Hyperoxia promotes polarization of the immune response in ovalbumin-induced airway inflammation, leading to a TH17 cell phenotype.
Previous studies have demonstrated that hyperoxia-induced stress and oxidative damage to the lungs of mice lead to an increase in IL-6, TNF-α, and TGF-β expression. Together, IL-6 and TGF-β have been known to direct T cell differentiation toward the TH17 phenotype. In the current study, we tested the hypothesis that hyperoxia promotes the polarization of T cells to the TH17 cell phenotype in response to ovalbumin-induced acute airway inflammation. Airway inflammation was induced in female BALB/c mice by intraperitoneal sensitization and intranasal introduction of ovalbumin, followed by challenge methacholine. After the methacholine challenge, animals were exposed to hyperoxic conditions in an inhalation chamber for 24 h. The controls were subjected to normoxia or aluminum hydroxide dissolved in phosphate buffered saline. After 24 h of hyperoxia, the number of macrophages and lymphocytes decreased in animals with ovalbumin-induced airway inflammation, whereas the number of neutrophils increased after ovalbumin-induced airway inflammation. The results showed that expression of Nrf2, iNOS, T-bet and IL-17 increased after 24 of hyperoxia in both alveolar macrophages and in lung epithelial cells, compared with both animals that remained in room air, and animals with ovalbumin-induced airway inflammation. Hyperoxia alone without the induction of airway inflammation lead to increased levels of TNF-α and CCL5, whereas hyperoxia after inflammation lead to decreased CCL2 levels. Histological evidence of extravasation of inflammatory cells into the perivascular and peribronchial regions of the lungs was observed after pulmonary inflammation and hyperoxia. Hyperoxia promotes polarization of the immune response toward the TH17 phenotype, resulting in tissue damage associated with oxidative stress, and the migration of neutrophils to the lung and airways. Elucidating the effect of hyperoxia on ovalbumin-induced acute airway inflammation is relevant to preventing or treating asthmatic patients that require oxygen supplementation to reverse the hypoxemia.


New treatment directions for IPF: current status of ongoing and upcoming clinical trials.
The main objective of this review is to explore the wide and expanding field of new clinical trials in IPF. Recent trials have confirmed the efficacy of the approved drugs pirfenidone and nintedanib; nonetheless, the discovery of new biological pathways has opened new horizons in this field. Areas covered: New strategies against matrix deposition are under study and so is for the role of immunity and autoimmunity. Recent advances in the use of stem cells are opening new possibilities for the recovery of damaged lung tissues. The role of microbioma is under investigation in order to evaluate the use of antibiotics in IPF treatment. Analysing all the new and the upcoming clinical trials, we are trying to offer a comprehensive view of the emerging new frontiers in the treatment of IPF. Expert commentary: The key points for the ongoing and upcoming clinical trials will be to avoid previous mistakes and to choose carefully both study populations and efficacy endpoints. The exciting possibility to enrol patients with progressive lung fibrosis, both idiopathic and not, could be a next step forward. How the existing therapies will fit in a futurist scenario of personalized medicine is still a challenge.


[Plastic surgery treatment of a nose tip amputation in an Eleven-Cities marathon skater].
A 41-year-old male participant of the 200 km Eleven Cities ice skating marathon in 1997 lost a large part of his nose tip as a result of hitting a bridge. Avascular replantation of the amputated nose tip combined with ice water cooling for three days did not result in revascularisation. Subsequently the entire nose tip was reconstructed by means of a paramedian forehead flap. This reconstruction was performed in three stages and had a good aesthetic result.


Serological survey of immunoglobulin G from Toxoplasma gondii infection in dairy goats in East Java, Indonesia.
Toxoplasma gondii infection is a significant issue of veterinary public health because it is potentially transmitted through goat milk. Therefore, the use of control measures and routine monitoring of toxoplasmosis in dairy goats is necessary. Serological analysis using antibodies can detect T. gondii infection. This study aimed to conduct an epidemiological study of T. gondii in dairy goats using antibody detection and risk factor identification. This was a cross-sectional study. We performed a serological analysis of T. gondii infection in dairy goats to evaluate the prevalence of toxoplasmosis. Random sampling was performed, including 132 lactating dairy goats. Toxoplasma-modified agglutination test was used as a serological test for immunoglobulin G with a sensitivity of 98.55%, specificity of 86.21%, and accuracy of 94.9%. A structured questionnaire was used to collect risk factor data, which were analyzed using the Chi-square and Fisher's exact tests. The statistical package for the social sciences v. 21 was used for statistical analyses. The seroprevalence of T. gondii in Malang and Lumajang Regency was 100% and 90.7%, respectively. A significant difference in prevalence of T. gondii was observed between the two districts. Livestock management practices that significantly influenced T. gondii seroprevalence included water sources (p < 0.05; relative risk [RR] = 1.151; 95% confidence interval [CI]: 1.044-1.269). Farmers' characteristics that significantly influenced T. gondii seroprevalence included education (p < 0.05; RR = 1.125; 95% CI: 1.037-1.221), main occupation (p < 0.05; RR = 1.118; 95% CI: 1.035-1.207), and position in the organization of dairy goats farmers (p < 0.05; RR = 1.141; 95% CI: 1.022-1.274). In East Java, the prevalence of T. gondii in dairy goats is high. This study provides detailed information regarding risk factors associated with T. gondii seroprevalence in dairy goats in East Java, Indonesia.


Conchal Cartilage in Surgical Reconstruction of Orbital Floor Fracture.
According to Kim and Jeong (2016), isolated orbital fractures are encountered in 4-16% of all facial fractures, and orbital fractures composed approximately 30--55% of the zygomaticomaxillary complex (ZMC) and naso-orbital-ethmoid (NOE) fractures. The ideal material for orbital floor fracture repair is one that is resorbable, osteoconductive, resistant to infection, minimally reactive, does not induce capsule formation, has a half-life that allows significant bone in-growth to occur, and is cheap and readily available. In this article, we report a case of a young female with an orbital floor fracture managed surgically using conchal cartilage and a review of literature.


Radiographic Description of Soft Tissue Attachments around the Elbow.
Quantitatively define the radiographic locations of the major soft-tissue attachments about the elbow. In 10 cadaveric elbows, the attachments of the medial ulnar collateral ligament, lateral ulnar collateral ligament, annular ligament, triceps, and biceps were marked with radiopaque spheres. Measurements were made on calibrated AP and lateral fluoroscopic images from known osseous landmarks. On AP radiographs; the anterior bundle of the MUCL (aMUCL) measured 28.6mm (95% CI, 27. 5-29.8mm) from the humeral attachment to the midpoint of the MUCL ridge on the ulna and 14.3mm, (95% CI 13.0-15.5) to the olecranon. The LUCL was 39.9mm (95% CI, 38.6 - 41.1mm) from the humeral attachment to the supinator crest attachment and 8.9mm (95% CI, 8.1-9.8mm) to the lateral epicondyle. On the lateral radiographs, the humeral attachment of the aMUCL to the medial coronoid was 27.1mm (95% CI, 25.9-28.2mm) and 9.3mm (95%CI, 17.5 -21.2mm) to the tip. The LUCL humeral attachment to the supinator crest was 45.4mm (95%CI, 44.1-46.8mm). The LUCL humeral attachment was located 8.9mm (95%CI, 8.0-9.7mm) posterior from the anterior humeral line. The soft-tissue attachments about the elbow were reproducibly demonstrated on radiographs in relation to osseous landmarks and radiographic lines. The radiographic relationships will allow for improved identification of the ligament and tendon attachment sites of the elbow for intraoperative assessment and postoperative evaluation following reconstruction.


[Interactions between lung and kidney in the critically ill].
Interactions between lung and kidney can significantly affect the course of acute diseases, a phenomenon that was first observed in the 1950s by describing pulmonary dysfunction in uremic patients. From animal experiments there is ample evidence for remote lung injury following acute kidney injury (AKI), with an increased risk for the development of pulmonary edema and acute respiratory distress syndrome (ARDS). Coincident ARDS and AKI are associated with higher rates of intubation and mechanical ventilation, significantly prolonged weaning from mechanical ventilation and increased mortality. On the other hand, acute lung diseases and mechanical ventilation can promote the development of AKI and are associated with increased mortality when AKI is also present. These bidirectional interactions may include hemodynamic adverse effects during mechanical ventilation or volume overload as well as the release or decreased clearance and metabolism of proinflammatory mediators (e.g., interleukin-6 and tumor necrosis factor-α), which may induce and aggravate distant organ injury. The aim of this work is to examine the interactions between lung and the kidney in critically ill patients, as well as discuss potential preventive approaches.


Ray-tracing analysis of capillary concentrators for macromolecular crystallography.
The use of capillary concentrators as X-ray condensers specifically for macromolecular X-ray diffraction experiments using synchrotron radiation is evaluated. Monocapillary and polycapillary designs are assessed by ray-tracing analysis to evaluate how effectively these capillary concentrators can increase the X-ray intensity onto a 50 micro m crystal.


[Early diagnosis of lung carcinoma].
Importance of the lung cancer (LC) in our country and in the world as well as possibilities of its active screening are described. In US the lung carcinoma represents the most frequent lethal cancer both in males and females. In the Czech Republic (CR), mortality due to LC has the first place among men and the third place among women. Incidence of LC in males has not increased and for several years it has been reaching about 100 per 100,000. In women during the last 30 years mortality has increased three times reaching frequency 22 per 100,000. In the year 2000, 5709 persons died for the disease. In CR, about 6 to 7% of patients can be expected to survive 5 years, in the western Europe it is about 8%, in US 13%. Results of the diagnostics and treatment of the lung cancer revealed question on the active screening. Among the methods available at present, the most promising for conditions in CR appears the use of the low-dose spiral CT scan in the risk population. The paper brings results of a study evaluating the possibilities of the recognition of asymptomatic stadia of LC and discusses ideas of a future international study assessing the effectiveness of LC screening using this method.


Development of a clickable designer monolignol for interrogation of lignification in plant cell walls.
Lignin is an abundant and essential polymer in land plants. It is a prime factor in the recalcitrance of lignocellulosic biomass to agricultural and industrial end-uses such as forage, pulp and papermaking, and biofuels. To better understand lignification at the molecular level, we are developing a lignin spectroscopic and imaging toolbox on one "negligible" auxiliary. Toward that end, we describe the design, synthesis, and characterization of a new designer monolignol, 3-O-propargylcaffeyl alcohol, which contains a bioorthogonal alkynyl functional group at the 3-O-position. Importantly, our data indicate that this monolignol does not alter the fidelity of lignification. We demonstrate that the designer monolignol provides a platform for multiple spectroscopic and imaging approaches to reveal temporal and spatial details of lignification, the knowledge of which is critical to reap the potential of energy-rich renewable plant biomass for sustainable liquid fuels and other diverse economic applications.


