unique context of displacement by natural disaster may limit the generalizability of our findings to other circumstances or residents experiencing gentrification.


Ars2 promotes proper replication-dependent histone mRNA 3' end formation.
Ars2 is a component of the nuclear cap-binding complex that contributes to microRNA biogenesis and is required for cellular proliferation. Here, we expand on the repertoire of Ars2-dependent microRNAs and determine that Ars2 regulates a number of mRNAs, the largest defined subset of which code for histones. Histone mRNAs are unique among mammalian mRNAs because they are not normally polyadenylated but, rather, are cleaved following a 3' stem loop. A significant reduction in correctly processed histone mRNAs was observed following Ars2 depletion, concurrent with an increase in polyadenylated histone transcripts. Furthermore, Ars2 physically associated with histone mRNAs and the noncoding RNA 7SK. Knockdown of 7SK led to an enhanced ratio of cleaved to polyadenylated histone transcripts, an effect dependent on Ars2. Together, the data demonstrate that Ars2 contributes to histone mRNA 3' end formation and expression and these functional properties of Ars2 are negatively regulated by interaction with 7SK RNA.


Differences in health literacy level of patients from public and private hospitals: a cross-sectional study in Turkey.
Policy-making based on a health literacy approach makes it a priority to develop people-centered public health strategies and programs, particularly in the time of COVID-19 across the world. This is the first study to assess health literacy levels of patients visiting public and private hospitals in Turkey and also compares these levels with sociodemographic and health-related variables by hospital type to suggest health policies aimed at improving the health literacy skills for patients with different socio-economic backgrounds. This is a cross-sectional study. The study was conducted on 948 outpatients from both hospital types in 2018. Health literacy was assessed using the validated Turkish version of the European Health Literacy Survey Questionnaire with 47 items. The level of health literacy and sociodemographic factors influencing it were analyzed using correlation and binary logistic regression tests. Patients from private hospital had better health literacy index score compared with the public hospital. The health-related variables, such as self-reported health and the presence of long-term illness, and sociodemographic characteristics, including education, age, and gender, were associated with health literacy for both public and private hospitals. Age and education were important predictors, whereas gender, long-term disease condition, self-reported health, and perceived income status were statistically significant variables for adequate health literacy in both hospital types. Participants from private hospital had better health literacy than that of public hospital. These findings could be used to help health policy makers to improve the current health literacy policy for patients and develop strategies by stakeholders for reducing barriers to obtaining health-related information.


A novel amber mutation in a beta zero-thalassaemia gene (beta 37TGG-->TAG), with direct detection by mapping the restriction fragments in amplified genomic DNA.
A novel amber mutation, a G to A substitution at the second position of codon 37 in the beta-globin gene that changes the tryptophan coding triplet (TGG) to a termination codon (TAG), was found in a Chinese beta-thalassaemia carrier. The mutant gene creates an additional Dde I recognition site and eliminates the Ava II site, so this point mutation can be directly identified by restriction enzyme analysis.


Arthroscopic Revision of Medial Rotator Cuff Failure Augmented With a Bioabsorbable Patch.
When revising failed double-row and suture-bridge rotator cuff repairs medial failures represent a potential feature. In the presence of a compromised healing environment, patch augmentation becomes a logical adjunct from a mechanical and biological point of view. A reproducible step-by-step revision technique is described that reinforces the weak central cuff area with an absorbable synthetic scaffold.


Robotic Lung Resection for Non-Small Cell Lung Cancer.
Robotic-assisted pulmonary lobectomy can be considered for patients able to tolerate conventional lobectomy. Contraindications to resection via thoracotomy apply to patients undergoing robotic lobectomy. Team training, familiarity with equipment, troubleshooting, and preparation are critical for successful robotic lobectomy. Robotic lobectomy is associated with decreased rates of blood loss, blood transfusion, air leak, chest tube duration, length of stay, and mortality compared with thoracotomy. Robotic lobectomy offers many of the same benefits in perioperative morbidity and mortality, and additional advantages in optics, dexterity, and surgeon ergonomics as video-assisted thoracic lobectomy. Long-term oncologic efficacy and cost implications remain areas of study.


