Single-Stranded DNA Binding Protein Encoded by the virE Locus of Agrobacterium tumefaciens.
The transfer process of T (transfer)-DNA of Agrobacterium tumefaciens is activated after the induction of the expression of the Ti plasmid virulence (vir) loci by plant signal molecules such as acetosyringone. The vir gene products then act to generate a free transferable single-stranded copy of the T-DNA, designated the T-strand. Although some vir proteins are responsible for the synthesis of the T-strand, others may mediate T-strand transfer to plant cells as part of a DNA-protein complex. Here, a novel 69-kilodalton vir-specific single-stranded DNA binding protein is identified in Agrobacterium harboring a nopaline-type Ti plasmid. This protein binds single-stranded but not double-stranded DNA regardless of nucleotide sequence composition. The molecular size of the vir-specific single-stranded DNA binding protein and its relative abundance in acetosyringone-induced Agrobacterium suggested that it might be the product of the virE locus; molecular cloning and expression of the virE region in Escherichia coli confirmed this prediction.


[Solubilization of unilamellar egg yolk phosphatidylcholine liposomes by N-alkyl-N,N-dimethylamine N-oxides].
The solubilization of extruded (100 nm) unilamellar egg yolk phosphatidylcholine (EYPC) liposomes by a series of N-alkyl-N,N-dimethylamine N-oxides (CnNO, n = 10-14 carbon atoms in the alkyl substituent) was studied using turbidimetry. The solubilizing concentration of CnNO (cS) was estimated as the CnNO concentration causing the half-maximum decrease in turbidance. From the linear cS dependence on EYPC concentration, the lipid--aqueous phase molar partition coefficient (Kp) and the CnNO:EYPC molar ratio in the CnNO + EYPC aggregates (nL:nEYPC) at cS were obtained: Kp = 82 +/- 25 and nL:nEYPC = 0.70 +/- 0.20 for C10NO, Kp = 507 +/- 215 and nL:nEYPC = 0.60 +/- 0.16 for C12NO, and Kp = 12357 +/- 93 and nL:nEYPC = 1.13 +/- 0.01 for C14NO. The value of Gibbs free energy of CnNO alkyl methylene group transfer from the aqueous to the lipid phase calculated from the Kp dependence on n is -1.2 +/- 0.2 RT (R = gas constant, T = absolute temperature), within the experimental error being the same as -1.026 +/- 0.006 RT obtained from the critical micellar concentrations of CnNO. The increased value of nL:nEYPC for C14NO is caused by the decreased hydrophobic mismatch of CnNO and EYPC hydrocarbon chain lengths. This mismatch results in a structural defect in the bilayer hydrophobic core, the primary cause of bilayer destabilization and solubilization.


It is highly unlikely that the development of an abdominal wall hernia can be attributable to a single strenuous event.
There is a commonly held belief that the development of a hernia can be attributed to a single strenuous or traumatic event. Hence, many litigants are successful in compensation claims, causing mounting financial burdens on employers, the courts, insurance companies and the tax-payer. However, there is very little scientific evidence to support this assertion. The aim of this study was to ascertain whether there was any causal link in this process. A total of 133 new patients with 135 abdominal herniae of all varieties (115 inguinal, 3 femoral, 9 umbilical, 4 incisional, and 4 ventral or epigastric), of which 25 were recurrent received structured questionnaires on arrival in the surgical clinic. These questionnaires covered all possible aetiological factors for hernia development (type of work, COAD, smoking, pregnancy, obesity, chronic bladder outflow obstruction, previous surgery including appendicectomy), in addition to any possible attribution to a single strenuous or traumatic event. We then reviewed the GP records in the surgery of all patients who answered positively to the latter possible cause. In the study group, 119 (89%) reported a gradual onset of symptoms. Of the 15 (12 male, 3 female; 11%) who believed that their hernia might be related to a single strenuous or traumatic event, 5 had no other aetiological factors. However, not one of the 15 was found to have contemporaneous forensic medical evidence to support their possible claim. We conclude that we are unable to find any clinical evidence to support the hypothesis that a hernia might develop as the result of one single strenuous or traumatic event. While we accept that this mechanism might still possibly occur, we believe that, at best, it is extremely uncommon. If a medical expert is preparing a report on such a case in a claim for personal injury, then they have a duty to the court to examine carefully all the contemporaneous medical records. If no clinical evidence exists to support the claim, then they have a duty to the court not to support the plaintiff's claim.


Adenocarcinoma of the small bowel - a case report.
The paper presents a rare case of a patient with adenocarcinoma of the small intestine who reported to the hospital due to non-specific gastrointestinal symptoms. Following diagnostic examinations, the patient underwent a surgery. The post-operative period proceeded with no complications. The case presented below confirms the usefulness of imaging examinations (abdominal CT) when pathologies within the small intestine are suspected. An accurate interpretation of the result was an indication for a surgical intervention, but the final diagnosis is still established on the basis of the histopathological examination.


Formulas for determining the dimensions of venous graft required for penile curvature correction.
To evaluate the quantity of penile veins for use as patch material for the treatment of penile curvature, we devised two formulas: from the calculus of applied civil engineering and a diagram from the goniometry of the cadavers' penises, respectively, and the techniques for their application. From March 1995 to July 2003, a total of 65 consecutive patients with penile curvature - 41 men with Peyronie's deformity and 24 with congenital penile deviations - underwent grafting with autologous deep dorsal veins with or without cavernosal veins as patch material. The patched veins required were calculated from the formula (pi)r(2)theta/45 degrees , which is derived from calculus. The tunical incision sector was meticulously performed in accordance with our diagram which is interpolated from seven male cadavers via goniometry and consequently the length of patched veins required was 2 (pi)r(theta)(')/theta. The corporotomy defect was fashioned with the detubularized veins after they were adequately prepared and spliced. In these patients, the average available area of the veins was 4.9 x 2.2 cm(2) (range, 4.5 x 1.8 to 5.6 x 2.4), which seemed adequate in all cases for patching, although 11 of them required two patches. Overall, 21 patients required a modified Nesbit's procedure on the contralateral/ipsilateral tunica to attain a satisfactory penile shape. Because of its anatomical vicinity and its availability as material, the deep dorsal vein associated with the cavernosal vein may play an indispensable role in grafting even with local anaesthesia on an outpatient basis.


Structural characteristics of active and inactive glutamate dehydrogenases from the hyperthermophile Pyrobaculum islandicum.
The enzymes from hyperthermophiles are generally extremely thermostable and lose little or no activity during long periods under a variety conditions. This high stability is very attractive, in that it gives the enzymes potential for use in numerous bioprocesses. My research group has investigated this high stability from the viewpoint of the relationship between function and structure. In this review, I describe the molecular mechanism underlying the extreme stability of unboiled NAD-dependent glutamate dehydrogenase from the hyperthermophile Pyrobaculum islandicum. I also describe the activation of the inactive recombinant enzyme produced in mesophilic Escherichia coli from the viewpoint of the relationship between structure and activity.


Mohs' micrographic surgery for Merkel cell carcinomas of the eyelid.
Merkel cell carcinoma (MCC) is a rare neuroendocrine tumour that may affect the eyelid. There is no consensus on the optimal treatment for eyelid MCC, and management remains controversial. Here we present our experience in a case of eyelid MCC treated by Mohs' micrographic surgery. Although this treatment has been advocated for general skin MCCs, there is very little experience with this technique in relation to eyelid MCCs. We suggest that Mohs' micrographic surgery may be an appropriate method of treating MCCs of the eyelid.


Chloroplast DNA Diversity of Tunisian Barley Landraces as Revealed by cpSSRs Molecular Markers and Implication for Conservation Strategies.
In Tunisia, barley local landraces are still cropped for human and animal consumption in some subsistence farming systems under marginal and stressed conditions. These high-value genetic resources present a potential source of resistance genes to biotic and abiotic stresses useful for both national and international breeders. Actually, they are represented by threatened small populations, which face a high risk of genetic erosion and progressive substitution by modern varieties. In this study, the genetic diversity of 60 Tunisian barley landraces was assessed using six chloroplast microsatellites. All loci were found polymorphic, with 2 or 3 alleles per locus. Thirteen alleles were detected across the studied sample, which were combined into 8 haplotypes, giving a haplotype diversity (Hd) of 0.847. High punctual and haplotype genetic diversity was observed for Tunisian barley landraces when compared to other germplasms from other regions of the world. The genetic structure analysis revealed two major clusters of Tunisian barley landraces, which confirms their multiorigin. This result was corroborated by the median-joining network showing the genetic relationships among the eight detected haplotypes. The AMOVA analysis revealed that 83% of the genetic variation is between populations, which requires the in situ and ex situ conservation of plant material for all Tunisian populations of barley landraces. Information on genetic variation within the chloroplast genome is of great interest to ensure an efficient conservation strategy that takes into account the preservation of the various maternal lineages of Tunisian barley.


Influenza A viruses of avian origin circulating in pigs and other mammals.
Influenza A viruses (IAVs) are zoonotic agents, capable of crossing the species barriers. Nowadays, they still constitute a great challenge worldwide. The natural reservoir of all influenza A viruses are wild aquatic birds, despite the fact they have been isolated from a number of avian and mammalian species, including humans. Even when influenza A viruses are able to get into another than waterfowl population, they are often unable to efficiently adapt and transmit between individuals. Only in rare cases, these viruses are capable of establishing a new lineage. To succeed a complete adaptation and further transmission between species, influenza A virus must overcome a species barrier, including adaptation to the receptors of a new host, which would allow the virus-cell binding, virus replication and, then, animal-to-animal transmission. For many years, pigs were thought to be intermediate host for adaptation of avian influenza viruses to humans, because of their susceptibility to infection with both, avian and human influenza viruses, which supported hypothesis of pigs as a 'mixing vessel'. In this review, the molecular factors necessary for interspecies transmission are described, with special emphasis on adaptation of avian influenza viruses to the pig population. In addition, this review gives the information about swine influenza viruses circulating around the world with special emphasis on Polish strains.