Can we prevent a second 'Gulf War syndrome'? Population-based healthcare for chronic idiopathic pain and fatigue after war.
In the 1991 Gulf War less than 150 of nearly 700,000 deployed US troops were killed in action. Today, however, over 1 in 7 US veterans of the war has sought federal healthcare for related-health concerns, and fully 17% of UK Gulf War veterans describe themselves as suffering from the 'Gulf War syndrome', a set of poorly defined and heterogeneous ailments consisting mainly of chronic pain, fatigue, depression and other symptoms. Even though over 250 million dollars of federally funded medical research has failed to identify a unique syndrome, the debate regarding potential causes continues and has included oil well smoke, contagious infections, exposure to chemical and biological warfare agents, and posttraumatic stress disorder. Historical analyses completed since the Gulf War have found that postwar syndromes consisting of chronic pain, fatigue, depression and other symptoms have occurred after every war in the 20th century. These syndromes have gone by a variety of names such as Da Costa's syndrome, irritable heart, shell shock, neurocirculatory asthenia, and battle fatigue. Though the direct causes of these syndromes are typically elusive, it is clear that war sets in motion an undeniable cycle of physical, emotional, and fiscal consequences for war veterans and for society. These findings lead to important healthcare questions. Is there a way to prevent or mitigate subsequent postwar symptoms and associated depression and disability? We argue that while idiopathic symptoms are certain to occur following any war, a population-based approach to postwar healthcare can mitigate the impact of postwar syndromes and foster societal, military, and veteran trust. This article delineates the model, describes its epidemiological foundations, and details examples of how it is being adopted and improved as part of the system of care for US military personnel, war veterans and families. A scientific test of the model's overall effectiveness is difficult, yet healthcare systems for combatants and their families are already being put to pragmatic tests as troops return from war in Iraq and Afghanistan and from other military challenges.


Isolation and functional characterization of Ca2+/H+ antiporters from cyanobacteria.
Genome sequences of cyanobacteria, Synechocystis sp. PCC 6803, Anabaena sp. PCC 7120, and Thermosynechococcus elongatus BP-1 revealed the presence of a single Ca2+/H+ antiporter in these organisms. Here, we isolated the putative Ca2+/H+ antiporter gene from Synechocystis sp. PCC 6803 (synCAX) as well as a homologous gene from a halotolerant cyanobacterium Aphanothece halophytica (apCAX). In contrast to plant vacuolar CAXs, the full-length apCAX and synCAX genes complemented the Ca2+-sensitive phenotype of an Escherichia coli mutant. ApCAX and SynCAX proteins catalyzed specifically the Ca2+/H+ exchange reaction at alkaline pH. Immunological analysis suggested their localization in plasma membranes. The Synechocystis sp. PCC 6803 cells disrupted of synCAX exhibited lower Ca2+ efflux activity and a salt-sensitive phenotype. Overexpression of ApCAX and SynCAX enhanced the salt tolerance of Synechococcus sp. PCC 7942 cells. Mutagenesis analyses indicate the importance of two conserved acidic amino acid residues, Glu-74 and Glu-324, in the transmembrane segments for the exchange activity. These results clearly indicate that cyanobacteria contain a Ca2+/H+ antiporter in their plasma membranes, which plays an important role for salt tolerance.


Primary socialization theory: the etiology of drug use and deviance. I.
The fundamental theorem of primary socialization theory is that normative and deviant behaviors are learned social behaviors, products of the interaction of social, psychological, and cultural characteristics, and that norms for social behaviors, including drug use, are learned predominantly in the context of interactions with the primary socialization sources. During adolescence, learning of social behaviors is frequently dominated by interactions with peer clusters. There are a number of additional postulates: 1) The strength of the bonds between the youth and the primary socialization sources is a major factor in determining how effectively norms are transmitted. 2) Any socialization link can transmit deviant norms, but healthy family and school systems are more likely to transmit prosocial norms. 3) Peer clusters can transmit either prosocial or deviant norms, but the major source of deviant norms is usually peer clusters. 4) Weak family/child and/ or school/child bonds increase the chances that the youth will bond with a deviant peer cluster and will engage in deviant behaviors. 5) Weak peer bonds can also ultimately increase the changes of bonding with deviant peers. Primary socialization theory is consistent with current research, has strong implications for improving prevention and treatment, and suggests specific hypotheses for further research.


Effects of alteration in fluid balance on angiotensinogen gene expression in the rat.
The renin-angiotensin system (RAS) functions in circulatory and fluid homeostasis. There is evidence that genes encoding the protein elements of this system (renin and angiotensinogen) are expressed in a variety of tissues and that interaction of the products of these genes within tissues may represent part of the physiological function of this system. Using a solution hybridization assay for rat angiotensinogen (Ao) gene which incorporates a quantitative sense RNA standard we have measured angiotensinogen gene expression (AGE) in rat liver, brain (basal forebrain and brain stem), kidney and heart (atrium and ventricle) from individual animals. The effect of a 48hr period of dehydration on gene expression was compared with age and sex-matched animals which had water available ad libitum. Dehydration lead to a significant increase in plasma osmolality (pOsm) and plasma angiotensin II immunoreactivity (pAII). AGE was unaffected by dehydration in liver, brain stem, kidney, atrium and ventricle. However, significant increases AGE were observed in basal forebrain. In individual animals there was a significant positive correlation between pOsm and basal forebrain gene expression regardless of hydration state. This selective activation of the Ao gene in the forebrain during dehydration supports other observations which suggest that an intra-cranial RAS may participate in hypothalamic mechanisms of fluid homeostasis.


Fluid-dynamic results of in vitro comparison of four pericardial bioprostheses implanted in small porcine aortic roots.
Small-sized aortic bioprostheses may cause high postoperative gradients. In clinical practice, it is difficult to compare bioprostheses from different manufactures, owing to the discrepancy between the true size and the nominal size of the prosthesis and the inter-patient variability in aortic root characteristics. In vitro studies provide accurate data, and using a system in which it is possible to implant bioprostheses in a true aortic root should enable a fair comparison to be made. The present study compared the four most widely used pericardial stented bioprostheses from different manufacturers surgically implanted in small annulus, to detect any differences in their fluid-dynamic performance. The four types of bioprostheses, each implanted in a randomized sequence in eight porcine aortic roots, with a native annulus of 2.1 cm, were tested in a mock loop at 65 ml of stroke volume by calculating hydrodynamic parameters, namely mean pressure drop and effective orifice area, performance index, valve resistance and % of energy loss. The prostheses that fitted the aortic root after sizing were as follows: a Magna Ease 21, a Trifecta 21, a Soprano-Armonia 20 and a Mitroflow 23. Effective orifice areas were 1.57 ± 0.2, 1.77 ± 0.2, 2.3 ± 0.3 and 1.75 ± 0.2 cm(2) (P < 0.001) for Magna Ease, Mitroflow, Trifecta and Soprano-Armonia, respectively. The mean gradients were 13.2 ± 3, 10.2 ± 3, 6.1 ± 2 and 9.6 ± 2 mmHg (P < 0.001) for Magna Ease, Mitroflow, Trifecta and Soprano-Armonia, respectively. The performance indices were 0.50 ± 0.06, 0.63 ± 0.08, 0.89 ± 0.13 and 0.56 ± 0.07 (P < 0.001) for Magna Ease, Mitroflow, Trifecta and Soprano-Armonia, respectively. The valve resistance, expressed in (dyn*s/cm(5)), was 69 ± 16, 55 ± 13, 33 ± 10 and 51 ± 11 (P < 0.001) for Magna Ease, Mitroflow, Trifecta and Soprano-Armonia, respectively. The percent of energy loss was 13.5 ± 0.5, 10.7 ± 2.5, 6.6 ± 1.6, 10.9 ± 1.8 (P < 0.001) for Magna Ease, Mitroflow, Trifecta and Soprano-Armonia, respectively. Our study combined the fluid-dynamic reproducibility of the in vitro study with, by using porcine aortic roots, the specificity of surgery. The results confirmed that bioprostheses are inherently obstructive compared with the native aortic valve and showed that bioprostheses with the pericardium outside the stent are more efficient.


Synthesis of Aromatic Sulfonamides through a Copper-Catalyzed Coupling of Aryldiazonium Tetrafluoroborates, DABCO·(SO2)2, and N-Chloroamines.
A copper-catalyzed aminosulfonylation of aryldiazonium tetrafluoroborates, DABCO·(SO2)2, and N-chloroamines is described. This coupling reaction provides an efficient and simple approach to a wide range of sulfonamides in moderate to good yields under mild conditions. Mechanistic investigation suggests that a radical process and transition-metal catalysis are merged in this tandem reaction.


Molecular phylogeny of Megaloceros giganteus--the giant deer or just a giant red deer?
Two fragments of mitochondrial DNA (mtDNA) of the cytochrome b gene (137 bp and 167 bp) were successfully isolated and sequenced from antlers and bones of five specimens of the Giant Deer (Megaloceros giganteus) to examine the phylogenetic position of Megaloceros giganteus within the family Cervidae. This is the first report on ancient DNA (aDNA) sequences from Megaloceros giganteus. A phylogenetic analysis based on parameter-rich models describes the evolutionary relationships between five individuals of fossil Megaloceros giganteus and 37 individuals of 11 extant species of the family Cervidae. The results support a "Cervus-Megaloceros" clade. The phylogenetic positions of sympatric Megaloceros and Cervus elaphus specimens in particular indicate either that the Megaloceros mtDNA gene pool did not evolve for a substantial time period as an entity distinct from Cervus elaphus until its extinction, or that Megaloceros contributed mtDNA to Cervus elaphus or vice versa. The results of this study allow the conclusion that the European Megaloceros giganteus is more related to its modern regional counterparts of the species of Cervus elaphus than recent claims have suggested.


