Transgenic mice expressing rabbit C-reactive protein exhibit diminished chemotactic factor-induced alveolitis.
The acute phase protein, C-reactive protein (CRP), can increase more than a thousandfold during acute inflammatory states, and it is known to modulate neutrophil-mediated inflammatory responses. We have previously shown that CRP inhibits chemotaxis of C5a-stimulated neutrophils in vitro and that rabbits with elevated CRP blood levels exhibit diminished pulmonary vascular permeability and neutrophil infiltration in a model of alveolitis. To study the effect of CRP on alveolitis induced by different chemoattractants, transgenic mice capable of expressing rabbit CRP in a dietary-inducible fashion were treated with inflammatory doses of the chemoattractants. Intratracheal installation of FMLP (8 x 10(-10) mol), LTB4 (2 x 10(-11) mol), or IL-8 (5 x 10(-12) mol) in normal CF1 mice resulted in significant (p<0.05) influx of neutrophils and protein into the alveolar space. Transgenic mice with elevated plasma levels of CRP showed significantly (p<0.05) diminished infiltration of neutrophils into bronchoalveolar lavage fluid (BALF) and significant reduction in BALF protein compared with that in normal mice. Rabbit CRP (10 to 500 micrograms/ml) inhibited in vitro neutrophil chemotaxis in a concentration-dependent fashion when stimulated by the various chemoattractants examined. These data show that rabbit CRP can modify both in vivo and in vitro neutrophil responses to several classes of chemoattractants and that CRP has a significant protective effect in alveolitis by reducing neutrophil influx and protein leakage into the lung.


Evaluation of nephrotoxicity and ototoxicity of aminosidine (paromomycin)-allopurinol combination in dogs with leishmaniosis due to Leishmania infantum: A randomized, blinded, controlled study.
Canine leishmaniosis due to Leishmania infantum is a widespread zoonotic disease. Although aminosidine can be an effective treatment, current therapeutic recommendations do not advocate its use, mainly due to concerns regarding the potential nephrotoxicity and ototoxicity of this drug. The aim of this randomized, blinded, controlled study was to evaluate the nephrotoxicity and ototoxicity of aminosidine-allopurinol combination and compare it with that of meglumine antimonate-allopurinol combination in non-azotemic dogs with leishmaniosis. Forty dogs with leishmaniosis were randomly assigned to be treated with either aminosidine at 15 mg/kg, subcutaneously, once daily for 28 days (group A) or with meglumine antimonate at 100 mg/kg, subcutaneously, once daily for 28 days (group B). In addition to either drug, dogs in both groups were administered allopurinol at 10 mg/kg per os twice daily for 2 months. Kidney function was evaluated through measurement of serum creatinine, urea nitrogen, inorganic phosphorus, and cystatin-c concentrations and complete urinalysis, including protein-to-creatinine ratio, at baseline and after 14, 28, and 60 days from the beginning of the treatment. At the same time points, vestibular and auditory functions were evaluated through neurological examination and brainstem auditory evoked response (BAER) recordings of wave I, wave V, inter-wave I-V latencies, and minimum hearing thresholds. None of the dogs developed clinicopathological evidence of kidney disease during the study. Serum creatinine concentration increased >0.3 mg/dl over baseline in 2 dogs in group A and in 5 dogs in group B. Parameters of kidney function were not significantly different or were improved compared to baseline and the only difference between the two groups was the lower concentration of serum creatinine in group A. None of the dogs developed peripheral vestibular syndrome or hearing impairment. At the end of the study, parameters of auditory function were not significantly different or were improved compared to baseline and there were no differences between the two groups. The results of this study show that the nephrotoxicity and ototoxicity of aminosidine, when administered to non-azotemic dogs with leishmaniosis at 15 mg/kg subcutaneously once daily for 28 days along with allopurinol, is minimal and does not differ from that of meglumine antimonate.


Multiple hydrolases in bean leaves (Phaseolus vulgaris L.) and the effect of the halo blight disease caused by Pseudomonas phaseolicola (Burkh.) Dowson.
Multiple forms of hydrolytic enzymes were demonstrated in extracts of healthy bean leaves (Phascolus vulgaris L.) and bean leaves infected with the halo blight organism [Pseudomonas phaseolicola (Burkh.) Dowson] by polyacrylamide disc electrophoresis. Bean leaves contained up to 4 acid phosphatase bands, 9 esterase bands active towards alpha-naphthyl acetate, and 7 esterase bands towards alpha-naphthyl butyrate. Only low or no activity was found for alkaline phosphatase, lipase, and aminopeptidase. Two artifacts are described which were observed with the lead phosphate method for acid phosphatase and the Tween method for demonstration of lipase. After infection with the halo blight organism the major acid phosphatase of the host increased during early and decreased at later infection stages. An acid phosphatase of bacterial origin with a more neutral pH optimum could be demonstrated in infected leaves. It is suggested that the bacterial acid phosphatase plays a role in uptake of metabolites by the pathogen. Several esterase bands decreased after infection. One host band with activity towards alpha-naphthyl butyrate increased. Also the pathogen showed an esterase band with high activity towards alpha-naphthyl butyrate.


Orientalism in Euro-American and Indian psychology: historical representations of "natives" in Colonial and postcolonial contexts.
The author examines the historical role of Euro-American psychology in constructing Orientalist representations of the natives who were colonized by the European colonial powers. In particular, the author demonstrates how the power to represent the non-Western "Other" has always resided, and still continues to reside, primarily with psychologists working in Europe and America. It is argued that the theoretical frameworks that are used to represent non-Westerners in contemporary times continue to emerge from Euro-American psychology. Finally, the author discusses how non-Western psychologists internalized these Orientalist images and how such a move has led to a virtual abandonment of pursuing "native" forms of indigenous psychologies in Third World psychology departments.


Comprehensive analysis of cancer hallmarks in cutaneous melanoma and identification of a novel unfolded protein response as a prognostic signature.
Molecular pathways regulating the initiation and development of melanoma are potential therapeutic targets for this aggressive skin cancer. Therefore, transcriptome profiles of cutaneous melanoma were obtained from a public database and used to systematically evaluate cancer hallmark pathways enriched in melanoma. Finally, the unfolded protein response pathway was screened out, and the unfolded protein response-related genes were used to develop a robust biomarker that can predict the prognosis of melanoma, especially for younger, metastatic and high Clark level patients. This biomarker was further validated in two other independent datasets. In addition, melanoma patients were divided into high- and low-risk subgroups by applying a risk score system. The high-risk group exhibited higher immune infiltration and higher expression of N6-methyladenosine RNA methylation regulators, and had significantly shorter survival times than the low-risk subgroup. Gene Set Enrichment Analysis revealed that, among the enriched genes, gene sets involved in immune response and the extracellular matrix receptor interaction were significantly activated in the high-risk group. Our findings thus provide a new clinical application for prognostic prediction as well as potential targets for treatment of melanoma.


Finnish sexual homicides: offence and offender characteristics.
Information on sexual homicide offenders is limited. The current study estimates the rate of sexual homicides in Finland and analyses sociodemographic characteristics, crime history, life course development, psychopathy, and psychopathology in sexual homicide and nonsexual homicide offenders. Crime reports and forensic examination reports of all offenders subjected to forensic examination and convicted for homicide in 1995-2004 (n=676) were retrospectively analyzed for offence and offender variables and scored with the Psychopathy Checklist-Revised. Eighteen sexual homicides (2.8%) were identified. Co-offending, strangulation and disposal of the body were more frequent crime scene variables in sexual than nonsexual homicides. Mental health problems and sexual abuse in childhood and sexual crime history were significantly more frequent in sexual than nonsexual homicide offenders. Over half of the sexual homicide offenders were psychopathic: compared to nonsexual homicide offenders they scored significantly higher on interpersonal and affective features of psychopathy.


Apical heterodimeric cystine and cationic amino acid transporter expressed in MDCK cells.
The luminal uptake of L-cystine and cationic amino acids by (re)absorptive epithelia, as found in the small intestine and the proximal kidney tubule, is mediated by the transport system b(0,+), which is defective in cystinuria. Expression studies in Xenopus laevis oocytes and other nonepithelial cells as well as genetic studies on cystinuria patients have demonstrated that two gene products, the glycoprotein rBAT and the multitransmembrane-domain protein b(0,+)AT, are required for system b(0,+) function. To study the biosynthesis, surface expression, polarity, and function of this heterodimer in an epithelial context, we established stable Madin-Darby canine kidney (MDCK) cell lines expressing rBAT and/or b(0,+)AT. Confocal immunofluorescence microscopy shows that both subunits depend on each other for apical surface expression. Immunoprecipitation of biosynthetically labeled proteins indicates that b(0,+)AT is stable in the absence of rBAT, whereas rBAT is rapidly degraded in the absence of b(0,+)AT. When both are coexpressed, they associate covalently and rBAT becomes fully glycosylated and more stable. Functional experiments show that the expressed transport is of the high-affinity b(0,+)-type and is restricted to the apical side of the epithelia. In conclusion, coexpression experiments in MDCK cell epithelia strongly suggest that the intracellular association of rBAT and b(0,+)AT is required for the surface expression of either subunit, which together form a functional heterocomplex at the apical cell membrane.


[Association between breast and colorectal cancer and polyps. Screening and epidemiological study].
Studies regarding the associations between different types of cancer in the same patient are very few and not always come to the same conclusions. Several hypothesis are suggested and particularly genetic and socioeconomical ones seem to offer an interpretation of this issue. Early detection of a second neoplasm allows to improve prognosis and survival. The knowledge of correlations between tumors help to select a population, with a high risk to develop a second cancer, to be included in a screening program. Nowadays thanks to early detection of breast cancer, ten years survival is more than 75%. Women who had breast cancer now live longer and so could have a higher risk to develop a second cancer. From September 1998 to September 1999 in our Department 71 patients operated for breast cancer, underwent screening colonscopy. No patients refused to be included in the study. Mean age was 61 years (range 36-87). Each patient had a clinician interview in order to explain the goals of the study. Results show that among all patients 3 (4.2%) presented a history of colon cancer, 18.3% (13 cases) presented large bowel polyps. In 84.60% patients (11 cases) polyps were found not over 40 cm. This study shows that 93% of patients (66 cases) had a relative with cancer history. Our results compared with those of other authors seem to show an increased risk for breast cancer patients in developing polyps or colon cancer, so we suggest to insert sigmoidoscopy in standard follow-up of breast cancer patients.


