Asymptomatic carotid bruit in patients who undergo coronary artery surgery.
The clinical significance of the presence of carotid bruit was evaluated in 643 patients who underwent coronary artery surgery alone or in combination with other cardiac procedures. Carotid bruit was heard in 31 patients (5%) who were neurologically asymptomatic. All of them underwent coronary artery surgery without additional carotid procedures, and none of them developed neurological deficits during the postoperative period. Of the remaining 612 patients, 18 were identified as having a history of focal neurological disorders, and 9 of them had carotid bruit. All were analyzed by means of noninvasive tests and angiography. Five underwent carotid endarterectomy prior to (2 patients) and simultaneously with (3 patients) a coronary bypass procedure. Seven patients developed neurological deficits postoperatively. Most of the deficits were not lateralized or focal but diffuse, which suggests global cerebral ischemia not related to carotid disease. Only 1 patient had proven carotid obstructive disease and underwent successful carotid thrombendarterectomy 10 days postoperatively. This study, although based on limited material, supports the hypothesis that patients with asymptomatic carotid bruit can safely undergo coronary artery surgery. In the group of patients without neurological symptomatology, postoperative neurological deficits were rarely caused by occlusive carotid disease. However, patients with asymptomatic carotid bruit should be closely followed with the goal of identifying those who are at risk of developing neurological deficits.


Synthesis of renewable diesel with the 2-methylfuran, butanal and acetone derived from lignocellulose.
In this work, the hydroxyalkylation/alkylation of 2-methylfuran (2-MF) with acetone and butanal was investigated over a series of solid acid catalysts. Among the investigated candidates, Nafion-212 resin demonstrated the highest activity and stability for both reactions. Butanal is more reactive than acetone in hydroxyalkylation/alkylation, which can be rationalized by the steric and electronic effects of alkyl group. Finally, the hydroxyalkylation/alkylation products as prepared were directly hydrodeoxygenated over Pd/C, Pt/C and Ni-WxC/C catalysts. Evidently higher carbon yields to diesel were obtained when hydroxyalkylation/alkylation product of 2-MF with butanal was used as the feedstock. This can be considered as another advantage of 2-MF-butanal route. It is interesting that Ni-WxC/C catalyst exhibited excellent catalytic performance and good stability in the hydrodeoxygenation of hydroxyalkylation/alkylation products, which made it a promising substitute for the noble metal catalysts.


The antiapoptotic effect of heme oxygenase-1 in endothelial cells involves the degradation of p38 alpha MAPK isoform.
Heme oxygenase-1 (HO-1) protects endothelial cells (EC) from undergoing apoptosis. This effect is mimicked by CO, generated via the catabolism of heme by HO-1. The antiapoptotic effect of CO in EC was abrogated when activation of the p38alpha and p38beta MAPKs was inhibited by the pyridinyl imidazole SB202190. Using small interfering RNA, p38beta was found to be cytoprotective in EC, whereas p38alpha was not. When overexpressed in EC, HO-1 targeted specifically the p38alpha but not the p38beta MAPK isoform for degradation by the 26S proteasome, an effect reversed by the 26S proteasome inhibitors MG-132 or lactacystin. Inhibition of p38alpha expression was also observed when HO-1 was induced physiologically by iron protoporphyrin IX (hemin). Inhibition of p38alpha no longer occurred when HO activity was inhibited by tin protoporphyrin IX, suggesting that p38alpha degradation was mediated by an end product of heme catabolism. Exogenous CO inhibited p38alpha expression in EC, suggesting that CO is the end product that mediates this effect. The antiapoptotic effect of HO-1 was impaired when p38alpha expression was restored ectopically or when its degradation by the 26S proteasome was inhibited by MG-132. Furthermore, the antiapoptotic effect of HO-1 was lost when p38beta expression was targeted by a specific p38beta small interfering RNA. In conclusion, the antiapoptotic effect of HO-1 in EC is dependent on the degradation of p38alpha by the 26S proteasome and on the expression of p38beta.


Resin based restorative dental materials: characteristics and future perspectives.
This review article compiles the characteristics of resin based dental composites and an effort is made to point out their future perspectives. Recent research studies along with few earlier articles were studied to compile the synthesis schemes of commonly used monomers, their characteristics in terms of their physical, mechanical and polymerization process with selectivity towards the input parameters of polymerization process. This review covers surface modification processes of various filler particles using silanes, wear behaviour, antimicrobial behaviour along with its testing procedures to develop the fundamental knowledge of various characteristics of resin based composites. In the end of this review, possible areas of further interests are pointed out on the basis of literature review on resin based dental materials.


JM-20 protects against 6-hydroxydopamine-induced neurotoxicity in models of Parkinson's disease: Mitochondrial protection and antioxidant properties.
We have previously shown that JM-20, a new chemical entity consisting of 1,5-benzodiazepine fused to a dihydropyridine moiety, protects against rotenone-induced neurotoxicity in an experimental model of Parkinson's disease (PD). The aim of this study was to investigate the effect of a novel hybrid molecule, named JM-20, in in vitro and in vivo models of PD induced by 6-hydroxydopamine (6-OHDA). PC-12 cells were exposed to 6-OHDA and treated with JM-20. Protection against mitochondrial damage induced by 6-OHDA was also investigated using isolated rat brain mitochondria. We found that JM-20 protected PC-12 cells against cytotoxicity induced by 6-OHDA and inhibited hydrogen peroxide generation, mitochondrial swelling and membrane potential dissipation. For in vivo experiments, adult male Wistar rats were lesioned in the substantia nigra pars compacta (SNpc) by 6-OHDA administration. JM-20 was orally administered (10, 20 or 40 mg/kg), intragastric via gavage, 24 h after surgery and daily for seven days. Treatment with JM-20 significantly reduced the percentage of motor asymmetry and increased vertical exploration. It improved the redox state of the SNpc and the striatal tissue of these animals. Also, JM-20 reduced glial fibrillary acidic protein overexpression and increased tyrosine hydroxylase-positive cell number, both in SNpc. Altogether, these results demonstrate that JM-20 is a potential neuroprotective agent against 6-OHDA-induced damage in both in vitro and in vivo models. The mechanism underlying JM-20 neuroprotection against 6-OHDA appears to be associated with the control of oxidative injury and mitochondrial impairment.


Self-perceived stress and the personality of mothers of children with central auditory processing disorders - Differences from mothers of typically developing children.
To investigate the relationship between self-perceived global stress and the personality traits of mothers of children with central auditory processing disorders (APD), and make a comparison with mothers of typically developing (TD) children. A cross-sectional study using two questionnaires - the Perceived Stress Scale (PSS-10) and the Short Big Five Markers (IPIP-BFM-20) - to assess five personality dimensions: extraversion, agreeableness, conscientiousness, emotional stability, and intellect/imagination. The study material included 187 mothers, of whom 108 were mothers of children with APD. The average age of the children with APD was 10 years. The average level of global stress was similar in mothers of children with APD and mothers of TD children. Mothers of APD children had significantly lower scores for personality dimensions such as: emotional stability, conscientiousness, and intellect/imagination. Increased perceived stress level in mothers of children with APD was inversely correlated with extraversion, conscientiousness, and emotional stability. However, for both groups of mothers, the only significant predictor of global stress level was emotional stability. Mothers of children with APD, despite having similar global stress levels to other mothers, were different in terms of three personality dimensions, and these, especially lowered emotional stability, may play a negative role in coping with global self-perceived stress. The results of this study might be helpful in parental support interventions, including psychological therapy and counselling, and also in parental implementation interventions aimed at mothers of children with APD, especially those mothers who have high global stress and/or low emotional stability.


Structure of a novel Ca2+ and calmodulin-dependent cyclic nucleotide phosphodiesterase inhibitor KS-619-1.
The structure of KS-619-1, a potent inhibitor of Ca2+ and calmodulin-dependent cyclic nucleotide phosphodiesterase, was determined to be 8,13-dioxo-3-(2-oxopropyl)-5,6,8,13-tetrahydro-1,7,9,11- tetrahydroxybenz[a]naphtacene-2-carboxylic acid by spectral studies of KS-619-1 and its methyl derivative.


The role of optic nerve blood flow in the pathogenesis of glaucoma.
Many theories have surfaced regarding the exact mechanisms behind glaucomatous damage, but the complex nature of the disease and the inaccessibility of the internal structures of the human eye have limited current knowledge. Increased intraocular pressure is the risk factor most often associated with glaucomatous optic neuropathy; ischemic insult to the optic nerve has also been suggested as a possible cause of cellular damage. The aim of this review is to cover the possible role of optic nerve head hemodynamics in the pathogenesis of glaucoma.


Scale for identification of "at risk" families for underfive deaths.
India currently has an infant mortality rate (IMR) of 73 and aims to reach 60 per 1000 live births by 2000 A.D. The "at risk" approach which has been traditionally used for Maternal and Child Health services could help to reduce costs. The main objective of the study was to identity socio-demographic "risk factors" at family level for underfive deaths and assess the validity and efficiency of a risk index scale for this purpose. A computerised database on about 71,000 individuals in 28 villages in Ballabgarh Block exists since 1987. All the underfive deaths in the study area during the period 1991-95 were compared with age and sex matched controls on socio-demographic variables. All variables which were found significant at 10% level were taken in for logistic regression. The variables found significant were used to construct a ten point scale. This scaling system was applied to all the families with an underfive child during the two year period 1996-97. Validity and efficiency of this approach was calculated. A total of 849 cases and their age and sex matched controls were studied. The variables which were significantly associated with risk of underfive deaths were: not received measles vaccine (2.19; 1.58-3.04), history of sibling death (2.03; 1.19-3.45), maternal illiteracy (1.86; 1.23-2.81), never used a contraceptive (1.59; 1.17-2.14), having more than 4 children (1.46; 1.04-2.05). About 40% of houses were labelled as high risk. The sensitivity and specificity were around 60%. The improvement in efficiency by the risk approach was 33%. Risk approach is helpful in identifying families who are at greater risk of having underfive deaths. It results in a modest increase in the efficiency of services.