Understanding the tonifying and the detoxifying properties of Chinese medicines from their impacts on gut microbiota and host metabolism: a case study with four medicinal herbs in experimental colitis rat model.
Chinese medicines (CMs) have emerged as an alternative therapy for ulcerative colitis through reinforcing the vital qi and/or eliminating the pathogenic factors according to the traditional Chinese medicinal theory. Presystemic interactions of CMs with gut microbiota and the associated metabolic network shift are believed to be essential to achieve their holistic health benefits in traditional oral application. This study first employed 16S rDNA-based microbial profiling and mass spectrometry-based urinary metabolomics to simultaneously evaluate four single CMs frequently prescribed as main constituent herbs for alleviating UC, the tonic ginseng and Astragali Radix (AR) and the detoxifying Scutellaria Radix (SR) and Rhubarb, on a dextran sodium sulfate (DSS)-induced colitis rat model, with aims to understanding the tonifying or detoxifying properties of CMs through clinical phenotypes, the common features and herb-specific signatures in gut microbial alterations and the associated host metabolic shifts. Colitis was induced in rats receiving 5% DSS for consecutive 7 days. Control group received water alone. Herbal groups received 5% DSS and respective herbal preparation by gavage once daily. Body weight, stool consistency, and rectal bleeding were recorded daily. Feces and urine were freshly collected at multiple time points. On day 7, blood and colon tissues were collected to determine anti-/pro-inflammatory cytokines levels, colonic myeloperoxidase activity, and histopathologic alterations. Gut microbiome was more prone to herb intervention than metabolome and displayed increasing associations with metabolic dynamics. Although both the tonic and the detoxifying herbs alleviated colitis and caused some similar changes in DSS-induced microbiome and metabolome disturbance, the tonic herbs were more effective and shared more common microbial and metabolic signatures. The detoxifying herbs elicited herb-specific changes. Rhubarb uniquely affected phenylalanine metabolism and established high correlations between Akkermansia muciniphila and Parasutterella and hydroxyphenylacetylglycine and phenylbutyrylglycine, while SR caused significant elevation of steroidal glucuronides dehydropregnenolone glucuronide and estriol glucuronide, both displaying exclusive correlations with genus Acetatifactor. Both tonic and detoxifying herbs tested ameliorated experimental colitis and elicited alternative microbial and host metabolic reprogramming. The findings highlight the importance of presystemic interactions with gut microbiota to host metabolic shifts and promote modern translation of tonic and detoxifying properties of CMs.


Environmental Regulation, Corporate Economic Performance and Spatial Technology Spillover: Evidence from China's Heavily Polluting Listed Corporations.
The relationship between environmental regulation, technology spillover, and economic performance has been the subject of intense scholarly debate in environmental economics for many years. The famous Porter hypothesis states that environmental regulation promotes both the economic performance and the environmental performance of corporations. However, the existing literature has paid relatively little attention to micro-level research and spatial spillover effects. This article endeavors to fill this gap by an empirical analysis of a sample of 900 of China's heavily polluting listed corporations for the period of 2013-2016. By utilizing spatial econometric methods to measure spatial direct and indirect effects and decomposing total factor productivity change into technical change, pure efficiency change, and scale efficiency change, we find that environmental regulation promotes corporate total factor productivity but widens the disparity between profitable and unprofitable corporations. Our results also suggest that the direct and indirect effects of environmental regulation and corporate profitability on promoting total factor productivity rely heavily on the efficiency changes, while the contribution of the key component, technical change, is insignificant.


The carpal tunnel.
The carpal bones are deeply convex anteriorly. This bony gutter is converted by the flexor retinaculum into a tube - the carpal tunnel, which conveys the median nerve, together with the long flexor tendons of the fingers and thumb, into the hand. It is of special interest to the surgeon because it is the site of a common nerve entrapment, the carpal tunnel syndrome.


A Review on Gallium Oxide Materials from Solution Processes.
Gallium oxide (Ga2O3) materials can be fabricated via various methods or processes. It is often mentioned that it possesses different polymorphs (α-, β-, γ-, δ- and ε-Ga2O3) and excellent physical and chemical properties. The basic properties, crystalline structure, band gap, density of states, and other properties of Ga2O3 will be discussed in this article. This article extensively discusses synthesis of pure Ga2O3, co-doped Ga2O3 and Ga2O3-metal oxide composite and Ga2O3/metal oxide heterostructure nanomaterials via solution-based methods mainly sol-gel, hydrothermal, chemical bath methods, solvothermal, forced hydrolysis, reflux condensation, and electrochemical deposition methods. The influence of the type of precursor solution and the synthesis conditions on the morphology, size, and properties of final products is thoroughly described. Furthermore, the applications of Ga2O3 will be introduced and discussed from these solution processes, such as deep ultraviolet photodetector, gas sensors, pH sensors, photocatalytic and photodegradation, and other applications. In addition, research progress and future outlook are identified.


Promoter methylation of the bone morphogenetic protein 6 gene in multiple myeloma.
Bone morphogenetic proteins (BMPs), which belong to the transforming growth factor-β superfamily, are multifunctional signaling molecules that have become of increasing interest in cancer research. Recent observations suggest that alterations in BMPs and BMP signaling are associated with tumorigenesis and disease progression in various types of malignancies. This study investigated the methylation status of the BMP6 gene promoter in various types of plasma cell proliferative disorders by combined bisulfite restriction analysis. While BMP6 methylation was not detected in any samples from monoclonal gammopathies of undetermined significance, intramedullary multiple myeloma (MM), plasma cell leukemia or solitary plasmacytoma, both case studies and cell line studies showed that multiple extramedullary plasmacytoma (MEP) consistently carried a methylated BMP6 promoter. The BMP6 methylation-positive MEP was an aggressive form of MM with extremely high levels of serum lactate dehydrogenase (LDH). Bisulfite sequencing analysis confirmed intensive methylation at CpG sites of the BMP6 promoter region. The methylation of BMP6 was correlated with decreased levels of mRNA transcripts. Expression of BMP6 was restored by the demethylating agent 5-aza-2'-deoxycytidine, suggesting that the methylation is associated with transcriptional silencing. Our study implied that BMP6 promoter methylation is not a common event in MMs, but occurs in aggressive MEP. These findings warrant further investigation to clarify whether BMP6 methylation together with elevated LDH could be a marker of poor prognosis in MEP patients who should be considered for early intensive treatment.


Geographical distribution of the herpes simplex virus type 1 BgKL variant in Japan suggests gradual dispersion of the virus from Shikoku Island to the other Islands.
Restriction endonuclease fragment length polymorphism (RFLP) is useful for the epidemiological study of herpes simplex virus type 1 (HSV-1). We report here the identification of a major BglII RFLP variant of HSV-1, designated BgKL, found in 27.0% of 636 HSV-1 clinical isolates. We have also established its geographic distribution in Japan. BgKL has an unusually large BglII K fragment. SalI cleavage analyses showed that 97% of BgKL variant isolates lack both the SalI C-J and the F-J cleavage sites and have an unusually large SalI D or E fragment, and 91% of the BgKL variants lack both SalI G and H fragments. Furthermore, 96% of BgKL isolates have an unusually small KpnI M fragment. Therefore, BgKL is a marker for these five mutations in most HSV-1 isolates and is a useful HSV-1 RFLP marker. The BgKL variant was found in 59% of HSV-1 isolates from Shikoku Island, 44% of HSV-1 isolates from the Chugoku region of Honshu Island, 31% of HSV-1 isolates from Kyushu Island, 0% of HSV-1 isolates from Okinawa Island, 49% of HSV-1 isolates from Osaka, 27% of HSV-1 isolates from Shiga, 13% of HSV-1 isolates from the Chubu Region, and 9% of HSV-1 isolates from the Tohoku Region of Honshu Island. Differences in the frequency of BgKL between the Shikoku-Chugoku-Osaka area (49%) and Kyushu, between Kyushu and Okinawa, between the Shikoku-Chugoku-Osaka area and Shiga, and between Shiga and Tohoku are all statistically significant. The BgKL frequency decreases in a geographical gradient suggest that this HSV-1 variant was dispersed from Shikoku to the surrounding regions and then to more distant regions. The BgKL frequency in Tokyo was similar to the nationwide average. These are the first data to suggest a geographic and demographic dispersion pattern of HSV-1. Implications for the epidemiology and diversification of HSV-1 are discussed.


Relationship between Cytotoxicity and Surface Oxidation of Artificial Black Carbon.
The lacking of laboratory black carbon (BC) samples have long challenged the corresponding toxicological research; furthermore, the toxicity tests of engineered carbon nanoparticles were unable to reflect atmospheric BC. As a simplified approach, we have synthesized artificial BC (aBC) for the purpose of representing atmospheric BC. Surface chemical properties of aBC were controlled by thermal treatment, without transforming its physical characteristics; thus, we were able to examine the toxicological effects on A549 human lung cells arising from aBC with varying oxidation surface properties. X-ray photoelectron spectroscopy, as well as Raman and Fourier transform infrared spectroscopy, verified the presence of increased amounts of oxygenated functional groups on the surface of thermally-treated aBC, indicating aBC oxidization at elevated temperatures; aBC with increased oxygen functional group content displayed increased toxicity to A549 cells, specifically by decreasing cell viability to 45% and elevating reactive oxygen species levels up to 294% for samples treated at 800 °C.


Rhombencephalitis: a series of 97 patients.
The term rhombencephalitis refers to inflammatory diseases affecting the hindbrain (brainstem and cerebellum). Rhombencephalitis has a wide variety of etiologies, some of them potentially severe and life threatening without proper early treatment. In this retrospective observational study, we reviewed the records of consecutively hospitalized patients at University Hospital of Bellvitge (Barcelona, Spain) from January 1990 to December 2008. Rhombencephalitis was defined as a brainstem and/or cerebellar condition demonstrated clinically or by neuroimaging, with pleocytosis (>4 cells/mm) in cerebrospinal fluid. Ninety-seven patients (48 female; mean age, 37 yr; range, 14-79 yr) fulfilled these criteria. We reviewed their clinical, cerebrospinal fluid, and radiologic characteristics. The mean follow-up was 5 years (range, 0-20 yr). The etiologies of rhombencephalitis were as follows: unknown cause (n = 31), multiple sclerosis (n = 28), Behçet disease (n = 10), Listeria monocytogenes infection (n = 9), paraneoplastic syndrome (n = 6) (3 cases associated with anti-Yo antibodies and 3 with anti-Tr antibodies), Epstein-Barr virus (n = 4), tuberculosis (n = 2), pneumococcal infection (n = 2), systemic lupus erythematosus (n = 1), lymphoma (n = 1), Brucella species infection (n = 1), JC virus (n = 1), and relapsing polychondritis (n = 1). Certain clinical, cerebrospinal fluid, and radiologic characteristics that are commonly seen in some of these etiologies can guide us in the first approach to the etiologic diagnosis of rhombencephalitis.