Effect of a sub-anaesthetic concentration of halothane on the ventilatory response to sustained hypoxia in healthy humans.
We selected nine normal subjects (8M, 1F; aged 25-43 yr) with brisk hypoxic ventilatory responses, and studied their ventilatory response to sustained isocapnic hypoxia (SaO2 82 (SEM 0.1) % for 25 min) in the presence and absence of 0.1% inspired halothane. Halothane had no significant effect on baseline ventilation or gas exchange. In the absence of halothane, ventilation increased initially from mean 7.57 (0.35) litre min-1 to 14.54 (0.91) litre min-1, and decreased subsequently to 10.74 (0.32) litre min-1 during hypoxia (both P < 0.05). In the presence of 0.1% inspired halothane, ventilation increased initially from 7.19 (0.47) litre min-1 to 12.08 (0.99) litre min-1 (P < 0.05), then decreased to 10.12 (0.28) litre min-1 during sustained hypoxia (ns compared with baseline normoxic ventilation). Halothane reduced significantly the initial increase in ventilation (P < 0.05), but did not enhance the subsequent decrease. These results confirm that a sub-anaesthetic concentration of halothane depresses the initial hypoxic ventilatory response; the response during prolonged periods of hypoxia is, however, less than the initial response and is reduced in the presence or absence of a sub-anaesthetic concentration of halothane.


Improving care planning and communication for frail older persons across the primary-secondary care interface.
Collaboration between general practitioners (GPs) and geriatricians should be at the forefront of the design and delivery of the care of frail older people. Primary care teams require high-quality, relevant and timely communication around assessment and care plans when patients return home from secondary care settings. The aim of this project was to develop effective handover communication between the frailty team and primary care for patients assessed and transferred home from an emergency department. The 'frailty letter to the GP' was designed, tested and adapted to accomplish this aim. This involved two PDSA (plan, do, study, act) cycles through which the letter was tested and adapted. Our measure of improvement was GPs' satisfaction with the letter with regards to its usefulness. Based on feedback, the letter was edited to reflect what the GPs needed in order to continue their patients' care. Joint planning with the clinical commissioning group GP leads, as well as the trust's transformation lead, was crucial to the final design of the letter that was well received by the GP colleagues. Local departments should examine current communication mechanisms for these patients, and, if found lacking, work collaboratively to improve these while also tracking relevant clinical outcomes.


Alternative acute oral toxicity assessment under REACH based on sub-acute toxicity values.
The REACH Regulation requires information on acute oral toxicity for substances produced or imported in quantities greater than one ton per year. When registering, animal testing should be used as last resort. The standard acute oral toxicity test requires use of animals. Therefore, the European Chemicals Agency examined whether alternative ways exist to generate information on acute oral toxicity. The starting hypothesis was that low acute oral toxicity can be predicted from the results of low toxicity in oral sub-acute toxicity studies. Proving this hypothesis would allow avoiding acute toxicity oral testing whenever a sub-acute oral toxicity study is required or available and indicates low toxicity. ECHA conducted an analysis of the REACH database and found suitable studies on both acute oral and sub-acute oral toxicities for 1,256 substances. 415 of these substances had low toxicity in the sub-acute toxicity study (i.e., NO(A)EL at or above the limit test threshold of 1,000 mg/kg). For 98% of these substances, low acute oral toxicity was also reported (i.e., LD50 above the classification threshold of 2,000 mg/kg). On the other hand, no correlation was found between lower NO(A)ELs and LD50. According to the REACH Regulation, this approach for predicting acute oral toxicity needs to be considered as part of a weight of evidence analysis. Therefore, additional sources of information to support this approach are presented. Ahead of the last REACH registration deadline, in 2018, ECHA estimates that registrants of about 550 substances can omit the in vivo acute oral toxicity study by using this adaptation.


Comparative outcomes of Thai children with acute lymphoblastic leukemia treated with two consecutive protocols: 11-year experience.
The aim of this study was to determine outcomes and prognostic features of children with acute lymphoblastic leukemia (ALL) treated with two modified St Jude Children's Research Hospital protocols at Ramathibodi Hospital (1997-2008). Event-free survival rates of the "previous protocol" were 88.3 ± 3.3% and 83.0 ± 3.9% and of the "current protocol" were 89.9 ± 3.4% and 88.0 ± 3.8%, at 3 and 5 years, respectively. Adverse prognostic features were identified only in the previous protocol study, including obesity, presenting leukocytes >100 × 10(9)/L, high-risk group, persistent blasts in a day-15 marrow and sepsis. Sepsis also conferred inferior overall survival rates of patients in both protocols. Steady improvement in cure rate over the past decade has clearly demonstrated the optimal use of treatment protocols and a multidisciplinary approach to implementing pediatric cancer care in Ramathibodi Hospital. Our future challenges are refinement in risk and treatment stratification and reduction of treatment-related toxicities, prioritizing death from infections.


Characterization of mixed chimerism in patients with chronic myeloid leukemia transplanted with T-cell-depleted bone marrow: involvement of different hematologic lineages before and after relapse.
We have characterized mixed chimerism (MC) in five patients with chronic myeloid leukemia (CML) who received transplants with T-cell-depleted bone marrow (BM) and who relapsed within 4 years after transplantation. To study the possible relation of MC with relapse, we purified different populations of leukocytes and analyzed their donor/recipient origin by a method based on polymerase chain reaction amplification of minisatellite DNA regions. Our results show that before relapse, all hematopoietic recipient cells are T cells, whereas monocytes, B, and natural killer (NK) cells are of donor origin. This observation does not appear to be specific for CML as similar results were found in two control patients with acute myeloid leukemia (AML). At the time of (CML) relapse, recipient granulocytes, monocytes, and erythrocytes appeared and progressively replaced the respective lineages of donor origin. No other lineages seemed to be involved as B cells and NK cells remained of donor origin and no significant changes in the number of recipient T cells were detected. In this respect relapse of CML after BM transplantation (BMT) seems not to be very different from the primary disease in chronic phase before transplantation. Furthermore, we conclude that after BMT, an association between mixed chimerism before relapse and the (CML) relapse does exist because both phenomena are consequences of T-cell depletion of the BM graft. However, this correlation might well be indirect as the MC caused by the recipient T cells appears to be independent of the one caused by the recurrent disease.


The spatial distribution of larvae of Culicoides impunctatus biting midges.
The spatial distribution of Culicoides impunctatus Goetghebuer (Diptera: Ceratopogonidae) larvae was sampled at a site in western Scotland, and geostatistical analyses were used to quantify spatial dependencies. Nested sampling and analysis indicated that most of the spatial variance occurred within distances of 160-640 cm, levelling off at distances >640 cm. Semivariograms for transformed data from three 100 m x 100 m grids showed similar, isotropic patterns for larval counts, soil organic content, soil water content and the distribution of Juncus spp. rushes, with the variance increasing with separation distance. High levels of significance were associated with power models used to describe the semivariograms, which was indicative of the absence of a plateau (or 'sill') in the respective data. Correlation analysis of transformed data revealed significantly positive relationships between larval counts and soil pH, soil percentage organic content, soil percentage water content and also the distribution of Sphagnum spp., Juncus spp. and Myrica gale. There were also significantly negative relationships between larval counts and the distribution of Pteridium aquilinum and all mosses other than Sphagnum spp. The results suggest a far more structured and predictable pattern of C. impunctatus larval sites than previous studies and are discussed in relation to their application in localized Culicoides control and to studies of the mechanisms determining the spatial distribution of C. impunctatus larvae.


Surveillance strategy of atrophic gastritis and intestinal metaplasia in a country with a high prevalence of gastric cancer.
It is not clear which screening examinations are best suited for gastric cancer prevention, especially in patients with atrophic gastritis and intestinal metaplasia. Therefore, we investigated the gastric cancer screening methods and intervals that are performed in clinical practice in an area with a high prevalence of gastric cancer. Eighty-seven physicians voted by keypad and discussed the consistency of endoscopic diagnosis of atrophic gastritis and intestinal metaplasia at the Annual Symposium of the Korean College of Helicobacter and Upper Gastrointestinal Research. Additionally, 100 core members of this academic society were asked via e-mail to complete the questionnaires related to screening strategies for gastric cancer. The most common recommendation for the subjects with intestinal metaplasia was an annual endoscopic follow-up (95.5% vs. 80.4% in the expert and non-expert groups, respectively; P = 0.118). Annual endoscopic follow-up was also the most predominant recommendation for atrophic gastritis (95.5% vs. 76.5%; P = 0.092), regardless of the physicians' endoscopic experience, position, and degree of the hospital. However, the correct answer rate for the diagnosis of normal endoscopic findings was only 16.7 and 14.1% in the expert and non-expert groups, respectively (P = 0.883). The most common practical screening strategy for patients with atrophic gastritis and intestinal metaplasia in Korea was annual endoscopic examination. However, a new program estimating individualized gastric cancer risk might be needed because of the low inter-observer agreement in the endoscopic diagnosis of atrophic gastritis and intestinal metaplasia.


Business Environment and Entrepreneurial Motivations of Urban Students.
College students' perceptions of entrepreneurial environments exert significant influence on their entrepreneurial motivations. With China's increased focus on entrepreneurship and innovation, an increasing number of college students have embarked on a journey of self-employment and entrepreneurship. Due to disparities in the urban entrepreneurial environments, however, their entrepreneurial ventures in urban spaces are characterized by extreme phenomena such as entrepreneurial clusters and human capital flight, thus constraining economic development. This study sampled 244 college students from Wenzhou, China, and analyzed their opinions on the relationship between their perceptions of the entrepreneurial environment and associated motivations. We concluded that college students' entrepreneurial motivations are significantly and positively affected by their perception of socio-economic conditions, education and training, and availability of financial and non-financial support, and insignificantly affected by their perceptions of the favorability of government policies as related to entrepreneurial development.