HIV-1 antibody testing strategy: evaluation of ELISA screening and western blot profiles in a mixed low risk/high risk patient population.
The Westmead HIV-1 antibody testing strategy showed that, regardless of ELISA screening kit manufacturer, sera which were repeatedly positive by two ELISA screening assays (one indirect and the other competitive format) had a 97-98% chance of being confirmed positive by Western blot for HIV-1 antibody or a less than 3% chance of either being identified as a seroconverter (1%) or a late stage AIDS patient (1.2%). Sera which were discordant by two ELISA screening assays had a less than 4% chance of either being confirmed positive by Western blot (2.5%) or identified as a seroconverter (1.3%). The incidence of non-specific indeterminate Western blot profiles were shown to be inversely proportional to the specificity of the ELISA screening kits used. The use of a recombinant envelope ELISA was able to confirm the viral specificity of HIV-1 envelope bands (gp160, 120 or 41) on Western blot. Guidelines suggested by the Australian National HIV Reference Laboratory, Fairfield Hospital, Melbourne, which categorized indeterminate or typical Western blot profiles into four reaction groups were found to be useful for the interpretation of Western blot patterns. A Western blot profile which is reactive for HIV-1 viral glycoproteins (gp160, 120 and 41) alone or in combination with not more than two other viral proteins (Indeterminate Group 4) and which is confirmed viral envelope specific by a recombinant envelope ELISA can be used as a predictor of seroconversion.


Age at exposure and Apc status influence the levels of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-DNA adducts in mouse intestine and liver.
We have previously shown that C57BL/6J-Min/+ (multiple intestinal neoplasia) mice, heterozygous for the Min mutation in the adenomatous polyposis coli gene, were more susceptible to intestinal tumorigenesis and had higher intestinal PhIP-DNA adduct levels after exposure to the food mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) on day 12 than on day 36 after birth [I.-L. Steffensen, H.A.J. Schut, J.E. Paulsen, A. Andreassen, J. Alexander, Intestinal tumorigenesis in multiple intestinal neoplasia mice induced by the food mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine: perinatal susceptibility, regional variation, and correlation with DNA adducts, Cancer Res. 61 (200l) 8689-8696]. In the present study, we have evaluated further whether this difference in susceptibility is related to adduct formation/removal, cell proliferation, apoptosis or expression of the nucleotide excision repair protein Xeroderma pigmentosum group A (XPA) in the intestines. Min/+ and +/+ (wild-type) mice were given a subcutaneous injection of 50 mg/kgbw PhIP on day 12 or 36, and the levels of PhIP-DNA adducts after 8, 12, 24 h, 3 or 7 days were quantified by use of 32P-postlabelling. In Min/+ mice, adduct levels were significantly higher after exposure on day 12 than on day 36 in the middle (1.5- to 8.5-fold) and distal (1.3- to 6.5-fold) small intestine from 8h to 3 days after administration of PhIP, but not in the colon and proximal small intestine. In the liver - a non-target organ for PhIP - adduct levels were 2.0- to 7.5-fold higher after exposure on day 12 than on day 36 from 8 to 24h after exposure. Adduct levels were generally higher in the middle (1.1- to 1.8-fold) and distal (1.1- to 2.0-fold) small intestines of Min/+ compared with +/+ mice after PhIP exposure on day 12, i.e. in the area of the intestines previously found also to have the highest number of tumors in Min/+ mice. PhIP increased cell proliferation and the number of apoptotic cells in the intestine and liver. However, the higher susceptibility to intestinal tumorigenesis in Min/+ mice exposed to PhIP at early age, or in Min/+ mice compared with +/+ mice, could not be explained by differences in cell proliferation, apoptosis or expression of the XPA repair protein.


Changes with age in total brain concentrations of biogenic amine neurotransmitters in coho salmon (Oncorhynchus kisutch Walbaum).
Whole brain content of several biogenic amines was determined in two age groups of coho salmon (Oncorhynchus kisutch Walbaum). Brains of presmolt salmon (about 5 months old) were compared to brains of homeward migrants (4 years old). Levels of dopamine and serotonin were significantly higher in the homeward migrants.


Utility of targeted next-generation sequencing assay to detect 1p/19q co-deletion in formalin-fixed paraffin-embedded glioma specimens.
Molecular classification of brain neoplasms is important for diagnosis, prognosis, and treatment outcome of histologically similar tumors. Oligodendroglioma is a glioma subtype characterized by 1p/19q co-deletion and IDH1/IDH2 mutations, which predict a good prognosis, responsiveness to therapy, and an improved overall survival compared to other adult gliomas. In a routine clinical setting, 1p/19q co-deletion is detected by interphase-FISH and SNP microarray, and somatic mutations are detected by targeted next-generation sequencing (NGS). The aim of this proof-of-principle study was to investigate the feasibility of using targeted NGS to simultaneously detect both 1p/19q co-deletion and somatic mutations. Among 247 consecutive patients with formalin-fixed paraffin-embedded brain tumors with various subtypes, NGS revealed 1p/19q co-deletion in 26 oligodendrogliomas and an IDH-wildtype astrocytoma, and partial loss across chromosomes 1p and 19q/whole-arm loss of 1p or 19q/copy neutral loss of heterozygosity in 11 nonoligodendrogliomas. For this 247 brain-tumor cohort, the overall sensitivity, specificity, and accuracy of detecting 1p/19q co-deletion by NGS in oligodendrogliomas were 96.2%, 99.6%, and 99.2%, respectively. The oligodendroglioma cohort had more mutations in IDH1/IDH2, CIC, FUBP1, and TERT, and fewer mutations in ATRX and TP53 than the nonoligodendroglioma cohort. This proof-of-concept study demonstrated that targeted NGS can simultaneously detect both 1p/19q co-deletion and somatic mutations, which can provide a more comprehensive genetic profiling for patients with gliomas using a single assay in a clinical setting.


Comparative study of the distribution of venous valves in the lower extremities of black Africans and Caucasians: pathogenetic correlates of prevalence of primary varicose veins in the two races.
The incidence of valves in the major veins of the lower extremities of Africans and Caucasians was studied. Valves are absent in the inferior vena cava in both races. In the common iliac veins, 1-7% of Caucasians and 1% of Africans have rudimentary valves. Normal valves exist in the following veins: the external iliac veins--22-33% of Caucasians and 9% of Africans; the femoral vein segment above the saphenofemoral junction--67-81% of Caucasians and 93% of Africans; the 3-cm-length of the femoral vein below the profundofemoral junction--90% of Caucasians and 100% of Africans; the terminal 3 cm of the great saphenous vein--100% Caucasians and 98% Africans. The lower incidence in the number of valves in Caucasians may account for the high prevalence (10-18%) of varicose veins in Caucasians; the reverse of this relationship is suggested for the low prevalence (1-2%) of the condition in Africans. Factors influencing the development of incompetent valves are discussed.


Transcriptional control by steroid hormones.
Gene regulation by steroid hormones leads to induction or repression of particular sets of genes. These effects are mediated by intracellular hormone receptors that, in the unliganded state, are maintained in an inactive form by unknown mechanisms possibly involving association with other cellular proteins. Induction of the mouse mammary tumor virus (MMTV) requires binding of the hormone receptor to a complex hormone-responsive element (HRE) located between 75 and 190 bp upstream from the start of transcription. The interaction of several receptor molecules with the four receptor binding sites in the HRE is highly cooperative on circular DNA molecules and each individual site is needed for optimal induction. In chromatin the HRE is precisely organized in phased nucleosomes. Following hormone treatment and receptor binding, changes in chromatin structure are detected that correlate with binding of transcription factors, including nuclear factor I, to the MMTV promoter. However, though nuclear factor I acts as a basal transcription factor on the MMTV promoter it does not cooperate with the hormone receptors in terms of binding to free DNA, and mutation of the nuclear factor I binding site does not eliminate hormonal stimulation. This residual induction is mediated by octamer motifs, upstream of the TATA box, that bind the ubiquitous transcription factor OTF-1. Mutation of these octamer motifs does not influence basal transcription in vitro, but completely abolishes the stimulatory effect of progesterone receptor.


