Mechanism and Origins of Enantioselectivity of Iridium-Catalyzed Intramolecular Silylation of Unactivated C(sp3)-H Bonds.
Density functional theory calculations were performed to investigate the iridium-catalyzed intramolecular silylation of unactivated C(sp3)-H bonds. The computations show that the in situ generated iridium(III) silyl dihydride species is the active catalyst, from which the followed migratory insertion and the transmetalation would generate the iridium(III) disilyl hydride species. The reaction was found to take place through an Ir(III)/Ir(V) catalytic cycle, and the C(sp3)-H bond oxidative addition constitutes the rate- and enantioselectivity-determining step. The steric repulsion and C-H···π interaction were found to account for the experimentally observed enantioselectivity.


Orientational disorder in Lambda-cobalt(III) sepulchrate trinitrate.
The crystal structure of Lambda-(1,3,6,8,10,13,16,19-octaazabicyclo[6.6.6]eicosane)cobalt(III) trinitrate, [Co(C(12)H(30)N(8))](NO(3))(3), consists of a sepulchrate moiety that serves as a macrobicyclic nitrogen cage for the Co(3+) cation, which is six-coordinated by N atoms, and three nitrate anions. The Co-sepulchrate group lies on a threefold axis (site symmetry 32), as do two symmetry-related and ordered nitrate groups (site symmetry 3), with which it is connected via N-H...O hydrogen bonds [Co-N = 5.1452 (12) A]. The third nitrate group is disordered as a result of symmetry requirements around the origin (site symmetry 32), and is further away from the Co-sepulchrate cage [Co-N = 6.3160 (8) A]. The structure is described by applying orientational disorder over six equivalent orientations for the disordered nitrate group, which is considered as an ideal planar molecule of regular trigonal geometry with its molecular plane rotated out of the ab plane and the molecular centre of gravity slightly shifted away from the origin. This new model for disorder clearly improves a previous crystal structure determination.


Serous ovarian neoplastic amylase (SONA): a potentially useful marker for serous ovarian tumors.
A series of cystic ovarian tumors was studied with regard to amylase activity in the cyst fluid. Large amounts of amylase activity were present only in those patients with endosalpingeal-type lining epithelium (serous ovarian neoplasms). The amylase activity from two such patients was further characterized using G75 Sephadex chromatography, DEAE Sephadex chromatography, agarose gel chromatography, isoelectric focusing, and heat inactivation studies. Serous ovarian neoplastic amylase (SONA) exhibited properties different from amylases of pancreatic and salivary gland origin. Serous ovarian neoplastic amylase (SONA) may be a pancreatic and salivary gland origin. Serous ovarian neoplastic amylase (SONA) may be a useful biochemical marker in diagnosing and managing patients with serous ovarian neoplasms.


[Influence on Strychni Semen's Analgesic Effect and Toxicity of Milk-Impregnated- Processing-Technology of Traditional Uighur Medicine].
To investigate the effects of different processing methods on analgesic effect and toxicity of Strychni Semen, and to provide the scientific basis of milk-impregnated-processing-technology of traditional Uighur medicine for toxic medicines. Three different methods, frying with sand of traditional Chinese medicine (1), cooled milk-impregnated-processing-technology of traditional Uighur medicine (2), and heated milk-impregnated-processing-technology of traditional Uighur medicine (3) were used to process raw Strychni Semen and the processed products were compared with those in the raw drug (4). Karber method was used to caculate the LD50. The LD50 of (4), (1), (2) and (3)were 273.0, 289.3, 289.3 and 339.2 mg/kg,successively. Low dose group of heated milk-impregnated-processing-technology, low and high dose groups of cooled milk-impregnated-processing-technology had significant inhibition on the acetic acid-induced writhing reaction in mice (P < 0.05). Strychni Semen processed by cooled and heated milk can enhance the analgesic effect in mice while improving the LD50 of mouse, which illustrates milk-impregnated-processing- technology's pharmacological mechanism on efficacy enhancing and toxicity reducing of Strychni Semen.


[Arrest of rhythmic disorders in an outpatient polyclinic].
The material has been collected for two years and covers 48 case with paroxysm of supraventricular paroxysmal tachycardia (28), auricular fibrillation (4), ventricular tachycardia (2), group and polytopic ventricular extrasystoles (14), with organic heart diseases (30) and with non-organic heart diseases (18). The paroxysms were coped with isolanid , tachmalin and lidocain , sow intravenous infusion under constant ECG, auscultatory and hemodynamic control and monitors. The number of the successfully coped paroxysms is 43. It proved to be possible to interrupt the rhythm disturbances under the conditions of non-integrated polyclinic in case of properly equipped functional consulting room. In this way the problem of early and effective treatment of rhythm disturbances under polyclinical conditions is solved, hence--avoiding both the unnecessary hospitalization of part of those patients and the delay in the initiation of effective treatment of the other part of them. The early diagnosis and adequate therapeutic behaviour of the physician towards the patient at their first contact till the moment of their transportation and hospitalization proved to be of particular significance. The out-patient department interruption of rhythm disorders should very cautiously be performed, particularly in case of ventricular tachycardia and polytopic extrasystoles, that being only their initial treatment.


Altered Phenotypes of Colonic and Peripheral Blood Follicular Helper and Follicular Cytotoxic T Cells in Mice with DSS-Induced Colitis.
Follicular helper T (Tfh), follicular regulatory T (Tfr), and follicular cytotoxic T (Tfc) cells play important roles in autoimmune diseases. Nevertheless, their changes of functional phenotypes in ulcerative colitis (UC), most importantly, their changes in colon tissue as the target-organ, have not been explored. DSS-colitis was induced in Balb/c mice and lymphocytes were collected from spleen, mesenteric lymph nodes, peripheral blood and colon. Tfh, Tfr, and Tfc cells were analyzed using flow cytometry based on their CD4+CXCR5+FOXP3-Tfh, CD4+CXCR5+FOXP3+Tfr and CD8+CXCR5+Tfc expressions. Various functional characterization markers including CD44, CD62L, TIGIT, CD226, PD-1, ICOS, Helios, CTLA-4 and Bcl6 were analyzed in the T cell subsets of the organs. Tfh and Tfr cells in the colon were significantly increased in DSS-colitis mice. Additionally, the proportions of Tfr and Tfc cells in the peripheral blood were also increased, while Tfc cell proportions in the colon were decreased. The proportion of naïve cells in the Tfh, Tfr and Tfc cells in the colon and peripheral blood decreased, while the proportion of effector memory T cells increased. The TIGIT+CD226-Tfh and Tfc cells were upregulated in the colon of DSS-colitis mice. The PD-1+, ICOS+ and PD-1+ICOS+ Tfh cells were increased in both the colonic and peripheral blood Tfh and Tfc of DSS-colitis mice. The Bcl6+ proportions in the Tfh and Tfr were increased in the colon of DSS-colitis mice. The colonic and peripheral blood Tfh and Tfc cells of DSS-colitis mice have a significantly activated T cell phenotype, which may play a significant role in the pathogenesis of UC.


Overexpression of a glutamine synthetase gene affects growth and development in sorghum.
Nitrogen is a primary macronutrient in plants, and nitrogen fertilizers play a critical role in crop production and yield. In this study, we investigated the effects of overexpressing a glutamine synthetase (GS) gene on nitrogen metabolism, and plant growth and development in sorghum (Sorghum bicolor L., Moench). GS catalyzes the ATP dependent reaction between ammonia and glutamate to produce glutamine. A 1,071 bp long coding sequence of a sorghum cytosolic GS gene (Gln1) under the control of the maize ubiquitin (Ubq) promoter was introduced into sorghum immature embryos by Agrobacterium-mediated transformation. Progeny of the transformants exhibited higher accumulation of the Gln1 transcripts and up to 2.2-fold higher GS activity compared to the non-transgenic controls. When grown under optimal nitrogen conditions, these Gln1 transgenic lines showed greater tillering and up to 2.1-fold increase in shoot vegetative biomass. Interestingly, even under greenhouse conditions, we observed a seasonal component to both these parameters and the grain yield. Our results, showing that the growth and development of sorghum Gln1 transformants are also affected by N availability and other environmental factors, suggest complexity of the relationship between GS activity and plant growth and development. A better understanding of other control points and the ability to manipulate these will be needed to utilize the transgenic technology to improve nitrogen use efficiency of crop plants.


Interleukin 10 hampers endothelial cell differentiation and enhances the effects of interferon α on lupus endothelial cell progenitors.
SLE is an autoimmune disease characterized by autoantibody generation, organ damage and an increased risk of cardiovascular disease. Generally considered an anti-inflammatory cytokine, IL-10 is increased in SLE and correlates with poor cardiovascular outcomes in the general population. The aim of this study was to explore the putative role of IL-10 in modulating endothelial function in SLE by examining the effects of this cytokine on endothelial progenitor cell/circulating angiogenic cell (EPC/CAC) differentiation. Human and murine control and lupus EPCs/CACs were differentiated into mature endothelial cells (ECs) in the presence or absence of graded concentrations of recombinant IL-10 with or without recombinant IFN-α or a neutralizing antibody to IL-10. IL-10-deficient mice were examined to assess the role of this cytokine in type I IFN-mediated inhibition of EC differentiation and neo-angiogenesis using an in vivo Matrigel plug assay. Serum IL-10 concentrations were measured via ELISA. IL-10 hampers EC differentiation in a dose-dependent manner. In murine EPC cultures, IL-10 is required to observe the inhibitory effects of type I IFNs on EPC function and neo-angiogenesis. In human SLE EPC/CAC cultures, neutralization of IL-10 significantly improved the differentiation of EPCs, and IL-10 enhanced type I IFN-mediated EPC/CAC dysfunction. The presence of IL-10 in serum inversely correlated with EPC/CAC function in SLE but not in control cells. IL-10 interferes with endothelial differentiation and may enhance the effects of type I IFN on vascular repair in SLE. IL-10 may be a relevant target for improving cardiovascular risk in SLE.