Lung and Gut Microbiota Changes Associated with Pseudomonas aeruginosa Infection in Mouse Models of Cystic Fibrosis.
Cystic fibrosis (CF) disease leads to altered lung and gut microbiomes compared to healthy subjects. The magnitude of this dysbiosis is influenced by organ-specific microenvironmental conditions at different stages of the disease. However, how this gut-lung dysbiosis is influenced by Pseudomonas aeruginosa chronic infection is unclear. To test the relationship between CFTR dysfunction and gut-lung microbiome under chronic infection, we established a model of P. aeruginosa infection in wild-type (WT) and gut-corrected CF mice. Using 16S ribosomal RNA gene, we compared lung, stool, and gut microbiota of C57Bl/6 Cftr tm1UNCTgN(FABPCFTR) or WT mice at the naïve state or infected with P. aeruginosa. P. aeruginosa infection influences murine health significantly changing body weight both in CF and WT mice. Both stool and gut microbiota revealed significantly higher values of alpha diversity in WT mice than in CF mice, while lung microbiota showed similar values. Infection with P. aeruginosa did not changed the diversity of the stool and gut microbiota, while a drop of diversity of the lung microbiota was observed compared to non-infected mice. However, the taxonomic composition of gut microbiota was shown to be influenced by P. aeruginosa infection in CF mice but not in WT mice. This finding indicates that P. aeruginosa chronic infection has a major impact on microbiota diversity and composition in the lung. In the gut, CFTR genotype and P. aeruginosa infection affected the overall diversity and taxonomic microbiota composition, respectively. Overall, our results suggest a cross-talk between lung and gut microbiota in relation to P. aeruginosa chronic infection and CFTR mutation.


Measurement system analysis on the external standard using an azeotropic mixture of ethylene glycol and detailed uncertainties.
Ethylene glycol is a super commodity chemical and it has vital roles in various applications. Its co-production with other chemicals, such as ethylene carbonate and glycerol carbonate, has promised cheaper production cost. Its quantification presents a challenge as its contaminants, such as ethylene carbonate, produce a signal-reducing effect in flame ionized detector. The aim of this study is to evaluate external standard to quantify the composition of glycol mixture. Measurement system analysis was employed on the external standard method. Reliability of the external standard is statistically significant with low p-values, excellent capability indices, and high F-values. The external standard is found to have remarkable precision and trueness as both capability indices are mirroring each other. Furthermore, the capability analysis has a strong correlation with quality measurement. Based on capability indices, the limit of detection is recommended at S/N = 25 and the limit of quantification is recommended at S/N = 100 for a reliable measurement. A high degree of reliability is achieved coherently as almost all uncertainties of coefficients of variations are less than 5%. The established method was validated and successfully applied to glycol mixture at azeotropic distillation pilot plant.


Impairment of maximal bilirubin secretion by cyclosporin A in the rat.
The effect of cyclosporin A on the maximal secretion of bilirubin was investigated in male Wistar rats. Following a saturating load of the pigment, intravenous administration of cyclosporin A as a single bolus (20 mg/kg) significantly reduced bile flow and bile acid secretion. The bilirubin secretory transport maximum was alos significantly reduced. The decreased excretion of the bile pigment corresponded both to bilirubin mono- and di-conjugates, the excretion of unconjugated bilirubin being slightly and non-significantly reduced. Plasma and liver bilirubin concentrations were significantly increased, while liver UDP-glucuronosyltransferase activity did not significantly differ between control and cyclosporin A-treated rats. Our data indicate that, although in cyclosporin A-treated rats there are no changes in the activities of others markers of hepatocellular dysfunction, the overall plasma to bile transfer of bilirubin is altered. The reduced hepatobiliary transport of the pigment is mainly caused by an impairment of its intracellular/canalicular transport.


Breast cancer: current developments in molecular approaches to diagnosis and treatment.
Due to the high heterogeneity of breast cancers, numerous recent patents describe improved methods of detection and classification which promise better patient prognosis and treatment. In particular, there has been a shift towards more effective genetic screening to identify specific mutations associated with breast tumours, which may lead to "personalised medicine" with improved outcomes. Two challenging areas of breast cancer research involve the development of treatments for the highly aggressive triple negative breast cancer subtype as well as the chemotherapy-resistant cancer stem cell subpopulation. In addition, despite numerous recent advances in breast cancer treatment in woman, male breast cancer remains poorly understood and there are limited therapies available which are developed specifically for men. This review serves to report on important developments in the treatment of breast malignancies patented in the past two years as well as to highlight the current gaps in the field of breast cancer therapeutics and areas which require further study.


Effect of prolonged tacrolimus treatment in idiopathic membranous nephropathy with nephrotic syndrome.
Tacrolimus has been used for idiopathic membranous nephropathy (IMN) therapy, but most patients who achieved remission showed a high relapse rate when tacrolimus was withdrawn after 6-12 months of therapy. We proposed that a prolonged therapeutic course should help reduce the relapse rate. A total of 42 patients with nephrotic syndrome caused by IMN were randomly divided into short-term (n = 20) and long-term (n = 22) groups. All patients received initial treatment with tacrolimus and prednisone for 6 months, and afterward only the long-term patient group was tapered with low-dose tacrolimus until 24 months. Over 85% of the patients achieved proteinuria reduction, serum albumin improvement and serum lipid recovery; the probability of remission in both groups was over 80% at 6 months. The remission rate was steady at over 80% after 12 and 24 months in the long-term group, but only 50 and 45%, respectively, in the short-term group. Nine patients (45%) relapsed in the short-term group after tacrolimus withdrawal, while not a single patient suffered recurrence in the long-term group. The concentration of tacrolimus remained similar between the two groups at 5-8 ng/ml during the initial 6 months, and was significantly decreased at 12 months compared to 6 months (p < 0.05), along with reduction of oral administration in the long-term group. Combined therapy of tacrolimus with prednisone can relieve IMN significantly; prolonged tacrolimus treatment at a low blood concentration can alleviate the illness persistently, with a low recurrence rate and gratifying safety.


Entecavir plus adefovir combination treatment for chronic hepatitis B patients after failure of nucleoside/nucleotide analogues.
The combination of entecavir, a nucleoside analogue, and adefovir, a nucleotide analogue, would be a promising salvage treatment for chronic hepatitis B (CHB) patients who fail nucleoside/nucleotide analogue (NA) regimens. A total of 89 CHB patients who had failed NA regimens and were treated with entecavir plus adefovir combination for at least 12 months were included. Mean baseline HBV DNA of patients was 6.16 ±1.44 log(10) IU/ml. Patients were classed by the number of previously failed NAs; 1 NA (lamivudine; n=15; Group 1), 2 NAs (lamivudine and either adefovir or entecavir; n=39; Group 2) and 3 NAs (lamivudine, adefovir and entecavir; n=35; Group 3). After 12 months of treatment, the mean reduction in HBV DNA was greater in Group 1 than in Group 2 or 3 (-5.81 ±1.71, -3.20 ±1.36 and -2.93 ±1.56 log(10) IU/ml, respectively; P<0.01). The rates of virological response (HBV DNA<2,000 IU/ml) were 100%, 79.5% and 34.3% (P<0.01), and the rates of complete virological response (HBV DNA<60 IU/ml) were 53.3%, 25.6% and 14.3% in Group 1, 2 and 3, respectively (P<0.01) at 12 months. Higher baseline HBV DNA (odds ratio =0.59; P=0.02) and increasing number of previously failed NAs (P<0.01) were independently associated with a lower rate of complete virological response at 12 months. Entecavir plus adefovir combination treatment was effective in achieving virological response in CHB patients after failure of NAs. However, its effect progressively decreased as the number of previously failed NAs increased.


Hydrogen/deuterium exchange of myoglobin ions in a linear quadrupole ion trap.
The hydrogen/deuterium (H/D) exchange of gas-phase ions of holo- and apo-myoglobin has been studied by confining the ions in a linear quadrupole ion trap with D(2)O or CD(3)OD at a pressure of several mTorr. Apo-myoglobin ions were formed by collision-induced dissociation of holo-myoglobin ions between the orifice and skimmer of the ion sampling system. The exchange takes place on a time scale of seconds. Earlier cross section measurements have shown that holo-myoglobin ions can have more compact structures than apo-myoglobin. Despite this, both holo-myoglobin and apo-myoglobin in charge states +8 to +14 are found to exchange nearly the same number of hydrogens (ca. 103) in 4 s. It is possible the ions fold or unfold to new conformations on the much longer time scale of the exchange experiment compared with the cross section measurements.


Home-based telemanagement in chronic heart failure: an 8-year single-site experience.
During an eight-year period, 358 patients with chronic heart failure (CHF) were enrolled in a six-month home-based telemanagement (HBT) programme. The efficacy of the programme was evaluated in two four-year periods, based on changes in clinical, functional, Quality of Life (QoL) status and rate of hospital readmission. The New York Heart Association (NYHA) class and the number of patients with comorbidities increased significantly in the second period, while the number of patients with beta-blockers decreased significantly (P < 0.01). Following the HBT programme, non-cardiovascular hospital readmission rate and all-cause readmission rate increased by 11% (P < 0.03) and 13% (P < 0.05), respectively. On re-evaluation after six months (238 patients) there was a general improvement in clinical, functional and QoL status and a significant increase in the mean daily dosage of beta-blockers prescribed. Our experience confirms that HBT for patients with CHF is associated with favourable effects on hospital readmission for cardiovascular reasons and on QoL. However, a more comprehensive multidisciplinary approach will probably be required to obtain favourable effects on total morbidity.


Charcot arthropathy of the lumbosacral spine mimicking a vertebral tumor after spinal cord injury.
Charcot spinal arthropathy is a rare, progressive type of vertebral joint degeneration that occurs in the setting of any preexisting condition characterized by decreased afferent innervation to the extent that normal protective joint sensation in the vertebral column is impaired. The authors report on a case of Charcot arthropathy of the lower lumbar spine mimicking a spinal tumor following cervical cord injury.


Selective increase in representations of sounds repeated at an ethological rate.
Exposure to sounds during early development causes enlarged cortical representations of those sounds, leading to the commonly held view that the size of stimulus representations increases with stimulus exposure. However, representing stimuli based solely on their prevalence may be inefficient, because many frequent environmental sounds are behaviorally irrelevant. Here, we show that cortical plasticity depends not only on exposure time but also on the temporal modulation rate of the stimulus set. We examined cortical plasticity induced by early exposure to 7 kHz tone pips repeated at a slow (2 Hz), fast (15 Hz), or ethological (6 Hz) rate. Certain rat calls are modulated near 6 Hz. We found that spectral representation of 7 kHz increased only in the ethological-rate-reared animals, whereas improved entrainment of cortical neurons was seen in animals reared in the slow- and fast-rate condition. This temporal rate dependence of spectral plasticity may serve as a filtering mechanism to selectively enlarge representations of species-specific vocalizations. Furthermore, our results indicate that spectral and temporal plasticity can be separately engaged depending on the statistical properties of the input stimuli.