A comparison of urethral pressure profilometry using microtip and double-lumen perfusion catheters in women with genuine stress incontinence.
To compare urethral pressure profilometry measurements using microtip transducer and double-lumen perfusion catheters. Prospective study. Tertiary referral urogynaecology unit. Three hundred and ninety two non-pregnant women with various lower urinary tract symptoms. Multichannel urodynamic investigations were performed using double-lumen perfusion catheters with external pressure transducers in 392 women. For those 301 (76.8%) diagnosed as having genuine stress incontinence, an investigation with microtip transducers followed. For data analysis, a mixed-effects model was used to evaluate changes in the urethral profilometry and an approach proposed by Bland and Altman was applied to access agreement between the two techniques. Of the 301 women with genuine stress incontinence, 272 were eligible for this study. In resting status, the differences between the two techniques were statistically significant (48.9cm H2O vs 73.4cm H2O, P = 0.0001) after adjusting for age. Moreover, the agreement study also confirmed that these two techniques do not agree sufficiently. Maximum urethral closure pressure obtained from the double-lumen catheter was significantly higher than that obtained from the microtip catheter. Use of the double-lumen catheter for the measurement of maximum urethral closure pressure can be considered a reliable technique since its reproducibility is as good as that of the microtip catheter. Therefore, the diagnosis of 'low pressure urethra' will be different between the two techniques.


Identification of beta-1,4-galactosyltransferase I as a target gene of HBx-induced cell cycle progression of hepatoma cell.
The hepatitis B virus-encoded HBx protein contributes to hepatocarcinogenesis with largely unknown mechanisms. It is widely known that N-linked oligosaccharides on glycoproteins are structurally altered during malignant transformation and these alterations are often associated with malignant transformation of cells. beta-1,4-galactosyltransferase I (GalT I) contributes to the biosynthesis of Galbeta-->4GlcNAc structure in the outer chain moieties of N-glycans. The difference of GalT I expression between normal liver and hepatoma tissues were investigated; the effect of HBx on GalT I expression was investigated; the role of GalT I in hepatoma cell growth and HBx-induced hepatoma cell growth were investigated. GalT I was highly expressed in hepatocellular carcinoma and transcriptionally up-regulated by HBx, and functioned as a positive growth regulator in hepatoma cells. Furthermore, decreasing the expression of GalT I in hepatoma cells reduced the ability of tumor formation in vivo and inhibited HBx-induced cell cycle progression. HBx-induced GalT I expression might contribute to HBx-mediated HCC development and progression.


Pentoxifylline treatment enhances antihypertensive activity of captopril through hemorheological improvement in spontaneously hypertensive rats during development of arterial hypertension.
The rheological properties of blood play a significant role in the onset and progression of arterial hypertension. The aim of our work was to evaluate the effect of the angiotensin-converting enzyme inhibitor captopril (20 mg/kg/d), pentoxifylline (PTX; 100 mg/kg/d), and the combination of captopril + PTX (20 + 100 mg/kg/d) on the hemodynamic and hemorheological parameters in spontaneously hypertensive rats (SHRs) during the development of arterial hypertension. In the group of animals that received captopril, the mean arterial pressure (MAP) was significantly lower by 30% due to a decrease in cardiac output of 23% and in total peripheral resistance (TPR) of 26% compared with the control group, whereas blood viscosity did not change significantly. PTX-treated SHRs had significantly lower MAP and TPR (by 19% and 31%, respectively) and blood viscosity (by 4%-6%) and a higher erythrocyte deformability index (by 1.5%-2%) than the control group. In the group of animals that received captopril + PTX, MAP and TPR were significantly lower, by 41% and 46%, than those in the control group, and by 16% and 27% than those in the captopril group. The combination of the angiotensin-converting enzyme inhibitor captopril and the hemorheological agent PTX, affecting various systems that are involved in blood pressure regulation, exhibits synergism and prevents an increase in arterial blood pressure during the development of arterial hypertension in SHRs (ie, from 5 to 11 weeks of life).


IL-10-producing regulatory B cells are decreased in patients with psoriasis.
Interleukin (IL)-10-producing regulatory B cells (B10 cells) have been shown to ameliorate psoriasis in mice. Human B10 progenitor cells are characterized as CD19(+)CD24(hi)CD38(hi) B cells that exert their regulatory functions via the production of IL-10. However, the role of B10 cells in the pathogenesis of psoriasis remains unclear. We examined B10 cells in patients with psoriasis and healthy controls. Peripheral blood mononuclear cells were isolated from psoriasis patients without a history of receiving any immunosuppressants during the 6-month period before enrollment in the study. Using flow cytometry, we determined the frequencies of blood B cell subsets, B10 progenitor cells, and B10 cells for 31 patients with psoriasis and 26 healthy controls. Both psoriasis patients and healthy controls showed similar frequencies of total B cells, IgD(+)CD27(-) naïve B cells, and IgD(-)CD27(+) memory B cells. However, the frequency of CD19(+)CD24(hi)CD38(hi) B10 progenitor cells was significantly higher in patients with psoriasis than in the healthy controls. In contrast, the frequency of B10 cells in patients with psoriasis was significantly lower than that in healthy controls. Furthermore, treatment with immunosuppressants resulted in a decrease in B10 progenitor cells and an increase in B10 cells. B10 progenitor cells were increased, while IL-10-producing regulatory B10 cells were decreased in patients with psoriasis, suggesting that B10 cells may be functionally impaired in patients with psoriasis.


Assessment of Countries' Preparedness and Lockdown Effectiveness in Fighting COVID-19.
The aim of this study was to assess the risks in confronting the coronavirus disease 2019 (COVID-19) pandemic and the ongoing lockdown effectiveness in each of Italy, Germany, Spain, France, and the United States using China's lockdown model simulation, and cases forecast until the plateau phase. Quantitative and qualitative historical data analysis. Total Risk Assessment (TRA) evaluation tool was used to assess the pre-pandemic stage risks, pandemic threshold fast responsiveness, and the ongoing performance until plateau. The Infected Patient Ratio (IPR) tool was developed to measure the number of patients resulting from 1 infector during the incubation period. Both IPR and TRA were used together to forecast inflection points, plateau phases, intensive care units' and ventilators' breakpoints, and the Total Fatality Ratio. In Italy, Spain, France, Germany, and the United States, an inflection point is predicted within the first 15 d of April, to arrive at a plateau after another 30 to 80 d. Variations in IPR drop are expected due to variations in lockdown timing by each country, the extent of adherence to it, and the number of performed tests in each. Both qualitative (TRA) and quantitative (IPR) tools can be used together for assessing and minimizing the pandemic risks and for more precise forecasting.


Evaluation of the clinical characteristics and prognostic factors of gastrointestinal mucosa-associated lymphoid tissue (MALT) lymphoma.
This study was undertaken to evaluate the clinical characteristics, prognostic factors, and long-term outcomes of patients with mucosa-associated lymphoid tissue (MALT) lymphoma in the gastrointestinal (GI) tract. Clinical and pathological features of patients with MALT lymphoma in the GI tract, who were treated consecutively at Tianjin Medical University Cancer Institute and Hospital from 2001 to 2011, were evaluated retrospectively. Among a total of 99 identified cases, 79.79% of lymphomas were localized in the stomach, 20.20% in the intestinal tract, and disseminated disease was detected in 35.4% of cases. The estimated 5-year overall survival (OS) and 5-year progression-free survival (PFS) rates were 73.1% and 65.1%, respectively. The comparison between stomach and intestinal tract lymphomas demonstrated no significant difference in characteristics, but nodal involvement was significantly lower in gastric MALT lymphoma (26.6%) as compared with intestinal tract MALT lymphoma (60%, P = 0.006). The outcomes of gastric and intestinal MALT lymphomas were similar (OS, P = 0.492; PFS, P = 0.408), and so was the survival between proximal and distal gastric lymphomas (OS, P = 0.077; PFS, P = 0.181). Serum lactate dehydrogenase level above normal was identified as the only adverse prognostic factor for both OS and PFS. The clinical characteristics and outcomes demonstrated no significant differences between gastric and intestinal tract MALT lymphomas. Serum lactate dehydrogenase level was an independent prognostic factor for the survival of GI MALT lymphoma.


Ultrasound-guided percutaneous fine-needle aspiration of solid pancreatic neoplasms: 10-year experience with more than 2,000 cases and a review of the literature.
To evaluate the diagnostic accuracy and complication rate of percutaneous ultrasound-guided fine-needle aspiration (US-FNA) of solid pancreatic neoplasms through the analysis of 10-year experiences of two centres. Clinical, radiological and pathologic data of 2,024 patients with solid pancreatic masses who underwent US-FNAs were retrospectively evaluated. Indications for aspiration were: unresectable lesions before neo-adjuvant therapy; doubtful imaging findings; and suspicion of uncommon neoplasms with prognostic or therapeutic implications such as metastases or lymphoma. US-FNAs were performed using aspiration needles with a cytopathologist present in centre 1. In centre 2, cytologic samples were collected with Chiba needles and separately evaluated by a cytopathologist. US-FNA had a diagnostic sample rate of 92.2 % (centre 1: 95.9 %; centre 2: 87.2 %). US-FNA repetition after non-diagnostic samples provided a diagnosis in 86.3 % of cases. Sensitivity, specificity, positive and negative predictive values, and accuracy were 98.7 %, 100 %, 100 %, 75.5 %, and 98.7 %, respectively. The complication rate was 0.8 %. Percutaneous US-FNA is a sensitive, accurate and safe method for the invasive diagnosis of solid pancreatic neoplasms. The use of aspiration needles and the on-site presence of a cytopathologist may lead to a high rate of diagnostic samples, thus reducing the need for US-FNA repetition. • Percutaneous ultrasound-guided fine-needle aspiration of pancreatic neoplasms is sensitive and accurate. • The short-term complication rate of percutaneous ultrasound-guided fine-needle aspiration is low. • Technical aspects may influence the rate of diagnostic samples.