A multicenter review of epidemiology and management of varicose veins for national guidance.
Varicose vein is a common surgical problems in India. This study was done to assess the clinico-epidemiological profile, risk factors and management practices in varicose veins. Medical records of 170 varicose vein cases admitted in tertiary care hospitals in Mangalore between May 2011 to April 2014 were reviewed retrospectively. Majority of cases 53(31.2%) were of the age group 41-50 years. Majority were males 127(74.7%) and majority were unskilled workers 101(59.4%). Superficial veins were involved in 123(72.4%) cases. Perforator followed by great saphenous vein were most frequently involved. Veins on the left side were more involved than on the right. Common symptoms at the time of presentation was ulceration 98(57.6%) followed by pain in the legs 96(56.5%). Ulceration was seen significantly more among females (p = 0.027) and among house wives (p = 0.004). Complications like eczema 46(27.1%), non-healing ulcers 21(12.3%) and deep vein thrombosis 10(5.9%) were reported among cases. Eczema was present significantly more among elderly patients aged above 60 years (p = 0.019). Risk factors like prolonged standing was observed in 86(50.6%) cases. This history was significantly seen among males (p = 0.001) and among those involved in unskilled occupations (p < 0.001). Recurrence of varicose vein was reported in 23(13.5%) cases. It was associated with patients of the age group 21-30 years (p = 0.021). Doppler ultrasound was the most common 120(70.6%) investigation done. Micronized purified flavonoid fraction was used in management in 15(8.8%) cases. Conservative management methods like limb elevation 50(29.4%) and compression stocking 36(21.2%) was advised to patients. Saphenous vein stripping was the most common surgical procedure 40(23.5%) performed. The high risk groups identified in this study need to be made aware of risk of developing varicose veins. Use of compression stocking at work place added with newer procedure in management could help in betterment in their quality of life.


Novel fast pesticides extraction (FaPEx) strategy coupled with UHPLC-MS/MS for rapid monitoring of emerging pollutant fipronil and its metabolite in food and environmental samples.
In this work, we demonstrated a new, environmental-friendly and effective sample preparation strategy named 'in-syringe-assisted fast pesticides extraction (FaPEx)' technique coupled with LC-MS/MS for the rapid identification and monitoring of emerging pollutant fipronil and its metabolite fipronil sulfone in chicken egg and environmental soil samples. FaPEx strategy comprising of two simple steps. Firstly, the sample was placed in the syringe and extracted using low-volume acetonitrile with NaCl and anhydrous MgSO4 salts. Secondly, the extractant was passed through in-syringe-based solid-phase extraction (SPE) kit containing cleanup sorbents and salt combinations (C18, primary secondary amine, and anhydrous MgSO4) for the cleanup process. Then, the obtained clean extractant was injected into LC-MS/MS for the quantification of target analytes. Various important parameters influencing the FaPEx performances, such as solvent type, salt type, salt amount, sorbent type, and amount, were examined and optimized. The method validation results showed excellent linearity with high correlation coefficients were ≥ 0.99. The estimated LODs were between 0.05-0.07 μg/kg, and LOQs ranged between 0.1-0.25 μg/kg for target analytes in both egg and soil sample matrices, and precision values were ≤7.90%. The developed method was applied to commercial chicken egg samples and environmental soil samples analysis. Spiked recoveries ranged between 88.75-110.91% for egg samples with RSDs ≤7.42% and 82.47-107.46% for soil samples with RSDs <7.37%. These results proved that the developed sample preparation method is a simple, fast, green, low-cost, and efficient method for the analysis of fipronil and its metabolites in food and environmental samples. Thus, this method can be applied as an alternative analytical methodology in routine and standard food and environmental testing laboratories.


Bioaccumulation of 10 trace elements in juvenile fishes of the Lower Paraná River, Argentina: implications associated with essential fish growing habitat.
This study assessed the concentration, bioconcentration, and bioaccumulation of As, Cd, Co, Cr, Cu, Mg, Mn, Ni, Pb, and Zn in juvenile fishes (Acestrorynchus pantaneiro, Brycon orbygnianus, Cyphocharax voga, Megaleporinus obtusidens, Odontesthes bonariensis, Pimelodus maculatus, Prochilodus lineatus, Salminus brasiliensis, and Schizodon borelli) in the Lower Paraná River (Argentina), the most extensive floodplain from the Plata Basin. The floodplain is crucial for the reproduction and growth of various species such as P. lineatus, M. obtusidens, and S. brasiliensis, which complete their life cycle in this environment. In total, 90 individuals were sampled for nitrogen stable isotope, and trace element analysis in muscle tissue, water, and sediment was analyzed. The results show that all the studied species bioaccumulate Cr, Mg, Ni, and Zn. In particular, B. orbygnianus and P. maculatus presented the highest bioaccumulation factor for Cr. A biodilution of Co through the food chain was observed. No positive correlation was found between element concentration and trophic level, but we observed significant differences between trophic guilds (herbivorous, omnivorous, and carnivorous). Our findings suggest that feeding habits determine trace element concentrations. To establish differential behavior between different species within the aquatic web further studies are necessary, particularly in the floodplain of the Paraná, which is a crucial nursery area for most commercially important fishes from the Plata Basin. Graphical abstract.