Is there sufficient evidence to supplement omega-3 fatty acids to increase muscle mass and strength in young and older adults?
Omega-3 (ω-3) is a polyunsaturated fatty acid with anti-inflammatory properties that presents three main forms: alpha-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid. Recently, studies performed in both young and older adults suggest that ω-3 may improve gains in muscle mass and/or enhance physical function. Thus, the aim of this narrative review was to evaluate the current evidence of ω-3 intake/supplementation on muscle/lean mass (LM) and physical function in young and older adults, and draw research-based conclusions as to the practical implications of findings. We first assessed whether ω-3 intake is associated with muscle mass and strength (observational studies), and then sought to determine whether evidence shows that supplementation of ω-3 increases muscle protein synthesis, LM and strength in adults and older adults (interventional studies). The search was carried out in PubMed and Scopus databases for the periods between 1997 and November 2018. The following keywords were used alone and in combination: ω-3, fish oil, muscle protein synthesis, muscle mass, lean mass, body composition, and physical function. In general, the evidence is mixed as to the effects of ω-3 supplementation on muscle mass in sedentary young and older adults; the hypertrophic effects of supplementation when combined with resistance training remain equivocal. Moreover, there is conflicting evidence as to whether supplementation confers a beneficial effect on muscle function in older adults. Importantly, this conclusion is based on limited data and more studies are needed before ω-3 supplementation can be recommended as a viable strategy for such purposes in clinical practice.


[The role of serum soluble interleukin 2 receptor (sIL-2R) levels in patients with renal cell carcinoma].
The correlation between the serum soluble interleukin-2 receptor (SIL-2R) levels and clinical stage is demonstrable in a variety of non-Hodgkin lymphomas. The prognostic significance of sIL-2R levels in the serum of patients with renal cell carcinoma (RCC) was investigated. sIL-2R were measured in patients with RCC (n=39) and normal control (n=6) by the enzyme immunoassay technique. Cases of RCC were classified according to the clinical stage, pathological grade and growth type. The IL-2R expression of RCC was evaluated by RT-PCR. The serum sIL-2R levels of patients with RCC showed significantly higher values than those of controls (p < 0.05). The serum sIL-2R levels in RCC were closely associated with the stage, grade and growth type of disease. The patients with high serum sIL-2R level (> = 1,000 U/L) exhibited a significantly poorer prognosis than those with low serum sIL-2R level (<1,000 U/L). The band of IL-R was detected only by using the template from the mRNA extracted from a resected tumor tissue of the RCC but not from the RCC cell lines. It was suggested that the measurement of serum sIL-2R levels is useful for predicting the prognosis.


"Drug" Discovery with the Help of Organic Chemistry.
The first step in "drug" discovery is to find compounds binding to a potential drug target. In modern medicinal chemistry, the screening of a chemical library, structure-based drug design, and ligand-based drug design, or a combination of these methods, are generally used for identifying the desired compounds. However, they do not necessarily lead to success and there is no infallible method for drug discovery. Therefore, it is important to explore medicinal chemistry based on not only the conventional methods but also new ideas. So far, we have found various compounds as drug candidates. In these studies, some strategies based on organic chemistry have allowed us to find drug candidates, through 1) construction of a focused library using organic reactions and 2) rational design of enzyme inhibitors based on chemical reactions catalyzed by the target enzyme. Medicinal chemistry based on organic chemical reactions could be expected to supplement the conventional methods. In this review, we present drug discovery with the help of organic chemistry showing examples of our explorative studies on histone deacetylase inhibitors and lysine-specific demethylase 1 inhibitors.


Calcium-dependent protein kinase CPK31 interacts with arsenic transporter AtNIP1;1 and regulates arsenite uptake in Arabidopsis thaliana.
Although arsenite [As(III)] is non-essential and toxic for plants, it is effectively absorbed through various transporters into the roots. Here we identified a calcium-dependent protein kinase (CPK31) response for As(III) tolerance in Arabidopsis. We identified CPK31 as an interacting protein of a nodulin 26-like intrinsic protein (NIP1;1), an aquaporin involved in As(III) uptake. Similarly to the nip1;1 mutants, the loss-of-function mutants of CPK31 improved the tolerance against As(III) but not As(V), and accumulated less As(III) in roots than that of the wild-type plants. The promoter-β-glucuronidase and quantitative Real-Time PCR analysis revealed that CPK31 displayed overlapping expression profiles with NIP1;1 in the roots, suggesting that they might function together in roots. Indeed, the cpk31 nip1;1 double mutants exhibited stronger As(III) tolerance than cpk31 mutants, but similar to nip1;1 mutants, supporting the idea that CPK31 might serve as an upstream regulator of NIP1;1. Furthermore, transient CPK31 overexpression induced by dexamethasone caused the decrease in As(III) tolerance of transgenic Arabidopsis lines. These findings reveal that CPK31 is a key factor in As(III) response in plants.


Effects of a Group Psychoeducation Program on Self-Stigma, Empowerment and Perceived Discrimination of Persons with Schizophrenia.
Self-stigma adversely affects recovery from schizophrenia. Analyses of self stigma reduction programs discovered that few studies have investigated the impact of education about the illness on self-stigma reduction. The objective of this study was to determine whether psychoeducation based on the principles of recovery and empowerment using therapeutic group factors assists in reduction of self-stigma, increased empowerment and reduced perception of discrimination in patients with schizophrenia. 40 patients participated in psychoeducation group program and were compared with a control group of 40 patients placed on the waiting list for the same program. A Solomon four group design was used to control the influence of the pretest. Rating scales were used to measure internalized stigma, empowerment and perception of discrimination. Two-way analysis of variance was used to determine the main effects and interaction between the treatment and pretest. Simple analysis of variance with repeated measures was used to additionally test effect of treatment onself-stigma, empowerment and perceived discrimination. The participants in the psychoeducation group had lower scores on internalized stigma (F(1,76)=8.18; p<0.01) than the patients treated as usual. Analysis also confirmed the same effect with comparing experimental group before and after psychoeducation (F(1,19)=5.52; p<0.05). All participants showed a positive trend for empowerment. Psychoeducation did not influence perception of discrimination. Group psychoeducation decreased the level of self stigma. This intervention can assist in recovery from schizophrenia.


[Social networks in schizophrenic disorders--a review].
In the fifties the "social network"-concept was developed in order to improve the analysis of the structure of different social groups; later on, its emphasis has shifted to the study of "personal networks", that deal with the structure of the social relations of a "focal individual". In the latter sense the term "social network" will be used in this paper. Social networks are discussed in terms of morphological characteristics such as the size or the number of clusters as well as in terms of interactional characteristics such as the number of social contacts of the focal person. Studies concerning the social networks of schizophrenics that have been carried out so far showed the following results: In comparison with the social networks of the mentally healthy those of schizophrenic patients are markedly smaller in size and contain a smaller number of clusters. The proportion of family members in the social networks of schizophrenics is higher than in those of the mentally healthy. Social relations of the latter generally show a more complex structure than those of the schizophrenics. The social networks of schizophrenics patients with multiple admissions are generally smaller than those of first admission schizophrenic patients who also have more extrafamilial contacts. -The last section of this paper discusses methodical problems of the existing studies that deal with the social networks of schizophrenic patients; some suggestions are made concerning the application of the network-concept to psychiatric therapy.


Papillary thyroid cancer in struma testis with malignant transformation in the lung associated with trisomy 17 successfully treated with total thyroidectomy and radioiodine ablation.
Struma testis is a rare entity, and there are only few reports on the malignant transformation of a testicular teratoma to papillary thyroid carcinoma in the literature. In this report, we describe the malignant transformation of struma testis with distant lung metastasis associated with trisomy 17 and a coexisting papillary microcarcinoma in the thyroid. A 56-year-old man presented after a left orchiectomy for an undescended left testicle. Pathologic examination identified a monodermal teratoma composed of thyroid parenchyma and associated with a 1.7-cm papillary thyroid carcinoma. Further evaluation showed a pulmonary mass on a chest CT scan. Total thyroidectomy revealed a 0.5-mm focus of papillary thyroid cancer, and removal of the lung mass confirmed metastatic papillary thyroid cancer. Array-comparative genomic hybridization of both tumors showed trisomy 17 in the struma testes and the lung metastasis. The patient responded well to radioactive iodine ablation and has no evidence of cancer 3 years later. To our knowledge, this is the first case of papillary thyroid cancer in struma testes metastatic to the lung. It highlights the difficulties in treating these patients. Surgery to remove cancer foci, followed by radioactive iodine ablation, resulted in an excellent response in our patient. Interestingly, trisomy 17, which has so far been observed only in noninvasive thyroid nodules, was associated with pulmonary metastasis in our patient.


Nickel/cobalt oxide-decorated 3D graphene nanocomposite electrode for enhanced electrochemical detection of urea.
A NiCo2O4 bimetallic electro-catalyst was synthesized on three-dimensional graphene (3D graphene) for the non-enzymatic detection of urea. The structural and morphological properties of the NiCo2O4/3D graphene nanocomposite were characterized by X-ray diffraction, Raman spectroscopy, and scanning electron microscopy. The NiCo2O4/3D graphene was deposited on an indium tin oxide (ITO) glass to fabricate a highly sensitive urea sensor. The electrochemical properties of the prepared electrode were studied by cyclic voltammetry. A high sensitivity of 166 μAmM(-)(1)cm(-)(2) was obtained for the NiCo2O4/3D graphene/ITO sensor. The sensor exhibited a linear range of 0.06-0.30 mM (R(2)=0.998) and a fast response time of approximately 1.0 s with a detection limit of 5.0 µM. Additionally, the sensor exhibited high stability with a sensitivity decrease of only 5.5% after four months of storage in ambient conditions. The urea sensor demonstrates feasibility for urea analysis in urine samples.


Response of broiler strains differing in body fat to inadequate methionine: live performance and processing yields.
Ross x Arbor Acres (RxAA) and Steggles x Arbor (SxAA) chicks were given all nutrients as advocated by NRC (1984) except for methionine. Corn and soybean meal were the sole CP sources, and both strains were compared when feeds were adequate and deficient in methionine (0 to 3 wk, .65 vs .42% with 24.2% CP and 3.20 kcal AME/g; 3 to 6 wk, .54 vs .46% with 20.7% CP and 3.21 kcal AME; and 6 to 8 wk, .35 vs .30% with 17.8% CP and 3.19 kcal AME, respectively). Cystine exceeded NRC (1984) recommendation with all feeds. Live weights of RxAA broilers were heavier throughout the experiment, but SxAA had the advantage in feed conversion. Adverse effects of low methionine on weight gain were apparent only during the first 6 wk, and SxAA responded to the deficiency more than RxAA from 0 to 3 wk. The SxAA birds had less abdominal fat when processed at both 6 and 8 wk than RxAA. Low methionine increased fat proportions at 6 wk but not at 8 wk. Percentage chilled carcass yield without abdominal fat was similar for each strain and decreased as a result of low methionine at both ages. Low methionine also reduced proportions of skinless boneless breast meat but only at 6 wk and particularly in SxAA birds. The increased ability of RxAA birds to deposit fat enabled additional feed intake, in turn, minimizing repercussion of inadequate methionine.