Current strategies employed in the manipulation of gene expression for clinical purposes.
Abnormal gene expression level or expression of genes containing deleterious mutations are two of the main determinants which lead to genetic disease. To obtain a therapeutic effect and thus to cure genetic diseases, it is crucial to regulate the host's gene expression and restore it to physiological conditions. With this purpose, several molecular tools have been developed and are currently tested in clinical trials. Genome editing nucleases are a class of molecular tools routinely used in laboratories to rewire host's gene expression. Genome editing nucleases include different categories of enzymes: meganucleses (MNs), zinc finger nucleases (ZFNs), clustered regularly interspaced short palindromic repeats (CRISPR)- CRISPR associated protein (Cas) and transcription activator-like effector nuclease (TALENs). Transposable elements are also a category of molecular tools which includes different members, for example Sleeping Beauty (SB), PiggyBac (PB), Tol2 and TcBuster. Transposons have been used for genetic studies and can serve as gene delivery tools. Molecular tools to rewire host's gene expression also include episomes, which are divided into different categories depending on their molecular structure. Finally, RNA interference is commonly used to regulate gene expression through the administration of small interfering RNA (siRNA), short hairpin RNA (shRNA) and bi-functional shRNA molecules. In this review, we will describe the different molecular tools that can be used to regulate gene expression and discuss their potential for clinical applications. These molecular tools are delivered into the host's cells in the form of DNA, RNA or protein using vectors that can be grouped into physical or biochemical categories. In this review we will also illustrate the different types of payloads that can be used, and we will discuss recent developments in viral and non-viral vector technology.


Regulation of S6 kinase activity in Madin-Darby canine kidney renal epithelial cells.
Mitogenic stimulation of mammalian cells results in increased serine phosphorylation of ribosomal protein S6. Phorbol esters, which stimulate protein kinase C activity, can also increase S6 phosphorylation. In order to further investigate the role of protein kinase C in the activation S6 kinase, we studied the stimulation of an S6 kinase activity in response to phorbol ester and epinephrine in a renal epithelial cell line, Madin-Darby canine kidney cells (MDCK). In these cells, S6 phosphorylating activity in cytosolic extracts was increased following the addition of phorbol ester to the intact cells. S6 kinase and protein kinase C activities were measured in separate fractions prepared by DEAE-Sephacel fractionation of cytosolic extracts prepared from the same cells. The time course and dose-response curves for the effects of phorbol 12-myristate 13-acetate (PMA) on S6 kinase activity were similar to those for its effects on protein kinase C binding to the membrane fraction, indicating that S6 kinase activation was correlated with protein kinase C activation. Epinephrine, acting via alpha1-adrenergic receptors, also stimulated S6 kinase activity in MDCK cells; the magnitude of this effect was similar to that of PMA. However, epinephrine causes only a slight and transient association of protein kinase C with the membrane. The effect of epinephrine on S6 kinase activity, unlike that of PMA, was dependent on the presence of extracellular calcium. A23187, a calcium ionophore, could also stimulate S6 kinase activity. These results suggest that S6 kinase can be activated through more than one signaling pathway in MDCK cells. The properties of the PMA-stimulated S6 kinase were further investigated following partial purification of the enzyme. The S6 kinase was distinct from protein kinase C by several criteria. Noteably, the S6 kinase was highly specific for S6 as substrate. These results show that phorbol esters, acting through protein kinase C, stimulate the activity of a unique S6 kinase. This S6 kinase can also be activated through a signaling pathway that appears to be dependent on increased intracellular calcium.


Nephrectomy for the failed renal allograft in children: predictors and outcomes.
There are no guidelines for the removal of a failed renal allograft, and its impact on subsequent dialysis and retransplantation has not yet been described. We performed a 10-year review of allograft failure to study the factors that determined an outcome of transplant nephrectomy and choice of subsequent renal replacement therapy in children with or without nephrectomy. A total of 34 children developed graft failure over the 10-year study period, of whom 18 (53 %) required transplant nephrectomy. The median graft survival was 1.1 (range 0.2-10.6) versus 7.5 (1.5-15.0) years in the nephrectomy and non-nephrectomy groups, respectively (p = 0.011). Children with graft failure within 1 year of transplantation were four-fold more likely to require transplant nephrectomy than those with graft failure after 1 year (p = 0.04). Renal biopsy performed at ≤ 8 weeks prior to graft loss showed Banff grade II acute rejection in 13 of the 18 children who required subsequent nephrectomy versus three of the 13 children who did not need nephrectomy (p = 0.01). Inflammation (fever, graft tenderness and raised C-reactive protein (CRP) in the 2 weeks preceding graft failure) was seen in 66 % of nephrectomized children, but not in any in the non-nephrectomy group (p = 0.0003 for CRP between groups). Banff II rejection, an inflammatory response and the time post-transplantation significantly and independently predicted the outcome of nephrectomy (p = 0.008, R (2) = 67 %). Human leukocyte antigen (HLA) antibody levels after graft failure were higher in the nephrectomy group (p = 0.0003), but there was no difference between groups in terms of the presence or class of donor-specific antibodies. Of the children with graft failure, 82 % required dialysis (61 % hemodialysis) and 35 % have to date been successfully retransplanted. Children with Banff II rejection, an inflammatory response and early graft loss are more likely to require transplant nephrectomy. Nephrectomy may be associated with higher circulating HLA antibody levels.


Accelerating shipping decarbonisation: A case study on UK shore power.
Shore power connects ships to land-side electricity grids, cutting fuel use in port to reduce carbon dioxide emissions and air pollution. It also enables the transition towards greater use of electric vessels. Despite these benefits, the global deployment of shore power is slow, particularly in countries such as the UK. This paper presents findings from a qualitative case study using two theoretical frameworks from the transitions literature to assess barriers to UK shore power deployment. The findings identify a need for capital funding and taxation policies, and illustrate that shipping's low status in the political hierarchy impedes implementation. Measures to strengthen interactions between shipping actors would help increase the political pressure required to implement policies supporting shore power and shipping more broadly. These changes in the governance and organisation of shipping are essential to deliver the near-term emission cuts necessary for aligning UK shipping emissions with the Paris Agreement.


The plasma pharmacokinetics and tissue distribution of dimethyl sulfoxide in mice.
We defined the plasma and tissue concentrations and pharmacokinetics of dimethyl sulfoxide (DMSO) in 22-34 g male Swiss Webster mice injected i.v. with 15% DMSO at a dosage of 1.5 mg per g. Concentrations of DMSO in alkalinized, perchloric acid extracts of tissue and plasma were determined by gas-liquid chromatography. Plasma concentrations of DMSO declined in a biexponential fashion that was well described by the equation Ct = 2.36 exp(-0.449 t) + 1.28 exp(-0.00768 t), indicating a t 1/2 (alpha) of 1.5 min and t 1/2 (beta) of 90 min. DMSO was rapidly and extensively distributed through tissues and was not concentrated in any particular tissue, although at 1 min after injection, the brain contained the lowest concentration of DMSO of any tissue studied. By 8 hr after injection, there was little DMSO in plasma or any tissue. Intravenous injection of DMSO produced neuro-muscular disturbances, hemolysis, and hemoglobinuria in all animals. Intravenous injection of DMSO produced little increase in plasma osmolality and did not produce any histological evidence of central nervous system or renal tubular damage.


Detection of endotoxin-like interleukin-1-inducing activity during in vitro dialysis.
In order to study the integrity of dialysis membranes to pyrogens, the dialysate side of a closed loop hemodialysis (HD) circuit was challenged with E. coli microfiltrate containing 500 ng/ml endotoxin. Three solutions, a) tissue culture medium/saline, b) 5% human serum albumin, and c) 10% fresh human plasma, were circulated in the blood loop for five hours. Samples drawn from the blood side were assayed for interleukin-1 (IL-1)-inducing activity on human mononuclear cells (MNC) in vitro. No IL-1-inducing substances were detected when saline or culture medium was circulated in the blood loop. Circulating 5% human serum albumin revealed IL-1-inducing activity in the samples drawn only after five hours of HD. However, the addition of 10% fresh human plasma to the blood side resulted in the appearance of an IL-1-inducing substance(s) after 15 minutes of HD. After 30 minutes, maximum IL-1-inducing activity was observed (control stimulation index, 3.30 +/- 0.67 SEM vs. 7.59 +/- 1.50, P less than 0.02). The IL-1-inducing activity of the samples was completely inhibited by polymyxin B, a cationic antibiotic which blocks the IL-1-inducing activity of endotoxin. Additional experiments demonstrated that in vitro MNC IL-1-production induced by the same E. coli microfiltrate is enhanced in the presence of 10% plasma. These studies demonstrate that: (a) in the presence of plasma, IL-1-inducing factors pass into the blood compartment of a dialysis system challenged with bacterial pyrogen; and (b) MNC production of IL-1 is enhanced in the presence of plasma.(ABSTRACT TRUNCATED AT 250 WORDS)


Actin and flagellin may have an N-terminal relationship.
There is an 8/13 sequence match between actin and flagellin in their N-terminal regions.