Loading capacity of zirconia implant supported hybrid ceramic crowns.
Recently a polymer infiltrated hybrid ceramic was developed, which is characterized by a low elastic modulus and therefore may be considered as potential material for implant supported single crowns. The purpose of the study was to evaluate the loading capacity of hybrid ceramic single crowns on one-piece zirconia implants with respect to the cement type. Fracture load tests were performed on standardized molar crowns milled from hybrid ceramic or feldspar ceramic, cemented to zirconia implants with either machined or etched intaglio surface using four different resin composite cements. Flexure strength, elastic modulus, indirect tensile strength and compressive strength of the cements were measured. Statistical analysis was performed using two-way ANOVA (p=0.05). The hybrid ceramic exhibited statistically significant higher fracture load values than the feldspar ceramic. Fracture load values and compressive strength values of the respective cements were correlated. Highest fracture load values were achieved with an adhesive cement (1253±148N). Etching of the intaglio surface did not improve the fracture load. Loading capacity of hybrid ceramic single crowns on one-piece zirconia implants is superior to that of feldspar ceramic. To achieve maximal loading capacity for permanent cementation of full-ceramic restorations on zirconia implants, self-adhesive or adhesive cements with a high compressive strength should be used.


Purification of human transcobalamin II-cyanocobalamin by affinity chromatography using thermolabile immobilization of cyanocobalamin.
Transcobalamin II-cyanocobalamin was isolated from Cohn fraction III of pooled human plasma by affinity chromatography on cyanocobalamin-Sepharose and some conventional separation methods. The affinity ligand cyanocobalamin was coupled to AH-Sepharose by a thermolabile linkage. The unsaturated binding protein was absorbed at 4 degrees C and eluted from the column at 37 degrees C as transcobalamin II-cyanocobalamin complex. The final preparation had a specific cyanocobalamin-binding capacity of 0.98 mol cyanocobalamin/mol transcobalamin II, the yield was 55% and the purification index amounted to 1.1 . 10(6). In dodecyl sulphate polyacrylamide gel electrophoresis one major protein band was observed at a molecular weight of 37 000 and a faint band at a molecular weight of 29 000. In polyacrylamide gel isolectric focusing the pure preparation turned out to be heterogeneous with isoelectric points ranging from pH 6.2 to 6.8, possibly by the occurrence of isoproteins.


Acute effects of pulmonary artery occlusion on the pool of alveolar surfactant.
Electron microscopic evidence has shown that the occlusion of one pulmonary artery acutely decreases the content of lamellar inclusion bodies in alveolar type II cells. We studied the effect of unilateral pulmonary artery occlusion (UPAO) on the estimated alveolar pool of saturated phosphatidylcholine (SPC). Under pentobarbital anesthesia 13 rabbits, spontaneously breathing, underwent UPAO for 1--7 hours by balloon catheter. Eight rabbits with balloon deflated in the pulmonary trunk served as controls. After sacrifice the lungs were excised and alveolar SPC was harvested by lavage. After UPAO the alveolar pool of SPC was significantly higher in the occluded lungs than in the unoccluded ones. The average difference was 33.7% after 1 hour and 14.5% after 2 hours. After 4 and 7 hours of occlusion the alveolar pools of SPC in occluded and unoccluded lungs were not significantly different. We suggest that the temporarily larger pool size in the occluded lungs was due to an increase in surfactant secretion, although we cannot rule out entirely a decrease in the rate of clearance.


Nitric-oxide-synthase-mediated cyclic guanosine monophosphate production in neonatal rat cerebellar prisms is resistant to calcineurin inhibition.
Although the macrolide immunosuppressant tacrolimus (FK506) is neuroprotective in animal models of focal and global cerebral ischaemia, the mechanism of this action is not known. FK506 inhibits the protein phosphatase calcineurin, whose substrates can include nitric oxide synthase (NOS), and the neuroprotective effect of FK506 has been attributed to inhibition of NOS activity. We have examined nitric oxide-mediated cyclic guanosine monophosphate (cGMP) accumulation in neonatal rat cerebellar prisms. As expected, N-methyl-D-aspartate (NMDA) induced a rapid, concentration dependent accumulation of cGMP that was inhibited by the NMDA receptor antagonist dizocilpine (MK801) and the NOS inhibitor L-nitro-arginine methyl ester. Phosphoserine immunopositivity following NMDA exposure was increased in the presence of FK506, confirming inhibition of calcineurin. However, FK506 had no effect on NMDA-stimulated cGMP accumulation. These findings suggest that the neuroprotective effect of FK506 may be mediated by mechanisms other than increased NOS phosphorylation.


Visual field loss in migraine.
Ocular symptoms are a common, though transient, initial component of migraine. Although permanent visual loss has been reported in a limited number of patients, detailed evaluations of the visual field using current techniques have not been conducted. This study examined the prevalence of visual field loss in patients with migraine, using an automated static perimeter. All patients had at least a 2-year history of migraine (as diagnosed by a neurologist) and no ocular problems (by history or as determined by a visual screening examination consisting of acuity, intraocular pressure [IOP], and evaluation of the disc). The authors' results for 60 migraine patients showed that 21 (35%) had some form of visual field abnormality (P less than 0.05). The prevalence of visual field loss was greater with increasing age and duration of disease. These results suggest that visual field loss from migraine may be more common than previously considered. This information also may be useful in elucidating the relationship between migraine and certain vascular conditions of the eye.