Effects of cations on binding, in membrane suspensions, of various opioids at mu-sites of rabbit cerebellum and kappa-sites of guinea-pig cerebellum.
At the mu-sites of rabbit cerebellum, NaCl, LiCl, KCl, choline chloride and MnCl2 were tested for potentiation and inhibition of the binding of several opioids. Naloxone, (-)-bremazocine and diprenorphine are mu-antagonists in pharmacological assays and their binding is potentiated by the lower concentrations and inhibited by the higher concentrations of NaCl. The binding of the agonists [3H]-[D-Ala2, MePhe4, Gly-ol5]enkephalin and [3H]-dihydromorphine is inhibited. MnCl2 potentiates the binding of the agonist [3H]-[D-Ala2, MePhe4, Gly-ol5]enkephalin but not the binding of the antagonists. The thresholds of inhibition and slopes of the dose-response curves for inhibition by MnCl2 and LiCl vary. This finding may indicate that potentiating effects of MnCl2 and LiCl are masked by simultaneous inhibition. At the kappa-sites of guinea-pig cerebellum, NaCl, KCl and MnCl2 inhibit the binding of [3H]-dynorphin A (1-8), [3H]-dynorphin A (1-9), [3H]-(-)-bremazocine, [3H]-tifluadom, and [3H]-diprenorphine. NaCl also causes a small potentiation of the binding of [3H]-diprenorphine, which is a kappa-agonist in the guinea-pig myenteric plexus but a kappa-antagonist in the rabbit vas deferens. The slopes of the inhibitory dose-response curves and the thresholds of inhibition vary with the different ligands. Therefore some potentiating effects may have been masked. The results support the view that NaCl, and perhaps LiCl, but not KCl and choline chloride, potentiate the binding of mu-antagonists but not the binding of mu-agonists. It is not yet possible to decide whether, at the kappa-site, there is a similar differentiation of the binding of agonists and antagonists.


Dendriform pulmonary ossification complicated by recurrent spontaneous pneumothorax: Two case reports and a review of the literature.
Dendriform pulmonary ossification (DPO) is a rare disease characterized by the presence of mature bone in the lung parenchyma with typical radiologic findings of diffuse and numerous calcified nodules. We present two cases of primary DPO complicated by recurrent spontaneous pneumothorax. Case 1 is a 53-year-old male with recurrent pneumothorax unresponsive to chest tube drainage or subtotal pleurectomy via video assisted thoracoscopy (VATS) who was finally treated with talc pleurodesis. Chest computed tomography (CT) revealed bilateral partially calcified reticulonodular opacities with a basal predominance. VATS biopsy revealed patchy foci of fibrous organizing pneumonia with multifocal ossifications confirming DPO histopathology. Pneumothorax recurred on the same side eight months later managed with talc pleurodesis. Case 2 is a 45-year-old Caucasian male who presented for evaluation of three prior spontaneous left-sided pneumothoraces occurring over eight years, treated with chest tube drainage and eventual talc pleurodesis. Chest CT demonstrated multiple high attenuation peripheral branching opacities greatest in the left lower lobe with several nonspecific, non-calcified pulmonary nodules. VATS biopsy revealed cicatrical organizing pneumonia with associated extensive intraalveolar ossification consistent with DPO. We describe two cases of DPO complicated by recurrent pneumothorax and reviewed the world literature. Summarized findings included a propensity for middle-aged males with a generally indolent course though pneumothorax was often refractory to initial chest tube drainage requiring more definitive mechanical management. There was also a predominance of primary disease without associated causes other than several reports of obstructive lung disease (asthma).


[The role of axonal transport in regulating the chemosensitivity of muscle spindles in the cat].
The effects of acetylcholine, subecholine and succinylcholine on the afferent activity of the m.EDL muscle spindles were compared before and after suppression of axonal transport by colchicine (20 nM, 30 min). The colchicine increased cholinergic sensitivity of nuclear-bag fibres: i. a. administration of cholinergic substances at concentrations tenfold lower than in control animals, produced a sharp enhancement of afferent activity of the muscle spindles. The increase of chemosensitivity was maximal to Ach and less obvious for subecholine and succinylcholine. No increase of activity could be produced by cholinomimetics in afferents originating from nuclear-chain fibres either in control, or after suppression of axonal transport.


Comparative Genomics of the Aeromonadaceae Core Oligosaccharide Biosynthetic Regions.
Lipopolysaccharides (LPSs) are an integral part of the Gram-negative outer membrane, playing important organizational and structural roles and taking part in the bacterial infection process. In Aeromonas hydrophila, piscicola, and salmonicida, three different genomic regions taking part in the LPS core oligosaccharide (Core-OS) assembly have been identified, although the characterization of these clusters in most aeromonad species is still lacking. Here, we analyse the conservation of these LPS biosynthesis gene clusters in the all the 170 currently public Aeromonas genomes, including 30 different species, and characterise the structure of a putative common inner Core-OS in the Aeromonadaceae family. We describe three new genomic organizations for the inner Core-OS genomic regions, which were more evolutionary conserved than the outer Core-OS regions, which presented remarkable variability. We report how the degree of conservation of the genes from the inner and outer Core-OS may be indicative of the taxonomic relationship between Aeromonas species.


RNA and macronuclear transcription in the ciliate Stylonychia mytilus.
Nuclear and cytoplasmic RNA of Stylonychia mytilus were analyzed on denaturing polyacrylamide gels. The molecular weight of rRNA precursor molecules is within a range of 2.1 x 10(6) daltons. A comparison between the electrophoretic pattern of nuclear non-ribosomal RNA and cytoplasmic mRNA indicates that a considerable amount of nuclear RNA sequences is of higher molecular weight than cytoplasmic RNA sequences. The molecular weight distribution of cytoplasmic RNA supports the assumption that also in Stylonychia an average sized mRNA molecule contains 1,200-1,500 nucleotides according to a molecular weight of 4 x 10(5) to 5 x 10(5) daltons. The size of the polyadenylic acid fragment of poly-A+ RNA molecules is about 120 nucleotides. The total mass of cytoplasmic RNA is around 7.5/10(10)g/cell, corresponding to 1.2 x 10(7) average sized mRNA molecules per cell. RNA excess hybridization experiments show that 60% of the DNA sequences are transcribed into nuclear RNA and that the cytoplasmic mRNA sequences are homologous to about 40% of macronuclear DNA sequences. There is no indication of different frequency classes within the mRNA. The number of different mRNA species in a Stylonychia cell is 1.2-1.5 x 10(4). On the average each of them is present about 1,000 times in every cell.


Postsynthetic Metalation Metal-Organic Framework as a Fluorescent Probe for the Ultrasensitive and Reversible Detection of PO43- Ions.
The self-assembly of a zinc salt with the novel ligand 4,4',4″-[(1,3,5-triazine-2,4,6-triyl)tris(sulfanediyl)]tribenzoic acid generated 3D microporous metal-organic frameworks (MOFs), namely, {[Zn4(L3-)2(O2-)(H2O)2]·4EtOH} n. The frameworks with multiple Lewis basic sites exhibit easily sensitized properties. After encapsulation of the Tb3+ cation in this Zn-MOF, the as-obtained fluorescent-functionalized Tb@Zn-MOFs not only maintain distinguished chemical stabilities but also exhibit strong characteristic emissions of trivalent terbium ions. Interestingly, Tb@Zn-MOF has been chosen to be a potential highly selective and sensitive luminescent platform for the reversible detection of PO43- ions in aqueous and living cell buffer solutions with a fast response time of 10 s and a low detection limit (0.1 ppm). Strikingly, this work presents the first example of a fluorescent sensor that can quantitate PO43- in simulated biological fluids and monitor these ions in the water system in a wide range of concentrations from 10-6 to 10-3 M.


Development and psychometric evaluation of the Khaini Smokeless Tobacco Dependence Scale.
Khaini is a smokeless tobacco (SLT) product commonly used in the South-Asian region. It is the most common smokeless tobacco product used in India, having a prevalence of 11.2% and is used by 104.1 million adults. No scales exist to assess khaini dependence. Existing scales available to assess dependence on smokeless tobacco products are not ideal as these are adapted from cigarette dependence scales and developed for western populations. This study aimed to develop a khaini dependence scale and assess its reliability and validity. Recommended methods for scale development were followed for item development, scale development and scale evaluation. Scale development was guided by a theoretical framework, a review of existing scales and in-depth interviews with 21 khaini users recruited from a tertiary care hospital in Mumbai, India. The process involved the identification of domains for dependence and the development of an item pool. Cognitive interviews and pre-testing were conducted with 20 khaini users to assess content validity. A cross-sectional survey with 323 khaini users was conducted, and Exploratory Factor Analysis (EFA) was used to determine the factor structure of the draft scale. The content validity, criterion validity (by cross-referencing with the cotinine level of users), convergent validity and internal consistency of the new scale were assessed. The final version of the Khaini SLT Dependence Scale (KSLTDS) had 20 items. EFA indicated an acceptable goodness of fit for a three-factor structure with physical, psychological and sociocultural-behavioral sub-scales. It showed evidence of acceptable criterion validity with cotinine (ρ=0.43, p=0.0002), convergent validity with FTND-ST (ρ=0.51, p<0.0001) and frequency of khaini use (ρ=0.38, p<0.0001). The sub-scales (α=0.87-0.90) showed acceptable internal consistency. The psychometric evaluation of the KSLTDS showed preliminary validity and reliability for assessing dependence on khaini, and therefore, it is appropriate for clinical and research purposes. Re-validation studies are required with various khaini user populations.


Dietary and nondietary determinants of vitamin K biochemical measures in men and women.
Few epidemiological studies that rely on the food frequency questionnaire (FFQ) for dietary assessment have measured biomarkers of vitamin K intake to independently confirm associations between self-reported dietary vitamin K intake and disease risk. Associations were examined between two sensitive biomarkers of vitamin K status, plasma phylloquinone and serum percent undercarboxylated osteocalcin (%ucOC), and self-reported usual phylloquinone intake as estimated from a FFQ. The influence of other dietary and nondietary factors on plasma phylloquinone concentrations was also examined. Dietary phylloquinone intake was estimated using a FFQ in 369 men and 468 women of the Framingham Offspring Study. The prevalence of high %ucOC concentrations (>/= 20%), suggestive of a low vitamin K status, was 44% in men and 54% in women, respectively. After multivariate adjustment, the odds of a high %ucOC was 2.5 greater for women (odds ratio: 2.5; 95% confidence interval [CI]: 1.2-5.1) and almost three times greater for men (odds ratio: 2.8; 95% CI: 1.3-5.9) in the lowest dietary phylloquinone intake quintile category compared to the highest quintile category. Fasting triglyceride concentrations, smoking status and season were associated with plasma phylloquinone concentrations, independent of dietary phylloquinone intake. Phylloquinone and green vegetable intake was linearly associated with plasma phylloquinone, after adjustment for potential confounding factors. There were limitations in the use of the FFQ to predict plasma phylloquinone, evident in an observed plateau effect and required nondietary adjustment factors. Despite these caveats, these findings support the use of a FFQ for a relative assessment of vitamin K status in population-based studies.