New potential treatment for cardiovascular disease through modulation of hemoglobin oxygen binding curve: Myo-inositol trispyrophosphate (ITPP), from cancer to cardiovascular disease.
The human body is a highly aerobic organism, which needs large amount of oxygen, especially in tissues characterized by high metabolic demand, such as the heart. Inadequate oxygen delivery underlies cardiovascular diseases, such as coronary artery disease, heart failure and pulmonary hypertension. Hemoglobin, the oxygen-transport metalloprotein in the red blood cells, gives the blood enormous oxygen carrying capacity; thus oxygen binding to hemoglobin in the lungs and oxygen dissociation in the target tissues are crucial points for oxygen delivery as well as potential targets for intervention. Myo-inositol trispyrophosphate (ITPP) acts as an effector of hemoglobin, shifting the oxygen dissociation curve to the right and increasing oxygen release in the target tissues, especially under hypoxic conditions. ITPP has been successfully used in cancer studies, demonstrating anti-cancer properties due to prevention of tumor hypoxia. Currently it is being tested in phase 2 clinical trials in humans with various tumors. First preclinical evidence also indicates that it can successfully alleviate myocardial hypoxia and prevent adverse left ventricular and right ventricular remodeling in post-myocardial infarction heart failure and pulmonary hypertension. The aim of the article is to summarize the current knowledge on ITTP, as well as to determine the prospects for its potential use in the treatment of many cardiovascular disorders.


The effectiveness of cervical screening: a population-based case-control study.
The cervical smear histories of 36 women with invasive cervical cancer were compared to those of 120 age-matched controls, drawn from local registrar's offices. Of the cases 47% were screened at least once, while for the controls this figure was 68%. The relative risk of getting invasive cervical cancer for women screened at least once compared to women who were never screened was 0.32. The most important confounding factor was age at first intercourse. Contrary to other studies however, it was found that women who were younger when having first intercourse were screened more often. After correcting the relative risk of screened vs unscreened for age at first intercourse, the relative risk became 0.22. When the length of the interval since the last smear was considered, the relative risk was 0.18 when the smear was made between 2 and 5 years earlier and 0.30 when this smear was made more than 5 years earlier. These results support the assumption that screening is effective in the prevention of invasive cancer of the uterine cervix. Even a screening interval of more than 5 years provides considerable protection.


In vivo studied on the metabolism of dibenzo [c,f]-[1,2] diazepine.
The in vivo metabolism of dibenzo [c,f]-[1,2] diazepine (I) was studied after i.p. administration to rats, in order to observe the influence of the heteroatom on the metabolic pathway. Metabolites were separated by chromatography and their structures elucidated by mass spectrometry, by both gas chromatography coupled with mass spectrometry and the direct inlet system. Six metabolites were identified, some of them by direct comparison with authentic samples.


Sensitivity of young rats to nicotine exposure: Physiological and biochemical parameters.
This work has investigated the effects of prolonged exposure of young rats to nicotine on some physiological and biochemical parameters. Wistar male rats (30 days old) were treated (s.c.) with saline or nicotine 5mg/kg/day for 28 or 56 days. They received five injections (1mg/kg) per day (8, 10, 12:00 a.m., 2 and 4:00 p.m.) on the dark period of the cycle. Nicotine exposure for 56 days reduced body and liver weights. Moreover, nicotine exposure for 28 or 56 days decreased the hepatic glycogen but not blood glucose levels. The activities of blood and hepatic PBG-synthase, and blood and cerebral acetylcholinesterase were not affected by in vivo exposure. However, these activities were inhibited by nicotine in vitro. Results show that although high levels of plasma cotinine were found in both intervals of exposures, the parameters here analyzed were not affected by prolonged nicotine exposure except the storage of glucose, and body and liver weights.


Neuronal correlates of appetite regulation in patients with schizophrenia: is there a basis for future appetite dysfunction?
Given the undesired metabolic side effects of atypical antipsychotic medication it is important to understand the neuronal basis related to processing of appetite regulation in patients affected by schizophrenia. Here we used functional magnetic resonance imaging (fMRI) to assess brain activity in response to food cues and neutral stimuli in twenty patients with schizophrenia and eleven healthy individuals. In addition to clinical and dietary habits assessments, we collected, in patients, measurements of fasting glucose, ghrelin, leptin, insulin, prolactin and lipids blood concentration and we correlated the cerebral activity with clinical and metabolic measures. Both groups engaged a common neuronal network while processing food cues, which included the left insula, primary sensorimotor areas, and inferior temporal and parietal cortices. Cerebral responses to appetitive stimuli in thalamus, parahippocampus and middle frontal gyri were specific only to schizophrenic patients, with parahippocampal activity related to hunger state and increasing linearly over time. Antipsychotic medication dosage correlated positively with a cognitive measure reflecting food cravings, whereas the severity of the disease correlated negatively with a cognitive measure indicating dietary restraint in eating habits. These cognitive variables correlated, in turn, with parahippocampal and thalamic neuronal activities, respectively. We identified a specific neural substrate underlying cognitive processing of appetitive stimuli in schizophrenia, which may contribute to appetite dysfunction via perturbations in processing of homeostatic signals in relation to external stimuli. Our results also suggest that both antipsychotic medication and the disease severity per se could amplify these effects, via different mechanisms and neuronal networks.


Adherence to national malaria clinical management and testing guidelines in selected private clinics of Gambela Town, Gambela Region, Ethiopia: a mixed method study.
The World Health Organization World Malaria Report of 2019 indicated an estimated 228 million cases of malaria occurred worldwide in 2018. More than 75% of the total area of Ethiopia is malarious, making malaria a leading public health problem in Ethiopia. Adherence to clinical guidelines improves the quality of care received by patients, thus improving patient outcomes. This study investigates healthcare workers' adherence to malaria testing and treatment guidelines in selected private clinics of Gambela Town, Ethiopia. A mixed study design involving a retrospective review of 425 patient files and 20 healthcare worker interviews in private clinics was implemented. Data were collected using pre-tested data collection forms. The collected data were then cleaned and entered into statistical software for analysis, with a level of significance set at < 0.05. A qualitative analysis was also conducted using healthcare worker interviews to identify the existing barriers to guideline adherence. Among the 430 cases of suspected malaria, only 65% were tested for malaria. Of those tested, 75% tested positive and 25% tested negative. The most common co-morbidity in patients treated for malaria was anaemia (30%), followed by gastroenteritis (10%). Patients with co-morbidities were more likely to receive appropriate treatment (p = 0.03) compared to those without co-morbidities. All healthcare workers interviewed were aware of the existence of the malaria treatment guidelines. However, many were not aware of the contents of the guidelines and only 40% had been trained to understand the guidelines. Overall, 85% of the workers claimed to adhere to guidelines, with 15% claiming non-adherence. The gap between knowledge of the malaria treatment guidelines and their application by healthcare workers remains wide. The level of knowledge of these guidelines was also low. Continuous training, follow-up, supportive supervision, and improved adherence to the malaria guidelines are therefore recommended.


Phase II trial of topotecan as a 21-day continuous infusion in patients with advanced or metastatic adenocarcinoma of the pancreas.
The aim of this study was to determine the efficacy and toxicity of topotecan administered as a 21-day continuous intravenous infusion in patients with advanced or metastatic adenocarcinoma of the pancreas. 26 previously untreated patients with advanced or metastatic pancreatic adenocarcinoma received topotecan at a dose of 0.5 mg/m2/day or 0.6 mg/m2/day as a continuous intravenous infusion for 21 days. Courses were repeated every 28 days. 26 patients were assessable for response and toxicity on an intent-to-treat basis. The initial 8 patients at a starting dose of 0.6 mg/m2/day experienced unacceptable myelosuppression and dose delays. The subsequent 18 patients, therefore began therapy at a dose of 0.5 mg/m2/day. The major toxicity of topotecan at this dose and schedule was myelosuppression, which was reversible and non-cumulative. There were no complete responses and two partial responses for a total response rate of 8% (95% confidence interval, 1-25%). Response durations were 17 and 45 weeks. Stable disease was seen in 3 patients. The median time to progression for all patients was 8 weeks and the median survival was 20 weeks. Topotecan given as a 21-day continuous intravenous infusion has a similar response rate and median survival to our previously reported study of the 5-day short infusion regimen in pancreatic carcinoma.


The forewing of a black cicada Cryptotympana atrata (Hemiptera, Homoptera: Cicadidae): Microscopic structures and mechanical properties.
Insects in nature flap their wings to generate lift force and driving torque to adjust their attitude and control stability. An insect wing is a biomaterial composed of flexible membranes and tough veins. In this paper, we study the microscopic structures and mechanical properties of the forewing of the black cicada, Cryptotympana atrata. The thickness of the wing membranes and the diameter of veins varied from the wing root to the tip. The thickness of the wing membranes ranged from 6.0 to 29.9 μm, and the diameter of the wing veins decreased in a gradient from the wing root to the tip, demonstrating that the forewing of the black cicada is a nonuniform biomaterial. The elastic modulus of the membrane near the wing root ranged from 4.45 to 5.03 GPa, which is comparable to that of some industrial membranes. The microstructure of the wing vein exhibited a hollow tubular structure with flocculent structure inside. The "fresh" sample stored more water than the "dry" sample, resulting in a significant difference in the elastic modulus between the fresh and dried veins. The different membrane thicknesses and elastic moduli of the wing veins near the root and tip resulted in varied degrees of deformation on both sides of the flexion line of the forewing during twisting. The measurements of the forewing of the cicada may serve as a guide for selecting airfoil materials for the bionic flapping-wing aircraft and promote the design and manufacture of more durable bionic wings in the future. RESEARCH HIGHLIGHTS: The distribution of the wing vein diameter and the wing membrane thickness indicated that the forewing of Cryptotympana atrata is composed of heterogeneous materials. The wing membrane and the outer wall of the wing vein are the layered structure with multilayer fibers, which has a great significance for improving the ability of the forewing to sustain aerodynamic loads. The elastic modulus of the wing membrane near the wing root is in the range of 4.45-5.03 GPa, which is comparable to that of membranes manufactured by industries. This is a suitable reference for selecting materials for making bionic aircraft wings. We proved that the elastic moduli of the "fresh" and "dry" wing veins differ greatly compared with those of the wing membrane. Because the wing vein microstructure exhibits an internal hollow tubular structure with flocculent structure inside, the "fresh" sample stores more water than the "dry" sample. The wing membrane near the wing root is thicker and reinforced by the main wing vein with a high elastic modulus. This renders the region near the wing root difficult to deform. The membrane far from the wing root is thinner and the elastic modulus of the nearby wing veins is smaller, making them more flexible.