The effects of nonsteroidal anti-inflammatory drugs on immune functions of human peripheral blood mononuclear cells.
It is generally accepted that the nonsteroidal anti-inflammatory drugs (NSAIDs) exhibit anti-inflammatory effects primarily through inhibition of prostaglandin (PG) synthesis. However, effects of NSAIDs on immune responses are not fully understood. This study investigated effects of indomethacin and a new NSAID (d-2-[4-(3-methyl-2-thienyl)phenyl]propionic acid, termed as M-5011 in this study) on cytokine production, lymphocyte proliferation, activities of natural killer (NK) and lymphokine activated killer (LAK) cells and secretion of immunoglobulin (Ig). Both indomethacin and M-5011 augmented interleukin (IL)-2 production, whereas they suppressed IL-6 production both at the protein and mRNA levels. These two NSAIDs augmented proliferation of phytohemagglutinin (PHA)-stimulated PBMC and enhanced NK and LAK cell activities. In contrast, indomethacin was more potent than M-5011 in inhibition of both PG synthesis and Ig secretions by pokeweed mitogen (PWM)-stimulated PBMC. These results suggest that these two NSAIDs equally augment cell-mediated immunity, whereas indomethacin was more potent than M-5011 in the inhibition of humoral immunity and PG synthesis.


Detection of a human hematopoietic progenitor cell capable of forming blast cell containing colonies in vitro.
A progenitor cell CFU-B1 (blast cell colony forming unit) present in human bone marrow and capable of producing blast cell containing colonies in vitro was detected using a serum containing semisolid culture system. The CFU-B1 has the capacity not only to undergo self-renewal, but also commitment to a number of hematopoietic lineages. This progenitor cell therefore has characteristics which suggest that it is identical to or closely related to the human pluripotent hematopoietic stem cell. Pretreatment of marrow cells with 5 fluorouracil facilitated detection of CFU-B1 derived colonies. The formation of CFU-B1 derived colonies was dependent upon the addition of media conditioned by the human bladder carcinoma cell line 5637. The ability of 5637 CM (conditioned media) to support blast cell colony formation was in part but not totally ablated by pretreatment of the CM with an IL-1 alpha (interleukin-1) neutralizing antibody. This data suggests that IL-1 alpha plays a role in the regulation of primitive events occurring during human hematopoiesis. IL-1 alpha might be exerting these effects by either acting directly on the CFU-B1, causing marrow accessory cells to elaborate other cytokines or by synergizing with cytokines already present in 5637 CM.


Willingness or unwillingness to perform cesarean section for impending preterm delivery at 24 weeks' gestation: a cost-effectiveness analysis.
This study was undertaken to compare the costs and health outcomes of 2 management options when encountering a 24-week gestation in labor. We constructed a decision model for willingness versus unwillingness to perform cesarean section for fetal indication (aggressive vs nonaggressive management). We modeled chance nodes for stillbirth, neonatal death, and long-term survival, with and without major morbidity. Main outcome measures were intact (healthy) infant and live infant. Cost-effectiveness analysis was conducted from a societal perspective to determine the cost-effectiveness of the 2 strategies. The probabilities of both intact survival (16.8% vs 12.9%) and survival with major morbidity (39.2% vs 19.4%) were higher with willingness to perform cesarean section. Nonaggressive management was less costly for delivery at 24 weeks' gestation. Aggressive management strategy would cost dollar 4,680,387 more than nonaggressive management for each additional intact infant, and dollar 766,241 more per additional live infant. Although the probability of survival is increased by physician willingness to perform cesarean section, the more cost-effective strategy is unwillingness because of a strong relationship to the increased probability of survival with major morbidity when physicians are willing to perform cesarean section for fetal indications.


Stimulation of monoclonal antibody production by human-human hybridoma cells with an elevated concentration of potassium or sodium phosphate in serum-free medium.
Potassium or sodium phosphate was found to stimulate the production of human monoclonal antibody by human-human hybridoma HB4C5. The addition of 15 mM Na-phosphate (pH 7.4) into serum-free culture medium increased the antibody production up to 4-fold, when seeded at cell density of 1×10(5) cells/ml in dishes. At the higher cell density of 5×10(5) cells/ml, K-phosphate was more effective than Na-phosphate, at the same concentration. In large-scale continuous culture, the addition of 10 mM Na-phosphate into serum-free culture medium stimulated antibody production by HB4C5 cells 6-fold.


11,11-Diphenyl-11H-indeno-[1,2-b]quinoxaline.
In the title compound, C27H18N2, the mean planes of the pendant benzene rings are approximately perpendicular to one another, making a dihedral angle of 79.3 (5)°; the indeno-[1,2-b]quinoxaline ring system (r.m.s. deviation = 0.1197 Å) is twisted with respect to the pendant benzene rings by 70.0 (4) and 67.6 (3)°. Weak aromatic π-π stacking [centroid-centroid separation = 3.628 (2) Å] and C-H⋯π inter-actions occur in the crystal.