Kinetic processivity of the two-step oxidations of progesterone and pregnenolone to androgens by human cytochrome P450 17A1.
Cytochrome P450 (P450, CYP) 17A1 plays a critical role in steroid metabolism, catalyzing both the 17α-hydroxylation of pregnenolone and progesterone and the subsequent 17α,20-lyase reactions to form dehydroepiandrosterone (DHEA) and androstenedione (Andro), respectively, critical for generating glucocorticoids and androgens. Human P450 17A1 reaction rates examined are enhanced by the accessory protein cytochrome b5 (b5), but the exact role of b5 in P450 17A1-catalyzed reactions is unclear as are several details of these reactions. Here, we examined in detail the processivity of the 17α-hydroxylation and lyase steps. b5 did not enhance reaction rates by decreasing the koff rates of any of the steroids. Steroid binding to P450 17A1 was more complex than a simple two-state system. Pre-steady-state experiments indicated lag phases for Andro production from progesterone and for DHEA from pregnenolone, indicating a distributive character of the enzyme. However, we observed processivity in pregnenolone/DHEA pulse-chase experiments. (S)-Orteronel was three times more inhibitory toward the conversion of 17α-hydroxypregnenolone to DHEA than toward the 17α-hydroxylation of pregnenolone. IC50 values for (S)-orteronel were identical for blocking DHEA formation from pregnenolone and for 17α-hydroxylation, suggestive of processivity. Global kinetic modeling helped assign sets of rate constants for individual or groups of reactions, indicating that human P450 17A1 is an inherently distributive enzyme but that some processivity is present, i.e. some of the 17α-OH pregnenolone formed from pregnenolone did not dissociate from P450 17A1 before conversion to DHEA. Our results also suggest multiple conformations of P450 17A1, as previously proposed on the basis of NMR spectroscopy and X-ray crystallography.


Small sustainable monetary incentives versus charitable donations to promote exercise: Rationale, design, and baseline data from a randomized pilot study.
Regular physical activity (PA) enhances weight-loss and reduces risk of chronic disease. However, as few as 10% of U.S. adults engage in regular PA. Incentive programs to promote PA have shown some promise, but have typically used incentives that are too large to sustain over time and have not demonstrated habit formation or been tested in community settings. This report presents the rationale and design of a randomized pilot study testing the feasibility and preliminary efficacy of small monetary incentives for PA (n=25) versus charitable donations in the same amount (n=25) versus control (n=25) over 12months among 75 low-active but otherwise healthy adults at a local YMCA. Incentives are based on YMCA attendance, which is verified by electronic swipe card data and is the primary study outcome, with self-reported minutes/week of PA assessed as a secondary outcome. Incentives are intentionally small enough-$1/session, maximum of $5/week-such that they could be indefinitely sustained by community organizations, privately-owned health clubs, healthcare organizations, or employers (e.g., employer fitness facilities). Costs of the incentive program for the sponsoring organization may be partially offset by increases in membership resulting from the appeal of the program. Moreover, if efficacious, the charitable donation incentive program may have the added benefit of building social capital for the sponsoring organization and potentially serving as a tax write-off, thus further offsetting the cost of the incentives. Findings will also have implications for the use of financially sustainable community-based incentive programs for other health-related behaviors (e.g., weight loss, smoking).


Use of epigenetic drugs in disease: an overview.
Epigenetic changes such as DNA methylation and histone methylation and acetylation alter gene expression at the level of transcription by upregulating, downregulating, or silencing genes completely. Dysregulation of epigenetic events can be pathological, leading to cardiovascular disease, neurological disorders, metabolic disorders, and cancer development. Therefore, identifying drugs that inhibit these epigenetic changes are of great clinical interest. In this review, we summarize the epigenetic events associated with different disorders and diseases including cardiovascular, neurological, and metabolic disorders, and cancer. Knowledge of the specific epigenetic changes associated with these types of diseases facilitates the development of specific inhibitors, which can be used as epigenetic drugs. In this review, we discuss the major classes of epigenetic drugs currently in use, such as DNA methylation inhibiting drugs, bromodomain inhibitors, histone acetyl transferase inhibitors, histone deacetylase inhibitors, protein methyltransferase inhibitors, and histone methylation inhibitors and their role in reversing epigenetic changes and treating disease.


Changing concepts in medical treatment.
In a community-even a small one-where physicians established in practice have intensity of purpose, continuing curiosity, healthy skepticism and the spirit of research, the medical atmosphere is one to attract and welcome young physicians who are recently graduated and eager to apply the knowledge gained from the specialists who taught them in medical schools. As the modern laboratory and other facilities and equipment now in use in teaching institutions become available in more and more small communities, general practice remote from the medical centers probably will have increasing allure for neophyte physicians upon whom great influence is being brought to bear to induce them to practice medicine where the need is greatest. Knowledge of the changes in concepts of medical treatment that have taken place in the life-span of the physicians already established in a community will help the young physician fit himself congenially and effectively into the methods of practice of his elder colleagues, with mutual benefit.


Ca2+ measurement with ion selective electrodes. The French coordinated evaluation of seven analyzers, for a better clinical relevance and acceptance.
The measurement of ionized calcium has evolved in the last decade, and can now be easily performed by clinical laboratories using direct potentiometric analyzers available from a number of manufacturers. An original protocol for a comparison of the analyzers was used through a parallel multicenter evaluation in France. Using newly developed aqueous buffered solutions, this study focused not only on the analytical performance and operational handling of analyzers, but also on possible interferences in biological samples and the clinical relevance of the measurement with respect to the techniques of sample collection. All the instruments exhibited good precision and linearity, and were easy to handle and robust for daily use. However, not all the models gave identical results on the same patient's specimen. The utility of some Ca2+ analyzers has been further enhanced by the ability to "correct" the results to pH 7.40, although care must be taken in the interpretation of these results. While there are a number of clear-cut situations in which Ca2+ measurement is more relevant than total calcium, it seems that chemical activity of Ca2+ in blood may sometimes be considered with great caution under pathological conditions. The role of Ca2+ measurement in routine will be discussed in relation to the potential benefits of the instruments in laboratories.


Evaluating different strategies for estimating treatment effects in observational studies.
Since the introduction of the propensity score (PS), methods for estimating treatment effects with observational data have received growing attention in the literature. Recent research has added substantially to the number of available statistical approaches for controlling confounding in such analyses. However, researchers need guidance to decide on the optimal analytic strategy for any given scenario. To address this gap, we conducted simulations evaluating both well-established methods (regression, PS weighting, stratification, and matching) and more recently proposed approaches (tree-based methods, local control, entropy balancing, genetic matching, prognostic scoring). The simulation scenarios included tree-based and smooth regression models as true data-generation mechanisms. We evaluated an extensive number of analysis strategies combining different treatment choices and outcome models. Key findings include 1) the lack of a single best strategy across all potential scenarios; 2) the importance of appropriately addressing interactions in the treatment choice model and/or outcome model; and 3) a tree-structured treatment choice model and a polynomial outcome model with second-order interactions performed well. One limitation to this initial assessment is the lack of heterogeneous simulation scenarios allowing treatment effects to vary by patient.


Treatment of multidrug-resistant Acinetobacter baumannii meningitis with ampicillin/sulbactam.
The clinical features and the outcomes of eight cases of nosocomial Acinetobacter baumannii meningitis treated with ampicillin/sulbactam are reported. All the patients had fever, neck stiffness or meningeal signs, and a low consciousness level, and in their cerebrospinal fluid (CSF), pleocytosis, a low glucose level, and an elevated protein level were noted. For all CSF isolates of A. baumannii, the MIC of ampicillin/sulbactam was < or = 8/4 microg/mL. The MICs of sulbactam by microdilution in two cases were 4 microg/mL. All isolates were resistant to cefotaxime, ceftriaxone, ceftazidime, ureidopenicillins, ciprofloxacin, and gentamicin. Seven isolates were resistant to imipenem. A. baumannii was isolated from other samples in seven episodes. All patients were treated with ampicillin/sulbactam (seven with 2 g/l g every 6 hours and one with 2 g/l g every 8 hours). Six patients were cured and two patients died of meningitis. There were no side effects with the ampicillin/sulbactam treatment. In conclusion, ampicillin/sulbactam may be effective as therapy for meningitis caused by A. baumanii resistant to imipenem and other beta-lactam drugs.


Efficient ablation of genes in human hematopoietic stem and effector cells using CRISPR/Cas9.
Genome editing via CRISPR/Cas9 has rapidly become the tool of choice by virtue of its efficacy and ease of use. However, CRISPR/Cas9-mediated genome editing in clinically relevant human somatic cells remains untested. Here, we report CRISPR/Cas9 targeting of two clinically relevant genes, B2M and CCR5, in primary human CD4+ T cells and CD34+ hematopoietic stem and progenitor cells (HSPCs). Use of single RNA guides led to highly efficient mutagenesis in HSPCs but not in T cells. A dual guide approach improved gene deletion efficacy in both cell types. HSPCs that had undergone genome editing with CRISPR/Cas9 retained multilineage potential. We examined predicted on- and off-target mutations via target capture sequencing in HSPCs and observed low levels of off-target mutagenesis at only one site. These results demonstrate that CRISPR/Cas9 can efficiently ablate genes in HSPCs with minimal off-target mutagenesis, which could have broad applicability for hematopoietic cell-based therapy.


A light microscopy study of pulps from traumatized permanent incisors with reduced pulpal lumen.
The pulps from 20 traumatized permanent maxillary incisors treated endodontically because progressive hard-tissue formation diminished the pulpal lumen, were studied with light microscopy. The tissue changes were characterized by a varied increase in collagen content. A marked increase in collagen content was associated with a marked decrease in number of cells. Areas of mineralized tissue resembling dystrophic mineralization were present in nine pulps. Osteoidlike tissue with included and lining cells was found adjacent to these mineralized areas in three pulps. In one pulp a moderate infiltration of inflammatory cells was noted, mostly lymphocytes. With the exception of the latter tooth, tissue changes in the pulps in no case warranted endodontic treatment.