Utilization and Outcomes of the Nikaidoh, Rastelli, and REV Procedures: An Analysis of The Society of Thoracic Surgeons Congenital Heart Surgery Database.
Aortic root translocation (Nikaidoh), Rastelli, and réparation à l'etage ventriculaire (REV) are repair options for transposition of the great arteries (TGA) with ventricular septal defects and left ventricular outflow tract obstruction (VSD-LVOTO) or double outlet right ventricle TGA type (DORV-TGA). This retrospective study using The Society of Thoracic Surgeons Congenital Heart Surgery Database evaluates surgical procedure utilization and outcomes of patients undergoing repair of TGA-VSD-LVOTO and DORV-TGA with a Nikaidoh, Rastelli, or REV procedure. A total of 293 patients underwent repair at 82 centers (January 2010 to June 2019). Most patients underwent a Rastelli (n = 165, 56.3%) or a Nikaidoh (n = 119, 40.6%) operation; only 3.1% (n = 9) underwent a REV. High-volume centers performed the majority of the repairs. Fewer Nikaidoh than Rastelli patients had prior cardiac operations (n = 57 [48.7%] vs n = 102 [63.0%]; P = .004). Nikaidohs had longer median cardiopulmonary bypass time (227 [interquartile range (IQR), 167-299] minutes vs 175 [IQR, 133-225] minutes; P < .001) and median aortic cross-clamp times (131 [IQR, 91-175] minutes vs 105 [IQR, 82-141] minutes; P = .0015). Operative mortality was 3.1% (95% confidence interval [CI], 1.0%-7.0%; n = 5) for Rastelli, 4.4% (95% CI, 1.4%-9.9%; n = 5) for Nikaidoh, and 11.1% (95% CI, 0.3%-48.3%, n = 1) for REV. The rates of cardiac arrest, unplanned reoperation, mechanical circulatory support, prolonged ventilation, and permanent pacemaker placement were higher in the Nikaidoh population but with 95% CIs overlapping those of the other procedures. Rastelli and Nikaidoh procedures are the prevalent repair strategies for patients with DORV-TGA and TGA-VSD-LVOTO. Most are performed at high-volume institutions, and early outcomes are similar.


Low incidence of limb-girdle muscular dystrophy type 2C revealed by a mutation study in Japanese patients clinically diagnosed with DMD.
Limb-girdle muscular dystrophy type 2C (LGMD2C) is an autosomal recessive muscle dystrophy that resembles Duchenne muscular dystrophy (DMD). Although DMD is known to affect one in every 3500 males regardless of race, a widespread founder mutation causing LGMD2C has been described in North Africa. However, the incidence of LGMD2C in Japanese has been unknown because the genetic background remains uncharacterized in many patients clinically diagnosed with DMD. We enrolled 324 patients referred to the Kobe University Hospital with suspected DMD. Mutations in the dystrophin or the SGCG genes were analyzed using not only genomic DNA but also cDNA. In 322 of the 324 patients, responsible mutations in the dystrophin were successfully revealed, confirming DMD diagnosis. The remaining two patients had normal dystrophin expression but absence of gamma-sarcoglycan in skeletal muscle. Mutation analysis of the SGCG gene revealed homozygous deletion of exon 6 in one patient, while the other had a novel single nucleotide insertion in exon 7 in one allele and deletion of exon 6 in the other allele. These mutations created a stop codon that led to a gamma-sarcoglycan deficiency, and we therefore diagnosed these two patients as having LGMD2C. Thus, the relative incidence of LGMD2C among Japanese DMD-like patients can be calculated as 1 in 161 patients suspected to have DMD (2 of 324 patients = 0.6%). Taking into consideration the DMD incidence for the overall population (1/3,500 males), the incidence of LGMD2C can be estimated as 1 per 560,000 or 1.8 per million. To the best of our knowledge, this is the first study to demonstrate a low incidence of LGMD2C in the Japanese population.


SIZE, SYMMETRY, AND SEXUAL SELECTION IN THE HOUSEFLY, MUSCA DOMESTICA.
Relationships between measures of body size, asymmetry, courtship effort, and mating success were investigated in the housefly, Musca domestica (Diptera: Muscidae). A previous study indicated that both male and female flies with low fluctuating asymmetry enjoyed enhanced mating success. The aim of our investigations was to determine whether the greater success of symmetrical males is due to variation in male mating effort or to female choice and whether males exhibited mate choice. However, our study found directional rather than fluctuating asymmetry with both male and female flies having, on average, longer left wings than right. Also, asymmetry was not related to mating success in either sex. Rather, both males and females appeared to exhibit choice on the basis of the size of potential mates, with males preferring females with long bodies and females preferring heavy males. Possible benefits from choice of large mates are discussed. The initial mating strikes (in which the male leaps onto the back of the female) did not appear to be targeted according to female morphology, and their frequency did not vary according to male morphology. This indicates that mate choice by both sexes according to size probably occurs during the later stages of courtship, when the flies are in intimate contact. Possible reasons for the absence of choice according to asymmetry are discussed.


Studies of idiotypic antibodies. Production and characterization of autoantiidiotypic antisera.
Rabbits were immunized with a hapten-protein conjugate and sera were collected for 189 days. The antihapten antibodies were purified by affinity chromatography, then the same animal that synthesized the antibody was reinjected with polymerized F(ab')(2) fragments of antihapten antibodies. Sera were collected after autoimmunization and tested by an indirect radioimmunoassay technique for reaction with [(125)I]F(ab')(2) fragments of the original antihapten antibody. Results showed that each individual responded to its own F(ab')(2) and the antisera were specific for antihapten antibodies of that individual. Quantitative allotype assays established the immunoglobulin nature of the labeled test antigen. Inhibition assays showed that the reaction was specifically inhibitable with hapten. The relationship of this system with other idiotypic systems and the possible autoimmune implications of autoantiidiotypic antibodies are discussed.


Idiopathic autonomic neuropathy: clinical, neurophysiologic, and follow-up studies on 27 patients.
We evaluated the natural history, electrophysiologic characteristics, spectrum of autonomic involvement, pathology, and laboratory features in 27 patients with idiopathic autonomic neuropathy who were followed up for a mean of 32 months. The typical features of idiopathic autonomic neuropathy include the absence of an associated disease, frequent history of preceding infection, and acute or subacute onset with a monophasic course. The spectrum of autonomic involvement ranges from panautonomic to selective adrenergic or cholinergic failure. There is infrequent involvement of somatic nerve fibers as assessed by routine nerve conduction studies. Pathologic features include the presence of a small inflammatory mononuclear cell infiltrate in the epineurium. Recovery tends to be gradual and frequently incomplete. The acute onset, frequent antecedent viral infection, selectivity of involvement by fiber type and autonomic level, and presence of perivascular mononuclear cell infiltration suggest that the underlying mechanism is likely to be immune-mediated. These observations may justify plasma exchange or other immunosuppressive modalities as early therapeutic intervention in patients with progressive disability.


Three and two hadron correlations in sq.rt.(S(NN))=200 GeV proton-proton and nucleus-nucleus collisions.
We compare the azimuthal correlations arising from three and two hadron production in p+p and Au+Au collisions at sq.rt.(S(NN))=200 GeV. We show that in Au+Au, the two away side partons in two-to-three processes have in average a smaller and a greater path length than the average path length of the away-side parton in two-to-two processes. Since in average the particle with the shortest path length in two-to-three processes loses less energy, with respect to the away-side particle in two-to-two processes, this effect leads to a relative enhancement of the ratio of two-to-three to two-to-two processes in Au+Au compared to p+p collisions. We argue that this phenomenon may be responsible for the shape of the away side in azimuthal correlations at the Relativistic Heavy-Ion Collider.


Perturbation transfer from the front to rear surface of laser-irradiated targets.
We present experimental results on the perturbation transfer of laser irradiated planar foils. Perturbed polystyrene foils were irradiated directly by laser at intensity of 6 x 10(13) W/cm(2). We measured perturbations on the foils by side-on x-ray backlighting technique. Perturbations on the rear surface due to the rippled shock front were observed just after the shock breakout. We also observed feed-through of perturbations on the laser-irradiated surface that grows due to the Rayleigh-Taylor instability.


Association of body mass index with mortality and functional outcome after acute ischemic stroke.
The relation between obesity and stroke outcome has been disputed. This study was aimed to determine the association of body mass index (BMI) with mortality and functional outcome in patients with acute ischemic stroke. Data were from a national, multi-centre, prospective, hospital-based register: the ChinaQUEST (Quality Evaluation of Stroke Care and Treatment) study. Of 4782 acute ischemic stroke patients, 282 were underweight (BMI < 18.5 kg/m2), 2306 were normal-weight (BMI 18.5 to < 24 kg/m2), 1677 were overweight (BMI 24 to <28 kg/m2) and 517 were obese (BMI ≥ 28 kg/m2). The risks of death at 12 months and death or high dependency at 3 and 12 months in overweight (HR: 0.97, 95% CI: 0.78-1.20; OR: 0.93, 95% CI: 0.80-1.09; OR: 0.95, 95% CI: 0.81-1.12) and obese patients (HR: 1.07, 95% CI: 0.78-1.48; OR: 0.96, 95% CI: 0.75-1.22; OR: 1.06, 95% CI: 0.83-1.35) did not differ from normal-weight patients significantly after adjusting for baseline characteristics. Underweight patients had significantly increased risks of these three outcomes. In ischemic stroke patients, being overweight or obese was not associated with decreased mortality or better functional recovery but being underweight predicted unfavourable outcomes.


The Challenges of Gastric Cancer Surgery during the COVID-19 Pandemic.
The aim of this study was to quantify the impact of the COVID-19 pandemic on the surgical treatment of patients with gastric cancer. Data from patients undergoing surgery for gastric cancer during the pandemic were analyzed and the results obtained were compared with the corresponding periods of 2016-2017 and 2018-2019. Various parameters were taken into consideration and their dynamics highlight significant changes in the pandemic year compared with the two pre-pandemic periods. Statistical analysis revealed a marked decrease in the number of surgeries performed during the pandemic (p < 0.001). Severe prognostic factors for gastric cancer, including weight loss and upper gastrointestinal hemorrhage, were associated with an increased number of postoperative fistulas, while emesis was statistically correlated with a more advanced cancer stage (p < 0.011). There was also a reduction in the total duration of hospitalization (p = 0.044) and postoperative hospitalization (p = 0.047); moreover, the mean duration of surgical intervention was higher during the pandemic (p = 0.044). These findings provide evidence for the significant changes in clinical and therapeutic strategies applied to patients undergoing surgery for gastric cancer during the study period. The ongoing pandemic has exerted a substantial and complex impact, the full extent of which remains yet to be fully comprehended.