Tuberculin skin test versus QuantiFERON-TB gold in-tube for latent tuberculosis screening in people living with HIV in a resource-limited setting.
To compare QuantiFERON-TB Gold-in-Tube (QFT) and tuberculin skin test (TST) in the diagnosis of latent tuberculosis infection (LTBI) among people living with HIV (PLWHIV). A cross-sectional study was carried out between 2017-2018. Tuberculin skin test and QFT were performed and their concordance was measured. The gold standard for LTBI was defined as positivity to any of the tests. A logistic regression model was carried out to predict the QFT result in patients with a negative TST. A total of 510 PLWHIV were included, with 409 (80.2%) being male. The mean age of the patients was 41.3 ± 11.8 years. The median time since HIV diagnosis was 5 years (IQR 2-10), with a median CD4+ count of 541 (IQR 340-757) cells/mm3. Overall, 20 patients had an isolated TST+, 22 an isolated QFT+ and 15 had both positive. Concordance between tests showed a kappa coefficient of .37. Overcrowding was the only predictor for a positive QFT after a negative TST (p = .003). There was fair agreement between tests in PLWHIV. In conditions of limited access to QTF, a TST-based strategy could be considered, with sequential use of QTF in high-risk patients with a negative result, especially those who live in overcrowded conditions.


An easy disinfection strategy for pipes connecting hemodialysis equipment.
A hemodialysis room has pipes connecting the console and central fluid equipment. While these pipes require disinfection, reports detailing disinfection strategies are unavailable. Therefore, we aimed to compare two easy disinfection strategies differing in sanitization frequency and sanitizer concentration. Reverse osmosis water (ROW) purifying equipment and six dialysis consoles were connected by 20 m of pipes. Only ROW flowed through these pipes, because the dialysate solution was constituted at each console. The pipes were sanitized by two strategies: (1) strong and monthly (hypochlorite concentration: 100 ppm) or (2) weak and weekly (5 ppm). Both strategies were easy because the sodium hypochlorite was simply added to the ROW tank. To estimate sanitization efficacy, endotoxin counts at the ROW tank outlet, the end of the pipe, and the pipe after the endotoxin-cutting filter in each console were measured monthly for six continuous months. These counts were compared between the two sanitization strategies. The endotoxin counts at the ROW tank outlet and the end of the pipe were 0.004-0.017 and 0.012-0.081 EU/mL, respectively, in the strong and monthly strategy, and 0.001-0.003 and 0.001-0.005 EU/mL, respectively, in the weak and weekly strategy. The endotoxin counts at the pipe after the endotoxin-cutting filter were less than 0.001 EU/mL during the study period in both strategies. A weekly disinfection strategy was more effective than a monthly one, despite the lower hypochlorite concentration. The present study suggests that frequency is the most important factor in the disinfection of pipes in a dialysis room.


Omentectomy vs omentum preservation for advanced gastric cancer: A systematic review and meta-analysis.
Currently, gastric cancer is the sixth most prevalent cancer in the world. The recommended treatment for advanced disease is gastrectomy with D2 lymphadenectomy. However, there is no consensus regarding the performance of an omentectomy as part of the treatment. The procedure is considered by some authors to be essential for the elimination of a micrometastasis since cells in the peritoneum prefer growing in milky spots in the omentum. On the other hand, retrospective studies demonstrated that there is the possibility that omentum preservation may not impact patients' overall survival. Therefore, the objective of this review was to quantify the effect of performing an omentectomy to determine whether it is necessary. Medline (PubMed), Embase, Cochrane, ClinicalTrials.gov and LILACS were searched up to September 2022. Selection was restricted to comparative studies in patients with advanced GC (≥T2). The certainty of evidence was assessed with GRADEPro and the risk of bias with ROBINS-I and RoB 2.0. Five cohort studies, and one randomized controlled trial (RCT) were included. The meta-analysis found that there were no significant differences between the procedures for overall survival, relapse-free survival, and peritoneal recurrence. Furthermore, in perioperative outcomes, a significant difference was only found in intraoperative bleeding, which was lower in patients who had their omentum preserved. Therefore, omentum preservation in patients with advanced gastric cancer has been shown to have no inferior results than resection in long-term outcomes.


Relationship between genotoxicity and oxidative stress induced by mercury on common carp (Cyprinus carpio) tissues.
Mercury is one of the most toxic metals in aquatic systems since it is able to induce neurobehavioral disorders as well as renal and gastrointestinal tract damage. The common carp Cyprinus carpio is an important species from both an ecological and economic viewpoint as it is consumed in many countries, the top producers being Mexico, China, India and Japan. The present study aimed to evaluate the relation between Hg-induced oxidative stress and genotoxicity in diverse tissues of C. carpio. Specimens were exposed to 0.01mgHg/L (the maximum permissible limit for aquatic life protection), and lipid peroxidation, protein carbonyl content and the activity of antioxidant enzymes were evaluated at 96h. Micronuclei frequency and DNA damage by comet assay were determined at 12, 24, 48, 72 and 96h. Hg induced oxidative stress and genotoxicity on exposed fish, since inhibition of antioxidant enzymes activity and increases in lipid peroxidation, DNA damage and micronuclei frequency occurred. Blood, gill and liver were more susceptible to oxidative stress, while blood were more sensitive to genotoxicity. In conclusion, Hg at concentrations equal to the maximum permissible limit for aquatic life protection induced oxidative stress and genotoxicity on C. carpio, and these two effects prove to be correlated.