Posterior Surgical Approach to the Knee.
Posterior knee approaches are reliable techniques to address the treatment of various pathologies of the posterior region of the knee, including Baker cyst excision, tibial plateau fracture fixation, posterior cruciate ligament avulsions and inlay reconstructions, femoral condyle cartilage procedures, posterior meniscal repair and loose body removal among others. Surgery in the posterior knee region can be challenging because of the presence of neurovascular structures including the tibial nerve, popliteal artery and vein, and common peroneal nerve; thus, it is less commonly performed. The purpose of this Technical Note is to describe the posteromedial approach to the knee, its anatomic considerations, and how to avoid complications related to the surgical approach.


p62 Promotes Malignancy of Hepatocellular Carcinoma by Regulating the Secretion of Exosomes and the Localization of β-Catenin.
p62 is a multi-domain protein and participates in a variety of cellular biological activities. p62 is also related to tumor malignancy. However, the underlying molecular mechanism of p62 regulating the progression of hepatocellular carcinoma (HCC) remains unclear. The expression levels of p62 in HCC tissues and adjacent non-tumor tissues were confirmed using the TCGA dataset and immunohistochemistry. Stable p62-overexpressing HepG2 cells and p62-knockdown MHCC97H cells were established with lentiviral vectors. Cell proliferation, migration, and invasion assays were carried out to investigate the role of p62 in HCC cells and HCC-derived exosomes. The relationship between p62 and β-catenin was investigated by immunofluorescence and co-immunoprecipitation assays. Male nude mice (BALB/c-nu/nu) were used to establish the xenograft tumors. We found that p62 was significantly upregulated in HCC, and a high level of p62 indicated the promotion of malignancy including cell proliferation, migration, and invasion. Exosomes derived from p62-overexpressing HepG2 also demonstrated the ability to promote tumor malignancy. Immunofluorescence and co-immunoprecipitation assays indicated that p62 interacts with β-catenin and regulates the localization of β-catenin to affect the intercellular junction. p62 also promotes tumor growth of HCC and down-regulates the expression of β-catenin in vivo. The results of this study concluded that p62 promotes the malignancy of HCC by regulating the secretion of exosomes and the localization of β-catenin. These findings may provide new ideas for the diagnosis and treatment of HCC.


Bioethanol production from mixed sugars by Scheffersomyces stipitis free and immobilized cells, and co-cultures with Saccharomyces cerevisiae.
Bioethanol can be produced from several biomasses including lignocellulosic materials. Besides 6-carbon sugars that represent the prevalent carbohydrates, some of these feedstocks contain significant amounts of 5-carbon sugars. One common limit of the major part of the xylose-fermenting yeasts is the diauxic shift between the uptake of glucose and xylose during the fermentation of mixed syrups. Thus, optimized fermentation strategies are required. In this paper the ability of Scheffersomyces stipitis strain NRRLY-11544 to ferment mixed syrups with a total sugar concentration in the range 40-80 g/L was investigated by using mono cultures, co-cultures with Saccharomyces cerevisiae strain Bakers Yeast Type II and single cultures immobilized in silica-hydrogel films. The experimental design for the fermentations with immobilized cells included the process analysis in function of two parameters: the fraction of the gel in the broth and the concentration of the cells loaded in the gel. Furthermore, for each total sugars level, the fermentative course of S. stipitis was analyzed at several glucose-to xylose ratios. The results indicated that the use of S. stipitis and S. cerevisiae in free co-cultures ensured faster processes than single cultures of S. stipitis either free or immobilized. However, the rapid production of ethanol by S. cerevisiae inhibited S. stipitis and caused a stuck of the process. Immobilization of S. stipitis in silica-hydrogel increased the relative consumption rate of xylose-to-glucose by 2-6 times depending on the composition of the fermentation medium. Furthermore the films performances appeared stable over three weeks of continuous operations. However, on the whole, the final process yields obtained with the immobilized cells were not meaningfully different from that of the free cells. This was probably due to concurrent fermentations operated by the cells released in the broth. Optimization of the carrier characteristics could improve the performances of the process with immobilized cells.


Low cytoplasmic mRNA levels of immunoglobulin kappa light chain genes containing nonsense codons correlate with inefficient splicing.
We have previously reported down-regulation of mRNA expression of some of the kappa light chain transgenes in a hybridoma derived from a secondary immune response. Of the five heavily mutated transgene copies present in that hybridoma, three included premature stop codons and were poorly represented at the mRNA level. Here we show that the nonsense mutations are the cause of the low mRNA levels. While we found no evidence that the reduction in mRNA abundance was attributable to an increased rate of cytoplasmic mRNA decay, the amount of cytoplasmic mRNA correlated with the accumulation of unspliced transcripts in the nucleus. Similar results were obtained with a chimeric immunoglobulin gene containing a premature chain termination codon in the variable gene segment. We suggest that inhibition of splicing induced by in-frame premature stop codons is an important mechanism for down-regulation of undesirable immunoglobulin transcripts.


Internal fixation in trapdoor-type orbital blowout fracture.
The most common orbital blowout fracture is a trapdoor type. In many cases of trapdoor fracture, the bony segment has a stable hinge consisting of a greenstick fracture and the sinus mucoperiosteum that is attached to the intact orbital wall. If the displaced bony segment opposite the hinge is reduced into the original position and fixed on the unaffected bone, the orbital fracture may be reconstructed by internal fixation of the bony segment itself rather than requiring substitution with alloplastic implants or a bone graft. In 20 cases of orbital blowout fracture of a trapdoor type, internal fixation was performed using a cantilever fixation technique (with a piece of titanium micromesh or a titanium microplate plus a microscrew) or a ledge fixation technique (with a piece of micromesh). In all cases, the orbital wall was accurately reconstructed in its normal anatomical position. The associated ocular problems disappeared except for mild diplopia in one patient and there were no surgical complications associated with the internal fixation. The advantages of internal fixation include anatomical reconstruction of the orbital wall; preservation of the original orbital bone and the mucoperiosteum of the sinus as an osteomucoperiosteal flap resulting in rapid wound healing and normal mucus drainage function of the sinus; the simplicity of the procedure; and consequently, the absence of surgery-related complications. This technique is presented as one of the preferred treatments for trapdoor-type orbital blowout fractures.


New Raman method for aqueous solutions: xi-function dispersion evidence for strong F(-)-water H-bonds in aqueous CsF and KF solutions.
The Raman xi-function dispersion method recently elucidated for the strong H-bond breaker, ClO4-, in water [G. E. Walrafen, J. Chem. Phys. 122, 094510 (2005)] is extended to the strongly H-bond forming ion, F-. Measuring the xi function is analogous to measuring DeltaG from the thermodynamic activity of the water, aH2O, as the stoichiometric mol fraction of the water in the solution decreases due to addition of an electrolyte or nonelectrolyte. xi is the derivative of the OH-stretching part of the Gibbs free energy with respect to the water mol fraction; xiomega identical with-RT[ partial differential ln(Iomega/IREF) partial differentialX2](T,P). I is the Raman intensity at omega (omega=Raman shift in cm-1); IREF, that at an arbitrary reference omega; and, X2 is the water mol fraction (X1=CsF or KF mol fraction). ln(Iomega/IREF) was found to be linear in X2 for the complete range of OH-stretching omega's, with correlation coefficients as large as 0.999 96. Linearity of ln(Iomega/IREF) versus X2 is an experimental fact for all omega's throughout the spontaneous Raman OH-stretching contour; this fact cannot be negated by relative contributions of ultrafast/fast, homogeneous/inhomogeneous processes which may underlie this linearity. Linearity in ln(Iomega/IREF) versus 1T, or in ln(Iomega/IREF) versus P, was also observed for the Raman H-bond energy DeltaE and pair volume DeltaV dispersions, respectively. A low-frequency maximum (MAX) and a high-frequency minimum (MIN) were observed in the xi function dispersion curve. Deltaxi=xiMIN-xiMAX values of -7000+/-800-cal/mol H2O for CsF, and the experimentally equal Deltaxi=-6400+/-1000-cal/mol H2O for KF, were obtained. These Deltaxi's are opposite in sign but have nearly the same absolute magnitude as the Deltaxi value for NaClO4 in water; Deltaxi=+8050+/-100-cal/mol H2O. A positive Deltaxi corresponds to a water-water H-bond breaker; a negative Deltaxi to a H-bond former; specifically, a F--water H-bond former, in the instant case. NaClO4 breaks water-water H-bonds and also gives rise to weak, long (3.0-3.3 A), severely bent (approximately 140 degrees), high-energy, ClO4--water interactions. Fluoride ion scavenges the extremely weak or non-hydrogen-bonded OH groups, thus forming strong, short, linear, low-energy, H-bonds between F- and water. The strength of the F--water H-bond is evident from the fact that the OH-stretching xi-function minimum is centered approximately 200-300 cm-1 below that of ice. The diagnostic feature of the Raman spectrum from F- in water is an intense, long, low-frequency OH-stretching tail extending 800 cm-1 or more below the 3300-cm-1 peak. A similar intense, long, low-frequency Raman tail is produced by the OH- ion, which is known to H-bond very strongly when protons from water are donated to its oxygen atom.


Transplantation of Cerebral Dopamine Neurotrophic Factor Transducted BMSCs in Contusion Spinal Cord Injury of Rats: Promotion of Nerve Regeneration by Alleviating Neuroinflammation.
Traumatic spinal cord injury (SCI) causes neuron death and axonal damage resulting in functional motor and sensory loss, showing limited regeneration because of adverse microenvironment such as neuroinflammation and glial scarring. Currently, there is no effective therapy to treat SCI in clinical practice. Bone marrow-derived mesenchymal stem cells (BMSCs) are candidates for cell therapies but its effect is limited by neuroinflammation and adverse microenvironment in the injured spinal cord. In this study, we developed transgenic BMSCs overexpressing cerebral dopamine neurotrophic factor (CDNF), a secretory neurotrophic factor that showed potent effects on neuron protection, anti-inflammation, and sciatic nerve regeneration in previous studies. Our results showed that the transplantation of CDNF-BMSCs suppressed neuroinflammation and decreased the production of proinflammatory cytokines after SCI, resulting in the promotion of locomotor function and nerve regeneration of the injured spinal cord. This study presents a novel promising strategy for the treatment of spinal cord injury.


Stochastic expression of fetal hemoglobin in adult erythroid cells.
The expression of fetal hemoglobin, Hb F, in the adult cells is cellularly restricted both in vivo and in culture. Because, in cultures of erythroid progenitors, subclones that express or fail to express Hb F are derived from the same erythroid stem cell, a mechanism must exist whereby Hb F expression segregates in the progeny of erythroid progenitors during their differentiation. We present mathematical analyses of experimental data which suggest that expression of Hb F in human adult erythroid cells occurs on a stochastic basis. We quantified Hb F expression among the subclones of erythroid bursts (clones) in vitro by labeling subclones with fluorescent anti-Hb F antibodies. The observed data were compared with predictions from a stochastic model with the assumption that the expression of Hb F in a subclone occurs with a probability P equal to the frequency of Hb F-expressing subclones in an experiment. There was good fit between the observed and predicted data with respect to: (i) the relative frequencies of monomorphic F+, monomorphic F-, and bimorphic F+/F- bursts, respectively; (ii) the size distributions among F+, F- and F+/F- bursts; and (iii) the proportions of subclones expressing Hb F within bimorphic F+/F- bursts. Given the hypothesis that erythroid progenitors which have an active Hb F program are less differentiated than cells which do not proceed to express Hb F, the stochastic event indicated by our analyses may be the probability that adult erythroid progenitor cells undergo terminal differentiation at an earlier stage than usual.