[A case of Bell's palsy associated with peginterferon Alfa-2a and ribavirin therapy for chronic hepatitis C virus infection].
Pegylated interferon alfa-2a (PEG-IFN) and ribavirin combination therapy is the first line treatment for chronic HCV infection. There are four reports of Bell's palsy associated with interferon-alpha (IFN-alpha) and ribavirin therapy. We report here a case of Bell's palsy that occurred in a patient with chronic HCV infection during combination PEG-IFN and ribavirin therapy. The patient was 49-year-old man with chronic hepatitis C for 2 years. The liver biopsy showed grade 1 and stage 1. Therapy with PEG-IFN (Pegasys) 180 microgram/week and ribavirin 1200 mg/day was initiated. After 3 weeks of treatment, the patient showed a loss of muscular tone on the left side of his face. A diagnosis of Bell's palsy was made, and the PEG-IFN and ribavirin therapy was stopped. Prednisolone 45 mg/d was given and then tapered for 8 weeks. His palsy improved over 6 weeks.


Host cell protein dynamics in recombinant CHO cells: impacts from harvest to purification and beyond.
During the production of recombinant protein products, such as monoclonal antibodies, manufacturers must demonstrate clearance of host cell impurities and contaminants to appropriate levels prior to use in the clinic. These include host cell DNA and RNA, product related contaminants such as aggregates, and importantly host cell proteins (HCPs). Despite the importance of HCP removal, the identity and dynamics of these proteins during cell culture and downstream processing (DSP) are largely unknown. Improvements in technologies such as SELDI-TOF mass spectrometry alongside the gold standard technique of ELISA has allowed semi-quantification of the total HCPs present. However, only recently have techniques been utilized in order to identify those HCPs present and align this with the development of approaches to monitor the dynamics of HCPs during both fermentation and downstream processing. In order to enable knowledge based decisions with regards to improving HCP clearance it is vital to identify potential problematic HCPs on a cell line and product specific basis. Understanding the HCP dynamics will in the future help provide a platform to rationally manipulate and engineer and/or select suitable recombinant CHO cell lines and downstream processing steps to limit problematic HCPs.


Systematic review: Can non-mydriatic cameras accurately detect diabetic retinopathy?
Diabetes puts many individuals at risk for developing diabetic retinopathy (DR). Non-mydriatic (NM) retinal photography without pharmacological pupil dilation can be used to detect DR, however, its value in a general clinical setting has not been established. The objective of this review is to evaluate the validity of NM retinal photos, as compared to the reference standard of seven standard stereoscopic 30 degree field photographs (7SF), for their use of detecting DR in community-dwelling adults. English articles were identified through MEDLINE (1992-2016), EMBASE (1992-2016), Center for Disease Control and Prevention, Food and Drug Administration, Health Canada, and Google Scholar (1992-2016). Only studies that examined the validity of NM retinal photos, without pharmacological pupil dilation, as compared to 7SF, used in a community-dwelling adult population were included. Risk of bias was assessed using the QUADAS-2. Of the 368 articles identified in the search, 6 articles met eligibility requirements. Sensitivities ranged from 64 to 97.9% and specificities ranged from 65.6 to 98%. Studies that used multiple field images to detect DR in a younger population generally produced higher quality photos and more valid results. The strongest validity indicators were reported in studies capturing multiple field images.


PATTERNS OF DESCENT IN CLONAL LINEAGES AND THEIR MULTILOCUS FINGERPRINTS ARE RESOLVED WITH COMBINED GENE GENEALOGIES.
Clonal lineages in the filamentous ascomycete (fungi) Sclerotinia sclerotiorum were determined by analysis of genealogies of four loci: the intergenic spacer of the nuclear ribosomal repeat (IGS; approximately 4 kb), the translation elongation factor (EF-1α; approximately 300 bp), an anonymous region (44.11; approximately 700 bp), and the calmodulin gene (CAL; approximately 400 bp). Three of the four loci are physically unlinked. The combined analysis of the four loci provided the best estimate of phylogeny, which is consistent with a pattern of some recombination among clonal lineages against a background of predominant clonality. Comparison of gene genealogies with a phylogeny inferred from DNA fingerprints and a combined phylogeny of the entire dataset identified convergent or parallel changes in fingerprints. Analysis of the entire data matrix allowed us to resolve patterns of descent among clonal lineages that could not be inferred from fingerprints alone and to discern recent episodes of divergence that were not detected in gene genealogies. Prerequisites for applying this approach to other systems are a haploid context for inferring multiple gene genealogies (such as the mitochondrial genome) that indicate limited recombination and another data matrix that identifies recently evolved genotypes.


[Effects of wuzi yanzong pills on lipid in rats with alcohol-induced liver injury].
Experiments showed that in the rat model of alcohol-induced liver injury, a dosage of the pills (1-2g/kg, ig) could increase the cholesterol level, lower the triglyceride level, and improve the fatty degeneration and necrosis of liver (P < 0.05-0.01). The results suggest that the important mechanism of the pills in protecting and treating alcoholic fatty liver, lies in the regulation of metabolism of the lipid, especially of the triglyceride.


The rice enhancer of zeste [E(z)] genes SDG711 and SDG718 are respectively involved in long day and short day signaling to mediate the accurate photoperiod control of flowering time.
Recent advances in rice flowering studies have shown that the accurate control of flowering by photoperiod is regulated by key mechanisms that involve the regulation of flowering genes including Heading date1 (Hd1), Early hd1 (Ehd1), Hd3a, and RFT1. The chromatin mechanism involved in the regulation of rice flowering genes is presently not well known. Here we show that the rice enhancer of zeste [E(z)] genes SDG711 and SDG718, which encode the polycomb repressive complex2 (PRC2) key subunit that is required for trimethylation of histone H3 lysine 27 (H3K27me3), are respectively, involved in long day (LD) and short day (SD) regulation of key flowering genes. The expression of SDG711 and SDG718 is induced by LD and SD, respectively. Over-expression and down-regulation of SDG711 respectively, repressed and promoted flowering in LD, but had no effect in SD. By contrast, down-regulation of SDG718 had no effect in LD but delayed flowering in SD. SDG711 and SDG718 repressed OsLF (a repressor of Hd1) respectively in LD and SD, leading to a higher expression of Hd1 thus late flowering in LD and early flowering in SD. SDG711 was also found to be involved in the repression of Ehd1 in LD. SDG711 was shown to directly target to OsLF and Ehd1 loci to mediate H3K27me3 and gene repression. The function of the rice E(z) genes in LD repression and SD promotion of flowering suggests that PRC2-mediated epigenetic repression of gene expression is involved in the accurate photoperiod control of rice flowering.


Anomalous separate origin of left anterior descending coronary artery: presented as acute anterior myocardial infarction.
Coronary artery anomalies are rare presentations in primary percutaneous coronary interventions of acute myocardial infarction. Herein, we report the case of a 59-year-old man with acute anterior myocardial infarction who had anomalous separate origin of left anterior descending artery (LAD) and left circumflex artery (LCX) from the left coronary aortic sinus. Coronary angiography showed a normal right coronary artery and LCX, but no visualization of the LAD. After several unsuccessful attempts to cannulate the LAD, we found the LAD ostium located by the side of the LCX ostium. There was total occlusion at proxymal LAD. Coronary computed tomography angiography demonstrated the precise, separate origin of LAD and LCX from the left coronary aortic sinus.


Comparison of bedside assessed arm and leg fluid filtration determined by venous congestion plethysmography in perioperative cancer patients: An observational study investigating agreement.
In recent years, pathophysiology and clinical impact of microvascular fluid filtration has regained interest. As the latest data in surgical patients have been published almost 20 years ago, there is need for further research to better understand fluid filtration during the perioperative period. Venous congestion plethysmography (VCP) provides a rapid and noninvasive method, which has been shown suitable for the assessment of fluid filtration in limbs. Fluid filtration assessed by VCP can be obtained from forearm and calf measurement sites, while in many clinical situations a reduced access to the patient often restricts the measurements to patient's forearm. We aimed to investigate if fluid filtration obtained from forearm and calf measurement site is interchangeable in nonsedated perioperative patients.Fluid filtration by VCP was obtained simultaneously from forearm and calf in patients with ovarian cancer at 4 time points during the perioperative course and assessed by the difference of volume changes of the limb between third and sixth minutes (VC6-3min) during venous congestion. VC6-3min obtained from forearm and calf measurement sites was compared with respect to agreement and evaluated regarding the association with the presence of leg edema.A total of 74 paired measurements were analyzed in 29 patients. Forearm VC6-3min was significantly higher than calf VC6-3min (median [25th; 75th quartile], 0.6 (0.4; 0.9) vs 0.4 [0.3; 0.6] %, P = 0.008). Bland-Altman and Polar analysis revealed a poor agreement between forearm and calf VC6-3min at predefined time points and changes of VC6-3min during the perioperative course (bias +0.23%, limits of agreement [LOA] -1.1% to 1.6%; angular bias -2.5°, radial LOA -82° to +77°). Forearm VC6-3min was significantly increased in patients with presence of leg edema (0.7 (0.5; 1.0) vs 0.5 (0.4; 0.6) %, P < 0.001) while calf VC6-3min did not differ in patients with and without edema.This study indicates that forearm and calf measurement sites are not interchangeable when bedside assessing fluid filtration by VCP in nonsedated perioperative patients. Considering that only forearm fluid filtration was related to the presence of edema, forearm measurement site should be chosen as a primary site for assessing fluid filtration.


Prediction of Chain Propagation Rate Constants of Polymerization Reactions in Aqueous NIPAM/BIS and VCL/BIS Systems.
Microgels have a wide range of possible applications and are therefore studied with increasing interest. Nonetheless, the microgel synthesis process and some of the resulting properties of the microgels, such as the cross-linker distribution within the microgels, are not yet fully understood. An in-depth understanding of the synthesis process is crucial for designing tailored microgels with desired properties. In this work, rate constants and reaction enthalpies of chain propagation reactions in aqueous N-isopropylacrylamide/N,N'-methylenebisacrylamide and aqueous N-vinylcaprolactam/N,N'-methylenebisacrylamide systems are calculated to identify the possible sources of an inhomogeneous cross-linker distribution in the resulting microgels. Gas-phase reaction rate constants are calculated from B2PLYPD3/aug-cc-pVTZ energies and B3LYPD3/tzvp geometries and frequencies. Then, solvation effects based on COSMO-RS are incorporated into the rate constants to obtain the desired liquid-phase reaction rate constants. The rate constants agree with experiments within a factor of 2-10, and the reaction enthalpies deviate less than 5 kJ/mol. Further, the effect of rate constants on the microgel growth process is analyzed, and it is shown that differences in the magnitude of the reaction rate constants are a source of an inhomogeneous cross-linker distribution within the resulting microgel.