Radiofrequency catheter ablation of idiopathic recurrent ventricular tachycardia with right bundle branch block, left axis morphology.
Idiopathic ventricular tachycardia with right bundle branch block and left axis deviation morphology is a well described clinical syndrome. Previous studies have mapped the tachycardia focus to the inferior septal region at the base of the posterior papillary muscle of the left ventricle. We describe two typical cases in a 20-year-old man and 29-year-old woman in which the tachycardia focus was localized with endocardial mapping techniques. In both cases the ventricular tachycardia focus was ablated with application of radiofrequency current at the inferior septal region. There were no complications of the procedures. The patients remain asymptomatic over follow-up of 7 and 4 months, respectively.


Testicular lesions of coprine and benzcoprine.
The effect on the testis of the disulfiram-like compounds benzcoprine (N-[1-ethoxycyclopropyl] benzamide) and coprine (N5-[1-hydroxycyclopropyl]-L-glutamine) was studied in rats and dogs. Severe degeneration of the seminiferous epithelium was induced in rats by subacute oral administration of each compound. 60 days after termination of treatment with benzcoprine most seminiferous tubules contained only occasional spermatogonia and the testicular weight was markedly decreased. The blood-testis barrier was unaffected in the benzcoprine-treated rats as judged by a lanthanum tracer technique. In dogs, oral administration of benzcoprine for 1 month caused impaired spermatogenesis, degeneration of germ cells and a decrease in the testicular weight. The results indicate that both compounds act directly on the germ cells. The effect is similar to that of alkylating compounds. Other effects of benzcoprine and coprine (bone marrow depression, lymphocytopenia, positive Ames test in organisms sensitive to base-pair substitution) are well-known properties of alkylating agents. In conclusion benzcoprine and coprine were found to cause severe changes in the testis in rats and dogs, probably due to a direct effect on the germ cells.


Ethical issues related to patient use of complementary and alternative medicine.
It is important for physicians to set aside their personal opinions and establish open lines of communication with patients about alternatives to conventional medical treatment.


Hepatic Arterial Infusion of Oxaliplatin, Fluorouracil, and Leucovorin in Hepatocellular Cancer with Extrahepatic Spread.
To compare treatment with hepatic arterial infusion of chemotherapy (HAIC) in patients with advanced hepatocellular carcinoma (HCC) with both extrahepatic spread (EHS) and intrahepatic tumor and patients with intrahepatic tumor only. This single-center retrospective study comprised 116 patients with advanced HCC with both intrahepatic tumor and EHS (EHS group; n = 50) or with intrahepatic tumor only (non-EHS group; n = 66) treated with HAIC including oxaliplatin, fluorouracil, and leucovorin between June 2014 and July 2016. Overall survival (OS) and radiologic responses to treatment were determined and compared between the 2 groups. Both the objective response rate and the clinical benefit rate were higher in the non-EHS group than in the EHS group (37.9% vs 16% objective response rate, P = .010; 81.8% vs 62% clinical benefit rate, P = .017). Median OS was not statistically different between the 2 groups (14.8 months vs 9.8 months, P = .068). Subgroup analysis of OS found that patients with lung metastases survived for a shorter time (OS 7 months) than patients with other metastatic sites (P = .003) and patients free of metastases (P = .001). HAIC is a potential treatment option for advanced HCC with limited extrahepatic metastases in a population with hepatitis B virus infection.


The Relationships among Anxiety, Subjective Well-Being, Media Consumption, and Safety-Seeking Behaviors during the COVID-19 Epidemic.
The COVID-19 epidemic has been confirmed as the largest scale outbreak of atypical pneumonia since the outbreak of severe acute respiratory syndrome (SARS) in 2003 and it has become a public health emergency of international concern. It exacerbated public confusion and anxiety, and the impact of COVID-19 on people needs to be better understood. Indeed, prior studies that conducted meta-analysis of longitudinal cohort research compared mental health before versus during the COVID-19 pandemic and proved that public health polices (e.g., city lockdowns, quarantines, avoiding gatherings, etc.) and COVID-19-related information that circulates on new media platforms directly affected citizen's mental health and well-being. Hence, this research aims to explore Taiwanese people's health status, anxiety, media sources for obtaining COVID-19 information, subjective well-being, and safety-seeking behavior during the COVID-19 epidemic and how they are associated. Online surveys were conducted through new media platforms, and 342 responses were included in the analysis. The research results indicate that the participants experienced different aspects of COVID-19 anxiety, including COVID-19 worry and perceived COVID-19 risk. Among the given media sources, the more participants searched for COVID-19 information on new media, the greater they worried about COVID-19. Furthermore, COVID-19 worry was positively related to safety-seeking behavior, while perceived COVID-19 risk was negatively related to subjective well-being. This paper concludes by offering some suggestions for future studies and pointing out limitations of the present study.