Structure-activity relationships of pyrrolizidine alkaloids in insect chemical defense against the orb-weaving spider Nephila clavipes.
Pyrrolizidine alkaloids (PAs) are known to protect Arctiidae moths and Danainae and Ithomiinae butterflies against the orb-weaving spider Nephila clavipes (Araneae, Araneidae, Tetragnathinae), which liberates adults of these insects unharmed from its web. We tested against this spider the role of eight PAs and one derived structure [an 89:11 mixture of the 12-membered macrocyclic diester free base integerrimine and senecionine and the respective N-oxide; two hydrolysis products from this mixture (the necine base retronecine, its respective N-oxide, and a mixture of integerriminic and senecionic necic acids); the 12-membered macrocyclic senkirkine; the 9-O-monoester free base senecioylretronecine and its respective N-oxide; and the 9-O-monoester free base callimorphine (a PA biosynthesized only by insects from retronecine)]. The mixture integerrimine-senecionine N-oxide seems to be more active than the respective free base [LibD50 (liberation dose 50) = 0.042 and 0.153 microg/dry weight of prey, respectively], but the difference in activity between the N-oxide and free base of the 9-O-monoester senecioylretronecine was slight (LibD50 = 0.167 and 0.104, respectively). Senkirkine, an otonecine base PA that does not form N-oxide and is not found in insects, was the less active, showing the highest LibD50 (0.354). The difference in antipredator activity between N-oxides and free bases from macrocyclic diesters and monoesters may be correlated with physicochemical properties of these molecules in interaction with the Nephila receptors. For the active structures, there was a significant correlation between dosage and antipredator activity. Both forms of retronecine and a necic acid mixture were inactive, supporting the hypothesis that PAs biosynthesized by insects from retronecine were originally produced and stored in order to optimize chemical defense. Comparison of dose/activity data with reported amounts of PAs in butterflies suggested that, in general, PA-specialist insects are protected against predation by Nephila.


Gays and lesbians in local races: a study of electoral viability.
Although lesbians and gays are more visible in the political arena than in the past, there is little published research on their electoral viability. This article helps to fill that void by presenting results of experimental research featuring respondents' reactions to a hypothetical candidate for a non-partisan city council seat. Sex and sexual orientation of the candidates were manipulated so that six categories were tested: a straight woman, a lesbian, a woman rumored to be lesbian, a straight man, a gay man, and a man rumored to be gay. The findings suggest that openly gay and lesbian candidates are seen as less viable than straight candidates or those rumored to be homosexual. Hence, the extent to which a candidate portrays his or her sexual orientation appears to make a difference in the chance to win elective office.


Combination of sLORETA and Nonlinear Coupling for Emotional EEG Source Localization.
The objective of the present study is to investigate the anatomical distribution of the cortical sources of emotional response to music videos by means of electroencephalogram (EEG) analysis. A novel methodology is introduced to determine the nonlinear couplings between different brain regions based on the coherence analysis, nonlinear features of EEG recordings and a source localization method, standard low resolution electromagnetic tomography (sLORETA). 32 channels of EEG time series of 32 subjects available in DEAP database were studied. The Lyapunov exponents and approximate entropy were applied to the EEG. The coherence for Lyapunov exponents and approximate entropy were calculated between each electrode paired to all other electrodes. Considering valence and arousal related effects, the sLORETA was applied to each above mentioned feature to determine emotional processing cortices. Using the proposed methodology, significant differences in sLORETA activity are observed between different emotional states. These changes were dominantly localized in the Brodmann 11 area (frontal lobe). In addition, some evidences provided that the left hemisphere is more activated to valence and arousal-related effects. Results suggest that considering two dimensions of emotions concurrently, a wider brain region was dominated in synchronization: superior frontal gyrus, middle frontal gyrus, and superior parietal lobule. Cooperating nonlinear coupling along with EEG source localization methods could provide an interesting tool for understanding the cortical specialization in emotional processes.


Psychosocial stress and cancer risk: a narrative review.
It is unclear which psychological factors (stressors, emotional correlates, and psychophysiological markers) induce cancer risk. This currently limits the potential for prevention strategies. The aim of this review is to bring forth evidence of stress as a determinant of cancer risk from a public health perspective, written for a broad public of practitioners and scientists. Based on a semisystematic literature search, the impact of different aspects/types of stress and the potential physiological and behavioral pathways are summarized, while highlighting further research, public health and clinical implications. Between 2007 and 2020, 65 case-control or cohort studies have been identified. Apart from overall cancer ( N = 24), 12 cancer types have been associated with psychological stress with most for breast ( N = 21), colorectal ( N = 11) and lung/prostate/pancreas cancer ( N = 8 each). Although the evidence regarding the mechanisms is still scarce, cancer development in relation to stress might be due to interacting and combined effects of different stress(or) types, but such interaction has not really been tested yet. The path from stress towards cancer incidence consists of a biological pathway with endocrinology and immunology as well as stress-induced behavioral pathways, including smoking, alcoholism, sleep disruption, an unhealthy diet, and low physical activity together with the related phenomenon of obesity. Not only the stress but also the stress-induced lifestyle should be targeted for cancer prevention and treatment. Future research should include a more diverse spectrum of cancer types (not only hormonal related like breast cancer) and of stress measures while also considering behavioral covariates.


Additional resources for medical student educators: an annotated review.
There are numerous resources available to help educators of medical students improve their methods of instruction. For example, several Internet sites exist that describe specific ways to teach and reinforce concepts basic to emergency medicine. Some of these sites also allow users to share their own experiences and teaching techniques. There are professional associations and organizations that specifically cater to the needs of those involved in the education and training of medical students and resident physicians. Educators may wish to take advantage of distance learning programs that offer instruction in areas such as adult learning, curriculum and teaching methods, and medical education evaluation and research. Finally, educators may wish to participate in professional development opportunities such as fellowships and online modules that have been designed to offer instruction on teaching skills, provide an arena for exchange of effective techniques, and acclimate faculty to academic medicine.


A1c variability can predict coronary artery disease in patients with type 2 diabetes with mean a1c levels greater than 7.
Recent studies suggested that the association of acute glucose variability and diabetic complications was not consistent, and that A1c variability representing long term glucose fluctuation may be related to coronary atherosclerosis in patients with type 1 diabetes. In this study, we attempt to determine whether or not A1c variability can predict coronary artery disease (CAD) in patients with type 2 diabetes. We reviewed data of patients with type 2 diabetes who had undergone coronary angiography (CAG) and had been followed up with for 5 years. The intrapersonal standard deviation (SD) of serially-measured A1c levels adjusted by the different number of assessments among patients (adj-A1c-SD) was considered to be a measure of the variability of A1c. Among the 269 patients, 121 of them had type 2 diabetes with CAD. In patients with A1c ≥7%, the mean A1c levels and A1c levels at the time of CAG among the three groups were significantly different. The ratio of patients with CAD was the highest in the high adj-A1c-SD group and the lowest in the low adj-A1c-SD group (P=0.017). In multiple regression analysis, adj-A1c-SD was an independent predictor for CAD in subjects with A1c ≥7% (odds ratio, 2.140; P=0.036). Patients with higher A1c variability for several years showed higher mean A1c levels. A1c variability can be an independent predictor for CAD as seen in angiographs of patients with type 2 diabetes with mean A1c levels over 7%.


Marchiafava-Bignami's Disease, as Etiologic Diagnosis of Athetosis.
The Marchiafava-Bignami disease, characterized by demyelination and necrosis of the corpus callosum, has typically been associated with chronic alcohol intake, and clinically has various symptoms and signs. However, several cases have been reported without alcohol association, and these - according to several publications - have some common points, such as preference for female, related to malnutrition, and radiological involvement of the splenium of the corpus callosum. We report a case of a patient with the characteristics described above and whose clinical manifestation was Athetosis. The authors associate this manifestation with the somatotopic distribution of the corpus callosum, and contribute to the etiologic diagnosis of Athetosis as a manifestation of the Marchiafava-Bignami disease, which has not been reported in the medical literature according to our review of the database.


Focus on the use of antidepressants to treat pediatric functional abdominal pain: current perspectives.
Chronic abdominal pain is frequently encountered in pediatric practice. A large proportion of cases meet Rome criteria for abdominal pain-functional gastrointestinal disorders (AP-FGIDs). These disorders are costly and, in some cases, lead to impairment of daily functioning and overall quality of life. Pathophysiologic mechanisms include early stressful events, visceral hypersensitivity, dysmotility, changes in intestinal microbiota, and altered central nervous system processing. They are considered disorders of the brain-gut interaction. The diagnosis is made on clinical grounds using symptom-based criteria (Rome criteria). Anxiety and depressive symptoms are more prevalent in patients with AP-FGIDs. Therefore, attention has been directed to the use of neuromodulators as potential interventions for AP-FGIDs. Antidepressants are one type of neuromodulators, and one of the most studied drugs for the management of AP-FGIDs in adult and pediatric population. Data available in pediatric population have significant limitations including nonuniform methodology with different study designs and primary endpoints. Evidence of the efficacy of antidepressants in the management of pediatric AP-FGIDs is not consistent. There is an urgent need for well-designed randomized clinical trials using age-appropriate validated outcome measures. Careful consideration must be given to adverse effects, particularly increased suicidal ideation.


[Heparan sulphate in association with indobufen in the treatment of chronic peripheral obliterative arteriopathy of the lower extremities. Controlled clinical trial].
The aim of this study has been to assess the efficacy and the safety of heparansulphate administered with indobufen in the treatment of occlusive arterial disease. In a controlled open study, nineteen out-patients with Fontaine's stage II occlusive arterial disease since one year were randomly assigned to treatment with indobufen 200 mg/day or indobufen 200 mg/day and heparansulphate 200 mg/day for 6 months. Efficacy assessments were based on functional evaluations (pain-free sub-maximal exercise ergometric test, ankle-arm pressure ratio at rest and after induced ischemia), on hemocoagulative parameters and on physical signs and subjective symptoms assessed monthly over the whole period of treatment. All patients but one who was lost to follow-up completed the study treatment period as foreseen by the experimental protocol. The results of the study show an improvement of 10.89% (day 30), 15.92% (day 60), 21.04% (day 90), 24.19% (day 120), 25.18 (day 150) 28.84% (day 180) end of study in ergometric test pain-free interval obtained by patients treated with heparansulphate and indobufen with respect to patients receiving indobufen alone. Also hemocoagulative parameters and signs and patients' subjective symptoms were positively influenced by the association heparansulphate and indobufen. On the whole, the results of the study indicate that heparansulphate in association with antiplatelet therapy with indobufen has a beneficial effect in the treatment of peripheral occlusive arterial disease.