Protection from Radiation-Induced Pulmonary Fibrosis by Peripheral Targeting of Cannabinoid Receptor-1.
Radiation-induced pulmonary fibrosis (RIF) is a severe complication of thoracic radiotherapy that limits its dose, intensity, and duration. The contribution of the endocannabinoid signaling system in pulmonary fibrogenesis is not known. Using a well-established mouse model of RIF, we assessed the involvement of cannabinoid receptor-1 (CB1) in the onset and progression of pulmonary fibrosis. Female C57BL/6 mice and CB1 knockout mice generated on C57BL/6 background received 20 Gy (2 Gy/min) single-dose thoracic irradiation that resulted in pulmonary fibrosis and animal death within 15 to 18 weeks. Some C57BL/6 animals received the CB1 peripherally restricted antagonist AM6545 at 1 mg/kg intraperitoneally three times per week. Animal survival and parameters of pulmonary inflammation and fibrosis were evaluated. Thoracic irradiation (20 Gy) was associated with marked pulmonary inflammation and fibrosis in mice and high mortality within 15 to 18 weeks after exposure. Genetic deletion or pharmacological inhibition of CB1 receptors with a peripheral CB1 antagonist AM6545 markedly attenuated or delayed the lung inflammation and fibrosis and increased animal survival. Our results show that CB1 signaling plays a key pathological role in the development of radiation-induced pulmonary inflammation and fibrosis, and peripherally restricted CB1 antagonists may represent a novel therapeutic approach against this devastating complication of radiotherapy/irradiation.


[Cataract surgery in a patient with megalocornea - a case report].
10 describe a rare case ot a patient wiTh megalocorneas wno underwent cataract surgery. A 52 years old patient with extremely wide corneas 16 mm in diameter in both eyes, was admitted to our department with cataract diagnosis. Four other male members of his family are known to have megalocorneas. This suggests X-linked recessive inheritance. The visual acuities were; 0.9 with correction -3.00 Dsph in the right eye and 0.6 with correction -5.50 Dsph in the left eye. Mosaic corneal dystrophy and slight iridodonesis was found in both eyes. Posterior subcapsular cataracts were seen in both eyes with predominance in the left eye. Moreover, flat peripheral retinal detachment in the lower part of the eye fundus was found, which was presumably long-lasting. Phacoemulsification through the clear corneal temporal micro-incision of 1.8 mm and the foldable intraocular lens IOL) implantation in the left eye were performed. The IOL refractive power was calculated with 101 Master and with standard contact ultrasound biometry. Preventive laser photocoagulation of the retina was performed in the right eye. No intraoperative and postoperative complications were observed. Two weeks after cataract surgery corrected visual acuity in the left eye was ii] with correction + 1.00 Dsph. The patient was very satisfied with the surgery result. Phacoemulsification with an implantation of foldable 101 in patients with megalocornea may be a safe procedure with very good functional results. Precise IOL power calculation may be difficult to achieve.


A novel GNAS variant presents with disorders of GNAS inactivation and cardiomyopathy.
The GNAS gene (OMIM#139320), located on chromosome 20q13.2, encodes for the alpha-subunit of the stimulatory signaling protein, Gsα protein. GNAS variants with inactivating properties are associated with Albright's hereditary osteodystrophy (AHO) and when maternally inherited, pseudohypoparathyroidism 1a (OMIM#103580), which includes multiple hormone resistance. In this clinical report we describe a novel GNAS variant, c.159A>G, p.K53N, in an individual with features consistent with AHO and pseudohypoparathyroidism 1a and its segregation through multiple maternal relatives, including two genotype positive maternal first cousins who also display features classic for AHO. The proband developed unique features including cardiomyopathy which required a heart transplant at 5 years old and immune dysregulation resulting in multisystem organ failure and ultimately, death at the age of 18 years. Additional investigations exploring alternative explanations for the proband's presentation were pursued including whole genome sequencing which was negative. We postulate that the atypical features seen in the proband may have resulted from dysregulated Gsα signaling in cardiac tissue. Future studies are needed to explore the properties of the K53N GNAS variant and this proposed mechanism.


Effects of resveratrol and methylprednisolone on biochemical, neurobehavioral and histopathological recovery after experimental spinal cord injury.
To investigate the neuroprotective effect of resveratrol in an experimental spinal cord injury (SCI) model in rats. Male Wistar albino rats weighing 200-250 g were randomized into six groups. Weight-drop trauma was performed for SCI. Group 1 underwent laminectomy alone. Group 2 underwent laminectomy followed by SCI. Groups 3, 4, 5, and 6 underwent laminectomy followed by SCI and received resveratrol (100 mg/kg), methylprednisolone (MP) (30 mg/kg), resveratrol (100 mg/kg) plus MP (30 mg/kg), and ethanol (2%), respectively. The rats were divided into two subgroups for biochemical analysis (killed at 24 h after surgery) and for neurobehavioral and histopathological evaluation (killed at 6 weeks after surgery). Posttraumatic neurological recovery after surgery was recorded weekly. Groups 3 and 5 revealed significantly lower malon-dialdehyde, nitric oxide, xanthine oxidase, and higher glutathione levels than group 4 (P<0.05). Neurological recovery rates were significantly better in groups 3 and 5 than group 4 (P<0.05). When spinal trauma size ratios were compared, there was no significant difference between treatment groups. Resveratrol treatment revealed better biochemical recovery in the acute stage of trauma than MP treatment. Although resveratrol and combined treatment revealed better neurobehavioral recovery than MP treatment; resveratrol, MP, and combined treatment modalities improved histopathological recovery at the same level in the final stage of the experiment. Future studies involving different doses of resveratrol and different doses combinations with MP could promise better results as each drug has a different anti-oxidative mechanism of action.


[Fourth ventricule epidermoid cyst: about a case].
Epidermoid cysts are rare benign tumors developed by ectodermic inclusions. They are usually located at the level of the pontocerebellar angle, the parasellar region and the temporal fossa. They exceptionally develop at the level of the fourth ventricle We report the case of a 47-year old woman admitted for intracranial hypertension syndrome associated with walking disorders. The diagnosis of fourth ventricle epidermoid cyst was evoked based on diffusion MRI data then confirmed intraoperatively and by histologic examination. Subtotal surgical excision was performed due to capsule adhesion to the upper part of the V4 floor. After a 36-month follow-up, the patient showed no signs of tumor recurrence.


Slow release formulations of inhaled rifampin.
Rifampin microspheres were prepared by spray drying using either polylactic acid (PLA) or poly(lactic-co-glycolic acid) (PLGA) polymers in different drug to polymer ratios (90:10 to 5:95, w/w). The in-vitro release characteristics, particle-size distribution, and cytotoxicity (in an alveolar macrophage cell line) and pharmacokinetics in rats after pulmonary instillation were evaluated. Increasing the polymer content from 10% to 95% slowed down the in vitro drug release with PLGA particles showing a steeper change with increasing polymer content (100% to 20% drug release over 6 h) than PLA particles (88% to 42% drug release over 6 h). PLA microsphere formulations revealed lack of cytotoxicity and a mass median aerodynamic diameter (MMDA) of 2.22-2.86 mum, while PLGA particles were larger (MMDA of 4.67-5.11 mum). Pharmacokinetics differed among the formulations with the 10% PLA formulation showing a distinct sustained release (t (max) of 2 h vs 0.5 h of free drug) and a systemic bioavailability similar to that of free drug. Formulations with high polymer content showed a lower relative bioavailability (30%). This suggested that an optimal release rate existed for which a distinct amount of drug was delivered over an extended period of time.


Biopreparation of (-)-(1S,3R,4S,6S)-6-hydroxymenthol and (-)-(1S,3R,4S)-1-hydroxymenthol from 1-menthol by Rhizoctonia solani AG-1-IA and IB.
Microbial transformation of 1-menthol (1) by six isolates of soil-borne plant pathogenic fungi Rhizoctonia solani AG-1-IA (Rs24, Joichi-2 and RRG97-1) and AG-1-IB (TR22, R147 and 110.4) as a biocatalyst was investigated. Twenty one days precultivation of Rhizoctonia solani AG-1-IA Rs24 and AG-1-IB 110.4 showed excellent yield (98.5-98.6%) of (-)-(1S,3R,4S,6S)-6-hydroxymenthol (2) and (-)-(1S,3R,4S)-1-hydroxymenthol (3) from 1.


Catamenial Pain in Umbilical Hernia with Spontaneous Reduction: An Unusual Presentation of a Rare Entity.
Spontaneous umbilical endometriosis occurring in absence of any previous abdominal or uterine surgery is extremely atypical. Its association with umbilical hernia is very rare and hernia getting spontaneously resolved has not been reported in literature so far. Here we report a case of a patient with spontaneous umbilical endometriosis associated with umbilical hernia which led to spontaneous hernia reduction. This was also associated with multiple uterine fibromyoma and bilateral ovarian endometrioma which were simultaneously treated by total abdominal hysterectomy with bilateral salpingo-oopherectomy along with surgical excision of the endometriotic tissue and repair of the abdominal wall defect. To the best of our knowledge, this is the first described case of spontaneous umbilical hernia reduction due to development of endometriosis.


Therapeutic effect of bone marrow mesenchymal stem cells on cold stress induced changes in the hippocampus of rats.
The present study aims to evaluate the effect of bone marrow mesenchymal stem cells on cold stress induced neuronal changes in hippocampal CA1 region of Wistar rats. Bone marrow mesenchymal stem cells were isolated from a 6-week-old Wistar rat. Bone marrow from adult femora and tibia was collected and mesenchymal stem cells were cultured in minimal essential medium containing 10% heat-inactivated fetal bovine serum and were sub-cultured. Passage 3 cells were analyzed by flow cytometry for positive expression of CD44 and CD90 and negative expression of CD45. Once CD44 and CD90 positive expression was achieved, the cells were cultured again to 90% confluence for later experiments. Twenty-four rats aged 8 weeks old were randomly and evenly divided into normal control, cold water swim stress (cold stress), cold stress + PBS (intravenous infusion), and cold stress + bone marrow mesenchymal stem cells (1 × 10(6); intravenous infusion) groups. The total period of study was 60 days which included 1 month stress period followed by 1 month treatment. Behavioral functional test was performed during the entire study period. After treatment, rats were sacrificed for histological studies. Treatment with bone marrow mesenchymal stem cells significantly increased the number of neuronal cells in hippocampal CA1 region. Adult bone marrow mesenchymal stem cells injected by intravenous administration show potential therapeutic effects in cognitive decline associated with stress-related lesions.