Cesarean scar pregnancy: A case report with surgical management after initially effective conservative treatment.
The incidence of cesarean scar pregnancies (CSPs) is increasing, possibly due to higher rates of cesarean sections. We report a case of a CSP with severe bleeding following initial conservative management, that was eventually treated surgically. A 33-year old woman with history of one cesarean section presented with abdominal pain and amenorrhea and was diagnosed with CSP. Conservative management with methotrexate was chosen and the treatment was regarded as successful after the expected reduction in serum hCG levels. Four days after the hospital discharge, the patient was readmitted with hemodynamic instability and an emergency laparotomy was performed to remove the remaining trophoblastic tissue. A CSP may present as a threatened miscarriage, or remain asymptomatic through the first trimester. Medical treatment may be successful, however a close follow-up is needed even after a reduction in serum hCG levels. We report a case of CSP that, following an initial apparently "successful" treatment with methotrexate, required surgical management due to heavy bleeding.


The role of radiotherapy in the treatment of localised intermediate and high grade non-Hodgkin's lymphoma in elderly patients.
The treatment of elderly patients with high or intermediate grade non-Hodgkin's lymphoma (NHL) remains difficult and controversial. In order to audit our own practice, 270 elderly patients treated between 1988 and 1993 with this diagnosis were retrospectively reviewed. 81 patients unfit for chemotherapy received fractionated radiotherapy for apparently localised stage I or II disease. The median age of the patients was 78 years (range 70-87 years). Forty stage I and 17 stage II patients had extra-nodal sites of disease. The radiation field included the primary site plus immediate adjacent nodes. After a median follow-up of 3.9 years the 5-year overall and disease-free survival rates were 33% and 31%, respectively. Age (hazard ratio (HR) 1.22, P = 0.03), stage (HR 5.50, P = 0.02) and lactate dehydrogenase level (HR 1.003, P = 0.004) were identified as independent risk factors for relapse. These factors can define a group in which radiotherapy can produce acceptable survival rates (age < or = 80 years, stage I and lactate dehydrogenase < or = 500). This group represented 34% of those patients where all these variables were recorded and had 5-year disease-free and overall survival rates of 56% and 62%, respectively.


Recurrence of colorectal cancer after hepatic resection.
Survival estimates of 95, 65, and 49 percent at 1, 3, and 5 years, respectively, after hepatic resection in 77 patients when all gross metastatic cancer was removed compare favorably with the series of Wagner et al [20] of untreated, apparently comparable patients. In the present series, recurrent disease was evident after hepatic resection, most commonly in the lungs; the liver; and locally, in that order. About half of the 45 patients with a second recurrence were operated on, and the recurrence was completely removed in roughly half of these patients. A median survival estimate of 31 months (range 1 to 67 months) after complete removal of the second recurrence was better than the survival estimate of 14 months (range 1 to 18 months) for those in whom the recurrence could not be removed (p less than 0.01). An elevated carcinoembryonic antigen level as the only indicator of recurrence after hepatic resection has proved to be an ominous prognostic sign.


Evidence for the association of target-site resistance in cyp51 with reduced DMI sensitivity in European Cercospora beticola field isolates.
Cercospora leaf spot caused by Cercospora beticola is the most relevant foliar disease in sugar beet cultivation. In the last decade a decreasing sensitivity of C. beticola towards demethylation inhibitors (DMIs) occurred. Different mechanisms mediating a reduced sensitivity towards DMIs have been identified in different plant pathogens to date, such as target site mutations, over-expression or active excretion of the fungicide. A sequencing of the cytochrome P450-dependent sterol 14α-demethylase gene sequence (cyp51) of diverse C. beticola isolates collected in different European countries with reduced DMI sensitivity was performed in order to find a possible correlation of mutations with higher EC50 values. The amino acid alterations Y464S, L144F and I309T combined with L144F were found to be associated with a reduced sensitivity. Furthermore, mutations I387M, M145W and M145W with E460Q were found uniquely. Additionally, constitutive and fungicide triggered expression of cyp51 was assayed by means of RT-qPCR. A very strong induction of cyp51 mRNA expression in sensitive isolates suggests that the fungal cells upregulate expression to maintain ergosterol biosynthesis in DMI presence. The less intensive cyp51 induction in isolates with higher EC50 values underlines the possible correlation of the found target-site mutations with reduced sensitivity. This study provides new results about possible alterations in the target gene mediating reduced sensitivity of C. beticola towards DMIs and hypothesized a fungicide induced over-expression of the target enzyme CYP51 as natural reaction of the fungus to fungicide application. © 2020 Society of Chemical Industry.


Possible target neurons of 5-hydroxytryptamine fibers in the lamprey spinal cord: immunohistochemistry combined with intracellular staining with Lucifer yellow.
Intracellular recordings were made from 76 neurons belonging to various cell types in the lamprey spinal cord, and these neurons were subsequently stained with Lucifer yellow. Sections were made of spinal cords containing Lucifer-yellow-filled neurons, and in the same sections 5-hydroxytryptamine (5-HT)-containing neurons and fibers were made visible with immunohistochemical methods. Motoneurons and lateral cells appeared to send part of their dendrites into a dense ventromedial 5-HT plexus, and these dendrites were adjacent to 5-HT varicosities. No or few 5-HT varicosities have been found adjacent to cell bodies or dendrites of sensory dorsal cells, giant interneurons, and edge cells. The combined application of intracellular staining and immunohistochemistry appeared to be suited to screen for possible transmitter-identified contacts on morphologically identified neurons.


Family Integrated Care in Uganda: a feasibility study.
To determine the feasibility of adapting Family Integrated Care to a neonatal hospital unit in a low-income country. Single-centre, pre/post-pilot study of an adapted Family Integrated Care programme in Uganda (UFICare). Special Care Nursery at a Ugandan hospital. Singleton, inborn neonates with birth weight ≥2 kg. As part of UFICare, mothers weighed their infant daily, assessed for severe illness ('danger signs') twice daily and tracked feeds. Feasibility outcomes included maternal proficiency and completion of monitoring tasks. Secondary outcomes included maternal stress, discharge readiness and post-discharge healthcare seeking. Fifty-three mother-infant dyads and 51 mother-infant dyads were included in the baseline and intervention groups, respectively. Most mothers were proficient in the tasks 2-4 days after training (weigh 43 of 51; assess danger signs 49 of 51; track feeds 49 of 51). Mothers documented their danger sign assessments 82% (IQR 71-100) of the expected times and documented feeds 83% (IQR 71-100) of hospital days. In the baseline group, nurses weighed babies 29% (IQR 18-50) of hospitalised days, while UFICare mothers weighed their babies 71% (IQR 57-80) of hospitalised days (p<0.001). UFICare mothers had higher Readiness for Discharge scores compared with the baseline group (baseline 6.8; UFICare 7.9; p<0.001). There was no difference in maternal stress scores or post-discharge healthcare seeking. Ugandan mothers can collaborate in the medical care of their hospitalised infant. By performing tasks identified as important for infant care, mothers felt more prepared to care for their infant at discharge.


Rebleeding and endometrial growth in women with postmenopausal bleeding and endometrial thickness < 5 mm managed by dilatation and curettage or ultrasound follow-up: a randomized controlled study.
To compare the frequency of rebleeding and endometrial growth during a 12-month follow-up period between women with postmenopausal bleeding and an endometrial thickness < 5 mm managed by dilatation and curettage, and those managed by ultrasound follow-up. Consecutive women with postmenopausal bleeding and an endometrial thickness < 5 mm were randomized to ultrasound follow-up after 3, 6, and 12 months (n = 48) or to primary dilatation and curettage with ultrasound follow-up at 12 months (n = 49). At all follow-up examinations, the endometrial thickness was measured and the women were asked about rebleeding. The endometrium was sampled at the 12-month examination, if sampling had not been performed previously because of rebleeding or endometrial growth. Rebleeding was reported by 33% (16/48) of the women in the ultrasound group and by 21% (10/48) of those in the dilatation and curettage group (P = 0.17). Endometrial growth to >or= 5 mm was found in 21% (10/48) of the women in the ultrasound group and in 10% (5/48) of those in the dilatation and curettage group (P = 0.16). No endometrial pathology was found in women with isolated rebleeding. Endometrial pathology during follow-up was found more often in women with endometrial growth than in those without (33% vs. 4%; P = 0.008). Rebleeding and endometrial growth are common during a follow-up period of 12 months in women with postmenopausal bleeding and an endometrial thickness < 5 mm, irrespective of whether or not dilatation and curettage is primarily carried out. If these women are managed by ultrasound follow-up, endometrial sampling should be performed if the endometrium grows, but not necessarily in the case of rebleeding without endometrial growth.