[Modern opportunities and prospects for studying pathogenesis, diagnosing and treating hereditary optic neuropathies].
To evaluate modern opportunities and prospects for studying pathogenesis and improving diagnostics and treatment of hereditary optic neuropathies (HON). The article presents summarized data on the pathogenesis, diagnostics, and treatment of HON based on modern methods of assessment. The results of long-term worldwide studies and those performed in the Research Institute of Eye Diseases in collaboration with several other institutions are presented. Genetic testing for mitochondrial and nucleus DNA mutations that have a known association with Leber's hereditary optic neuropathy (LHON) and autosomal dominant optic neuropathy (ADON) allow verification only in half of the cases. Particular features of hereditary diseases, such as incomplete penentrance, variable expression, clinical polymorphism, difficulties in detection of hereditary sings, and genetic heterogeneity, are shown to complicate the diagnosis of HON. Spectral retinal tomography revealed characteristic morphometric changes in the macular region and peripapillary nerve fiber layer in the acute stage of LHON. Hereditary optic neuropathies result from a genetically determined decrease in mitochondrial respiratory chain complexes activity, which is associated with a decrease in ATP production. From that standpoint, studying of mitochondrial oxidative phosphorylation biochemical defects in LHON and ADON is an option for detection of mitochondrial dysfunction. Results of a newly proposed method of mitochondrial membrane potential assessment in skin fibroblasts, which can be used for differential diagnosis of mitochondrial optic nerve diseases, are presented. Possible therapeutic measures for HON are discussed. In the prevailing number of cases the described clinical, molecular genetic, and cytological methods ensure proper diagnosis of hereditary optic neuropathies. Prospects of HON treatment, rather ambiguous, are associated with further studying of pathogenesis, development of drugs and gene therapy.


Semantic priming with product verification but not production.
Campbell and Reynvoet (2009) found that time to name a single-digit target was about 8 ms faster if preceded by a near prime (±1) compared to a far prime (at least ±3) when prime-digit pairs were interleaved with number comparisons (9↑3; name larger) and not when they were interleaved with multiplication problems (9×3; state product). This is consistent with the claim by previous researchers that magnitude comparison can enable a semantic pathway for digit naming whereas number-fact retrieval can inhibit it. To pursue this, the current study compared priming in the context of multiplication production (9×3=?) versus multiplication verification (e.g., 9×3=24, true or false). Multiplication production, but not verification, may inhibit semantic digit naming to reduce naming-related interference with verbal number production. Indeed, semantic priming of digit naming occurred only in verification and not production blocks. This supports the conclusion that multiplication production can inhibit semantic mediation of digit naming, which is enabled in other number processing tasks (e.g., comparison, verification) that do not compete with naming for verbal number production processes.


Cyclin D1: mechanism and consequence of androgen receptor co-repressor activity.
Androgen receptor regulation is pivotal for prostate growth and development. Activation of the receptor is dictated by association with androgen (ligand) and through interaction with co-activators and co-repressors. We have shown previously that cyclin D1 functions as a co-repressor to inhibit ligand-dependent androgen receptor activation. We demonstrate that cyclin D1 directly binds the N terminus of the androgen receptor and that this interaction is independent of ligand. Furthermore, we show that the interaction occurs in the nucleus and does not require the LXXLL motif of cyclin D1. Although two distinct transactivation domains exist in the N terminus (AF-1 and AF-5), the data shown support the hypothesis that cyclin D1 targets the AF-1 transactivation function. The constitutively active AF-5 domain was refractory to cyclin D1 inhibition. By contrast, cyclin D1 completely abolished androgen receptor activity, even in the presence of potent androgen receptor co-activators. This action of cyclin D1 at least partially required de-acetylase activity. Finally, we show that transient, ectopic expression of cyclin D1 results in reduced cell cycle progression in androgen-dependent LNCaP cells independent of CDK4 association. Collectively, our data support a model wherein cyclin D1 has a mitogenic (CDK4-dependent) function and an anti-mitogenic function (dependent on regulation of the AF-1 domain) that can collectively control the rate of androgen-dependent cellular proliferation. These findings provide insight into the non-cell cycle functions of cyclin D1 and provide the impetus to study its pleiotropic effects in androgen-dependent cells, especially prostatic adenocarcinomas.


Long-term evidence on cooperation and cultural differences in public goods dilemmas.
It is hard to isolate human cooperation features outside the prevalent experimental laboratory context in a controlled setting. Since cooperation rates are very context-sensitive, a new setting-a public goods game in an online game-is analysed. This unique dataset addresses multiple critical issues: it is more realistic, individuals have an intrinsic motivation to play, there are no observer effects, and data are available for more than 18 000 individuals playing over 10 months. Participants come from 10 countries, which allows us to test for cultural influences on cooperation. We find small differences in cooperation rates between countries, ranging from 8.5% (Argentina) to 14.1% (Greece). Moreover, cooperation remains stable over long periods of time. Different cultural, economic and religious backgrounds do not seem to have a discernible influence on cooperation rates. Instead, individual differences seem to play a larger role. Finally, cooperation levels may be lower than suggested by experiments from the classical laboratory context.


Subfractionation of ficoll gradient purified synaptosomes: GABA uptake by the subfractions.
The classical synaptosomes preparation purified on discontinuous Ficoll gradient has been sufractionated into three further subfractions by introducing more Ficoll density layers. Among the three subfractions, the lightest one was the one which was more difficult to obtain in reproducible amounts and was only partially characterized in terms of labelled GABA uptake. The heaviest one most probably is largely made up of partially damaged nerve endings. The central one was the most reproducible in terms of yield and labelled GABA uptake and actually was the one we studied more thoroughly in terms of morphology, labelled GABA uptake and its pharmacology. A comparison has been made with the classical "total" purified synaptosomes fraction. An interesting result of these experiments is a paradoxical effect of the glial uptake inhibitor beta-alanine. This substance appears to favor, in both "total" and "central" fraction synaptosomes, a redistribution of taken up GABA from contaminating glia to actual nerve endings.


Metallothionein IIA is up-regulated by hypoxia in human A431 squamous carcinoma cells.
The expression of metallothionein IIA (MT-IIA) was investigated in A431 human squamous carcinoma cells exposed to hypoxia (pO < or = 0.01% of atmospheric pO2) and subsequent reoxygenation. Northern analysis showed that MT-IIA mRNA levels were significantly increased during 14 h of hypoxia and during reoxygenation. Western blotting confirmed that total MT protein levels were also increased in response to these stresses. Evidence of the transcriptional control of MT-IIA expression in hypoxic and in reoxygenated A431 cells was found using a 0.2-kilobase sequence of the proximal 5'-regulatory region of the MT-IIA gene in a chloramphenicol acetyltransferase reporter gene construct. Thus the proximal promoter of the human MT-IIA gene appears to contain a hypoxic response element(s). These observations indicate that MT-IIA may have an important role in the stress responses of cells in solid tumors.


Disodium valproate: new preparation. An alternative for acute mania after lithium failure or intolerance.
(1) The reference treatment for mania is lithium. Lithium can be combined with a neuroleptic in patients who also have psychotic disorders (especially with aggressiveness). Carbamazepine is a second-line alternative. (2) Marketing authorisation has now been granted in France for disodium valproate (divalproate). (3) Disodium valproate is a complex composed of one molecule of sodium valproate and one molecule of valproic acid. Its effects are identical to those of valproate sodium. (4) The clinical file on disodium valproate mainly comprises two double-blind trials. In one trial involving 43 patients in whom lithium was ineffective or poorly tolerated, the efficacy of divalproate, measured using a validated scale, was significantly superior to that of the placebo. (5) The other trial, involving 179 patients, confirmed the efficacy of divalproate versus a placebo, and showed that divalproate was roughly as effective as lithium. (6) The efficacy of divalproate has not been compared with that of carbamazepine. It has not yet been demonstrated that carbamazepine remains effective when lithium is inadequate. (7) The adverse effect profile of divalproate mainly comprises gastrointestinal and neuropsychological disorders. A few cases of severe hepatitis and pancreatitis have also been reported. (8) In practice, in cases of lithium intolerance or inefficacy, divalproate is worth trying for patients with acute mania, before trying carbamazepine.


Uncovering Brain Differences in Preschoolers and Young Adolescents with Autism Spectrum Disorder Using Deep Learning.
Identifying brain abnormalities in autism spectrum disorder (ASD) is critical for early diagnosis and intervention. To explore brain differences in ASD and typical development (TD) individuals by detecting structural features using T1-weighted magnetic resonance imaging (MRI), we developed a deep learning-based approach, three-dimensional (3D)-ResNet with inception (I-ResNet), to identify participants with ASD and TD and propose a gradient-based backtracking method to pinpoint image areas that I-ResNet uses more heavily for classification. The proposed method was implemented in a preschool dataset with 110 participants and a public autism brain imaging data exchange (ABIDE) dataset with 1099 participants. An extra epilepsy dataset with 200 participants with clear degeneration in the parahippocampal area was applied as a verification and an extension. Among the datasets, we detected nine brain areas that differed significantly between ASD and TD. From the ROC in PASD and ABIDE, the sensitivity was 0.88 and 0.86, specificity was 0.75 and 0.62, and area under the curve was 0.787 and 0.856. In a word, I-ResNet with gradient-based backtracking could identify brain differences between ASD and TD. This study provides an alternative computer-aided technique for helping physicians to diagnose and screen children with an potential risk of ASD with deep learning model.


Management of chronic peripheral artery disease patients with indication for endovascular revascularization.
With an increasing global burden of patients with chronic peripheral artery disease (PAD) the safe and effective provision of lower limb revascularisation is a growing medical need. Endovascular procedures for the treatment of PAD have become a crucial cornerstone of modern vascular medicine, and the first line revascularisation approach if technically feasible and taking patient choice into consideration. With the increasing age of patients with PAD and the increasing number of comorbidities open vascular surgery is also often not feasible. We outline a framework of key messages, endorsed by the board of the European Society of Vascular Medicine for pre-, peri- and post procedural management of patients requiring endovascular arterial procedures of the lower limbs. These key messages emphasize the important and increasing role of interventional vascular physicians.