Medical Education during COVID-19: Response at one medical school.
The COVID-19 pandemic has caused a significant toll on healthcare across the globe. The pandemic caused many other consequences, including economic implications and teaching consequences, notably in higher education throughout the world. COVID-19 and the resulting closure of university campuses have had many impacts on Health Professions Education (HPEd), affecting all aspects, including teaching methods, assessment methods, curricula, student-teacher relationships, student selection processes, and student well-being. It has had significant effects on the setting in which students are required to learn more skills such as psychomotor skills. This manuscript aims to investigate the changes implemented in medical education during the pandemic and describe one medical school's response to medical education changes during the pandemic. This study was a combination of a case study done by in-depth investigation of the current context at one medical school during the pandemic and action research done by gathering information to change a condition in a particular place. Many changes were implemented in medical education, including online teaching for basic science courses (first two years of the program) and online assessments (video-based remote proctoring) in the program's first two years. Such courses as Clinical Skills are using telemedicine/telehealth concepts in training. There were changes such as video-based remote proctoring of NBME shelf-examinations even in the assessments of clerkships/clinical rotations. Adaptations of medical education during this pandemic is highly dependent on technology. Most of the changes will be practiced until the campuses are open. We need to understand that these changes were made over this unprecedented period, i.e. the pandemic as an emergency rather than as a normal change process.


Effect of asymptomatic carotid artery disease on cognitive outcome after cardiopulmonary bypass.
This prospective study reinvestigates the effect of asymptomatic carotid artery disease on the cognitive outcome after cardiopulmonary bypass (CPB) (Harrison et al., 1989). Patients (N = 104) scheduled for cardiac surgery using CPB were classified in one of two groups based on the results of a preoperative duplex B mode Doppler scan of the internal carotid arteries. All patients received a neuropsychological examination before surgery, 8 days after surgery, and 6 months after surgery (n = 79). When group data are considered, patients showed evidence of selective cognitive dysfunction early after surgery. These dysfunctions were resolved by the sixth postoperative month. We found no indications that the presence of asymptomatic carotid artery disease increased the incidence of cognitive disturbances after CPB or differentially affected the postoperative performance. We conclude that mild to moderate asymptomatic carotid artery disease does not appear to play a major role in the genesis of postoperative neuropsychological sequelae.


Effectiveness of three intensities of smoking cessation treatment in primary care.
The purpose of this study was to compare the effectiveness of three smoking cessation programs of varying intensity applied in a primary care setting. Participants were 89 individuals randomly assigned to one of three treatment groups: brief counseling plus information pamphlet, self-help program with telephone follow-up, and intensive behavioral treatment. At the 12-mo. follow-up, intensive behavioral treatment (42.8% abstinence) was more effective than the self-help program (27.5%), which was in turn more effective than counseling (12.9%). Continued abstinence was also higher in the intensive treatment group (37.9%) than in the self-help (17.2%) and the counseling groups (9.7%), although these differences only reached statistical significance in the first and third of these groups. Treatment adherence was higher in the intensive behavioral group (82.8% of participants attended all the sessions) than in the self-help group (61.8% completed the program). The results appear to confirm a dose-response effect in the treatment of smokers and indicate satisfactory acceptability of intensive behavioral programs applied in primary care.


Present day's standards in microsurgery of low-grade gliomas.
Low-grade gliomas are slow growing intrinsic lesions that induces a progressive functional reshaping of the brain. Surgical removal of these lesions requires the combined efforts of a multidiscipinary team of neurosurgeon, neuroradiologist, neuropsychologist, neurophysiologist, and neurooncologists that all together contribute in the definition of the location, extension, and extent of functional involvement that a specific lesion has induced in a particular patient. Each tumor has induced particular and specific changes of the functional network, that varies among patients. This requires that each treatment plan should be tailored to the tumor and to the patient. When this is reached, surgery should be accomplished according to functional and anatomical boundaries, and has to aim to the maximal resection with the maximal patient functional preservation. This can be reached at the time of the initial surgery, depending on the functional organization of the brain, or may require additional surgeries, eventually intermingled with adjuvant treatments. The use of so called brain mapping techniques extend surgical indications, improve extent of resection with greater oncological impact, minimization of morbidity and increase in quality of life. To achieve the goal of a satisfactory tumor resection associated with the full preservation of the patients abilities, a series of neuropsychological, neurophysiological, neuroradiological and intraoperative investigations have to be performed. In this chapter, we will describe the rationale, the indications and the modality for performing a safe and rewarding surgical removal of low-grade gliomas by using these techniques, as well as the functional and oncological results.


Calcitonin gene-related peptide induced relaxation of the rabbit iris dilator muscle.
Calcitonin gene-related peptide (CGRP) and Substance P (SP) -immunoreactive nerves have been found in the anterior uvea of various mammalian species. Although SP is known to play a major role in control of pupil motility in rabbits, little is known about the effect of CGRP on the iris smooth muscles. We isolated iris sphincter and dilator muscles from rabbit eyes and investigated the mechanical responses and intracellular cyclic AMP (cAMP) levels in these muscles. CGRP (up to 0.1 microM) had no effect on either the resting muscle tone or the amplitude of contraction evoked by field stimulation of the sphincter. On the other hand, CGRP (0.1 microM) relaxed dilator muscle which had been pre-contracted by phenylephrine and reduced the amplitude of contraction evoked by field stimulation. These responses were antagonized by CGRP (8-37), a CGRP antagonist. The phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX), dose-dependently inhibited the contraction evoked by field stimulation. However, 3 microM IBMX had no effect on CGRP inhibition of twitch contraction in this preparation. CGRP had little effect on cAMP production in dilator muscle either with or without IBMX. In conclusion, the miosis which occurs during an ocular inflammatory response, when both CGRP and SP are thought to be released from terminals of sensory neurons, results from CGRP relaxation of the dilator and from the strong contractile effect of SP on the sphincter. Adenylate cyclase activation does not seem to be involved in the relaxant effect of CGRP on the dilator.


[A case of angiomatous meningioma near the geniculate ganglion].
A 57-year-old male was admitted with pulsatile tinnitus and hearing disturbance of the right ear and right peripheral facial palsy. Otological examination revealed a pulsatile red mass in his right ear and right conductive hearing disturbance. CT and MRI showed the mass lesion at his right middle fossa near the geniculate ganglion. Right external carotid angiogram disclosed a tumor stain fed by the middle meningeal artery. The tumor was removed via a combination of subtemporal and transmastoidal approaches. Histologically, this tumor was diagnosed as angiomatous meningioma partly with meningotheliomatous meningioma. Meningioma in this region is very rare. We discussed its clinical and radiological characteristics in comparison with chemodectoma and facial neurinoma at the geniculate ganglion.


Numerical evaluation of changes in the cytoplasmic microtubule complex of C3H mouse cells by optical diffractometry and of changes in cell shape by Fourier analysis.
MO mouse cells in culture on glass were treated with taxol, or nocodazole, or incubated at 4 degrees C to alter their cytoplasmic microtubule complex (CMTC). From each treated group and from an untreated group, 30 cells stained with an antiserum against tubulin, were photographed under the photomicroscope, and negatives were analysed by optical diffractometry. Differences between groups of cells were tested by variance analysis. Phase-contrast micrographs of the same cells were used for Fourier analysis of cell shape. Both types of analyses provided numerical objective data about changes in the CMTC and in cell shape that were typical for the kind of treatment. We conclude that optical diffractometry of immunostained cells and Fourier analysis of cell shape are complementary to photomicroscopy for the study of the CMTC in cell populations cultured on an artificial substrate.


Requirement of cysteine residues in exons 1-6 of the extracellular domain of the luteinizing hormone receptor for gonadotropin binding.
The functional importance of cysteine residues in the extracellular domain and the extracellular loops (EL1 and EL2) to hormone binding of the rat luteinizing hormone receptor (LHR) was investigated. For this purpose, cysteines in the seven-transmembrane holoreceptor (Form A) and its hormone-binding splice variant (Form B) were replaced by serine residues, and mutant receptors were expressed in COS1 and/or insect cells. Within the extracellular domain, individual replacement of all four cysteines from Exon 1 abolished hormone binding activity, and replacement of Cys-109 and Cys-134 from exons 5 and 6 caused a 75% decrease in both cell surface and total cellular solubilized LHR hormone binding activity. Mutations of Cys-257 and -258 (Exon 9), Cys-321 and -331, and Cys-417 and -492 of EL1 and EL2, respectively (Exon 11), showed no surface hormone binding activity on intact cells, but exhibited wild type levels of total hormone binding activity when recovered from detergent-solubilized cellular extracts. This finding indicated that expression of high affinity LHR binding activity at the cell surface is independent of the acquisition of the high affinity binding conformation. Other cysteine residues, including Cys-282 (exon 10), and Cys-314 (exon 11) were not essential for hormone binding activity or plasma membrane insertion. This study demonstrates that the functional hormone binding domain utilizes all cysteines N-terminal to exon 7 and localizes the binding site to this N-terminal region of the extracellular domain.


Functional brain connectivity during exposure to the scale and color of interior built environments.
Understanding brain activity linked to built environment exposure is important, as it may affect underlying cognitive, perceptual, and emotional processes, which have a critical influence in our daily life. As our time spent inside buildings is rising, and mental health problems have become more prevalent, it is important we investigate how design characteristics of the built environment impact brain function. In this study, we utilized electroencephalography to understand whether the design elements of scale and color of interior built environments modulate functional brain connectivity (i.e., brain network communication). Using a Cave Automatic Virtual Environment, while controlling indoor environmental quality responsible for physiological comfort, healthy adult participants aged 18-55 years (66 for scale, subset of 18 for color), were exposed to context-neutral indoor room scenes presented for two-minutes each. Our results show that both enlarging and reducing scale enhanced theta connectivity across the left temporoparietal region and right frontal region. We also found when reducing the built environment scale, there was a network exhibiting greater high-gamma connectivity, over the right frontoparietal region. For color, the condition (blue) contrasted to our achromatic control (white) increased theta connectivity in the frontal hemispheres. These findings identify a link between theta and gamma oscillations during exposure to the scale and color of the built environment, showing that design characteristics of the built environment could affect our cognitive processes and mental health. This suggests that, through the design of buildings, we may be able to mediate performance and health outcomes, which could lead to major health and economic benefits for society.