Students' perspectives on the educational environment, Faculty of Medical Sciences, Trinidad.
The Dundee Ready Education Environment Measure (DREEM) was administered to 70 final-year medical students and 36 first-year medical interns (pre-registration house officers). The overall total mean DREEM scores for the five subscales-namely, students' perceptions of the atmosphere, students' perceptions of learning, students' social self-perceptions, students'perceptions of teachers and students' academic self-perceptions-was 109.9 and the total mean scores for the subgroups-male students, male interns, female students and female interns-were 103.39, 111.82, 111.33 and 113.15, respectively. The lowest scores were assigned to students' social self-perceptions and students' perceptions of the atmosphere. All of the participants except the male interns recorded the highest scores for the subscale academic self-perceptions.


Protective role of Ocimum canum plant extract in alcohol-induced oxidative stress in albino rats.
Ethanol is the most frequently abused drug and causes a variety of pathological disturbances. It causes toxicity to tissues by generating free radicals during the course of its metabolism that can damage cellular structure and function, especially in hepatocytes. This study investigates the preventive and protective effects of Ocimum canum on alcohol-induced oxidative stress. Male Wistar rats were used in three separate experiments. First, two groups of six rats each (normal control and alcohol-treated) were used to establish hepatotoxicity. The alcohol-treated group showed a significant increase in TBARS and decreased activities of SOD, catalase, GSH, alpha-tocopherol and ascorbic acid. Second, the preventive effect of the O. canum extract was assessed. Four groups of rats (six in each group) were used and the experimental groups were treated with ethanol and graded doses of the extract for four weeks. Normal control and alcohol-treated groups were also assessed. Lipid peroxidation and antioxidant potential were quantified in plasma samples, which showed that the extract had a preventive effect. Third, the curative effect of the extract was assessed. The rats were divided into four groups comprising a normal control group on a normal diet and three other groups given alcohol for four weeks to establish alcohol toxicity. One of the alcohol groups was used as a control and the other two alcohol groups were given graded doses of the extract. After four weeks the rats were sacrificed in order to assess the lipid peroxidation and antioxidant potentials. The results indicated that the O. canum extract had hepatoprotective abilities against alcohol-induced oxidative stress.


Fatty Acid Supplementation During in vitro Embryo Production Determines Cryosurvival Characteristics of Bovine Blastocysts.
In vitro production (IVP) embryos have a reduced quality and poor cryotolerance in comparison to in vivo embryos. This study investigated whether free fatty acid (FFA) conditions, fatty acid free (FAF)- synthetic oviduct fluid (SOF) without or with 25 μM of saturated stearic (C18:0) or unsaturated oleic (C18:1) acid during the first 5 IVP days, relate to quality and cryosurvival of day 8 blastocysts. Apart from the blastocyst scores, both 1) number and size of lipid droplets of fresh blastocysts and 2) total number and apoptotic and necrotic cells, before and after freezing-thawing, were scored by confocal microscopy. Blastocyst rates were significantly lower in the FAF SOF condition in comparison to other groups. Interestingly, blastocysts originating from the C18:1 group, with a significantly higher lipid content, and blastocysts from the FAF SOF group demonstrated a high cryosurvival rate (70.1 and 67.4%, respectively) comparable with in vivo blastocysts (68%), in contrast to the poor cryosurvival of C18:0 exposed embryos (17.6%). In all freeze-thawed embryos the average amount of apoptotic and necrotic cells increased albeit that the C18:0 condition rates were higher (43.2%) when compared to C18:1 (26.0%) and FAF SOF conditions (26.5%). The current data show that FFA administered during early embryonic development significantly affect the cryotolerance of blastocysts.


Hereditary hypotrichosis simplex of the scalp.
Hereditary hypotrichosis simplex of the scalp is a genotrichosis characterized by sparse or absent scalp hair without structural defects, in the absence of other ectodermal or systemic abnormalities. We describe two Spanish families with hypotrichosis of the scalp. We believe these families have Toribio and Quiñones type hereditary hypotrichosis simplex of the scalp.


Subungual Onycholemmal Cysts: A Case Report.
Subungual onycholemmal cysts (SOCs) are rare nail abnormalities. The clinical findings vary and include onychodystrophy, ridging, nail bed pigmentation, and thickening, but most often SOCs do not cause any symptoms and are accidental findings. In this case report, we present a case of a woman with pigmentation of the toenail, suspect for melanoma. Surprisingly, the histopathological examination showed SOCs. We discuss the histological features of SOCs, etiology, and differential diagnoses.


Effects of chronic stress on the auditory system and fear learning: an evolutionary approach.
Stress is a complex biological reaction common to all living organisms that allows them to adapt to their environments. Chronic stress alters the dendritic architecture and function of the limbic brain areas that affect memory, learning, and emotional processing. This review summarizes our research about chronic stress effects on the auditory system, providing the details of how we developed the main hypotheses that currently guide our research. The aims of our studies are to (1) determine how chronic stress impairs the dendritic morphology of the main nuclei of the rat auditory system, the inferior colliculus (auditory mesencephalon), the medial geniculate nucleus (auditory thalamus), and the primary auditory cortex; (2) correlate the anatomic alterations with the impairments of auditory fear learning; and (3) investigate how the stress-induced alterations in the rat limbic system may spread to nonlimbic areas, affecting specific sensory system, such as the auditory and olfactory systems, and complex cognitive functions, such as auditory attention. Finally, this article gives a new evolutionary approach to understanding the neurobiology of stress and the stress-related disorders.


Impact of islet transplantation on diabetes complications and quality of life.
Insulin represents a life-saving therapy for patients with type 1 diabetes but, despite appropriate treatment, it prevents only partially long-term diabetic complications, while generating fatal hypoglycemic episodes. Islet transplantation gained attention because of its safety, effectiveness, and minimal invasiveness; however it remains a procedure reserved for a selected group of patients. The introduction of the Edmonton Protocol in 2000, based on a newly designed steroid-free immunosuppressive protocol, revamped the course of islet transplantation. The main goal of islet transplantation remains insulin independence, although the effect of islet transplantation can be more comprehensively evaluated in terms of frequency of hypoglycemic episodes and impact on diabetic complications and quality of life. Islet transplantation was shown to have positive consequences on cardiovascular, renal, neurologic, and ocular diabetic complications. The proof of concept for cellular replacement therapy in diabetes has been established with islet transplantation, it only needs to be improved and rendered widely available.


Chemical composition, in vitro antiparasitic, antimicrobial and antioxidant activities of Frankenia thymifolia Desf.
This study was performed on the derived fractions [chloroform (FT-C), ethyl acetate (FT-E) and n-butanol (FT-B)] of the 70% ethanol extract prepared from Frankenia thymifolia, endemic to North Africa. The fractions showed high total phenolic and flavonoid contents particularly FT-E. These results agreed with their antioxidant effects. Indeed, all the fractions were able to scavenge 1,1-diphenyl-2-picrylhydrazyl radical, with a better power of FT-E. These results were supported by the inhibition of β-carotene oxidation assay. The fractions showed moderate activity against Acanthamoeba castellanii and Leishmania amazonensis with a better activity of FT-E against A. castellanii. Moreover, FT-B exhibited an interesting antimicrobial activity against all tested bacteria. The phytochemical investigation of the most active fractions (FT-E and FT-B) led to the isolation and structural determination of six compounds. The observed biological activities may be associated with the presence of quercetin and its derivatives found in the chemical composition of these fractions.


Laccase: a green catalyst for the biosynthesis of poly-phenols.
Laccases (benzene diol: oxidoreductases, EC 184.108.40.206) are able to catalyze the oxidation of various compounds containing phenolic and aniline structures using dissolved oxygen in water. Laccase structural features and catalytic mechanisms focused on the polymerization of aromatic compounds are reported. A description about the most recent research on the biosynthesis of chemicals and polymers is made. Selected applications of this technology are considered as well as the advantages, shortcomings and future needs related with the use of laccases.


Morphometric analysis and roosting ecology of bat species Pteropus Medius in Mansehra, Khyber Pakhtunkhwa, Pakistan.
Morphometric measurement and roosting ecology of Pteropus medius were aimed to find out in Mansehra district of KP, Pakistan. Total 3149 numbers of bats were found in eight biological spots visited; Baffa Doraha, Darband, Dadar, Jallu, Hazara University, Garhi Habibullah Chattar Plain and Jabori, in total 299 numbers of different species of trees including; Morus alba, Pinus raxburghi, Eucalyptus camaldulensis, Morus nigra, Grevillea robusta, Brousonetia papyrifera, Platanus orientalis, Ailanthus altissima, Hevea brasiliensis and Populus nigra. Morphometric features were measured and found vary according to sex of the bats. The average wing span, wing`s length from tip of wing to neck, from thumb to tip of wing and the body`s length from head and claws were recorded to be 102.98 cm, 49.07cm, 28.7 cm and 22.78 cm respectively in males while 93.67 cm, 44.83cm, 24.78cm and 22.78 cm respectively in female bats. Mean circumference of the body including wings and without wing were measured as 22.78 cm and 17.29 cm in males and that of female were 20.07 cm and 16.9 cm. Average length of thumb 3.64 cm, ear`s length 3.1 cm, snout 5.62cm, eye length were 1.07 cm for both sexes and length between the feet in extended position were16.3 cm. Generally different measurement of males bodies were found to be greater than female such as mean body surface area, mass, volume and pressure were found to be 2691.79 cm2, 855.7gm,1236.4 ml and 295.77 dyne/ c m 3 for male and 2576.46 cm2, 852.71gm,1207 ml and 290.2 dyne/ c m 3 respectively for female. While weight and density for both males and females bats were same with mean of 8.59 newton and 0.701 g/m3. Findings of current reports can add valued information in literature about bats, which can be used for species identification and conservation.