Multi-slice computed tomography 5-minute delayed scan is superior to immediate scan after contrast media application in characterization of intracranial tuberculosis.
The aim of this study was to determine whether the diagnosis of intracranial tuberculosis (TB) can be improved when multi-slice computed tomography (MSCT) scans are taken with a 5-min delay after contrast media application. Pre- and post-contrast CT scans of the head were obtained from 30 patients using a 16-slice spiral CT. Dual-phase acquisition was performed immediately and 5 min after contrast agent injection. Diagnostic values of different images were compared using a scoring system applied by 2 experienced radiologists. We found 526 lesions in 30 patients, including 22 meningeal thickenings, 235 meningeal tuberculomas/tubercles, and 269 parenchymal tuberculomas/tubercles. Images obtained with 5-min delayed scan time were superior in terms of lesion size and meningeal thickening outlining in all disease types (P<0.01). The ability to distinguish between vascular sections from the cerebral sulcus and tubercle was also improved (P<0.01). Image acquisition with 5-min delay after contrast agent injection should be performed as a standard scanning protocol to diagnose intracranial TB.


Modulated two-dimensional charge-carrier density in LaTiO3-layer-doped LaAlO3/SrTiO3 heterostructure.
The highly mobile two-dimensional electron gas (2DEG) formed at the polar/nonpolar LaAlO3/SrTiO3 (LAO/STO) heterostructure (HS) is a matter of great interest because of its potential applications in nanoscale solid-state devices. To realize practical implementation of the 2DEG in device design, desired physical properties such as tuned charge carrier density and mobility are necessary. In this regard, polar perovskite-based transition metal oxides can act as doping layers at the interface and are expected to tune the electronic properties of 2DEG of STO-based HS systems dramatically. Herein, we investigated the doping effects of LaTiO3(LTO) layers on the electronic properties of 2DEG at n-type (LaO)(+1)/(TiO2)(0) interface in the LAO/STO HS using spin-polarized density functional theory calculations. Our results indicate an enhancement of orbital occupation near the Fermi energy, which increases with respect to the number of LTO unit cells, resulting in a higher charge carrier density of 2DEG than that of undoped system. The enhanced charge carrier density is attributed to an extra electron introduced by the Ti 3d(1) orbitals from the LTO dopant unit cells. This conclusion is consistent with the recent experimental findings (Appl. Phys. Lett. 2013, 102, 091601). Detailed charge density and partial density of states analysis suggests that the 2DEG in the LTO-doped HS systems primarily comes from partially occupied dyz and dxz orbitals.


Measles virus infects and suppresses proliferation of T lymphocytes from transgenic mice bearing human signaling lymphocytic activation molecule.
Humans are the only natural reservoir of measles virus (MV), one of the most contagious viruses known. MV infection and the profound immunosuppression it causes are currently responsible for nearly one million deaths annually. Human signaling lymphocytic activation molecule (hSLAM) was identified as a receptor for wild-type MV as well as for MV strains prepared as vaccines. To better evaluate the role of hSLAM in MV pathogenesis and MV-induced immunosuppression, we created transgenic (tg) mice that expressed the hSLAM molecule under the control of the lck proximal promoter. hSLAM was expressed on CD4(+) and CD8(+) T cells in the blood and spleen and also on CD4(+), CD8(+), CD4(+) CD8(+), and CD4(-) CD8(-) thymocytes. Wild-type MV, after limited passage on B95-8 marmoset B cells, and the Edmonston laboratory strain of MV infected hSLAM-expressing cells. There was a direct correlation between the amount of hSLAM expressed on the cells' surface and the degree of viral infection. Additionally, MV infection induced downregulation of receptor hSLAM and inhibited cell division and proliferation of hSLAM(+) but not hSLAM(-) T cells. Therefore, these tg mice provide the opportunity for analyzing and comparing MV-T cell interactions and MV pathogenesis in cells expressing only the hSLAM MV receptor with those of tg mice whose T cells selectively express another MV receptor, CD46.


Latin American Women´s Beliefs, Views and Ideas About Sexual Assertiveness: A Focus Group Study in Cuenca (Ecuador).
In an attempt to extend our understanding of how social contexts co-create female sexuality in Latin America, the aim of the current study was to explore the beliefs, views, and ideas about sexual assertiveness in Latino emerging adult women. Seventeen women between 22 and 30 years old living in Cuenca, Ecuador, participated in focus groups. A constructivist grounded theory approach was used to analyze the data. Findings suggest that the overall views about sexual assertiveness in emerging adult women can be grouped into five categories: (1) gender role schemata; (2) concerns about the partner's thoughts and reactions; (3) gendered attitudes towards the use of specific methods of contraception; (4) talking about sexual histories as a challenging task; and (5) replication of family patterns. The findings of this study are discussed within existing literature that highlights the influence of gender role schemata on sexual assertiveness. Finally, a plea for more culturally sensitive research is formulated as well as some educational - the need to reinforce sex education programs - and clinical - highlighting the ability to be sexually assertive from the start of a relationship - implications are mentioned.


Comparing the effect of intestinal bacteria from rabbit, pig, and chicken on inflammatory response in cultured rabbit crypt and villus.
Rabbit is susceptible to intestinal infection, which often results in severe inflammatory response. To investigate whether the special community structure of rabbit intestinal bacteria contributes to this susceptibility, we compared the inflammatory responses of isolated rabbit crypt and villus to heat-treated total bacteria in pig, chicken, and rabbit ileal contents. The dominant phylum in pig and chicken ileum was Firmicutes, while Bacteroidetes was dominant in rabbit ileum. The intestinal bacteria from rabbit induced higher expression of toll-like receptor 4 (TLR4) in rabbit crypt and villus (P < 0.05). TLR2 and TLR3 expression was obviously stimulated by chicken and pig intestinal bacteria (P < 0.05) but not by those of rabbit. The ileal bacteria from those three animals all increased the expression of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) in crypts and villus (P < 0.05). Chicken and pig ileal bacteria also stimulated the expression of anti-inflammatory factors interferon beta (IFN-β) and IL-10 (P < 0.05), while those of rabbit did not (P > 0.05). In conclusion, a higher abundance of Gram-negative bacteria in rabbit ileum did not lead to more expressive pro-inflammatory cytokines in isolated rabbit crypt and villus, but a higher percentage of Lactobacillus in chicken ileum might result in more expressive anti-inflammatory factors.


[Treatment of severe Rhesus erythroblastosis].
Report about the management of cases of severe Rhesus erythroblastosis. One case is specially discussed because of it's actuality. This was a patient with severe Rh-sensitization (OOD at 450 mm from the beginning of the 30th week of gestation in zone III according to Liley). Because of the haemolytic disease and the chronic fetal distress the Caesarean section was already performed in the 32nd week of gestation after Betamethason treatment of the mother. The Lecithin-Sphingomyelin (L/S) ratio in the amniotic fluid as a criterium of fetal lung maturity raised almost twicefold (from 0.9 to 1.6) after Cortison treatment. The intensive care (assisted ventilation with PEEP, correction of the acidosis and transfusion of packed red cells) of the severely anaemic (Hb 3.5 g%, Hk 15 vol.%) and hydropic newborn was already started in the delivery room. The newborn developed no RDS and was discharged healthy. With reference to this and other cases the management of severe Rh-sensitization before the 34th week of gestation is discussed. Premature infants are mainly susceptable to the development of a Respiratory Distress syndrome (RDS). After antepartum Cortison treatment for prevention of an RDS the date of confinement should be arranged earlier. The value of an early Caesarian section after antepartum Glucocorticoid treatment as compared to the application of intrauterine transfusions in cases of severe erythroblastosis is discussed. It is also reported about recent methods of treatment of severe conditions of hydrops fetalis.


Glycyrrhetinic Acid Antagonizes Pressure-Induced Venous Remodeling in Mice.
Development of spider veins is caused by the remodeling of veins located in the upper dermis and promoted by risk factors such as obesity or pregnancy that chronically increase venous pressure. We have repeatedly shown that the pressure-induced increase in biomechanical wall stress is sufficient to evoke the formation of enlarged corkscrew-like superficial veins in mice. Subsequent experimental approaches revealed that interference with endothelial- and/or smooth muscle cell (SMC) activation counteracts this remodeling process. Here, we investigate whether the herbal agent glycyrrhetinic acid (GA) is a suitable candidate for that purpose given its anti-proliferative as well as anti-oxidative properties. While basic abilities of cultured venous SMCs such as migration and proliferation were not influenced by GA, it inhibited proliferation but not angiogenic sprouting of human venous endothelial cells (ECs). Further analyses of biomechanically stimulated ECs revealed that GA inhibits the DNA binding capacity of the mechanosensitive transcription factor activator protein-1 (AP-1) which, however, had only a minor impact on the endothelial transcriptome. Nevertheless, by decreasing gelatinase activity in ECs or mouse veins exposed to biomechanical stress, GA diminished a crucial cellular response in the context of venous remodeling. In line with the observed inhibitory effects, local transdermal application of GA attenuated pressure-mediated enlargement of veins in the mouse auricle. In summary, our data identifies GA as an inhibitor of EC proliferation, gelatinase activity and venous remodeling. It may thus have the capacity to attenuate spider vein formation and remodeling in humans.


The functional diffusion map: an imaging biomarker for the early prediction of cancer treatment outcome.
Functional diffusion map (fDM) has been recently reported as an early and quantitative biomarker of clinical brain tumor treatment outcome. This approach spatially maps and quantifies treatment-induced changes in tumor water diffusion values resulting from alterations in cell density/cell membrane function and microenvironment. This current study was designed to evaluate the capability of fDM for preclinical evaluation of dose escalation studies and to determine if these changes were correlated with outcome measures (cell kill and overall survival). Serial T2-weighted were carried out on rodents with orthotopically implanted 9L brain tumors receiving three doses of 1,3-bis(2-chloroethyl)-1-nitrosourea (6.65, 13.3, and 26.6 mg/kg, i.p.). All images were coregistered to baseline T2-weighted images for fDM analysis. Analysis of tumor fDM data on day 4 posttreatment detected dose-dependent changes in tumor diffusion values, which were also found to be spatially dependent. Histologic analysis of treated tumors confirmed spatial changes in cellularity as observed by fDM. Early changes in tumor diffusion values were found to be highly correlative with drug dose and independent biologic outcome measures (cell kill and survival). Therefore, The fDM imaging biomarker for early prediction of treatment efficacy can be used in the drug development process.