Vibrio cholerae in the horn of Africa: epidemiology, plasmids, tetracycline resistance gene amplification, and comparison between O1 and non-O1 strains.
The prevalence of Vibrio cholerae O1 and non-O1 has been investigated in numerous Somali regions of the Horn of Africa from 1983 to 1990. From January 1983 to January 1985 and between December 1986 and December 1990, no strains of V. cholerae O1 and 226 strains (5.3%) of V. cholerae non-O1 were isolated from 4,295 diarrhea cases. During a cholera epidemic in 1985 and 1986, the overall case-fatality rate was 13% and the attack rate was 3-3.5 per 1,000 population. Matched case-control studies identified a waterborne route of transmission. A drug-susceptible Ogawa strain from Ethiopia caused the introduction of the disease into northern Somalia. There were two major resistant derivatives of the original strain, and the one resistant to ampicillin, kanamycin, streptomycin, sulfonamide, and tetracycline (TC) predominated in the spreading disease. In 1986, susceptible Ogawa strains quickly displaced this resistant strain. The two incompatibility group C plasmids responsible for the resistance patterns had complex and scattered differences in their structures. Physical analysis of the plasmid DNA region coding for TC resistance demonstrated its genetic amplification in highly resistant variants of Ogawa strains.


Did the COVID-19 Pandemic Prolong the Time Till Diagnosis and Worsen Outcomes for Children with Acute Appendicitis?
Background and Objectives: Our aim was to see if the COVID-19 pandemic led to an increase of time until diagnosis, operation, and time spent in Emergency room (ER), and if it resulted in more cases of complicated appendicitis and complication rates in children. Materials and Methods: We conducted a retrospective analysis of patients admitted to the Pediatric Surgery Department with acute appendicitis during a 4-month period of the first COVID-19 pandemic and compared it to the previous year data-the same 4-month period in 2019. Results: During the pandemic, the time spent in the ER until arriving at the department increased significantly 2.85 vs. 0.98 h p < 0.001, and the time spent in the department until the operation 5.31 vs. 2.66 h, p = 0.03. However, the time from the beginning of symptoms till ER, operation time and the length of stay at the hospital, as well as the overall time until operation did not differ and did not result in an increase of complicated appendicitis cases or postoperative complications. Conclusions: The COVID-19-implemented quarantine led to an increase of the time from the emergency room to the operating room by 4 h. This delay did not result in a higher rate of complicated appendicitis and complication rates, allowing for surgery to be postponed to daytime hours if needed.


The Rab5A gene of marine fish, large yellow croaker (Larimichthys crocea), and its response to the infection of Cryptocaryon irritans.
Rab GTPases, members of the Ras superfamily, encode monomeric G-proteins. Rab proteins regulate key steps in membrane traffic transport and endocytic pathway of host immune responses. Rab5A is involved in immune regulation, particularly in T cell migration and macrophage endocytosis in higher vertebrates. However, little is known of the molecular structure of Rab5A gene in marine teleost fish species and its expression profile during the parasite infection. In this study, the full-length cDNA sequence and genomic structure of Rab5A gene of the large yellow croaker (Larimichthys crocea) (LycRab5A), one of the most economical marine fishes, were identified and characterized. The LycRab5A protein, containing the ATPase/GTPase binding motifs and the effector molecules binding motifs, was highly homologous to that of other animals. The expression plasmid containing LycRab5A cDNA fused with GST was engineered and transformed into Escherichia coli to produce recombinant protein GST-LycRab5A, which was purified to prepare a polyclonal antibody specifically against LycRab5A. Subcellular localization revealed that LycRab5A expressed in the membrane and cytoplasm. Based on real-time PCR and Western blot analysis, we found that both mRNA and protein of LycRab5A were expressed in all tissues we examined; especially it was highly expressed in blood and gill. Interestingly, both mRNA and protein of LycRab5A were substantially up-regulated when parasitic ciliate protozoan (Cryptocaryon irritans) was infected. The expression of LycRab5A was reached to the maximal level at 24 h after infection. The line of evidence suggested that LycRab5A might play an important role in large yellow croaker defense against parasite infection. Moreover, on the basis of protein interaction, it was found that the LycRab5A interacted with myosin light chain (designated as LycMLC), a crucial protein in the process of phagocytosis. This discovery might contribute better understanding to the molecular events involved in fish immune responses.


Exercise Variability Did Not Affect Muscle Thickness and Peak Force for Elbow Flexors After a Resistance Training Session in Recreationally-Trained Subjects.
The purpose of this study is to measure the acute effects of exercise variability on muscle thickness and physical performance after two resistance training (RT) protocols using the same or different exercises in recreationally-trained subjects. Fifteen resistance-trained men (23.1 ± 2.6 years, 83.4 ± 16.6 kg, 173.5 ± 8.3cm) performed one of two RT protocols: SINGLE: six sets of 10RM/two-minutes rest of the unilateral biceps curl exercise using cables or MIX: six sets of 10RM/two-minutes rest for the unilateral biceps curl exercises (cable: three sets and dumbbells: three sets, randomly). Muscle thickness (MT) and peak force (PF) were measured ten-minutes before (control), pre-RT session, and post-RT (immediately after and 15-minutes after). All acute RT variables were measured during both RT protocols: the maximal number of repetitions (MNR), the total number of repetitions (TNR), time under tension (TUT), and rating of perceived exertion (RPE). Two-way ANOVA (2 x 4) was used to test differences between RT protocol (SINGLE and MIX) and time (control, pre-test, post0, and post15) for MT and PF. Two-way ANOVAs (2 x 6) were used to test differences between RT protocol (SINGLE and MIX) and sets for MNR, RPEset, and TUT. For PF and MT, there were significant differences in time for both RT protocols (p < 0.05), however, there were not statistical differences between RT protocols. For MNR, RPEset, and TUT, there were significant differences in time (p < 0.05), however, there were not statistical differences between RT protocols. In conclusion, both RT protocols induced a similar increase in MT for elbow flexors and a reduction in peak force.


Sulfur-doped gallium phosphide nanowires and their optoelectronic properties.
Sulfur-doped gallium phosphide nanowires were synthesized in a high yield by a facile sublimation of ball-milled mixture powders in a confined reaction zone. The nanowires have diameters in the range of 50-200 nm and lengths up to tens of micrometers. They consist of single-crystalline zinc blende structure crystals with a (111) growth direction. Electron energy-loss spectroscopy reveals that the sulfur doping occurs in the uniform forms of the body. Amorphous Ga-O containing a self-catalyst growth mechanism is proposed based on the detailed characterizations. Photoluminescence shows strong visible emissions at room temperature, indicating their potential applications in light sources, laser or light emitting display devices.


Diversity in the fine specificity and idiotypic profile of mouse anti-HLA-DR monoclonal antibody elicited with the syngeneic anti-idiotypic monoclonal antibody F5-830.
Four hundred and sixty-six hybridomas were generated from a BALB/c mouse immunized with the syngeneic anti-idiotypic mAb F5-830 that recognizes an idiotope in the Ag-combining site of mAb AC1.59. At an appropriate concentration, the latter reacts with a determinant expressed by HLA-DR1, DRw8, and DRw9 Ag and subtypes of HLA-DR4 and DRw6 allospecificities. Serologic and immunochemical assays identified eight anti-HLA-DR anti-anti-idiotypic mAb. They are heterogeneous in their reactivity with a panel of HLA-typed B lymphoid cells: like mAb AC1.59, the anti-anti-idiotypic mAb MA1/38, MA1/40, MA1/47, and MA1/98 recognize the determinant shared by HLA-DR1, DRw8, and DRw9 Ag and subtypes of HLA-DR4 Ag. On the other hand, the anti-anti-idiotypic mAb MA1/52, MA1/157, MA1/281, and MA1/285 have a more restricted reactivity, inasmuch as the corresponding determinant(s) is detectable on only some of the allospecificities recognized by mAb AC1.59. Each anti-anti-idiotypic mAb varies in its extent of reactivity with HLA-DR allospecificities. These results suggest differences in the fine specificity of anti-HLA-DR anti-anti-idiotypic mAb and in the structural characteristics of the mAb AC1.59 defined determinant shared by HLA-DR1, DRw8, and DRw9 Ag and subtypes of DR4 allospecificities. Furthermore, the anti-anti-idiotypic mAb are heterogeneous in terms of expression of idiotopes and of their spatial relationship with their Ag-combining site. The heterogeneity in the characteristics of anti-HLA-DR antibodies elicited with anti-idiotypic mAb F5-830 suggests that the Id cascade triggered by immunization with incompatible HLA allospecificities may account for the changes in the anti-HLA antibody specificity that have been observed in the course of an immune response to mismatched HLA alloantigens.


Effect of Entecavir on the Intestinal Microflora in Patients with Chronic Hepatitis B: A Controlled Cross-Sectional and Longitudinal Real-World Study.
This study aimed to analyze the diversity of intestinal flora in patients with chronic hepatitis B (CHB) and investigate the effect of entecavir on the intestinal flora in these patients. Thirty patients with CHB and 30 healthy controls were recruited from the Department of Infectious Diseases and Department of Gastroenterology of Shanghai Tongji Hospital between January 2017 and December 2018. Stool samples were collected for the detection of intestinal flora by high-throughput sequencing. Patients with CHB received antivirus therapy with entecavir for 8 weeks. The biochemical and virological responses were assessed and the intestinal flora were compared. After entecavir treatment, the blood levels of alanine aminotransferase (ALT), interleukin-6 (IL-6), IL-8, tumor necrosis factor (TNF), and hepatitis B virus (HBV) DNA reduced significantly in patients with CHB and the species abundance of intestinal flora increased markedly. In patients with CHB, the unique genera included Butyrivibrio, Phaseolus acutifolius, and Prevotellaceae NK3B31 group before treatment and Howardella, Candidatus Stoquefichus, Citrobacter, Dysgonomonas, Faecalicoccus, Methanobrevibacter, Mitsuokella, Mobilitalea, Succinivibrio, Gluconobacter, and Plesiomonas after treatment. The abundance of the following genera increased significantly after entecavir treatment in patients with CHB: Clostridium sensu stricto 1, Erysipelotrichaceae UCG-007, and Intestinibacter. The abundance of Streptococcus, Atopobium, and Murdochiella reduced markedly after entecavir treatment in patients with CHB. After 8-week entecavir treatment, the blood biochemical, immunological, and virological responses improved significantly, the species abundance of intestinal flora increased markedly, and there were unique genera in patients with CHB before and after treatment.