Towards clinical application of pronuclear transfer to prevent mitochondrial DNA disease.
Mitochondrial DNA (mtDNA) mutations are maternally inherited and are associated with a broad range of debilitating and fatal diseases. Reproductive technologies designed to uncouple the inheritance of mtDNA from nuclear DNA may enable affected women to have a genetically related child with a greatly reduced risk of mtDNA disease. Here we report the first preclinical studies on pronuclear transplantation (PNT). Surprisingly, techniques used in proof-of-concept studies involving abnormally fertilized human zygotes were not well tolerated by normally fertilized zygotes. We have therefore developed an alternative approach based on transplanting pronuclei shortly after completion of meiosis rather than shortly before the first mitotic division. This promotes efficient development to the blastocyst stage with no detectable effect on aneuploidy or gene expression. After optimization, mtDNA carryover was reduced to <2% in the majority (79%) of PNT blastocysts. The importance of reducing carryover to the lowest possible levels is highlighted by a progressive increase in heteroplasmy in a stem cell line derived from a PNT blastocyst with 4% mtDNA carryover. We conclude that PNT has the potential to reduce the risk of mtDNA disease, but it may not guarantee prevention.


Review of skull base surgery in a Nigerian teaching hospital.
There is dearth of information on skull base surgery in Nigerians. This study was conducted to determine types of skull base lesions describe surgical approaches to the lesions and determine outcome of surgical management of the lesions over the study period. We retrospectively reviewed the case notes of the patients who underwent skull base neurosurgical procedures between January 2001 and June 2007 in our centre. We obtained information on demography, clinical presentation, diagnosis, cranial computerised tomography findings, type of surgery, intraoperative findings and outcome of surgical management at the time of discharge from the hospital. Brain tumours were diagnosed in 28 patients, head injuries in 9 patients and one patient each had anterior encephalocele and frontal sinus mucocele. Eighteen patients had frontal craniotomy, three patients had temporal craniotomy and two patients had lateral rhinotomy in addition to bifrontal craniotomy. Two patients had frontoorbitotomy while retrosigmoid craniectomy was performed in one patient. Thirty three patients showed significant postoperative improvement at discharge. Brain tumour was the most common indication for skull base surgery in our centre. These tumours were mainly located in the anterior cranial fossa. Frontal craniotomy was the most common surgical approach. Non-availability of modern neurosurgical facilities confined us to the use of mainly traditional approaches. The availability of these facilities will assist in improving our management outcome in the future.


European health policy challenges.
Few countries are immune to the international health care 'virus' of reform, with many countries regularly re-cycling changes that shift costs and benefits in ways that are arbitrary, inefficient and offer short term political palliation. Much of this activity has little evidence base and reveals lack of clarity in defining public policy goals, establishing trade-offs and aligning incentive structures with these objectives. Well established failures in health care delivery systems such as variations in medical practice and continuing absence of systematic outcome measurement, have persisted for decades as nations grapple inefficiently with recurring problems of expenditure inflation and waiting times. The lack of emphasis on evidence to inform the efficient management of chronic disease and the reduction of health inequalities is a product of perverse incentives and managerial inertia that maintains the incomes of powerful interest groups.


Sexual dimorphism of porcine amelogenins: male-specific amelogenins have strong adsorption properties onto apatite crystals.
The present studies were undertaken to investigate the sexual dimorphism of porcine amelogenins and to gain information as to whether excesses of male amelogenins, if any, possess functional significance in protein-crystal interactions. Enamel proteins, including the intact full-length amelogenins and their degraded polypeptides, were isolated from the secretory enamel of male and female pigs. To identify the amelogenins among the separated pools of male- and female-matrix proteins, rabbit anti-C13 and C25 peptide sera were used, which reacted specifically with the conserved C-terminal domain. Immunoblotting showed that a few extra members of the amelogenins, sharing common epitopes at the C-terminus, were recognized in male products. The apparent yield of the male amelogenins was only marginal, on the basis of their stained intensities on the gel, but the secreted male amelogenins demonstrated selective (probably the strongest among the amelogenins) adsorption properties onto apatite crystals. Reflecting the general symmetric electrophoretic profiles of the male- and female-enamel proteins in toto, there were no sex-linked differences in the protein-crystal interaction and the resulting regulatory function of crystal precipitation.


A comparative study on the phoE genes of three enterobacterial species. Implications for structure-function relationships in a pore-forming protein of the outer membrane.
The cloned phoE genes from Enterobacter cloacae and Klebsiella pneumoniae are normally expressed and regulated in Escherichia coli K-12, and their products are correctly assembled into the outer membrane. Differences between the three PhoE proteins were found with binding of two out of ten monoclonal antibodies directed against the cell-surface-exposed part and in pore characteristics, but not in phage receptor function. The DNA sequences of the E. cloacae and K. pneumoniae phoE genes were determined and used to predict the primary structures of the encoded proteins. In the upstream non-coding regions, which showed more variations among the three genes than the coding regions, conserved sequences were identified which might be involved in regulation of phoE gene expression. Comparison of the predicted PhoE primary structures revealed a high degree of homology, with 81% of the amino acid residues being identical in all three proteins. Four small variable regions were found where differences are the most pronounced, corresponding to regions which were previously predicted to be exposed at the cell surface. Implications of the sequence comparison for structure-function relationships in PhoE protein are discussed.


Update on the Genetics of Dystonia.
Mainly due to the advent of next-generation sequencing (NGS), the field of genetics of dystonia has rapidly grown in recent years, which led to the discovery of a number of novel dystonia genes and the development of a new classification and nomenclature for inherited dystonias. In addition, new findings from both in vivo and in vitro studies have been published on the role of previously known dystonia genes, extending our understanding of the pathophysiology of dystonia. We here review the current knowledge and recent findings in the known genes for isolated dystonia TOR1A, THAP1, and GNAL as well as for the combined dystonias due to mutations in GCH1, ATP1A3, and SGCE. We present confirmatory evidence for a role of dystonia genes that had not yet been unequivocally established including PRKRA, TUBB4A, ANO3, and TAF1. We finally discuss selected novel genes for dystonia such as KMT2B and VAC14 along with the challenges for gene identification in the NGS era and the translational importance of dystonia genetics in clinical practice.


Shear ordering in polymer photonic crystals.
Optical scattering spectra are recorded in situ on flowing colloidal polymeric nanocomposites which are sheared into photonic crystals at 150 degrees C using a high-pressure quartz-cell multipass rheometer. Broadband spectroscopy of the resonant Bragg scattering peak allows the direct observation of crystal formation and melting of monodisperse core-shell particles. A range of flow conditions of this solventless, highly viscous melt reveals four distinct regimes of crystal growth and decay which match a simple rheological model. Extraction of crystal thickness, order and lattice spacing are validated by one-dimensional electromagnetic simulations.


Universal pathogen-reduced plasma in elective open-heart surgery and liver resection.
ABO-incompatible transfusions and transfusion-related lung injury are today the leading transfusion-related causes of death in the developed world. Since anti-A and anti-B antibodies in plasma can give rise to serious, even fatal, transfusion reactions, ABO-identical/compatible plasma is indicated, but presents a logistical challenge and a risk for transfusion of incorrect plasma. In an effort to circumvent these problems, an ABO-independent universally applicable, pathogen-reduced plasma, Uniplas, has been developed and proven safe and efficacious for use in adults through prospective, randomized, controlled open-heart surgery studies and in prospective, parallel group, controlled liver resection studies. The results of these trials are presented and discussed in relation to solvent/detergent (SD) treated plasma, in general. The cost effectiveness of pathogen-reduced plasma is low because of the very low risk for transfusion transmitted viral infections in the developed world (US 2 to 9 million dollars per quality-adjusted life year). However, taking into account the combined safety of Uniplas with regard to transfusion-related lung injury, pathogen reduction and independence of ABO blood groups, the cost per gained life year is reduced to US 40,000 dollars to 100,000 dollars.


Sub-50 nm template fabrications for nanoimprint lithography using hydrogen silsesquioxane and silicon nitride.
The sub-50 nm templates are successfully fabricated using hydrogen silsesquioxane (HSQ) and silicon nitride on silicon substrate. The HSQ template is directly patterned by e-beam direct writing. The cured HSQ pattern is used for the template of nanoimprint process. The silicon nitride template is reactively ion etched by ZEP resist mask pattern which is prepared by e-beam direct writing using ZEP resist. The line widths of HSQ templates and ZEP patterns after developments are between 22-30 nm and 24-30 nm, respectively. The line width of silicon nitride templates without performing descum is same as that of the ZEP pattern but shows a rough surface. When plasma descum was performed before RIE, the line width of silicon nitride templates increased from 27 nm to 35 nm and has a clean surface. The HSQ template fabrication results in this study will be promise for sub-nm imprint process.


Follow-up by combined cytology and human papillomavirus testing for patients post-cone biopsy: results of a long-term follow-up.
The goal of this study was to evaluate the clinical implications of integrating human papillomavirus (HPV) testing into a long-term follow-up and management protocol for women postconization for high-grade cervical intraepithelial neoplasia (CIN2-3). Sixty-seven women were followed-up by Pap smears and HPV type and load testing (mean follow-up, 63 months; range, 50-72). Patients with persistent abnormal cytology on two consecutive smears and those with positive HPV test results (whatever their cytologic findings) were referred for colposcopy-directed biopsy. Patients histologically diagnosed with CIN2-3 and those with high-load HPV (whatever their histologic findings) underwent repeat conization or hysterectomy for residual disease. At follow-up, 29 (43.2%) women had positive cytology or positive HPV results and were referred for colposcopy. Eleven (37.9%) had high-grade cervical intraepithelial neoplasia or high-load HPV results and were further treated by reconization/hysterectomy. The respective positive predictive values of high-load HPV and low-grade squamous intraepithelial lesions were 100 and 60% for any CIN and 90 and 15% for CIN2-3. Only five of nine cases with a final diagnosis of CIN2-3 were originally identified by cytology: the other four were detected only by parallel evaluation by HPV testing. High-load HPV results with normal cytology or low-grade lesions harbored an 80% risk for CIN2-3. Adding HPV load assessment to the follow-up protocol of women postconization due to CIN2-3 lesions could help detect high-grade residual disease among low-grade lesions and normal cytology cases while concomitantly and safely bestowing the advantage of lowering the rates of colposcopic referrals and surgical procedures.