Virtual walking training program using a real-world video recording for patients with chronic stroke: a pilot study.
The purpose of this study was to investigate the effectiveness of the virtual walking training program using a real-world video recording on walking balance and spatiotemporal gait parameters in patients with chronic stroke. Fourteen patients with chronic stroke were randomly assigned to either the experimental group (n = 7) or the control group (n = 7). The subjects in both groups underwent a standard rehabilitation program; in addition, the experimental group participated in the virtual walking training program using a real-world video recording for 30 mins a day, three times a week, for 6 wks, and the control group participated in treadmill gait training for 30 mins a day, three times a week, for 6 wks. Walking balance was measured using the Berg Balance Scale (BBS) and the Timed Up and Go test. Gait performance was measured using an electrical walkway system. In walking balance, greater improvement on the Berg Balance Scale (experimental group: 4.14 vs. control group: 1.85) and the Timed Up and Go test (-2.25 vs. -0.94) was observed in the experimental group compared with the control group (P <; 0.05). In the spatiotemporal gait parameters, greater improvement on velocity (25.40 vs. 9.74) and cadence (26.71 vs. 11.11) was observed in the experimental group compared with the control group (P <; 0.05). This study demonstrated the positive effects of the virtual walking training program using a real-world video recording on gait performance. These findings suggest that the virtual walking training program using a real-world video recording may be a valid approach to enhance gait performance in patients with chronic stroke.


Histological subtype of renal cell carcinoma significantly affects survival in the era of partial nephrectomy.
To analyze whether the histological subtype of renal cell carcinoma (RCC) affects survival after surgical resection in contemporary patients, and if so, whether prognostic significance differs according to the type of surgical resection or tumor stage. From 2006 to 2014, 2,237 patients underwent surgical resection (25% radical nephrectomy and 75% partial nephrectomy [PN]) for nonmetastatic RCC at a tertiary referral center. Estimated survival function curves and Cox regression models evaluated the effect of histological subtype on recurrence-free survival (RFS) and overall survival (OS). Interaction analyses tested whether the effect of histological subtype depends on the type of surgical resection or tumor stage. Patients with RCC stage T2 or lower and those with low-grade conventional clear cell, papillary or chromophobe RCC of any stage had 5-year RFS probabilities>90%. Patients with clear cell papillary RCC stage T3 or greater had predicted 5-year RFS of 81%. However, 5-year OS probabilities were>94% for clear cell papillary RCC of any stage. High-grade conventional clear cell and papillary RCC stage T2 or lower, low-grade conventional clear cell and chromophobe RCC of any stage conferred 5-year OS probabilities of >93%. Unclassified RCC demonstrated the lowest OS probabilities at any stage. In multivariable analyses, histological subtype affected RFS (P<0.0001) and OS (P = 0.026) following surgical resection, with no differences in this association for radical nephrectomy vs. PN (RFS, P = 0.2; OS, P = 0.4), and across pathologic stages (RFS, P = 0.1; OS, P = 0.3). Compared with low-grade conventional clear cell RCC, chromophobe (hazard ratio [HR] = 0.72, 95% CI: 0.30-1.75) and papillary RCC (HR = 0.30, 95% CI: 0.09-0.97) conferred lower risk of recurrence. Chromophobe (HR = 0.67, 95% CI: 0.30-1.52) and clear cell papillary RCC (HR = 0.91, 95% CI: 0.12-6.78) conferred the lowest risk of all-cause mortality. In the era of PN for RCC, histological subtype remained a significant predictor of survival, regardless of type of surgical resection or tumor stage.


Conservative management of overactive bladder in children: evaluation of clinical and urodynamic results.
Overactive bladder in children may indicate serious anatomic as well as functional changes in both the lower and upper urinary tracts. In order to prevent such problems, these patients should be diagnosed quickly and treated appropriately. In this study, children with diurnal and nocturnal enuresis symptoms (without any underlying neurological pathology) were evaluated and the long-term follow-up results are discussed. Between 2001 and 2004, 95 children with an average age of 8.1 years (1-13 years), referring with complaints of diurnal incontinence, nocturnal enuresis and recurrent urinary tract infections, were included in the study. Apart from conventional evaluation and ultrasonographic and urodynamic examinations, voiding cysto-urethrography was performed in children with upper tract changes. Seventy-three children (76.8%) completely responded to medical treatment, in 12 children (12.6%) the clinical status has been significantly improved, and in the remaining 10 children (10.5%) conservative management was unsuccessful. Of the children demonstrating complete response or significant improvement, 18 children (18.9%) continued to be under medication during 3-22 months of follow up with a mean maintenance period of 7.4 months. Average time to resolution in all groups was 2.6 years (0.2-3.8 years). Conservative therapy (especially oral anticholinergic agents) in children with overactive bladder is effective when applied appropriately (especially in patients with evident detrusor instability) with adequate follow up. Taking the effect of behavioural factors into account, biofeedback training programs in addition to medical treatment should solve the problem in the majority of cases.


A platelet aggregating substance contained in xanthine oxidase preparation from cow's milk.
Superoxide-generating system (xanthine-xanthine oxidase system) induced the platelet aggregation and the release of 3H-serotonin from washed human platelet. However, the aggregation was induced even when xanthine substrate was excluded from the system or when the activity of xanthine oxidase was completely abolished by the addition of 1.6 mM allopurinol to the system. Xanthine oxidase preparation from cow's milk was chromatographed on Sephadex G-200 column, and it was found that the platelet aggregating substance was separated from xanthine oxidase activity by this procedure. The aggregating activity of the substance was destroyed by boiling it for 3 min. Its molecular weight was estimated to be about 17,000. The levels of malondialdehyde and thromboxane B2 production in the platelets were increased during the aggregating 9 and 4 times, respectively, compared to those of resting cells.


Habitat structure and predators: choices and consequences for rodent habitat specialists and generalists.
Both habitat structure and risk of predation are thought to influence rodent community composition in different habitats, but experiments on the degree to which these factors determine the use of habitat by rodents are lacking. I sought to discover (1) if cover density altered habitat choice and (2) if cover density affected the vulnerability to predators of two rodents, a habitat specialist and a habitat generalist. In laboratory experiments, the habitat specialist, the red-backed vole (Clethrionomys gapperi), preferred greater densities of both vertical (wall) and horizontal (ceiling) cover. The habitat generalist, the deer mouse (Peromyscus maniculatus), also preferred greater densities of vertical and horizontal cover, but its preferences were weaker and more inconsistent than those of C. gapperi In tests of vulnerability to domestic ferrets, C. gapperi were more vulnerable in arenas with less vertical cover, while P. maniculatus did not differ in vulnerability between the two vertical cover densities used. Vulnerability to predators in differing densities of horizontal cover was not tested because of the reduced differences in preference for this cover type between the rodent species. Risk of predation is one explanation for C. gapper's inherent preference for denser cover.


Upregulation of HLA-F expression by BK polyomavirus infection induces immune recognition by KIR3DS1-positive natural killer cells.
BK polyomavirus-associated nephropathy is a common complication after kidney transplantation leading to reduced graft function or loss. The molecular pathogenesis of BK polyomavirus-induced nephropathy is not well understood. A recent study had described a protective effect of the activating natural killer cell receptor KIR3DS1 in BK polyomavirus-associated nephropathy, suggesting a role of NK cells in modulating disease progression. Using an in vitro cell culture model of human BK polyomavirus infection and kidney biopsy samples from patients with BK polyomavirus-associated nephropathy, we observed significantly increased surface expression of the ligand for KIR3DS1, HLA-F, on BK polyomavirus-infected kidney tubular cells. Upregulation of HLA-F expression resulted in significantly increased binding of KIR3DS1 to BK polyomavirus-infected cells and activation of primary KIR3DS-positive natural killer cells. Thus, our data provide a mechanism by which KIR3DS-positive natural killer cells can control BK polyomavirus infection of the kidney, and rationale for exploring HLA-F/KIR3DS1 interactions for immunotherapeutic approaches in BK polyomavirus-associated nephropathy.


Direct Delivery of Antisense Oligonucleotides to the Middle and Inner Ear Improves Hearing and Balance in Usher Mice.
Usher syndrome is a syndromic form of hereditary hearing impairment that includes sensorineural hearing loss and delayed-onset retinitis pigmentosa (RP). Type 1 Usher syndrome (USH1) is characterized by congenital profound sensorineural hearing impairment and vestibular areflexia, with adolescent-onset RP. Systemic treatment with antisense oligonucleotides (ASOs) targeting the human USH1C c.216G>A splicing mutation in a knockin mouse model of USH1 restores hearing and balance. Herein, we explore the effect of delivering ASOs locally to the ear to treat hearing and vestibular dysfunction associated with Usher syndrome. Three localized delivery strategies were investigated in USH1C mice: inner ear injection, trans-tympanic membrane injection, and topical tympanic membrane application. We demonstrate, for the first time, that ASOs delivered directly to the ear correct Ush1c expression in inner ear tissue, improve cochlear hair cell transduction currents, restore vestibular afferent irregularity, spontaneous firing rate, and sensitivity to head rotation, and successfully recover hearing thresholds and balance behaviors in USH1C mice. We conclude that local delivery of ASOs to the middle and inner ear reach hair cells and can rescue both hearing and balance. These results also demonstrate the therapeutic potential of ASOs to treat hearing and balance deficits associated with Usher syndrome and other ear diseases.