Defence reaction in dental pulp after pulp capping and partial pulpectomy in dogs.
The dental pulp was capped indirectly or directly, or partial vital pulpectomy was performed on the 12 functionally most important teeth of 24 beagle dogs. For pulp capping, calcium hydroxide was used, followed by zinc phosphate as a lining, and the preparation was restored with amalgam or composite material. Histological sections were prepared and examined for degree and type of pulp inflammation (hyperaemia, pulpitis, necrosis or gangrene). Degenerative changes of dental pulp (vacuolation, calcification, amyloid or hyaline changes) were also determined. For indirect pulp capping the width of predentine in crown and root dental pulp was measured, and for direct pulp capping and partial pulpectomy (vital pulpotomy) the width and quality of the dentinal bridge were graded. The radical method of partial vital pulpectomy of the coronal part of the dental pulp in dogs produced better quality and continuity of the dentinal bridge than the less radical method of direct pulp capping. This was particularly obvious in small single root teeth such as incisors.


Laparoscopic correction of congenital portosystemic shunt in children.
Congenital portosystemic shunt is a rare clinical entity that may progress to jaundice, severe encephalopathy, and pulmonary hypertension and require surgical correction or coil embolization. We present a novel approach to the management of children with congenital portosystemic shunt by means of a minimally invasive surgical technique. Congenital portosystemic shunts were identified between the superior mesenteric vein and inferior vena cava in case 1 and between the splenic vein and left renal vein in case 2. Both of them were successfully ligated by laparoscopic approach, and catheters were subsequently replaced to monitor portal venous pressure. The patients tolerated the procedure well, and short-term results were excellent. Laparoscopic ligation of congenital portosystemic shunt is technically feasible and less invasive to the management of patients with congenital portosystemic shunts, preventing late onset, life-threatening complications.


MRI of endometriotic cysts in association with ovarian carcinoma.
Although mural nodules are considered to be the most important hallmark in the recognition of ovarian cancers accompanied with endometriotic cysts, benign neoplasms and even inflammatory diseases can show similar MRI findings. We sought to clarify the MRI characteristics of malignancy accompanied with endometriotic cysts of the ovary. Contrast-enhanced MRI was performed and endometriosis was pathologically confirmed in 49 patients with endometriotic cysts displaying mural nodules. Malignancy was pathologically diagnosed in 33 patients and benignity, in 16. Clinical data including patient age and MRI findings in terms of the size of the endometriotic cysts, number of loculi, presence of shading of the cysts, size of the mural nodules, signal intensity of the mural nodules on T1- and T2-weighted images, and contrast enhancement of the mural nodules were retrospectively reviewed. Statistical analysis of each parameter used the Mann-Whitney U test. The mean age of the patients and mean size of the endometriotic cysts were significantly higher in patients with a malignant condition than in those with a benign condition. Contrast enhancement of the mural nodules was observed in 97% of malignant and 44% of benign tumors. The size of the mural nodules was significantly larger in patients with a malignant condition than in those with a benign condition. Differences in size between the bilateral diseases, multilocularity, existence of shading, and the signal intensities of mural nodules were not significantly different between the malignant and benign conditions. Endometriotic cysts with enhanced mural nodules are not always complicated with malignancy. In elderly patients, the presence of large enhanced nodules on large endometriotic cysts is more likely to indicate malignancy.


Cardiac surgical patients' telephone calls use of a decision-making algorithm.
CARDIAC SURGERY, ALTHOUGH becoming relatively common, still poses a significant life stress for patients. As a result of managed care contracting, length of stay has decreased to an average of 4-6 days. The Transitional Care Model was the framework used in identifying a way to bridge the gap between home and hospital. Providing patients with the unit's telephone number and encouraging them to call with questions was the means established toward this end. Algorithms were developed around the seven most frequently occurring problems so that nurses would be able to offer interventions consistent with our program. Approximately 300 telephone calls have been logged in annually. Weekly review of the log revealed compliance with the algorithms and appropriate recommendations made by nurses.


The concept of sickness behavior: a brief chronological account of four key discoveries.
Neurons do not have receptors to detect bacteria or viruses, yet the presence of these microorganisms can cause a sickness behavior syndrome that includes, e.g., fever, anorexia, and lethargy. Because the immune system has receptors capable of detecting these non-cognitive stimuli, how the immune system transmits a message to the brain has been studied to understand why behavior is altered in sick animals. The focus has been on several cytokines secreted by leukocytes; these include interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha (TNF-alpha). These cytokines are secreted by activated mononuclear phagocytic cells, and numerous studies show that both peripheral and central injection of IL-1beta, IL-6, and TNF-alpha induce sickness behavior. Moreover, these cytokines and their receptors are present in the brain and inhibiting the secretion of cytokines or blocking their receptors in the brain blocks or abrogate the behavioral responses induced by inflammatory stimuli. Because the sickness behavior syndrome modulates the immune system and enhances recovery, the interplay between the immune system and central nervous system is an essential part of the overall host defense against pathogenic microorganisms. The purpose of this brief paper is to provide a chronological description of four critical advances that have led to the current understanding of how the immune system communicates with the brain to induce sickness behavior. Results from several key studies will be discussed, which showed that: (1) sickness behavior is a motivational state; (2) sickness behavior is a well-organized adaptive response to infection; (3) cytokines produced by activated leukocytes induce sickness behavior; and (4) cytokines transmit messages from the periphery to the brain using humoral and neural pathways.


The effects of residence duration in high background radiation areas on immune surveillance.
The effective dose received by humans from natural sources is about 2.4 mSv y(-1), but this is 10.2 mSv y(-1) for inhabitants of Ramsar, a city in northern Iran. Carcinogenesis is one of the most studied effects of radiation, especially in high doses. Nonetheless carcinogenesis of low doses is uncertain. A recent epidemiological study in high background radiation areas of Ramsar showed that the cancer incidence in this era is lower than neighbors. The reason of this different behavior is under study yet. NK cells, helper, and Cytotoxic T cells are most important components of the tumor immune surveillance. The counts and activities of these cells and also leukocytes, lymphocyte, neutrophil cells, and other important parameters were studied in the residents of Ramsar with different duration of exposure to chronic low dose radiation. Fifty residents of high background radiation areas, who were between 25 and 35 years and fully healthy, were selected randomly and their consent was obtained. Then, 2 cc fresh peripheral bloods were taken in sterile conditions. Complete blood cell counts were performed by an automatic hematology analyzer and CD4+, CD8+, NK, and CD107a+ cell counts were determined by monoclonal antibodies and flowcytometry. CD4+ and CD8+ percentages and the CD4/CD8 ratio were determined and the data were analyzed using SPSS 16. The percentages of CD4+ cells increase, but the counts of CD107a+ cells decline in higher exposure durations. The other parameters did not have significant regression with exposure duration. These confirm that living in high background radiation areas may induce changes in the immune system gradually and address more investigations.


Transverse-electric/transverse-magnetic polarization converter using 1D finite biaxial photonic crystal.
We show that by using a one-dimensional anisotropic photonic structure, it is possible to realize optical wave polarization conversion by reflection and transmission processes. Thus a single incident S(P) polarized plane wave can produce a single reflected P(S) polarized wave and a single transmitted P(S) polarized wave. This polarization conversion property can be fulfilled with a simple finite superlattice (SL) constituted of anisotropic dielectric materials. We discuss the appropriate choices of the material and geometrical properties to realize such structures. The transmission and reflection coefficients are calculated in the framework of the Green's function method. The amplitude and the polarization characteristics of reflected and transmitted waves are determined as functions of frequency, wave vector k(parallel) (parallel to the interface), and the orientations of the principal axes of the layers constituting the SL. Specific applications of these results are given for a SL consisting of alternating biaxial anisotropic layers NaNO(2)/SbSI sandwiched between two identical semi-infinite isotropic media.


Treatment strategies for obsessive-compulsive disorder.
In the last decades, the treatment of obsessive-compulsive disorder (OCD) has improved significantly with the introduction into the clinical practice of the selective serotonin reuptake inhibitors (SSRIs): this has led to a renewed interest in this condition and development of appropriate therapeutic strategies, including non-pharmacological techniques. The aim of this paper is to present a comprehensive and critical review of pharmacological and non-pharmacological treatments usually adopted in the management of OCD. MEDLINE and PubMed (1980 - 2009) databases were searched for English-language articles by using the following keywords: OCD, clomipramine, SSRIs, resistance, predictor of response, cognitive-behavioral therapy, exposure and response prevention, repetitive transcranial magnetic stimulation, deep brain stimulation, neurosurgery, electroconvulsive therapy. The reader will gain an exhaustive review of the advantages and disadvantages of the treatments usually adopted in OCD, with a special focus on resistance and clinical features that can be used as predictors of response. Obsessive-compulsive disorder is a common psychiatric condition that can be adequately managed with the currently available therapeutic options. Although a certain percentage of patients do not achieve complete clinical remission, improvement of some of their core symptoms permits them to live more satisfying lives and to reach a better social adjustment.


A covering method for detecting genetic associations between rare variants and common phenotypes.
Genome wide association (GWA) studies, which test for association between common genetic markers and a disease phenotype, have shown varying degrees of success. While many factors could potentially confound GWA studies, we focus on the possibility that multiple, rare variants (RVs) may act in concert to influence disease etiology. Here, we describe an algorithm for RV analysis, RareCover. The algorithm combines a disparate collection of RVs with low effect and modest penetrance. Further, it does not require the rare variants be adjacent in location. Extensive simulations over a range of assumed penetrance and population attributable risk (PAR) values illustrate the power of our approach over other published methods, including the collapsing and weighted-collapsing strategies. To showcase the method, we apply RareCover to re-sequencing data from a cohort of 289 individuals at the extremes of Body Mass Index distribution (NCT00263042). Individual samples were re-sequenced at two genes, FAAH and MGLL, known to be involved in endocannabinoid metabolism (187Kbp for 148 obese and 150 controls). The RareCover analysis identifies exactly one significantly associated region in each gene, each about 5 Kbp in the upstream regulatory regions. The data suggests that the RVs help disrupt the expression of the two genes, leading to lowered metabolism of the corresponding cannabinoids. Overall, our results point to the power of including RVs in measuring genetic associations.