Who crashes their car following wrist fracture?
Wrist fractures are common injuries associated with high disability in the early recovery period. The impact of wrist fractures on safe return to drive is not understood. (1) To compare the proportion of adults who were drivers in car crashes before and after wrist fracture; (2) To examine potential factors (demographic and/or clinical) associated with increased odds of being a driver in a car crash following wrist fracture. Retrospective cohort study. Three state-wide government datasets (MainRoads Western Australia [WA], Hospital Morbidity Data Collection and the Emergency Department Data Collection) were used to obtain and link demographic, clinical and car crash information relating to adults with a wrist fracture sustained between 2008 and 2017. McNemar's tests were used to compare the proportion of drivers in a car crash within the 2 years prior to and following the fracture date. Multivariable logistic regressions were used to identify if any variables were associated with increased odds of crashing in the post-fracture period. Data relating to 37,107 adults revealed a 3.3% (95% CI 3.0%-3.6%, p < 0.05) decrease in the proportion of drivers in a car crash following wrist fracture, persisting for the entire 2 years post-fracture, when compared to the proportion who crashed before their fracture. Those with more severe wrist fracture injury patterns had 79%(95% CI 1.07-3.0, p = 0.03) higher odds of having a crash in the first 3 months following their injury, compared to those with isolated wrist fracture injuries. These results inform and update return to drive recommendations. The reduced proportion of drivers involved in crashes following wrist fracture persisted for 2 years; longer than the expected physical recovery timeframe. It is important that hand therapists actively educate the sub-group of adults with more severe wrist fracture injury patterns of the increased likelihood of car crash for the 3 months following their fracture.


Profile preferences of Korean American orthodontic patients and orthodontists.
The purpose of this study was to determine differences in preference for Korean American facial profiles among Korean American orthodontic patients with 2 levels of acculturation, Asian American orthodontists, and Caucasian orthodontists. Images of 1 male and 1 female Korean American adult were animated to move parts of the faces from an extreme retrusive position to an extreme protrusive position by using the Perceptometrics computer program. Three movies were created of the nose, lips, and chin for each image. Three groups of judges, ie, 18 Korean American orthodontic patients, 17 Asian orthodontists, and 18 Caucasian orthodontists selected the most pleasing position and the zone of acceptability as a measure of tolerance. Statistically significant differences were found between Caucasian orthodontists and Korean American orthodontic patients for the most pleasing and midpoint of acceptability positions of female nose and male chin, with no differences in the zone of acceptability position among the groups. In general, the Korean American orthodontic patients preferred a more protrusive nose on the female image and more retrusive chin on the male image than Caucasian orthodontists for the most pleasing and midpoint of acceptability positions, with similar zone of acceptability for all 3 groups.


The functional and organoleptic characterization of a dairy-free dessert containing a novel probiotic food ingredient.
New eating habits and diversification of tastes of consumers have led to the scientific community and the food industry to expand the range of probiotic foods and novel probiotic ingredients. Scant information is available about the viability and functionality of probiotics during shelf life and its effect on the nutritional characteristics of dairy-free products. The aim of the study was to formulate a fermented dairy-free dessert using a novel food ingredient based on a pumpkin by-product and containing Lactobacillus casei (ATCC®393™) (NFI). The effect of NFI and the soluble solids (SS) of soy milk on the probiotic viability, physical stability, colour, and firmness of dairy-free dessert was studied using a response surface methodology. The different levels of SS and NFI significantly (p < 0.05) affected the response variables. Thereafter, two formulations were selected and the physico-chemical, nutritional and organoleptic characterization were evaluated. The L. casei count reached the desired therapeutic level (>107 UFC mL-1) after gastrointestinal digestion at 21 days of storage. In general, both the fermentation process and storage reduced (p < 0.05) the content of phytic acid, raffinose and stachyose, which implies a nutritional improvement of the final product. Scores above 5.0 on a 9-point scale were obtained for colour, odour, texture and overall acceptability in the consumer acceptance test. Therefore, a dairy-free dessert with good physical properties, suitable nutritional characteristics, and sensorial acceptability could be successfully formulated with the NFI.


Academia and the medical group practice interface: the 2003 Institute of Medicine quality report and medication management.
University Physicians, Inc., has been impacted by the rising cost of professional liability insurance in recent years. Our internal risk management program needed to be enhanced to heighten provider sensitivity to the challenges certain practice processes (e.g., paper medical records) posed, and to tie this information to new patient and risk management strategies. The Institute of Medicine's 2003 report Priority Areas for National Action: Transforming Health Care Quality and the Agency for Healthcare Research and Quality's 2004 report Closing the Quality Gap: A Critical Analysis of Quality Improvement Strategies were used to establish priorities and develop indicators for measurement. A case study is presented on how these reports, combined with the Joint Commission on Accreditation of Healthcare Organization's 2006 National Patient Safety Goals for ambulatory care, were used to assess the group's risk profile and to implement practice changes to minimize risk.


Distribution in the genus Streptomyces of a homolog to nusG, a gene encoding a transcriptional antiterminator.
The presence of the vbrA gene encoding the transcriptional antiterminator NusG equivalent protein of Streptomyces virginiae was tested for in 73 Streptomyces species by Southern hybridization. Fifty-five strains (75%) including S. griseus, S. lividans TK-21 and S. coelicolor A3(2) showed clear hybridization signals, indicating wide distribution of vbrA or vbrA homologs in Streptomyces species. With hybridization patterns against 3 different probes, i.e., probes covering vbrA alone, the downstream gene rplK alone, and both vbrA-rplK, the 55 strains were classified into 4 groups. In the groups I, II and III (total 50 strains) vbrA was found to be adjacent to rplK, indicating that the gene arrangement vbrA-rplK is common in Streptomyces and that these genes may constitute a part of gene cluster encoding several components of the transcription and translation apparatus, as in Escherichia coli.


Apoptotic effect of IP(6) was not enhanced by co-treatment with myo-inositol in prostate carcinoma PC3 cells.
Inositol hexaphosphate (IP(6)) is a major constituent of most cereals, legumes, nuts, oil seeds and soybean. Previous studies reported the anticancer effect of IP(6) and suggested that co-treatment of IP(6) with inositol may enhance anticancer effect of IP(6). Although the anticancer effect of IP(6) has been intensively studied, the combinational effect of IP(6) and inositol and involved mechanisms are not well understood so far. In the present study, we investigated the effect of IP(6) and myo-inositol (MI) on cell cycle regulation and apoptosis using PC3 prostate cancer cell lines. When cells were co-treated with IP(6) and MI, the extent of cell growth inhibition was significantly increased than that by IP(6) alone. To identify the effect of IP(6) and MI on apoptosis, the activity of caspase-3 was measured. The caspase-3 activity was significantly increased when cells were treated with either IP(6) alone or both IP(6) and MI, with no significant enhancement by co-treatment. To investigate the effect of IP(6) and MI of cell cycle arrest, we measured p21 mRNA expression in PC3 cells and observed significant increase in p21 mRNA by IP(6). But synergistic regulation by co-treatment with IP(6) and MI was not observed. In addition, there was no significant effect by co-treatment compared to IP(6) treatment on the regulation of cell cycle progression although IP(6) significantly changed cell cycle distribution in the presence of MI or not. Therefore, these findings support that IP(6) has anticancer function by induction of apoptosis and regulation of cell cycle. However, synergistic effect by MI on cell cycle regulation and apoptosis was not observed in PC3 prostate cancer cells.


EFFECTS OF PARENTAGE AND SIZE OF THE POLLEN LOAD ON PROGENY PERFORMANCE IN CAMPANULA AMERICANA.
To examine the effects of maternal and paternal parentage and the size of the pollen load on seed size and weight and on progeny performance we conducted a controlled crossing experiment using a natural population of Campanula americana. We found that seed size was positively correlated with early seedling performance for all but one of traits we measured (days to emergence), but was not significantly correlated with any of the later vegetative measures or reproductive output. We detected significant effects due to the maternal parent for the vegetative traits days to emergence, days to first leaf, and final plant height, as well as total seed weight, and mean seed weight per fruit. Significant paternal effects were found for all of the seedling traits except number of leaves after vernalization. The progeny from fruits receiving high pollen loads significantly outperformed the progeny from fruits receiving low pollen loads for the traits days to first and second leaf, numbers of leaves after vernalization, and days to first flower. These results not only demonstrate the importance of parentage and seed weight on progeny performance, but also indicate that variations in the size of the pollen load may be important in seedling establishment in natural populations.


Molecular cloning of Mus dunni endogenous virus: an unusual retrovirus in a new murine viral interference group with a wide host range.
Mus dunni endogenous virus (MDEV) is activated from cells of the Asian wild mouse M. dunni (also known as Mus terricolor) in response to treatment with either 5-iodo-2'-deoxyuridine or hydrocortisone. MDEV represents a new murine retrovirus interference group and thus appears to use a different receptor for entry into cells than do other murine retroviruses. Here we show that MDEV is also not in the gibbon ape leukemia virus or RD114 virus interference groups. A retroviral vector with an MDEV pseudotype was capable of efficiently infecting a wide variety of cells from different species, indicating that the MDEV receptor is widely expressed. We isolated a molecular clone of this virus which exhibited no hybridization to any cloned retrovirus examined, suggesting that MDEV has an unusual genome. One copy of a possible retrovirus element that weakly hybridized with MDEV was present in the genomes of laboratory strains of mice, while no such elements were present in other species examined. A virus activated by 5-iodo-2'-deoxyuridine from cells of a BALB/c mouse, however, was not related to MDEV by either hybridization or interference analyses.


Courtship stimulates aromatase activity in preoptic area of brain in male ring doves.
Aromatase activity was quantified in vitro in different regions of the basal forebrain of male ring doves at various times after the initiation of courtship. By 24 h after the introduction of a female dove into the cage of a male, there was a significant, nearly two-fold, increase in aromatase activity which was confined to the ventromedial preoptic area (VM-POA) where enzyme activity was concentrated. This increase in aromatase activity, which was sustained through day 5 of courtship, presumably serves to activate nest-oriented behavior.