Bilateral cerebellar infarction: a rare complication of scorpion sting.
Complications following scorpion sting are common in India and can be fatal. Stroke following scorpion sting is a rare complication and can occur by various mechanisms such as hypertension, hypotension, DIC, myocarditis and venom-induced vasculitis. We present a rare case of extensive cerebellar infarction following scorpion sting, which has rarely been reported in medical literature. To study the clinical profile of two patients presenting with an acute onset of cerebellar symptoms following a scorpion sting. To evaluate the possible causes of the stroke and to study the relation of their symptoms to the scorpion sting. Two young women presented with a history of acute onset of dysarthria, ataxia and incoordination following scorpion sting. They did not have any known risk factors for stroke. They had cerebellar type of dysarthria and cerebellar signs on both sides along with incoordination. A CT-scan of the brain showed bilateral extensive cerebellar infarctions. They were investigated for other causes of stroke without any positive results. With treatment the patients made a gradual but complete recovery. Since there was no evidence of hypertension, hypotension, myocarditis or disseminated intravascular coagulation, we can conclude that the patients had suffered a thrombotic stroke caused by the vasculotoxic action of the scorpion venom.


Financial stress and debt in clinical psychology doctoral students.
Few studies examine the financial burden of clinical psychology doctoral programs and its impact on achievements, stress, and mental health. The current study sought to better understand students' financial stress and debt, and how financial stress may impact their mental health and the attainment of personal and professional milestones. Students (N = 912) completed an online survey assessing demographics, sources of income and expenditures, mental health, and milestones. After accounting for yearly inflation, stipends have not kept pace with the average cost of living in the United States. Over one-third of students indicated that they had no expendable pretax income after paying for their education and typical living expenses. Additionally, over 80% reported acquiring additional debt in graduate school to offset their living expenses. Financial concerns were associated with delays in major life milestones (e.g., buying a car/house, getting married/starting a family, having children), as well as avoiding medical (34.2%) or mental (41.4%) health care, with 17.5% of participants experiencing a health crisis they could not afford while in graduate school. Financial stress was associated with an increase in time spent thinking about finances, higher rates of depression and anxiety symptoms, and decreased sleep. Many clinical psychology doctoral students experience financial stress and are often unable to afford basic educational, personal living, and health care expenses, likely worsening mental health. Academic programs and leadership are encouraged to increase student stipends, improve financial transparency, provide access to health care, and alleviate financial stress and debt.


Kinetic study of the replacement of porcine small intestinal submucosa grafts and the regeneration of meniscal-like tissue in large avascular meniscal defects in dogs.
Porcine small intestinal submucosa (SIS) was used to replace large, avascular defects in the medial menisci of dogs. Twelve dogs received SIS grafts and 3 dogs were left untreated as controls. Dogs were evaluated at 4, 8, and 12 weeks by means of lameness scoring and ultrasonography. Dogs were sacrificed at 1, 6, or 12 weeks after implantation, and the tissue at the site of meniscal resection was evaluated for gross and histologic appearance, cross-sectional and surface area, and collagen types I and II. The femoral and tibial condyles were assessed for articular cartilage damage. Control dogs were significantly more lame than grafted dogs 8 and 12 weeks after instrumentation. Grafted dogs' replacement tissue appeared meniscal-like when evaluated grossly and ultrasonographically 12 weeks after instrumentation. The amount of replacement tissue was significantly greater in both cross-sectional and surface area for grafted dogs than for controls at all time points. Histologically, the SIS biomaterial could be identified in all grafted dogs at 1 week post-implantation, but in none at 6 weeks post-implantation. Subjectively, grafted dogs' replacement tissue was histologically superior to that of controls with respect to tissue type, organization, and architecture. Collagen types I and II immunoreactivity in grafted menisci were similar to that of normal menisci. Control dogs had significantly more articular cartilage damage than grafted dogs. SIS appears to induce regeneration of meniscal-like tissue in large, avascular meniscal defects in dogs, resulting in superior clinical function and articular cartilage protection compared to ungrafted controls.


A system-based comparison of gene expression reveals alterations in oxidative stress, disruption of ubiquitin-proteasome system and altered cell cycle regulation after exposure to cadmium and methylmercury in mouse embryonic fibroblast.
Environmental and occupational exposures to heavy metals such as methylmercury (MeHg) and cadmium (Cd) pose significant health risks to humans, including neurotoxicity. The underlying mechanisms of their toxicity, however, remain to be fully characterized. Our previous studies with Cd and MeHg have demonstrated that the perturbation of the ubiquitin-proteasome system (UPS) was associated with metal-induced cytotoxicity and apoptosis. We conducted a microarray-based gene expression analysis to compare metal-altered gene expression patterns with a classical proteasome inhibitor, MG132 (0.5 microM), to determine whether the disruption of the UPS is a critical mechanism of metal-induced toxicity. We treated mouse embryonic fibroblast cells at doses of MeHg (2.5 microM) and Cd (5.0 microM) for 24 h. The doses selected were based on the neutral red-based cell viability assay where initial statistically significant decreases in variability were detected. Following normalization of the array data, we employed multilevel analysis tools to explore the data, including group comparisons, cluster analysis, gene annotations analysis (gene ontology analysis), and pathway analysis using GenMAPP and Ingenuity Pathway Analysis (IPA). Using these integrated approaches, we identified significant gene expression changes across treatments within the UPS (Uchl1 and Ube2c), antioxidant and phase II enzymes (Gsta2, Gsta4, and Noq1), and genes involved in cell cycle regulation pathways (ccnb1, cdc2a, and cdc25c). Furthermore, pathway analysis revealed significant alterations in genes implicated in Parkinson's disease pathogenesis following metal exposure. This study suggests that these pathways play a critical role in the development of adverse effects associated with metal exposures.


Influence of neuropathic pain on nicotinic acetylcholine receptor plasticity and behavioral responses to nicotine in rats.
Tobacco smoking is particularly evident in individuals experiencing chronic pain. This complex relationship is poorly understood at both molecular and behavioral levels. Here, we describe experiments aimed at understanding whether a chronic pain state induces neuroadaptations into the brain or peripheral nerves that involve nicotinic acetylcholine receptors (nAChRs) and whether these neuroadaptations directly lead to increased vulnerability to nicotine addiction or to the development of coping strategies to relieve pain symptoms. We found that ligation of the rat L5 spinal nerve led to a dramatic downregulation in the mRNA expression levels of all nAChR subunits examined in dorsal root ganglia and a time-dependent downregulation of discrete subunits, particularly in the cingulate cortex and the amygdala. Spinal nerve ligation and sham-operated rats showed minor or no changes in patterns of acquisition and motivation for nicotine taking. Spinal nerve ligation rats also showed similar vulnerability to nicotine seeking as sham animals when reinstatement was induced by nicotine-associated cues, but failed to reinstate lever pressing when relapse was induced by nicotine priming. Spinal nerve ligation and sham rats were equally sensitive to nicotine-induced anxiety-like behavior and antinociception; however, nicotine produced a potent and long-lasting antiallodynic effect in spinal nerve ligation rats. These results demonstrate that chronic pain leads to plasticity of nAChRs that do not directly facilitate nicotine addictive behaviors. Instead, nicotine potently decreases allodynia, an effect that could lead to increased nicotine consumption in chronic pain subjects.


Upstream stimulatory factor activates the vasopressin promoter via multiple motifs, including a non-canonical E-box.
We have described previously a complex E-box enhancer (-147) of the vasopressin promoter in small-cell lung cancer (SCLC) extracts [Coulson, Fiskerstrand, Woll and Quinn, (1999) Biochem. J. 344, 961-970]. Upstream stimulatory factor (USF) heterodimers were one of the complexes binding to this site in vitro. We now report that USF overexpression in non-SCLC (NSCLC) cells can functionally activate vasopressin promoter-driven reporters that are otherwise inactive in this type of lung cancer cell. Site-directed mutagenesis and electrophoretic mobility-shift analysis demonstrate that although the -147 E-box contributes, none of the previously predicted E-boxes (-147, -135, -34) wholly account for this USF-mediated activation in NSCLC. 5' Deletion showed the key promoter region as -52 to +42; however, USF-2 binding was not reliant on the -34 E-box, but on a novel adjacent CACGGG non-canonical E-box at -42 (motif E). This mediated USF binding in both SCLC and USF-2-transfected NSCLC cells. Mutation of motif E or the non-canonical TATA box abolished activity, implying both are required for transcriptional initiation on overexpression of USF-2. Co-transfected dominant negative USF confirmed that binding was required through motif E for function, but that the classical activation domain of USF was not essential. USF-2 bound motif E with 10-fold lower affinity than the -147 E-box. In NSCLC, endogenous USF-2 expression is low, and this basal level appears to be insufficient to activate transcription of arginine vasopressin (AVP). In summary, we have demonstrated a novel mechanism for USF activation, which contributes to differential vasopressin expression in lung cancer.


Identification of essential amino acid residues in valine dehydrogenase from Streptomyces albus.
Cys-29 and Cys-251 of Streptomyces albus valine dehydrogenase (ValDH) were highly conserved in the corresponding region of NAD(P)(+)-dependent amino acid dehydroganase sequences. To ascertain the functional role of these cysteine residues in S. albus ValDH, site-directed mutagenesis was performed to change each of the two residues to serine. Kinetic analyses of the enzymes mutated at Cys-29 and Cys-251 revealed that these residues are involved in catalysis. We also constructed mutant ValDH by substituting valine for leucine at 305 by site-directed mutagenesis. This residue was chosen, because it has been proposed to be important for substrate discrimination by phenylalanine dehydrogenase (PheDH) and leucine dehydrogenase (LeuDH). Kinetic analysis of the V305L mutant enzyme revealed that it is involved in the substrate binding site. However it displayed less activity than the wild type enzyme toward all aliphatic and aromatic amino acids tested.


Parotid gland radiation dose-xerostomia relationships based on actual delivered dose for nasopharyngeal carcinoma.
Xerostomia induced by radiotherapy is a common toxicity for head and neck carcinoma patients. In this study, the deformable image registration of planning computed tomography (CT) and weekly cone-beam CT (CBCT) was used to override the Hounsfield unit value of CBCT, and the modified CBCT was introduced to estimate the radiation dose delivered during the course of treatment. Herein, the beams from each patient's treatment plan were applied to the modified CBCT to construct the weekly delivered dose. Then, weekly doses were summed together to obtain the accumulated dose. A total of 42 parotid glands (PGs) of 21 nasopharyngeal carcinoma patients were analyzed. Doses delivered to the parotid glands significantly increased compared with the planning doses. V20 , V30 , V40 , Dmean , and D50 increased by 11.3%, 28.6%, 44.4%, 9.5%, and 8.4% respectively. Of the 21 patients included in the study, eight developed xerostomia and the remaining 13 did not. Both planning and delivered PG Dmean for all patients exceeded tolerance (26 Gy). Among the 21 patients, the planning dose and delivered dose of Dmean were 30.6 Gy and 33.6 Gy, respectively, for patients with xerostomia, and 26.3 Gy and 28.0 Gy, respectively, for patients without xerostomia. The D50 of the planning and delivered dose for patients was below tolerance (30 Gy). The results demonstrated that the p-value of V20 , V30 , D50 , and Dmean difference of the delivery dose between patients with xerostomia and patients without xerostomia was less than 0.05. However, for the planning dose, the significant dosimetric difference between the two groups only existed in D50 and Dmean . Xerostomia is closely related to V20 , V30 , D50 , and Dmean .