Particle engineering of benzoic acid by spherical agglomeration.
The influence of process conditions on the properties of benzoic acid spherical agglomerates, are investigated. Agglomerates are produced in a fed-batch agitated tank process. Benzoic acid is dissolved in ethanol and the solution is mixed with the bridging liquid, before being fed into an agitated aqueous solution. A broader investigation has been performed using heptane as the bridging liquid, and in further experiments different bridging liquids are compared. The results show that the bridging liquid has an influence on the product properties, with diethyl ether and ethyl acetate being at the extreme end with no agglomerates formed at all. Using any of the other five solvents (chloroform, toluene, heptane, pentane, or cyclohexane) spherical agglomerates are formed, as long as a sufficient amount of the bridging liquid is used. The results show that the particle size and strength increase with increasing amount of bridging liquid, and with decreasing temperature. At amount of bridging liquid producing optimum particle shape, the largest agglomerates are produced when using either cyclohexane operating at 5 °C, or using toluene in a process at 20 °C. The highest particle fracture stress is obtained using toluene as the bridging liquid regardless of temperature. The particle shape depends on the bridging liquid, and becomes completely spherical when toluene or pentane is used. For four of the solvents the particle morphology improves with decreasing temperature, but for cyclohexane the result is the opposite. By continued agitation beyond the completion of the feeding, particle size and strength gradually increases and also the shape gradually becomes more spherical. High compressibility and low elastic recovery suggest that the particles are favorable for direct tabletting. The results are analyzed and discussed against capillary theory and granulation mechanisms.


Magnetic multipole line-cusp plasma generator for neutral beam injectors.
The magnetic multipole line-cusp device developed by MacKenzie and associates has been adapted for use as a neutral beam ion source. It has produced high-density, large volume, quiescent, uniform hydrogen plasmas, which makes it a potential candidate for use as a plasma generator for neutral beam injectors. The device is a water-cooled cylindrical copper discharge chamber (25 cm in diameter by 36 cm long) with one end enclosed by a set of extraction grids with a 15-cm-diam multi-aperture pattern. The chamber wall serves as an anode and is surrounded by an external system of rare-earth cobalt magnets arranged in a line-cusp geometry of 12 cusps; plasma is produced by electron emission from a hot cathode assembly. This source has achieved extracted beam currents of 12 A at 18.5 kV, radial plasma density uniformities of +/-5% over a 15-cm diameter, noise levels of less than +/-0.5%, and arc efficiencies (beam current/arc power) of 0.6 A/kW.


Dynamic heterogeneity flow promotes binding reactions in a dense system of hard annular sector particles.
We perform molecular dynamics simulations on a system of hard annular sector particles (ASPs) to investigate the reaction-dynamics relationship. The dimerization reaction zone, mixing reaction zone including dimerization and n-merization (n > 2), and arrested region are observed successively as area fraction φA increases from low to high. In this work, we focus on the properties of the concentrated arrested region (φA≥ 0.400). The results show that for systems at φA≥ 0.400, the ratio of n-merization increases with φA and n-merization finally becomes the dominant reaction in the system; dynamic heterogeneity (DH) is observed and is demonstrated to originate from the divergent size of clusters consisting of high-mobility particles; the particles with a high translational or rotational mobility are found to have a high ability to react with other particles at φA > 0.400; more interestingly, binding reactions are found to correlate spatially with DH at φA > 0.400. Our work sheds new light on understanding the role of DH in binding reactions or specific-site recognition assembly in a crowded environment.


Constrained X-ray tensor tomography reconstruction.
Quite recently, a method has been presented to reconstruct X-ray scattering tensors from projections obtained in a grating interferometry setup. The original publications present a rather specialised approach, for instance by suggesting a single SART-based solver. In this work, we propose a novel approach to solving the inverse problem, allowing the use of other algorithms than SART (like conjugate gradient), a faster tensor recovery, and an intuitive visualisation. Furthermore, we introduce constraint enforcement for X-ray tensor tomography (cXTT) and demonstrate that this yields visually smoother results in comparison to the state-of-art approach, similar to regularisation.


Unconventional Temperature Dependence of the Anomalous Hall Effect in HgCr_{2}Se_{4}.
At sufficiently low temperatures, many quantum effects, such as weak localization, electron-electron interaction (EEI), and Kondo screening, can lead to pronounced corrections to the semiclassical electron transport. Although low temperature corrections to longitudinal resistivity, ordinary Hall resistivity, or anomalous Hall (AH) resistivity are often observed, the corrections to three of them have never been simultaneously detected in a single sample. Here, we report on the observation of sqrt[T]-type temperature dependences of the longitudinal, ordinary Hall and AH resistivities at temperatures down to at least 20 mK in n-type HgCr_{2}Se_{4}, a half-metallic ferromagnetic semiconductor that can reach extremely low carrier densities. For the samples with moderate disorder, the longitudinal and ordinary Hall conductivities can be satisfactorily described by the EEI theory developed by Altshuler et al., whereas the large corrections to AH conductivity are inconsistent with the existing theory, which predicts vanishing and finite corrections to AH conductivity for EEI and weak localization, respectively.


Universal scaling in transient creep.
We present experimental evidence that pressure solution creep does not establish a steady-state interface microstructure as previously thought. Conversely, pressure solution controlled strain and the characteristic length scale of interface microstructures grow as the cubic root of time. Transient creep with the same scaling is known in metallurgy (Andrade creep). The apparent universal scaling of pressure solution transient creep is explained using an analogy with spinodal dewetting.


Rat liver aromatic L-amino acid decarboxylase: spectroscopic and kinetic analysis of the coenzyme and reaction intermediates.
The physiochemical properties of the coenzyme in rat liver aromatic L-amino acid decarboxylase (AADC) expressed in Escherichia coli have been studied by spectroscopic analysis of the enzyme, its reaction intermediates, and its complexes with substrate analogs. The enzyme, having one pyridoxal 5'-phosphate (PLP) per subunit, shows a prominent absorption maximum at 335 nm and a weaker one at 425 nm. The spectrum did not essentially change in the pH range of 6.0-8.0. When the coenzyme was excited at 335 nm, it emitted fluorescence primarily at 520 nm. The structure for the absorption at 335 nm was ascribed to the enolimine form of the PLP-lysine Schiff base. On the reaction of AADC with L-3,4-dihydroxyphenylalanine (L-dopa), the absorption of PLP showed biphasic changes before reaching a steady-state. Results of both pre-steady-state and steady-state kinetic analyses were consistent with the model that the reaction proceeds as shown in the equation: E + S<==>X1<==>X2-->E + P. The rate constant was determined for each step, and the Km value for L-dopa was obtained as 0.086 mM. The absorption spectra of the two intermediates, X1 and X2, were postulated from the calculation of the absorption changes during the first and the second steps of the reaction in which X1 and X2 showed an absorption maximum at 425 and 380 nm, respectively, with a concomitant decrease in absorbance at 335 nm. These predicted absorption spectra of X1 and X2 showed striking resemblances to those of AADC complexed with dihydroxyphenylacetic acid (DOPAc) and L-dopa methyl ester (DopaOMe), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


Organophosphorus and other inhibitors of brain 'neurotoxic esterase' and the development of delayed neurotoxicity in hens.
1. The delayed neurotoxic effects of some organophosphorus compounds are associated with phosphorylation of the active site of a nervous-tissue enzyme capable of hydrolysing phenyl phenylacetate. 2. Neurotoxic organophosphorus compounds and some carbamates and sulphonyl fluorides progressively inhibit the enzyme, attaching a substituent covalently at the active site. 3. Prolonged inhibition of the enzyme by phenyl N-benzyl-N-methylcarbamate or phenylmethane-sulphonyl fluoride does not lead to neurotoxic effects. 4. Prior inhibition of the enzyme by carbamates or sulphonyl fluorides in vivo prevents the neurotoxic effects of several organophosphorus compounds. 5. After dosage of hens with protective compounds, protection lasts until about 70% of the enzyme site again becomes available for phosphorylation. 6. Reaction of all the inhibitors at the active site of the enzyme leads to the same inhibitory effect with respect to hydrolysis of phenyl phenylacetate but does not in all cases lead to delayed neurotoxicity. It is concluded that the nature of the group substituted at the enzyme active site determines the toxic response.


Retention of 239Pu in the mouse lung and estimation of consequent dose following inhalation of sized 239PuO2.
The retention of 239Pu in the lungs of SAS/4 mice following inhalation exposure to sized 239PuO2 particles is described. When the initial alveolar deposition (IAD) was less than 200 Bq, retention of 239Pu could be described by a two-component exponential expression, about 90% being cleared with a half-time of about 40 days and the remainder with a half-time of about 150 days. Similar amounts of 239Pu were retained up to 3 months with IADs greater than 800 Bq, but clearance was impaired thereafter, the half-time of the second component increasing to about 720 days. The retention of 239Pu was independent of the particle size of the administered 239PuO2. Studies of the retention of 239Pu by individual lobes indicated that there were intrinsic interlobar differences which were enhanced at higher IADs. Lung clearance was also studied by the measurement of 239Pu in feces excreted by groups of mice in the period immediately prior to sacrifice. The estimation of radiation dose to lung is discussed.


Artificial Spores: Immunoprotective Nanocoating of Red Blood Cells with Supramolecular Ferric Ion-Tannic Acid Complex.
The blood-type-mismatch problem, in addition to shortage of blood donation, in blood transfusion has prompted the researchers to develop universal blood that does not require blood typing. In this work, the "cell-in-shell" (i.e., artificial spore) approach is utilized to shield the immune-provoking epitopes on the surface of red blood cells (RBCs). Individual RBCs are successfully coated with supramolecular metal-organic coordination complex of ferric ion (FeIII) and tannic acid (TA). The use of isotonic saline (0.85% NaCl) is found to be critical in the formation of stable, reasonably thick (20 nm) shells on RBCs without any aggregation and hemolysis. The formed "RBC-in-shell" structures maintain their original shapes, and effectively attenuate the antibody-mediated agglutination. Moreover, the oxygen-carrying capability of RBCs is not deteriorated after shell formation. This work suggests a simple but fast method for generating immune-camouflaged RBCs, which would contribute to the development of universal blood.