Fabrication and characterization of novel diopside/silk fibroin nanocomposite scaffolds for potential application in maxillofacial bone regeneration.
Novel freeze-dried porous composite scaffolds were prepared from natural polymer of silk fibroin (SF) as a matrix and from diopside nanoceramic as a bioactive reinforcing agent through a freeze-drying method. Considering the superiority of both diopside and SF in terms of mechanical and biochemical properties (in comparison to similar ceramics and polymers, especially in maxillofacial specific applications), we investigated the effect of diopside nanoparticle contents. Microstructure studies illustrated that the bioactive diopside nanoparticles were distributed throughout the fibroin matrix. Enough porosity, desired surface properties, high mechanical strength and excellent in vitro biocompatibility were achieved during the fabrication of the nanocomposite scaffolds without any extra modifications.


Health Care Hotspotting: A Scoping Review.
Super-utilizers of the health care system compose a small percentage of the population, yet use the most health care resources. Hotspotting addresses this issue by providing high-quality, personalized care to this population. This review examined how hotspotting has been defined, implemented, and measured. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guided this review. Twelve databases were searched for hotspotting interventions in practice settings. Sixteen studies were included. Hotspotting was primarily defined by the Camden Coalition of Healthcare Providers and relied on multiple professions, including nursing. Hotspotting interventions addressed access to care, social determinants of health, patient engagement, and health literacy. Some studies indicated that hotspotting reduced readmissions and emergency department visits and increased use in social services. Patients benefit from an interprofessional, personalized approach to their care planning. Hotspotting can lead to high-quality care through building trusted relationships.


Incident Early- and Later-Onset Type 2 Diabetes and Risk of Early- and Later-Onset Cancer: Prospective Cohort Study.
We evaluated prospectively the association between incident early-onset (diagnosed before 40 years of age) and later-onset type 2 diabetes and early-onset (diagnosed before 50 years of age) and later-onset cancer risk. We prospectively followed 228,073 eligible participants in the Nurses' Health Studies for up to 38 years. Hazard ratios (HRs) and 95% CI were estimated using Cox models. We documented 18,290 type 2 diabetes, 6,520 early-onset cancer, and 36,907 later-onset cancer cases during follow-up. In fully adjusted analyses, early-onset type 2 diabetes was associated with increased risk of early-onset total cancer (HR [95% CI] 1.47 [1.06-2.04]), diabetes-related cancer (2.11 [1.38-3.23]), and obesity-related cancer (1.75 [1.08-2.82]), and the risk elevations were restricted to those with a BMI at 18 years of age of ≥21 kg/m2 (total cancer: 1.75 [1.20-2.56]; diabetes-related cancer: 2.43 [1.50-3.94]; and obesity-related cancer: 1.84 [1.05-3.22]). Early-onset type 2 diabetes was associated with higher risk of later-onset diabetes-related and obesity-related cancer specifically among individuals with higher BMI at 18 years of age. Later-onset type 2 diabetes was associated with a higher risk of later-onset total cancer (1.15 [1.11-1.20]), diabetes-related cancer (1.17 [1.12-1.22]), and obesity-related cancer (1.18 [1.13-1.24]). In analyses based on refined timing, the HRs attenuated substantially with aging. Incident early-onset type 2 diabetes was associated with increased risk of early-onset total cancer and diabetes- and obesity-related cancer, especially in those with higher BMI at 18 years of age. The impact of early-onset type 2 diabetes on cancer risk may be inherently stronger than that of later-onset type 2 diabetes.


Perception of faces in schizophrenia: Subjective (self-report) vs. objective (psychophysics) assessments.
Face perception impairment in schizophrenia has been demonstrated, mostly through experimental studies. How this laboratory-defined behavioral impairment is associated with patients' perceptual experience of various faces in everyday life is however unclear. This question is important because a first-person account of face perception has direct consequences on social functioning of patients. In this study, we adapted and administered a self-reported questionnaire on narrative perceptual experience of faces along with psychophysical assessments of face perception in schizophrenia. The self-reported questionnaire includes six rating items of face-related functioning in everyday life, providing a subjective measure of face perception. The psychophysical assessment determines perceptual threshold for discriminating different facial identities, providing an objective measure of face perception. Compared to controls (n = 25), patients (n = 35) showed significantly lower scores (worse performance) in the subjective assessment and significantly higher thresholds (worse performance) in the objective assessment. The subjective and objective face perception assessments were moderately correlated in controls but not in patients. The subjective face perception assessments were significantly correlated with measurements of a social cognitive ability (Theory of Mind), again in controls but not in patients. These results suggest that in schizophrenia the quality of face-related functioning in everyday life is degraded and the role that basic face discrimination capacity plays in face-related everyday functioning is disrupted.