Correlates of Hearing Aid Use in UK Adults: Self-Reported Hearing Difficulties, Social Participation, Living Situation, Health, and Demographics.
Hearing impairment is ranked fifth globally for years lived with disability, yet hearing aid use is low among individuals with a hearing impairment. Identifying correlates of hearing aid use would be helpful in developing interventions to promote use. To date, however, no studies have investigated a wide range of variables, this has limited intervention development. The aim of the present study was to identify correlates of hearing aid use in adults in the United Kingdom with a hearing impairment. To address limitations in previous studies, we used a cross-sectional analysis to model a wide range of potential correlates simultaneously to provide better evidence to aid intervention development. The research was conducted using the UK Biobank Resource. A cross-sectional analysis of hearing aid use was conducted on 18,730 participants aged 40 to 69 years old with poor hearing, based on performance on the Digit Triplet test. Nine percent of adults with poor hearing in the cross-sectional sample reported using a hearing aid. The strongest correlate of hearing aid use was self-reported hearing difficulties (odds ratio [OR] = 110.69 [95% confidence interval {CI} = 65.12 to 188.16]). Individuals who were older were more likely to use a hearing aid: for each additional year of age, individuals were 5% more likely to use a hearing aid (95% CI = 1.04 to 1.06). People with tinnitus (OR = 1.43 [95% CI = 1.26 to 1.63]) and people with a chronic illness (OR = 1.97 [95% CI = 1.71 to 2.28]) were more likely to use a hearing aid. Those who reported an ethnic minority background (OR = 0.53 [95% CI = 0.39 to 0.72]) and those who lived alone (OR = 0.80 [95% CI = 0.68 to 0.94]) were less likely to use a hearing aid. Interventions to promote hearing aid use need to focus on addressing reasons for the perception of hearing difficulties and how to promote hearing aid use. Interventions to promote hearing aid use may need to target demographic groups that are particularly unlikely to use hearing aids, including younger adults, those who live alone and those from ethnic minority backgrounds.


XRD and Mössbauer spectroscopy investigation of Mn substituted CuFe2O4 nanoparticles.
The effect of Mn substitution in Cu ferrite may present a challenge, as there are three transition metals ions distributed among the two available crystallographic sub lattices. This system also presents complicated super exchange interactions. In this study a series of five powdered samples with composition Cu(1-x)Mn(x)Fe2O4 were investigated using XRD and transmission Mössbauer spectroscopy. The variation of lattice parameter, crystallite size, and Mössbauer parameters of the product formed with the variation in the concentration of Mn has been studied. XRD study revealed the formation of pure phase spinels with FCC cubic structure having particle size ranging from 7.2 nm to 20 nm. Lattice constant value showed constant increase with increasing Mn concentration. AFM image confirms the formation of spherical shaped nanoparticles. Mössbauer spectroscopy proves to be an excellent tool for probing the local environment of Fe atoms present in such materials. Results show two sets of six finger patterns for all the samples with two double line pattern obtained for the composition with x = 0.75 and 1.0, indicating the presence of Fe in both A and B site. Increase in Mn concentration first increases the hyperfine field and then it gradually decreases. This effect is observed at both the sites. This effect is due to the relative strengths of Fe-O-X super exchange (X = Fe, Mn, Cu) as well as number of different nearest neighbour of A and B sites. The unexpected behaviour for the last two compositions can be explained by the presence of particle size distribution that results in superparamagnetic behaviour.


Diagnostics of type 1 diabetes must be improved
Incidence of type 1 diabetes in children and adolescents continues to increase but diagnosis is often delayed and keto-acidosis too common. More information is needed. General auto-antibody screening can be discussed.


Clinical and demographic features with outcome predictors of adult patients with acute intoxication admitted to a medical intensive care unit in the Mediterranean part of Croatia.
The objective of the study was to assess the demographics, clinical parameters, and outcome of acute intoxications among adult patients admitted to a medical intensive care unit in southern Croatia. An observational retrospective study was conducted over a 1-year period. The subjects were patients admitted to the intensive care unit for acute poisoning. In all, 81 subjects (32.1% females) aged 43.16 ± 14.77 years were admitted to the intensive care unit because of poisoning (14.97% of the total annual intensive care unit admissions). Psychiatric disorders were previously established in 76.5% participants, and 69.1% of all acute intoxications were classified as suicidal. Non-suicidal subjects differed from suicidal subjects in age (37.36 ± 9.71 vs. 45.75 ± 15.93 years; P = 0.009), in pCO2 (6.38 ± 1.78 vs. 5.50 ± 1.26 kPa; P = 0.020), in length-of-stay in intensive care unit (median 1.00, interquartile range 1.00 vs. median 2.00, interquartile range 2.00 days; P = 0.022), and in length-of-stay in hospital (median 2.00, interquartile range 2.00 vs. median 10.50, interquartile range 15.25 days; P < 0.001). Three (3.7%) patients died. Pharmaceutical psychoactive drug intoxications were the most common poisoning cases; of these, diazepam was the most frequent (16.8%), followed by ethanol (9.0%) and alprazolam (7.8%). Benzodiazepines/hypnotics were the most common group (28.7%), followed by antipsychotics (13.2%). Intoxications with more than 1 poison accounted for the largest number of cases (67.9%). The number of toxins was significantly correlated with length-of-stay in the hospital (rho = -0.265; P = 0.008), systolic blood pressure (rho = -0.318; P = 0.002), and diastolic blood pressure (rho = -0.262; P = 0.009). The electrocardiogram was considered abnormal in 50.62% of the cases. Acute intoxicants were most commonly caused by psychiatric pharmaceutical drugs. Multidrug exposure was a typical pattern of acute intoxication.


Pre-plaque conformational changes in Alzheimer's disease-linked Aβ and APP.
Reducing levels of the aggregation-prone Aβ peptide that accumulates in the brain with Alzheimer's disease (AD) has been a major target of experimental therapies. An alternative approach may be to stabilize the physiological conformation of Aβ. To date, the physiological state of Aβ in brain remains unclear, since the available methods used to process brain tissue for determination of Aβ aggregate conformation can in themselves alter the structure and/or composition of the aggregates. Here, using synchrotron-based Fourier transform infrared micro-spectroscopy, non-denaturing gel electrophoresis and conformational specific antibodies we show that the physiological conformations of Aβ and amyloid precursor protein (APP) in brain of transgenic mouse models of AD are altered before formation of amyloid plaques. Furthermore, focal Aβ aggregates in brain that precede amyloid plaque formation localize to synaptic terminals. These changes in the states of Aβ and APP that occur prior to plaque formation may provide novel targets for AD therapy.


Using the phacoemulsification crescent knife in dacryocystorhinostomy.
Dacryocystorhinostomy is an effective treatment for nasolacrimal duct obstruction. Most techniques employ a conventional blade or knife in making the incision of the nasal mucosa and lacrimal sac. The authors describe the use of a phacoemulsification crescent knife for this purpose. This technique can be effective and at the same time safer and easier to perform.


How is the AIE mechanism profoundly changed in an ESIPT family: the novel introduction of a tetraphenylethene group onto (Z)-3-(quinolin-2-ylmethylene)-3,4-dihydroquinoxalin-2(1H)-one.
It is reported that two derivatives of (Z)-3-(quinolin-2-ylmethylene)-3,4-dihydroquinoxalin-2-(1H)-one (1) with a tetraphenylethene (TPE) group introduced at amide N atom of the dihydroquinoxalinone moiety (2) or at phenyl ring of the quinoline fragment (3) are synthesized, and the derivatives exhibit a remarkably enhanced aggregation-induced emission (AIE) activity than the parent. Although both the parent and the derivatives have the characteristic of an excited state intramolecular proton transfer (ESIPT), the AIE mechanism of 2 and 3 is totally different from that of 1. The considerably stronger emission of 3 than that of 2 should be attributed to the unique crystallization-induced emission enhancement (CIEE) effect.


Image quality of cone beam computed tomography for evaluation of extremity fractures in the presence of metal hardware: visual grading characteristics analysis.
To evaluate image quality and interobserver reliability of a novel cone-beam CT (CBCT) scanner in comparison with plain radiography for assessment of fracture healing in the presence of metal hardware. In this prospective institutional review board-approved Health Insurance Portability and Accountability Act of 1996-complaint study, written informed consent was obtained from 27 patients (10 females and 17 males; mean age 44 years, age range 21-83 years) with either upper or lower extremity fractures, and with metal hardware, who underwent CBCT scans and had a clinical radiograph of the affected part. Images were assessed by two independent observers for quality and interobserver reliability for seven visualization tasks. Visual grading characteristic (VGC) curve analysis determined the differences in image quality between CBCT and plain radiography. Interobserver agreement was calculated using Pearson's correlation coefficient. VGC results displayed preference of CBCT images to plain radiographs in terms of visualizing (1) cortical and (2) trabecular bones; (3) fracture line; (4) callus formation; (5) bridging ossification; and (6) screw thread-bone interface and its inferiority to plain radiograph in the visualization of (7) large metallic side plate contour with strong interobserver correlation (p-value < 0.05), except for visualizing large metallic side plate contour. For evaluation of fracture healing in the presence of metal hardware, CBCT image quality is preferable to plain radiograph for all visualization tasks, except for large metallic side plate contours. Advances in knowledge: CBCT has the potential to be a good diagnostic alternative to plain radiographs in evaluation of fracture healing in the presence of metal hardware.


Theory and Modeling of RNA Structure and Interactions with Metal Ions and Small Molecules.
In addition to continuous rapid progress in RNA structure determination, probing, and biophysical studies, the past decade has seen remarkable advances in the development of a new generation of RNA folding theories and models. In this article, we review RNA structure prediction models and models for ion-RNA and ligand-RNA interactions. These new models are becoming increasingly important for a mechanistic understanding of RNA function and quantitative design of RNA nanotechnology. We focus on new methods for physics-based, knowledge-based, and experimental data-directed modeling for RNA structures and explore the new theories for the predictions of metal ion and ligand binding sites and metal ion-dependent RNA stabilities. The integration of these new methods with theories about the cellular environment effects in RNA folding, such as molecular crowding and cotranscriptional kinetic effects, may ultimately lead to an all-encompassing RNA folding model.


Periodontal infection in adult-onset Still's disease patient: clinical and haematological considerations.
In this case report, the authors described the first case of a patient with adult-onset Still's disease (AOSD) who presents advanced periodontal infection. AOSD is a rare systemic inflammatory disorder of unknown aetiology, characterised by spiking fever, usually exceeding 39°C, an evanescent salmon pink rash, arthritis and multiorgan involvement. Periodontal infection is a pathogen-induced oral inflammatory disease affecting the supporting tissues of teeth and is currently considered as a risk factor for cardiovascular disease. Several cytokines capable of inducing systemic effects are produced during the course of this infection and the values of serum markers of inflammation, such as C reactive protein (CRP), may significantly decrease after periodontal treatment. Although AOSD can produce elevations in CRP, similar increase may be produced by periodontal infection, suggesting the need for medical and dental diagnosis when evaluating the sources of acute-phase responses in systemic autoimmune disease patients.