Ectodomain shedding of the Notch ligand Jagged1 is mediated by ADAM17, but is not a lipid-raft-associated event.
Notch signalling is an evolutionarily conserved pathway involved in cell-fate specification. The initiating event in this pathway is the binding of a Notch receptor to a DSL (Delta/Serrate/Lag-2) ligand on neighbouring cells triggering the proteolytic cleavage of Notch within its extracellular juxtamembrane region; a process known as proteolytic 'shedding' and catalysed by members of the ADAM (a disintegrin and metalloproteinase) family of enzymes. Jagged1 is a Notch-binding DSL ligand which is also shed by an ADAM-like activity raising the possibility of bi-directional cell-cell Notch signalling. In the present study we have unequivocally identified the sheddase responsible for shedding Jagged1 as ADAM17, the activity of which has previously been shown to be localized within specialized microdomains of the cell membrane known as 'lipid rafts'. However, we have shown that replacing the transmembrane and cytosolic regions of Jagged1 with a GPI (glycosylphosphatidylinositol) anchor, thereby targeting the protein to lipid rafts, did not enhance its shedding. Furthermore, the Jagged1 holoprotein, its ADAM-cleaved C-terminal fragment and ADAM17 were not enriched in raft preparations devoid of contaminating non-raft proteins. We have also demonstrated that wild-type Jagged1 and a truncated polypeptide-anchored variant lacking the cytosolic domain were subject to similar constitutive and phorbol ester-regulated shedding. Collectively these data demonstrate that Jagged1 is shed by ADAM17 in a lipid-raft-independent manner, and that the cytosolic domain of the former protein is not a pre-requisite for either constitutive or regulated shedding.


The palliative value of tumor necrosis factor alpha-based isolated limb perfusion in patients with metastatic sarcoma and melanoma.
Both patients with soft tissue sarcoma (STS) and patients with melanoma have limited treatment possibilities once the tumor has metastasized systemically. In patients with extremity STS or bulky melanoma in-transit metastases, the local tumor burden may be so problematic that, even in patients with systemically metastasized disease, an amputation may be inevitable. Isolated limb perfusion (ILP) has proven to be an excellent, local, limb-saving treatment option in patients with locally advanced extremity tumors. In this study, the authors investigated the palliative value of the ILP procedure to avoid amputation in patients who had Stage IV STS and melanoma. From 1991 to 2003, of 339 tumor necrosis factor alpha (TNF)-based ILPs, 51 procedures were performed for either Stage IV STS (n = 37 patients) or Stage IV melanoma (n = 14 patients). All patients underwent an ILP with TNF and melphalan of the upper limb (n = 4 patients) or the lower limb (n = 47 patients) with 26-140 mg melphalan and 2-4 mg TNF. The overall response in patients with Stage IV STS was 84%, and their median survival was 12 months after ILP. Limb salvage was achieved in 36 of 37 patients, with 1 patient undergoing amputation due to treatment toxicity. In the patients with Stage IV melanoma, the complete response rate was 43%. All patients with melanoma preserved their limb during a median survival of 7 months. TNF-based ILP is an excellent procedure that provided tumor control and limb salvage for the short survival of patients with metastasized, very bulky, limb-threatening tumors of the extremity.


Glomerular expression of neuronal activity-regulated pentraxin precedes the development of anti-Thy-1-induced progressive glomerulosclerosis.
Although it is clear that genetic predispositions play a role in progressive glomerulosclerosis, identification of specific genes is difficult because of natural genetic heterogeneity among individuals. We have reported a differential susceptibility to progressive glomerulosclerosis after induction of experimental glomerulonephritis anti-Thy-1 nephritis in Lewis rat substrains. Glomerular lesions in Lewis/Møllegard rats resolve spontaneously, whereas Lewis/Maastricht (Lew/Maa) rats develop progressive glomerulosclerosis. This predisposition for progressive glomerulosclerosis is governed by unknown genes that are expressed by renal cells. Here, differential gene expression analysis using a rat complementary DNA micro array revealed neuronal activity-regulated pentraxin (Narp) as a candidate gene involved in the remodeling or progression of damaged glomeruli. Glomerular Narp mRNA expression was monitored during disease in both Lewis sub strains. Immunohistochemistry revealed that Narp protein is exclusively expressed in Lew/Maa glomeruli 7 and 14 days after induction of anti-Thy-1 nephritis. Double-immunofluorescent staining showed that proliferating mesangial cells and parietal epithelial cells (PECs) at sites of adhesion to podocytes are partially Narp-positive, whereas podocytes fail to express Narp. Immunohistochemistry in nephritic Wistar, unilaterally nephrectomized Wistar and Sprague-Dawley rats showed that Narp protein is present only in strains that develop progressive glomerulosclerosis but never in strains that show remodeling. We conclude that Narp is a predictor for anti-Thy-1 nephritis-induced glomerulosclerosis and its expression by PECs may be involved in the progression to glomerulosclerosis.


[Interleukin-8 gene expression before and after the pulse treatment with methylprednisolone in primary nephrotic syndrome of children].
Primary nephrotic syndrome (PNS) is one of the common renal diseases in children, the pathogenesis of which is unclear. Evidences suggested that the proteinuria of NS is associated with the increased expression of the interleukin-8 (IL-8) genes. The purpose of the study was to evaluate the serum concentration and mRNA expression of IL-8 before and after the methylprednisolone pulse therapy (MPT) in PNS. Thirty children with PNS diagnosed from December 2000 to October 2001 were enrolled in this study (patients group). They were not treated with glucocorticoid at least within the recent 3 months. The children aged from 1.5 to 14 years (mean 8.5 years), and included 24 boys and 6 girls. Eighteen healthy children were selected as control group after physical examination. The children in control group aged from 2 to 14 years (mean 8 years) and included 13 boys and 5 girls. All patients were treated with MPT intravenously (30 mg/kg) for successive 3 days followed by oral prednisone. The serum protein level of IL-8 was measured by ELISA according to the manufacturer's instructions. Human IL-8 ELISA kit was purchased from Jingmei corporation Shenzhen, China. And the concentration was obtained after drawing the standard curve. The expression of IL-8 gene was detected with RT-PCR method. The important reverse transcription reagent kit and Trizol reagent were all bought from GIBCO BRL, USA. Statistical analysis of rank sum test was adopted for data processing. Comparison of the serum IL-8 level in the same patient before and after the therapy showed significant difference [29.59 (7.14-352.08) ng/L vs. 10.80 (4.27-77.86) ng/L, u = 4.26, P < 0.01]. The serum level in patient group before the therapy increased obviously in comparison to the level of the control group [10.37 (5.46-33.31) ng/L, u = 4.53 P < 0.01]. The serum level of IL-8 in patient group after the therapy also showed significant difference compared to the control group (u = 2.73 P < 0.01). The mRNA expression of IL-8 in the same patient before and after therapy showed significant difference [0.862 (0.776-0.95) vs. 0 (0-0.754), u = 3.902 P < 0.01]. IL-8 may be involved in the pathogenesis of PNS because of the significant increase of the serum IL-8 level and PBMC IL-8 mRNA expression in nephrotic syndrome children. Methylprednisolone pulse therapy in PNS was able to inhibit the protein production and PBMC mRNA expression of IL-8, so the therapeutic mechanism of MPT in PNS might be associated with the inhibition of IL-8 expression.


Signatures of spin-glass behaviour in PrIr2B2 and heavy fermion behaviour in PrIr2B2C.
The magnetic and transport properties of PrIr(2)B(2) and PrIr(2)B(2)C have been investigated by dc and ac magnetic susceptibility, specific heat, electrical resistivity and magnetoresistance measurements. PrIr(2)B(2) forms in CaRh(2)B(2)-type orthorhombic crystal structure (space group Fddd). At low fields the dc magnetic susceptibility of PrIr(2)B(2) exhibits a sharp anomaly near 46 K which is followed by an abrupt increase below 10 K with a peak at 6 K, and split-up in ZFC and FC data below 46 K. In contrast, the specific heat exhibits only a broad Schottky type hump near 9 K which indicates that there is no long range magnetic order in this compound. The thermo-remanent magnetization is found to decay very slowly with a mean relaxation time τ = 3917 s. An ac magnetic susceptibility measurement also observes two sharp anomalies; the peak positions strongly depend on the frequency and shift towards high temperature with an increase in frequency, obeying the Vogel-Fulcher law as expected for a canonical spin-glass system. The two spin-glass transitions occur at freezing temperatures T(f1) = 36 K and T(f2) = 3.5 K with shifts in the freezing temperatures per decade of frequency δT(f1) = 0.044 and δT(f2) = 0.09. An analysis of the frequency dependence of the transition temperature with critical slowing down, τ(max)/τ(0) = [(T(f)-T(SG))/T(SG)](-zν), gives τ(0) = 10(-7) s and exponent zν = 8, and the Vogel-Fulcher law gives an activation energy of 84 K for T(f1) and 27.5 K for T(f2). While zν = 8 is typical for spin-glass system, the characteristic relaxation time τ(0) = 10(-7) s is very large and comparable to that of superspin-glass systems. An addition of C in PrIr(2)B(2) leads to PrIr(2)B(2)C which forms in LuNi(2)B(2)C-type tetragonal structure (space group I4/mmm) and remains paramagnetic down to 2 K. The specific heat data show a broad Schottky type anomaly, which could be fairly reproduced with CEF analysis which suggests that the ground state is a CEF-split singlet and the first excited state singlet is situated 15 K above the ground state. The Sommerfeld coefficient γ∼300 mJ mol(-1) K(-2) of PrIr(2)B(2)C is very high and reflects a heavy fermion behaviour in this compound. We believe that the heavy fermion state in PrIr(2)B(2)C has its origin in low lying crystal field excitations as has been observed in PrRh(2)B(2)C.


A Drosophila mutant of LETM1, a candidate gene for seizures in Wolf-Hirschhorn syndrome.
Human Wolf-Hirschhorn syndrome (WHS) is a multigenic disorder resulting from a hemizygous deletion on chromosome 4. LETM1 is the best candidate gene for seizures, the strongest haploinsufficiency phenotype of WHS patients. Here, we identify the Drosophila gene CG4589 as the ortholog of LETM1 and name the gene DmLETM1. Using RNA interference approaches in both Drosophila melanogaster cultured cells and the adult fly, we have assayed the effects of down-regulating the LETM1 gene on mitochondrial function. We also show that DmLETM1 complements growth and mitochondrial K(+)/H(+) exchange (KHE) activity in yeast deficient for LETM1. Genetic studies allowing the conditional inactivation of LETM1 function in specific tissues demonstrate that the depletion of DmLETM1 results in roughening of the adult eye, mitochondrial swelling and developmental lethality in third-instar larvae, possibly the result of deregulated mitophagy. Neuronal specific down-regulation of DmLETM1 results in impairment of locomotor behavior in the fly and reduced synaptic neurotransmitter release. Taken together our results demonstrate the function of DmLETM1 as a mitochondrial osmoregulator through its KHE activity and uncover a pathophysiological WHS phenotype in the model organism D. melanogaster.