Natural death of adult Onchocerca volvulus and filaricidal effects of doxycycline induce local FOXP3+/CD4+ regulatory T cells and granzyme expression.
Immunosuppression in human filarial disease involves regulatory T cells. We hypothesized that natural or worm antigen-induced FOXP3 regulatory T cells could be involved locally, suppressing effector cells via granzymes. Natural and treatment-induced death of worms implies enhanced exposure to worm antigens. Therefore, we examined FOXP3+T cells and granzyme expression in onchocercomas harbouring adult Onchocerca volvulus worms, with respect to worm viability, productivity, the patient's immune status and filaricidal treatment. The immunohistological analysis revealed that dead adult worms were strongly associated with FOXP3+T cells in generalized hyporeactive onchocerciasis. FOXP3+ cells hardly expressed granzymes, but cell contacts with granzyme A+ or B+ cells were frequent. While suramin directly kills most adult worms within 6 months, the Wolbachia depleting antibiotic doxycycline indirectly causes adult worm degeneration within 18 months. Contrary to suramin, depletion of Th1-driving endobacteria most strongly promoted FOXP3+T cells and granzyme-expressing cells. In hyperreactive patients, FOXP3+ cells were less frequent. This is the first demonstration of local FOXP3+Treg cells in human filariasis and their induction by natural worm death and anti-parasitic treatment. We newly report granzyme responses to helminths and their association with immunosuppression. FOXP3+Treg and granzyme+ cells might locally suppress defence against newly acquired worms.


Group O RBCs: where is universal donor blood being used.
There have been recurrent shortages of group O blood due to insufficient inventory and use of group O blood in ABO non-identical recipients. We performed a 12-year retrospective study to determine utilization of group O Rh-positive and Rh-negative red blood cells (RBCs) by recipient ABO group. Reasons for transfusing group O blood to ABO non-identical recipients were also assessed. Utilization data from all group O Rh-positive and Rh-negative RBCs transfused at three academic hospitals between April 2002 and March 2014 were included. Data were extracted from Transfusion Registry for Utilization Surveillance and Tracking, a comprehensive database with inventory information on all blood products received at the hospitals. Extracted data included product type, ABO and Rh, final disposition (transfused, wasted, outdated), and demographic and clinical data on all patients admitted to hospital. Descriptive statistics were performed using sas 9.3. There were 314 968 RBC transfusions: 151 645 (48·1%) were group O, of which 138 136 (91·1%) RBC units were transfused to group O individuals. ABO non-identical recipients received 13 509 group O RBCs (8·9%). The percentage of group O RBCs transfused to ABO non-identical recipients by fiscal year varied from 7·8% to 11·1% with a steady increase from 2011 to 2013. Reasons for this included: trauma, outdating, outpatient usage and shortages. The practice of transfusing O RBCs to non-O individuals has been increasing. Specific hospital and blood supplier policies could be targeted to change practice, leading to a more sustainable group O red blood cell supply.


Influenza: seasonality and travel-related considerations.
This review aims to summarize the transmission patterns of influenza, its seasonality in different parts of the globe, air travel- and cruise ship-related influenza infections and interventions to reduce transmission. The seasonality of influenza varies globally, with peak periods occurring mainly between October and April in the northern hemisphere (NH) and between April and October in the southern hemisphere (SH) in temperate climate zones. However, influenza seasonality is significantly more variable in the tropics. Influenza is one of the most common travel-related, vaccine-preventable diseases and can be contracted during travel, such as during a cruise or through air travel. Additionally, travellers can come into contact with people from regions with ongoing influenza transmission. Current influenza immunization schedules in the NH and SH leave individuals susceptible during their respective spring and summer months if they travel to the other hemisphere during that time. The differences in influenza seasonality between hemispheres have substantial implications for the effectiveness of influenza vaccination of travellers. Health care providers should be aware of influenza activity when patients report travel plans, and they should provide alerts and advise on prevention, diagnostic and treatment options. To mitigate the risk of travel-related influenza, interventions include antivirals for self-treatment (in combination with the use of rapid self-tests), extending the shelf life of influenza vaccines to enable immunization during the summer months for international travellers and allowing access to the influenza vaccine used in the opposite hemisphere as a travel-related vaccine. With the currently available vaccines, the most important preventive measure involves optimizing the seasonal influenza vaccination. It is also imperative that influenza is recognized as a travel-related illness among both travellers and health care professionals.


Crystallization and preliminary X-ray diffraction studies of tobacco necrosis virus.
Tobacco necrosis virus is a spherical plant virus consisting of 180 copies of coat protein and a single-stranded RNA. The virus has been crystallized in cubic space group P4(2)32 with a = 338 A. The locations and the orientations of the two virus particles in the unit cell have been determined on the basis of the symmetries of both the particle and the crystal. The crystal diffracts X-rays to at least 2.5 A resolution and is quite stable to X-ray beams (1 A = 0.1 nm).