[Examination of the constancy of the medium optical density of conventional chest radiographs].
To determine whether the medium optical density of conventional chest radiographs is constant. 47 PA chest radiographs were digitized to measure the optical density and its dynamic range of normal and pathologically altered lungs. For constant exposure factors and a correctly positioned region of interest, the medium optical density deviates only minimal despite differences in AP chest diameter, entry dose and dynamic range, and is largely independent of the pathologic pulmonary findings. Digitization of the radiograph enables the determination of the physical parameters used to operate the imaging system, such as medium optical density, image contrast, image latitude and density distribution, in accordance to the guidelines of the German Medical Association. If the region of interest encompasses the clinically relevant region of the lung, the measured value of the optical density corresponds with only minor variation to the average value of the entire lung region.


Interaction between HBS-beta-o-thalassemia and alpha-thalassemia.
We have defined the clinical and laboratory characteristics of a group of patients with HbS-beta o-thalassemia plus alpha-thalassemia, by analysis of erythrocyte indices, hemoglobin A2 and F levels, globin biosynthesis studies and alpha-globin gene mapping. Patients with HbS-beta o + alpha-thalassemia closely resembled individuals with HbS-beta o-thalassemia except for balanced globin synthesis ratios and a lower HbF level. The frequency of painful crises, leg ulceration, aseptic necrosis of bone and acute chest syndrome was similar in HbS-beta o + alpha-thalassemia patients and controls with sickle cell anemia (HbSS), HbSS-alpha-thalassemia and HbS-beta o-thalassemia. These findings are consistent with previous work which failed to show a reduction in the vaso-occlusive severity of sickle cell disease by the coexistence of alpha-thalassemia.


Changes in wingstroke kinematics associated with a change in swimming speed in a pteropod mollusk, Clione limacina.
In pteropod mollusks, the gastropod foot has evolved into two broad, wing-like structures that are rhythmically waved through the water for propulsion. The flexibility of the wings lends a tremendous range of motion, an advantage that could be exploited when changing locomotory speed. Here, we investigated the kinematic changes that take place during an increase in swimming speed in the pteropod mollusk Clione limacina. Clione demonstrates two distinct swim speeds: a nearly constant slow swimming behavior and a fast swimming behavior used for escape and hunting. The neural control of Clione's swimming is well documented, as are the neuromuscular changes that bring about Clione's fast swimming. This study examined the kinematics of this swimming behavior at the two speeds. High speed filming was used to obtain 3D data from individuals during both slow and fast swimming. Clione's swimming operates at a low Reynolds number, typically under 200. Within a given swimming speed, we found that wing kinematics are highly consistent from wingbeat to wingbeat, but differ between speeds. The transition to fast swimming sees a significant increase in wing velocity and angle of attack, and range of motion increases as the wings bend more during fast swimming. Clione likely uses a combination of drag-based and unsteady mechanisms for force production at both speeds. The neuromuscular control of Clione's speed change points to a two-gaited swimming behavior, and we consider the kinematic evidence for Clione's swim speeds being discrete gaits.


Tirzepatide: A Novel, Once-weekly Dual GIP and GLP-1 Receptor Agonist for the Treatment of Type 2 Diabetes.
Gastrointestinal hormones are currently used to treat type 2 diabetes mellitus (T2D). Incretin preparations with gastric inhibitory polypeptide (GIP) activity or glucagon-like peptide-1 (GLP-1) provide new means for controlling blood glucose levels, body weight, and lipid metabolism. GIP, an incretin, has not been used due to lack of promising action against diabetes. However, recent studies have shown that GIP has an important effect on glucagon and insulin secretion under normoglycaemic conditions. Co-existence of GIP with GLP-1 and glucagon signalling leads to a stronger effect than that of GLP-1 stimulation alone. The development of a GIP/GLP-1R unimolecular dual agonist with affinity for both GIP and GLP-1 receptors is under investigation, and the drug is expected to be clinically available in the near future. Tirzepatide, a GIP/GLP-1R unimolecular dual agonist, regulates metabolism via both peripheral organs and the central nervous system. The SURPASS phase III clinical trials conducted for tirzepatide comprise 10 clinical trials, including five global trials and the global SURPASS-CVOT trial, with >13,000 patients with T2D (ClinicalTrials.gov Identifier: NCT04255433). The clinical application of tirzepatide as a therapy for T2D may provide new insights into diabetic conditions and help clarify the role of GIP in its pathogenesis.


[Epidemiology of penicillin resistant pneumococci.].
Penicillin resistant and multiresistant pneumococci have become common all over the world. Pneumococci resistant to cefotaxime and ceftriaxone have only become established in the USA, Spain and South Africa, although recently such strains have been described in the UK. Resistance to cefotaxime and ceftriaxone may spread faster than penicillin resistance. With B-lactam resistant and multiresistant pneumococci, the choice of antimicrobials is reduced to a single class of antimicrobials, the glycopeptides. Penicillin resistant pneumococci were introduced in Iceland in 1988, and had gained 20% incidence in pneumococcal infections in 1993. This rapid spread was associated with serogroups 6, 19 and 23, of which serotype 6B (multiresistant) was by far the most prevalent. During this period the incidence of penicillin resistant pneumococci remained low in the other Nordic countries. Since the practice of medicine is very similar in these countries, it was important to search for epidemiological clues that would explain the difference. The following risk factors have been shown to be important in epidemiological studies conducted in Iceland: most Icelandic children attend day-care centres, where they have numerous contacts with children with respiratory tract infections during the long winter months. Antimicrobial usage was high in children attending day care centres. The popularity of the sulpha-trimethoprim combination in Iceland may also be important, as it was shown to be an independent risk factor. Total use of antimicrobial agents declined in Iceland in the years 1991-1993 following a propaganda campaign against misuse and legislative changes that increased the cost of the antimicrobials for patients. The antimicrobial use in day-care centres was significantly reduced from 1992 to 1995. In 1994 the incidence of penicillin resistant pneumococci decreased to 17% (from 20% in 1993). Hopefully reduction in antimicrobial use will continue and contribute to further lowering of resistance levels.


Retinal pigment epithelial detachments in the elderly: classification and outcome.
Sixty-four eyes of 57 elderly patients with pigment epithelial detachments (PEDs) were studied with the aim of describing their morphological features and identifying prognostic factors. They were classified into four groups according to the following characteristics: early fluorescence, late fluorescence, shallow detachment with limited fluorescence ('drusen type'), irregular fluorescence. The following conclusions were drawn: 30% developed demonstrable subretinal new vessels; all groups except the drusen type were susceptible, the irregular group being particularly prone. 10% developed retinal pigment epithelial tears, and these occurred almost exclusively in the slow fluorescent group. Flattening of PEDs was a feature of drusen type and early fluorescent groups. Most patients lost vision. RPE tears occurred within a few months of presentation with immediate loss of vision; likewise rapid loss of vision followed the development of demonstrable new vessels, though not necessarily in those with changes thought to imply the presence of new vessels. Flattening after prolonged detachment was associated with pigment epithelial atrophy and invariable loss of vision. Visual acuity was maintained consistently only in those eyes with persistent detachment.


Mental health disparities.
Mental health disparities have received increased attention in the literature in recent years. After considering 165 different health disparity conditions, the Federal Collaborative for Health Disparities Research chose mental health disparity as one of four topics warranting its immediate national research attention. In this essay, we describe the challenges and opportunities encountered in developing a research agenda to address mental health disparities in the United States. Varying definitions of mental health disparity, the heterogeneity of populations facing such disparity, and the power, complexity, and intertwined nature of contributing factors are among the many challenges. We convey an evolving interagency approach to mental health disparities research and guidance for further work in the field.


Patterns and frequency of renal abnormalities in Fanconi anaemia: implications for long-term management.
Fanconi anaemia (FA) is an inherited disease with bone marrow failure, variable congenital and developmental abnormalities, and cancer predisposition. With improved survival, non-haematological manifestations of FA become increasingly important for long-term management. While renal abnormalities are recognized, detailed data on patterns and frequency and implications for long-term management are sparse. We reviewed clinical course and imaging findings of FA patients with respect to renal complications in our centre over a 25-year period to formulate some practical suggestions for guidelines for management of renal problems associated with FA. Thirty patients including four sibling sets were reviewed. On imaging, 14 had evidence of anatomical abnormalities of the kidneys. Two cases with severe phenotype, including renal abnormalities, had chronic kidney disease (CKD) at diagnosis. Haematopoietic stem cell transplantation was complicated by significant acute kidney injury (AKI) in three cases. In three patients, there was CKD at long-term follow-up. All patients had normal blood pressure. Evaluation of renal anatomy with ultrasound imaging is important at diagnostic workup of FA. While CKD is uncommon at diagnosis, our data suggests that the incidence of CKD increases with age, in particular after haematopoietic stem cell transplantation. Monitoring of renal function is essential for management of FA. Based on these long-term clinical observations, we formulate some practical guidelines for assessment and management of renal abnormalities in FA.


Long-term vasodilator therapy for heart failure: clinical response and its relationship to hemodynamic measurements.
To assess the clinical efficacy of chronic vasodilator therapy for refractory congestive heart failure, the long-term follow-up (mean 13 months, range 3-30 months) was evaluated in 56 patients treated with hydralazine, usually in combination with nitrates. In the first 6 months, 73% improved subjectively and 59% improved by one or two New York Heart Association classifications; early improvement was usually sustained. Mortality was high, 22% at 6 months and 37% at 12 months, but was significantly lower in patients who had a clinical response to vasodilators (21% in responders vs 55% in nonresponders at 1 year). The only clinical indicator that differentiated responders from nonresponders was the presence or absence of symptomatic progression before initiation of vasodilator therapy. Pulmonary artery pressure, pulmonary capillary wedge (PCW) pressure and stroke work index (SWI) before and during vasodilator therapy correlated with clinical response and survival. Fifteen of 20 patients with PCW < 20 mm Hg and SWI greater than or equal to 30 g-m/m2 improved and survived, compared with two of 19 with PCS greater than or equal to 20 mm Hg and SWI < 30 g-m/m2. Patients who did not have acute hemodynamic improvement generally did not improve clinically, but neither the percentage change nor the absolute change in any hemodynamic variable predicted outcome in the remaining patients. The findings of this study indicate that vasodilators produce clinical improvement in many patients with refractory heart failure and that hemodynamic measurements are helpful in predicting the outcome of therapy.