In situ hybridization for the study of gene expression in neuro-otologic research.
In situ hybridization histochemistry technology was developed for future application to neuro-otologic research. This method allowed the detection of cellular mRNA in tissue sections from the temporal bone or brainstem after cRNA/mRNA hybridization. To produce specific cRNA, single-stranded 35S-labeled cRNA (complimentary to target mRNA) is transcribed from commercially available plasmid vectors. These vectors contain promotor sequences for specific synthesis of RNA, and polylinker regions that will accept cloned DNA inserts for virtually any target nucleic acid sequence of interest. The protocol used in this research was optimized for studies that included concomitant immunohistochemical evaluation. The combination of in situ hybridization and immunohistochemistry provides the only method to correlate molecular information (gene expression) with biochemical or molecular markers, such as peptides or proteins (mRNA translation products) on individual cells in the temporal bone or brainstem. Using these techniques, we examined the distribution of the neuropeptide calcitonin gene-related peptide in rat temporal bone and brainstem sections using calcitonin gene-related peptide (CGRP) antisera and CGRP cRNA probes. We used in situ hybridization histochemistry with a cRNA probe complementary to the 3'-end noncoding sequence of the alpha CGRP mRNA and immunohistochemistry with a polyclonal antibody to the (TYR)CGRP23-37 to study the distribution of CGRP mRNA and CGRP-like immunoreactivity in the central and peripheral facial nerve. Numerous motoneuron cell bodies in the facial nucleus and accessory seventh nucleus and cell bodies in the gustatory geniculate ganglion were found to contain CGRP mRNA and the CGRP peptide.(ABSTRACT TRUNCATED AT 250 WORDS)


Direct observation of the thermal equilibria among lumirhodopsin, metarhodopsin I, and metarhodopsin II in chicken rhodopsin.
Using low-temperature time-resolved spectroscopy, we have directly observed thermal back reaction of metarhodopsin I (meta I) to lumirhodopsin (lumi) and that of metarhodopsin II (meta II) to meta I in chicken rhodopsin to demonstrate the presence of thermal equilibria among lumi, meta I, and meta II. The back reaction from meta I to lumi was observed when the rhodopsin sample irradiated at -35 degrees C was warmed to -20 degrees C, while that from meta II to meta I was observed when the sample irradiated at -10 degrees C was cooled to -20 degrees C. Thermodynamic parameters of lumi, meta I, and meta II were calculated from the equilibrium constants estimated by analyzing the spectra of the equilibrium states at temperatures ranging from -30 to -10 degrees C. The results showed that meta I has an enthalpy and an entropy considerably smaller than those of lumi and meta II, while the difference in thermodynamic parameters between lumi and meta II is not so large. These results suggest that meta I is a crucial stage of conversion of the light energy captured by the chromophore into restricted conformations of the chromophore and/or protein, from which a large conformational change of the protein starts to form meta II.


Sporadic Creutzfeldt-Jakob disease: clinical and diagnostic characteristics of the rare VV1 type.
Recently, six molecular subtypes of sporadic CJD (sCJD) have been identified showing differences regarding the disease course, neuropathologic lesion patterns, and sensitivity to diagnostic tools. Only isolated cases of the rare VV1 type have been reported so far. To describe the clinical characteristics and neuropathologic lesion profiles in nine cases. In the years 1993 until late 2003, 571 definite neuropathologically confirmed cases of sporadic CJD were identified in Germany. Of these, nine were homozygous for valine and displayed type 1 of the pathologic PrPSc in the brain (VV1 type). The authors describe eight men and one woman belonging to the VV1 type. All patients were relatively young at disease onset (median 44 years vs 65 years in all sCJD) with prolonged disease duration (median 21 months vs 6 months in all sCJD). During the initial stages, their main clinical signs were personality changes and slowly progressive dementia as well as focal neurologic deficits. None of the nine VV1 patients had periodic sharp-wave complexes (PSWCs) in the EEG. Only two out of seven displayed the typical signal increase of the basal ganglia on MRI, whereas signal increase of the cortex was seen in all patients. The 14-3-3 protein levels were elevated in CSF in all cases tested. The clinical diagnosis of the VV1 type of sCJD can be best supported by the 14-3-3 test and cortical signal increase on MRI. Because of the young age at onset vCJD is sometimes suspected as a differential diagnosis. MRI plays an important role in differentiating these two disease types and should be performed early during the disease course.


The Location and Effects of Visual Hemisphere-Specific Stimulation on Reading Fluency in Children With the Characteristics of Dyslexia.
Fluency is used as an indicator of reading proficiency. Many students with reading disabilities are unable to benefit from typical interventions. This study is designed to replicate Lorusso, Facoetti, Paganoni, Pezzani, and Molteni's (2006) work using FlashWord, a computer program that tachistoscopically presents words in the right or left visual hemi-field in English and locates through fMRI imaging the processing areas involved in fluency development. Our participants were 15 students who were ages 8 to 19 years and had reading disabilities randomly assigned to Intervention ( n = 9) and Delayed Intervention ( n = 6) groups. Functional imaging studies focused on analyzing activations in the left hemisphere (LH) superior temporal gyrus, the inferior frontal gyrus, and the LH inferior occipito-temporal/fusiform area (visual-word form area [VWFA]). Analysis of intervention data showed that 6 of the 9 Intervention group participants (67%) achieved levels of automatic processing and increased their reading rate by an average of 20 words per minute after participating in the FlashWord intervention. Analyses of fMRI group activation maps and mean activation levels in regions of interest document processing changes in VWFA activations that could be related to the increase in reading speed and confirm these locations as essential to developing fluency.


Preoperative assessment in endometrial cancer. Is triage for lymphadenectomy possible?
We sought to examine whether a preoperative assessment with usual means, available in most hospitals (preoperative histology, pelvic MRI, serum CA-125) can confidently exclude from a full staging surgical procedure low-risk endometrial carcinoma (EC) patients according to ESMO-ESTRO-ESGO criteria (stage I endometrioid EC, grade 1 or 2, myometrial invasion <50% and negative lymphovascular space invasion). We retrospectively identified all EC patients that underwent total hysterectomy with bilateral salpingo-oophorectomy (TH-BSO) plus lymph node dissection (LND) as primary treatment for endometrioid tumors from January, 2000 to December, 2010. Extensive review was made through patients' medical records. Having set the final pathology report as the "gold standard", we applied the ESMO-ESGO-ESTRO criteria to classify patients into risk categories (low-risk and non-low risk). We also evaluated preoperative risk status using combined data from preoperative biopsy, pelvic MRI and serum CA-125. We classified patients according to the following criteria: grade 1 or 2 on preoperative histology, myometrial invasion on MRI <50% and serum CA-125 <35 IU/ml, in low risk group. Receiver operating characteristic (ROC) curves were plotted. The area under the ROC curve (AUC), quantifying the overall ability of the combined preoperative assessment to discriminate between patients at low and non-low risk, was the primary outcome of our study. False negative rate was the secondary outcome. Preoperative data on histology, MRI and CA-125 levels were available for 292 patients. The sensitivity and specificity of combined preoperative assessment to discriminate between low- and non-low risk EC patients according to ESMO-ESTRO-ESGO criteria were 96.1% and 73.6% respectively. AUC of the corresponding ROC curve was 0.849. False negative rate was 3.8% (9/235). Among the 9 patients falsely classified as low-risk, one patient had nodal metastasis (1/9, 11.1%) after full staging. A selective LND strategy for EC patients based on preoperative assessment is possible and would probably be cost-effective, while not jeopardizing patients' survival or patient quality of life (QoL).


[Repetitive movement of the upper limbs: results of exposure evaluation and clinical investigation in wood sanding in Bergamo].
The authors report their findings regarding a risk assessment study and clinical tests carried out among a group of 121 workers whose job was to sandpaper and buff timber products. The results of the risk assessment indicate that the job in question is at significant risk for the development of WMSDs in relation to the principal risk factors (repetitiveness, force, posture, short recovery periods). The clinical tests, undertaken by medical staff, complied with the anamnestic models proposed by EPM. The results showed that 21 workers were above the anamnestic threshold, and were thus referred for specialist examinations. As a result of the latter, the relevant diagnoses were made. A positive correlation was reported between the occupational exposure level and the clinical abnormalities detected.


Respiratory effects of diazepam/methadone combination in rats: a study based on concentration/effect relationships.
Methadone may cause respiratory depression and fatalities. Concomitant use of benzodiazepines in methadone-treated patients for chronic pain or as maintenance therapy for opiate abuse is common. However, the exact contribution of benzodiazepines to methadone-induced respiratory toxicity remains debatable. We investigated the respiratory effects of the combination diazepam (20mg/kg)/methadone (5mg/kg) in the rat, focusing on methadone concentration/effect relationships. Respiratory effects were studied using arterial blood gases and whole-body plethysmography. Plasma concentrations of both R- and S-methadone enantiomers were measured using high-performance liquid chiral chromatography coupled to mass spectrometry. To clarify mechanisms of diazepam/methadone interaction, methadone metabolism was investigated in vitro using rat liver microsomes. Diazepam/methadone co-administration significantly increased methadone-related effects on inspiratory time (p<0.001) but did not significantly alter the other respiratory parameters when compared with methadone alone, despite significant increase in the area under the curve of plasma R-methadone concentrations measured during 240 min (p<0.05). Diazepam/methadone co-incubation with microsomes in vitro resulted in a significant inhibition of methadone metabolism (p<0.01), with 50%-inhibitory diazepam concentrations of 25.02 ± 0.18 μmol/L and 25.18 ± 0.23 μmol/L for R- and S-methadone, respectively. We concluded that co-administration of high-doses of diazepam and methadone in rats is not responsible for additional respiratory depression in comparison to methadone alone, despite significant metabolic interaction between the drugs. In humans, although our experimental data may suggest the relative safety of benzodiazepine/methadone co-prescription, physicians should remain cautious as other underlying conditions may enhance this drug-drug interaction.


Saliva as a non-invasive diagnostic tool for inflammation and insulin-resistance.
Saliva has been progressively studied as a non-invasive and relatively stress-free diagnostic alternative to blood. Currently, saliva testing is used for clinical assessment of hormonal perturbations, detection of HIV antibodies, DNA analysis, alcohol screening, and drug testing. Recently, there has been increasing interest in evaluating the diagnostic potential of saliva in obesity, inflammation, and insulin-resistance. Current literature has demonstrated elevated levels of inflammatory biomarkers including C-reactive protein, tumor necrosis factor-α, interleukin-6, and interferon-γ in saliva of obese/overweight children and adults. Salivary antioxidant status has also been studied as a measure of oxidative stress in individuals with type 2 diabetes. Further, several studies have demonstrated correlations of salivary markers of stress and insulin resistance including cortisol, insulin, adiponectin, and resistin with serum concentrations. These findings suggest the potential diagnostic value of saliva in health screening and risk stratification studies, particularly in the pediatric population, with implications for inflammatory, metabolic and cardiovascular conditions. However, additional studies are required to standardize saliva collection and storage procedures, validate analytical techniques for biomarker detection, and establish reference ranges for routine clinical use. The purpose of this review is to summarize and evaluate recent advancements in using saliva as a diagnostic tool for inflammation and insulin-resistance.