A Five Year Study of Comparison of Characteristics and In-hospital Complications of Acute Myocardial Infarction Between Elderly and Younger Patients.
Elderly patients suffering from acute myocardial infarction (AMI) can present differently and their outcome may be different from those of younger patients. A prospective study looking into the characteristics and in-hospital complications of AMI in the elderly patients, comparing to those of the younger patients, was conducted. All AMI patients admitted into our hospital from April 1991 to March 1996 were enrolled. Those patients greater than 70 years were classified as elderly patients. During the 5 year period, there were 241 elderly AMI patients (mean age of 77 years) and 357 younger patients (mean age of 60 years). In the elderly group, 48.0% were female as compared to 24.0% in the younger group (p is less than 0.0001). For the in-hospital complications, 29.5% of elderly patients had cardiogenic shock as compared to 14.6% in younger patients (p is less than 0.0001). There were also significantly more elderly patients suffering from atrial arrhythmias (11% vs. 6% in younger patients, p is less than 0.05). Both groups of patients had similar incidence of ventricular arrhythmias and various types of heart block. Health care professionals taking care of these patients should be aware of these differences and well prepared to tackle these complications.


The expression of the cerato-platanin gene is related to hyphal growth and chlamydospores formation in Ceratocystis platani.
Cerato-platanin (CP) is a protein produced by Ceratocystis platani, the causal agent of canker stain disease of plane trees. CP is the first member of the 'cerato-platanin family', and its role as a pathogen-associated molecular pattern (PAMP), inducing defence responses both in host and nonhost plants, is established. However, the primary role of CP and its homologues in the fungal life remains unknown. In the present work, we investigated the regulation of the cp gene during the in vitro growth of C. platani in different conditions and under the effect of potential stress factors. Fungal growth and conidiogenesis were also analysed. Results showed that cp is a single-copy gene whose expression level is strictly associated with hyphal growth and with chlamydospores formation. The analysis of a 1368 bp 5'-flanking region revealed putative motifs that could be involved in the regulation of gene expression in response to stress and developmental cues. Taking into account the localization of CP in the fungal cell wall and the recently published 3D structure of the protein, our results support a role for CP in growth and developmental processes of C. platani.


Dalfampridine in multiple sclerosis: from symptomatic treatment to immunomodulation.
Multiple sclerosis (MS) is a neurodegenerative disease that is deemed to affect more than 2.1 million people worldwide, and for which there is no cure. Early symptoms of MS are believed to result from axonal demyelination leading to slowing or blockade of impulse conduction. The blockade of K+ channels has been proven to improve conduction deficiencies secondary to demyelination in patients with MS. Dalfampridine is a K+ channel blocker that was recently approved by FDA for the symptomatic treatment of ambulation hardship in MS. Understanding the mechanisms by which Dalfampridine exerts its therapeutic effects is a complex issue as it blocks a wide variety of K+ channels that are distributed across multiple cell types in the nervous system but also in the immune system, and because of their molecular identities remaining unknown. This review describes Dalfampridine potential roles at the cellular and molecular levels in MS pathogenesis.


Impact of thresholding on the consistency and sensitivity of diffusion MRI-based brain networks in patients with cerebral small vessel disease.
Thresholding of low-weight connections of diffusion MRI-based brain networks has been proposed to remove false-positive connections. It has been previously established that this yields more reproducible scan-rescan network architecture in healthy subjects. In patients with brain disease, network measures are applied to assess inter-individual variation and changes over time. Our aim was to investigate whether thresholding also achieves improved consistency in network architecture in patients, while maintaining sensitivity to disease effects for these applications. We applied fixed-density and absolute thresholding on brain networks in patients with cerebral small vessel disease (SVD, n = 86; ≈24 months follow-up), as a clinically relevant exemplar condition. In parallel, we applied the same methods in healthy young subjects (n = 44; scan-rescan interval ≈4 months) as a frame of reference. Consistency of network architecture was assessed with dice similarity of edges and intraclass correlation coefficient (ICC) of edge-weights and hub-scores. Sensitivity to disease effects in patients was assessed by evaluating interindividual variation, changes over time, and differences between those with high and low white matter hyperintensity burden, using correlation analyses and mixed ANOVA. Compared to unthresholded networks, both thresholding methods generated more consistent architecture over time in patients (unthresholded: dice = .70; ICC: .70-.78; thresholded: dice = .77; ICC: .73-.83). However, absolute thresholding created fragmented nodes. Similar observations were made in the reference group. Regarding sensitivity to disease effects in patients, fixed-density thresholds that were optimal in terms of consistency (densities: .10-.30) preserved interindividual variation in global efficiency and node strength as well as the sensitivity to detect effects of time and group. Absolute thresholding produced larger fluctuations of interindividual variation. Our results indicate that thresholding of low-weight connections, particularly when using fixed-density thresholding, results in more consistent network architecture in patients with longer rescan intervals, while preserving sensitivity to disease effects.


Chronic gastric ulceration causes matrix metalloproteinases-9 and -3 augmentation: alleviation by melatonin.
Matrix metalloproteinases (MMPs) are a family of zinc-dependent enzymes capable of degradation of extracellular matrix (ECM) and key player in various inflammatory diseases. We investigated the regulation of MMPs in chronic gastric ulceration in mice. We generated chronic gastric ulcers in mice by indomethacin and examined the activity and expression of MMP-9 and -3 in stomach. Melatonin (N-acetyl-5-methoxytryptamine) treatment has also been applied to mice to characterize the changes in expression and activities of MMPs in gastric tissues. We observed significant upregulation of MMP-9 and -3 expressions and activities in stomach with increasing doses and duration of indomethacin that corroborated with increased activity of activator protein (AP)-1. Substantial damage in gastric epithelial layer was found during chronic ulceration. Melatonin suppressed MMP-9 and -3 expressions and activities during prevention and healing of chronic gastric ulcers. It also suppressed protein oxidation, lipid peroxidation and antioxidant enzymes. Additionally, expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-8 was significantly high in ulcerated stomachs while melatonin treatment blocked them to control level. We found elevated phosphorylation of extracellular-regulated kinase (ERK)1/2 and c-Jun N-terminal kinase (JNK) during chronic gastric ulceration, which were significantly reversed by melatonin. Moreover, expression of NF-κB, c-fos and c-jun were inhibited by melatonin resulting down regulation of MMP-9 and -3 expressions. In summary, oxidative stress is preceded by chronic inflammation that enhances the expression of MMP-9 and -3, while melatonin arrests both of them via reduction of AP-1 activity during protection of ulcer.


Thermosensitive Hydration of Four Acrylamide-Based Polymers in Coil and Globule Conformations.
To characterize the thermosensitive coil-globule transition in atomistic detail, the conformational dynamics of linear polymer chains of acrylamide-based polymers have been investigated at multiple temperatures. Therefore, molecular dynamic simulations of 30mers of polyacrylamide (AAm), poly-N-methylacrylamide (NMAAm), poly-N-ethylacrylamide (NEAAm), and poly-N-isopropylacrylamide (NIPAAm) have been performed at temperatures ranging from 250 to 360 K for 2 μs. While two of the polymers are known to exhibit thermosensitivity (NEAAm, NIPAAm), no thermosensitivity is observed for AAm and NMAAm in aqueous solution. Our computer simulations consistently reproduce these properties. To understand the thermosensitivity of the respective polymers, the conformational ensembles at different temperatures have been separated according to the coil-globule transition. The coil and globule conformational ensembles were exhaustively analyzed in terms of hydrogen bonding with the solvent, the change of the solvent accessible surface, and enthalpic contributions. Surprisingly, independent of different thermosensitive properties of the four polymers, the surface affinity to water of coil conformations is higher than for globule conformations. Therefore, polymer-solvent interactions stabilize coil conformations at all temperatures. Nevertheless, the enthalpic contributions alone cannot explain the differences in thermosensitivity. This clearly implies that entropy is the distinctive factor for thermosensitivity. With increasing side chain length, the lifetime of the hydrogen bonds between the polymer surface and water is extended. Thus, we surmise that a longer side chain induces a larger entropic penalty due to immobilization of water molecules.


Cooperative oncogenic effect and cell signaling crosstalk of co‑occurring HER2 and mutant PIK3CA in mammary epithelial cells.
Though incidence of PI3K oncogenic mutation is prominent in breast cancer (20-30%), pharmacological targeting of this signaling pathway alone has failed to provide meaningful clinical benefit. To better understand and address this problem, we conducted genome-wide analysis to study the association of mutant PI3K with other gene amplification events. One of the most significant copy number gain events associated with PIK3CA mutation was the region within chromosome 17 containing HER2. To investigate the oncogenic effect and cell signaling regulation of co-occurring PIK3CA-H1047R and or HER2 gene, we generated cell models ectopically expressing mutant PIK3CA, HER2 or both genetic alterations. We observed that cells with both genetic alterations demonstrate increased aggressiveness and invasive capabilities than cells with either genetic change alone. Furthermore, we found that the combination of the HER2 inhibitor (CP-724714) and pan PI3K inhibitor (LY294002) is more potent than either inhibitor alone in terms of inhibition of cell proliferation and colony formation. Significantly, four cell signaling pathways were found in common for cells with HER2, mutant PIK3CA and cells with both genetic alterations through an Affymetric microarray analysis. Moreover, the cells with both genetic alterations acquired more significant replication stress as shown by enriched signaling pathways of cell cycle checkpoint control and DNA damage response signaling. Our study suggests co-occurrence of oncogenic HER2 and mutant PIK3CA cooperatively drives breast cancer progression. The cells with both genetic alterations obtain additional features of replication stress which could open new opportunity for cancer diagnostics and treatment.


Application of nanoimprinting technique for fabrication of trifocal diffractive lens with sine-like radial profile.
The fabrication of submicron-height sine-like relief of a trifocal diffractive zone plate using a nanoimprinting technique is studied. The zone plate is intended for use in combined trifocal diffractive–refractive lenses and provides the possibility to form trifocal intraocular lenses with predetermined light intensity distribution between foci. The optical properties of the designed zone plate having the optical powers 3 D, 0, −3D in the three main diffraction orders are theoretically and experimentally investigated. The results of the theoretical investigations are in good agreement with experimental measurements. The effects of the pupil size (lens diameter) as well as the wavelength-dependent behavior of the zone plate are also discussed.


Epidemiologic aspects of the malaria transmission cycle in an area of very low incidence in Brazil.
Extra-Amazonian autochthonous Plasmodium vivax infections have been reported in mountainous regions surrounded by the Atlantic Forest in Espírito Santo state, Brazil. Sixty-five patients and 1,777 residents were surveyed between April 2001 and March 2004. Laboratory methods included thin and thick smears, multiplex-PCR, immunofluorescent assay (IFA) against P. vivax and Plasmodium malariae crude blood-stage antigens and enzyme-linked immunosorbent assay (ELISA) for antibodies against the P. vivax-complex (P. vivax and variants) and P. malariae/Plasmodium brasilianum circumsporozoite-protein (CSP) antigens. Average patient age was 35.1 years. Most (78.5%) were males; 64.6% lived in rural areas; 35.4% were farmers; and 12.3% students. There was no relevant history of travel. Ninety-five per cent of the patients were experiencing their first episode of malaria. Laboratory data from 51 patients were consistent with P. vivax infection, which was determined by thin smear. Of these samples, 48 were assayed by multiplex-PCR. Forty-five were positive for P. vivax, confirming the parasitological results, while P. malariae was detected in one sample and two gave negative results. Fifty percent of the 50 patients tested had IgG antibodies against the P. vivax-complex or P. malariae CSP as determined by ELISA. The percentages of residents with IgM and IgG antibodies detected by IFA for P. malariae, P. vivax and Plasmodium falciparum who did not complain of malaria symptoms at the time blood was collected were 30.1% and 56.5%, 6.2% and 37.7%, and 13.5% and 13%, respectively. The same sera that reacted to P. vivax also reacted to P. malariae. The following numbers of samples were positive in multiplex-PCR: 23 for P. vivax; 15 for P. malariae; 9 for P. falciparum and only one for P. falciparum and P. malariae. All thin and thick smears were negative. ELISA against CSP antigens was positive in 25.4%, 6.3%, 10.7% and 15.1% of the samples tested for "classical" P. vivax (VK210), VK247, P. vivax-like and P. malariae, respectively. Anopheline captures in the transmission area revealed only zoophilic and exophilic species. The low incidence of malaria cases, the finding of asymptomatic inhabitants and the geographic separation of patients allied to serological and molecular results raise the possibility of the existence of a simian reservoir in these areas.


Uncoupling protein 3 content is decreased in skeletal muscle of patients with type 2 diabetes.
Recently, a role for uncoupling protein-3 (UCP3) in carbohydrate metabolism and in type 2 diabetes has been suggested. Mice overexpressing UCP3 in skeletal muscle showed reduced fasting plasma glucose levels, improved glucose tolerance after an oral glucose load, and reduced fasting plasma insulin levels. However, data regarding the expression of UCP3 in patients with type 2 diabetes is inconsistent, and so far, there have been no reports of UCP3 protein content. Here we compared, for the first time, the protein levels of UCP3 in vastus lateralis muscle in 14 male type 2 diabetic patients (age 49.8 +/- 2.1 years; BMI 27.2 +/- 1.2 kg/m(2); mean +/- SE) with 16 male control subjects (age 48.0 +/- 1.9 years; BMI 23.4 +/- 0.6 kg/m(2)). We found that UCP3 protein levels were twice as low in patients with type 2 diabetes compared with control subjects (117 +/- 16 vs. 58 +/- 12 AU; P = 0.007). There was no correlation between UCP3 content and BMI. In conclusion, UCP3 content is lower in type 2 diabetic patients compared with healthy control subjects. These results are consistent with a role for UCP3 in glucose homeostasis and suggest a role for UCP3 in type 2 diabetes.


The evaluation of lateral pterygoid signal intensity changes related to temporomandibular joint anterior disc displacement.
The aim of this study was to evaluate lateral pterygoid muscle (LPM) signal intensity changes related to different degrees of disc status groups using magnetic resonance imaging (MRI). Four groups were established according to disc displacement of examined temporomandibular joint (TMJ) and opposing TMJ. MRI scans were obtained with a 1.5 T device. The signal intensity was measured from the sagittal slice where midportion of the muscle belly was observed. The regions of interest were placed over the superior and inferior heads of LPM. To normalize differences in signal intensity, signal intensity of the grey matter and white matter of the brain was also measured. Signal intensity ratio (SIR) was calculated. Measurements were performed in both T1- and T2-weighted images. In the intergroup comparisons, a statistically significant difference was found for SIR1 sup., SIR1 inf., SIR2 sup. and SIR2 inf. variables (p < 0.01). According to multiple comparison test (Tukey), no significant difference was found between group 0 and group 1 for SIR1 sup., SIR1 inf., SIR2 sup. and SIR2 inf. variables (p > 0.05). For SIR1 sup., SIR1 inf., SIR2 sup. and SIR2 inf. variables, significant differences were found between five binary comparison groups (1-2, 1-3, 2-3, 0-2, 0-3) (p < 0.05). In conclusion, SIR is correlated with the degree of disc displacement. The internal derangement of the opposite joint did not affect SIR of superior and inferior heads of examined LPM in both T1- and T2-weighted images. The inferior head of LPM was also found affected by disc displacement.


Enhanced Hydrogen Evolution Reactivity of T'-Phase Tungsten Dichalcogenides (WS2, WSe2, and WTe2) Materials: A DFT Study.
The hydrogen evolution reaction (HER) plays a crucial role in hydrogen gas production. Layers of transition-metal dichalcogenides (TMDs) possess adjustable electronic structures, and TMDs with H-phase structures have been proposed as substitute HER catalysts. Nonetheless, there are few systematic theoretical analyses of the HER catalytic properties of TMDs with T'-phase structures. Using a DFT calculation, we investigated the electrocatalytic properties of W-based dichalcogenides (WS2, WSe2, and WTe2) through defect engineering. It was found that the interaction of H atoms with the basal plane can be tuned using non-metallic atomic doping, especially with P, thereby enhancing catalytic activity. Furthermore, the computation results demonstrated that high P-doping concentrations can enhance the number of active sites and exhibit a suitable ΔGH*.


Hydrogen-bonded 1,2-bis(4-pyridyl)ethylene and maleic acid.
The title compound (systematic name: 4,4'-ethylenedipyridinium dimaleate), C(12)H(12)N(2)(2+).2C(4)H(3)O(4)(-), is a 1:2 adduct of 1,2-bis(4-pyridyl)ethylene (BPE) and maleic acid (MA). The interaction between the two components in the molecular complex is due to intermolecular hydrogen bonding via an N(+)-H.O(-) hydrogen bond.


[Tissue distribution of galactosyl daphnoretin liposomes in rats].
To study the tissue distribution of galactosyl daphnoretin liposomes in rats. At the dose of 10 mg•kg⁻¹, daphnoretin solution, daphnoretin liposomes, and galactosyl daphnoretin liposomes were administered to healthy SD rats via tail vein injection. The blood and tissue of heart, liver, spleen, lung, kidney, stomach, small intestine, brain and thymus were collected at 5, 15, 30, 45, 60, 120, 240, 360 min after administration. The concentrations of daphnoretin in plasma and tissue samples were determined by HPLC. The results showed that galactosyl daphnoretin liposomes group had the highest concentration of daphnoretin in liver of unit weight at different time points; and at all of the time points, the target index DTI values of galactosyl daphnoretin liposomes to liver were greater than that of daphnoretin liposomes. Compared with daphnoretin solution, the AUC0-6 and Cmax of galactosyl daphnoretin liposomes in liver were 2.23, 5.22 times, respectively. This indicated that galactosyl daphnoretin liposomes can be concentrated at liver, with a significant liver targeting effect.


Efficient photocatalytic degradation of volatile organic compounds by porous indium hydroxide nanocrystals.
Nanosized porous In(OH)(3) photocatalysts with high surface areas (as much as 110 m(2)*g(-1)) were successfully synthesized by peptization of colloidal precipitates under ultrasound radiation. The resulting catalysts were characterized by X-ray powder diffraction (XRD), thermogravimetric analysis, nitrogen adsorption, transition electron microscopy, and UV-vis diffuse reflection spectroscopy. The photocatalytic activities of the samples were evaluated by the gas-phase decomposition of several volatile organic pollutants (acetone, benzene, and toluene) under UV light illumination and were compared with that of the commercial titania (Degussa P25). Results revealed that the as-synthesized In(OH)(3) exhibited much higher photocatalytic activity and durability than both In(2)O(3) and TiO(2). One, therefore, can conclude that nanosized In(OH)(3) has potential application in environmental treatment, especially in the removal of benzene-containing exhaust emissions from shoemaking plants in China. The excellent photocatalytic performance of In(OH)(3) can be attributed to its strong oxidation capability, abundant surface hydroxyl groups, and high BET surface area as well as the porous texture.


Oseltamivir pharmacokinetics in morbid obesity (OPTIMO trial).
Detailed pharmacokinetics to guide oseltamivir (Tamiflu®) dosing in morbidly obese patients is lacking. The OPTIMO trial was a single-centre, non-randomized, open-label pharmacokinetic study of single-dose and steady-state oral oseltamivir phosphate and its carboxylate metabolite in healthy, morbidly obese [body mass index (BMI) > 40)] and healthy, non-obese (BMI < 30) subjects. In the morbidly obese versus control subjects, respectively, the single-dose median oseltamivir oral clearance (CL/F) [840 (range 720-1640) L/h versus 580 (470-1800) L/h] was higher, the area under the curve from time zero to infinity (AUC(0-∞)) [89 (46-104) ng·h/mL versus 132 (42-160) ng·h/mL] was lower and the volume of distribution (V/F) [2320 (900-8210) L versus 1670 (700-7290) L] was unchanged. In the morbidly obese versus control subjects, respectively, the single-dose median oseltamivir carboxylate CL/F [22 (17-40) L/h versus 23 (12-33) L/h], AUC(0-∞) [3100 (1700-4100) ng·h/mL versus 3000 (2100-5900) ng·h/mL] and V/F [200 (130-370) L versus 260 (150-430) L] were similar. Similar results for oseltamivir and oseltamivir carboxylate CL/F, AUC₀₋₁₂ and V/F values were observed in the multiple-dose study. With single and multiple dosing, the systemic exposure to oseltamivir is decreased but that of oseltamivir carboxylate is largely unchanged. Based on these pharmacokinetic data, an oseltamivir dose adjustment for body weight would not be needed in morbidly obese individuals.