Differentiation of human neuroblastoma cell line IMR-32 by sildenafil and its newly discovered analogue IS00384.
Sildenafil, a phosphodiesterase-5 inhibitor is FDA approved drug against erectile dysfunction. It is currently undergoing many clinical trials, alone or in combinations against different diseases. Treatment of neural progenitor cells with sildenafil is known to regulate their basal cGMP levels and enhance neurogenesis and differentiation. cGMP as well as cAMP are known to play a central role in the maintenance, repair and remodelling of the nervous system. In the present study, we report the neurodifferentiation property of sildenafil in neuroblastoma cancer cell line IMR-32. Sildenafil was found to induce the formation of neurite outgrowths that were found expressing neuronal markers, such as NeuN, NF-H and βIII tubulin. IS00384, a recently discovered PDE5 inhibitor by our laboratory, was also found to induce neurodifferentiation of IMR-32 cells. The effect of IS00384 on differentiation was even more profound than sildenafil. Both the compounds were found to elevate and activate the Guanine nucleotide exchange factor C3G, which is a regulator of differentiation in IMR-32 cells. They were also found to elevate the levels of cGMP and activate the AMPK-ACC and PI3K-Akt signalling pathways. These pathways are known to play important role in cytoskeletal rearrangements necessary for differentiation. This study highlights the role of phosphodiesterases-5 in neurodifferentiation and use of sildenafil and IS00384 as small molecule tools to study the process of cellular differentiation.


Animal models of rheumatoid arthritis-associated interstitial lung disease.
Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is an irreversible pathologic condition of unknown cause, commonly involving the joint and the lung with variable amounts of fibrotic change. In contrast to rheumatoid arthritis or other chronic interstitial lung diseases such as interstitial pulmonary fibrosis, there is so far no extensively accepted or implemented animal model for this disease. To provide guidance for those who are investigating the pathogenesis of RA-ILD with animal models. An analysis of papers from PubMed during 1978-2020. We outline the present status quo for animal models of RA-ILD about their modeling methods and pathogenesis, compare their pros and cons with respect to their ability to mimic the clinical and histological features of human disease and discuss their applicability for future research. There is no doubt that these animal models do provide valuable information relating to the pathogenesis of RA-ILD and the development of effective therapeutic drugs. Nevertheless, these animal models can not entirely recapitulate clinical pathology and have some limitations in experimental research application. Therefore, it should be emphasized that we should improve and explore animal models in more accordance with the pathogenesis and clinical characteristics of human RA-ILD. These established animal models of the disease can significantly progress our understanding of the etiology of RA-ILD, the fundamental mechanisms of its pathogenesis and the identification of new bio-markers, and can contribute to the development and implementation of novel treatment strategies.


Marginal reduction in surface NO2 attributable to airport shutdown: A machine learning regression-based approach.
Emissions from aviation and airport-related activities degrade surface air quality but received limited attention relative to regular transportation sectors like road traffic and waterborne vessels. Statistically, assessing the impact of airport-related emissions remains a challenge due to the fact that its signal in the air quality time series data is largely dwarfed by meteorology and other emissions. Flight-ban policy has been implemented in a number of cities in response to the COVID-19 spread since early 2020, which provides an unprecedented opportunity to examine the changes in air quality attributable to airport closure. It would also be interesting to know whether such an intervention produces extra marginal air quality benefits, in addition to road traffic. Here we investigated the impact of airport-related emissions from a civil airport on nearby NO2 air quality by applying machine learning predictive model to observational data collected from this unique quasi-natural experiment. The whole lockdown-attributable change in NO2 was 16.7 μg/m3, equals to a drop of 73% in NO2 with respect to the business-as-usual level. Meanwhile, the airport flight-ban aviation-attributable NO2 was 3.1 μg/m3, accounting for a marginal reduction of 18.6% of the overall NO2 change that driven by the whole lockdown effect. The airport-related emissions contributed up to 24% of the local ambient NO2 under normal conditions. Additionally, the average impact of airport-related emissions on the nearby air quality was ∼0.01 ± 0.001 μg/m3 NO2 per air-flight. Our results highlight that attention needs to be paid to such a considerable emission source in many places where regular air quality regulatory measures were insufficient to bring NO2 concentration into compliance with the health-based limit.


Estimation of integral curves from high angular resolution diffusion imaging (HARDI) data.
We develop statistical methodology for a popular brain imaging technique HARDI based on the high order tensor model by Özarslan and Mareci [10]. We investigate how uncertainty in the imaging procedure propagates through all levels of the model: signals, tensor fields, vector fields, and fibers. We construct asymptotically normal estimators of the integral curves or fibers which allow us to trace the fibers together with confidence ellipsoids. The procedure is computationally intense as it blends linear algebra concepts from high order tensors with asymptotical statistical analysis. The theoretical results are illustrated on simulated and real datasets. This work generalizes the statistical methodology proposed for low angular resolution diffusion tensor imaging by Carmichael and Sakhanenko [3], to several fibers per voxel. It is also a pioneering statistical work on tractography from HARDI data. It avoids all the typical limitations of the deterministic tractography methods and it delivers the same information as probabilistic tractography methods. Our method is computationally cheap and it provides well-founded mathematical and statistical framework where diverse functionals on fibers, directions and tensors can be studied in a systematic and rigorous way.


[Use of antibiotics, in a pediatric hospital, for respiratory infection and diarrheal disease].
The World Health Organization (WHO) reports an increasing unjustified use of antibiotics in the treatment of Acute Respiratory Infections (ARI) and Acute Diarrheal Diseases (ADD) in children under five years of age. This has generated problems such as polypharmacy and the inappropriate use of antibiotics; characterized by incorrect dosage, use in viral infections, prescription inconsistent with clinical guidelines. To analyze the prescription of antibiotics, their diagnostic-therapeutic congruence, as well as the correct filling of the medical prescription, in a tertiary level hospital in Mexico. Observational, descriptive cross-sectional study. The electronic medical prescriptions made during the period January-December 2017 with a clinical diagnosis of ARI and EDA were analyzed. Of a total of 21,446 boys and girls under five years of age, 10,233 prescriptions were issued for the treatment of ARI and ADD diagnoses. 80% of the prescriptions complied with the items indicated in the electronic file. The prescription of antibiotics showed a prudent use of antibiotics both in the management of acute diarrheal diseases and in the management of acute respiratory diseases. Diagnostic-therapeutic congruence was found in most of the cases in the prescriptions analyzed.


Spin Brazil-nut effect and its reverse in a rotating double-walled drum.
The segregation of binary mixtures in a filled rotating double-walled drum is explored by simulations. Based on the characteristics of self-gravity and the centrifugal force, we argue that both percolation and buoyancy effects dominate the segregation process. The simulational results show that up to long enough times the segregation state is controlled by the rotational speed, the particle radius and density. At low rotational speeds, the smaller and heavier particles tend to accumulate towards the inner drum wall and the bigger and lighter ones towards the outer drum wall, while the segregation pattern reverses completely at higher rotational speeds. Two typical phase diagrams in the space of the density and radius ratio of bigger particles to smaller particles further confirm the predictions.


Effects of benzodiazepines administration on identification of facial expressions of emotion: a meta-analysis.
Benzodiazepines, a class of commonly prescribed drugs, were shown to cause cognitive impairments in several domains. However, the effect of benzodiazepines on social cognition is still unclear. In order to clarify how benzodiazepines administration affects the identification of facial expressions of emotion (FEE), we conducted a meta-analysis of 8 empirical studies (N = 153 benzodiazepines, N = 153 placebo). Results showed that participants receiving benzodiazepines were less accurate at identifying facial expressions of anger compared with those receiving placebo (M = - 0.52). Regarding the remaining facial expressions, the meta-analysis did not reveal significant differences between the groups. We discuss several factors that may explain the differences in the identification of emotions in facial expressions associated with benzodiazepines administration. Additionally, the relevance of assessing the effects of benzodiazepines when used on a long-term basis is addressed.


Radon in homes: determining risks and preventing exposures.
Knowledge about the effects of radon disintegration products and their levels in the nation's homes indicates that in a small proportion of homes these radioactive substances are increasing the inhabitants' risks of lung cancer. Testing for the problem and reducing its magnitude are the homeowner's responsibility. While practical methods for testing are known, they may not be easily available in all regions. Present understanding of the techniques of prevention and remediation is less satisfactory.


Lactosylsphingosine-reactive antibody and CEA in patients with colorectal cancer.
The sera of 71 patients with colorectal cancer were examined for lactosylsphingosine-reactive antibody and CEA. Fifteen of those patients were studied repeatedly over extensive periods of time. The antibody was determined by the semiquantitative radioimmunoabsorption technique using lactosylsphingosine-polyacrylamide conjugate and [125I]-labelled anti-human IgG. Excessive antibody levels were invariably found In serum samples of all 39-patients who were examined before or within 2 months after surgery. Serum samples of certain patients became negative for the presence of high antibody levels usually between 3 and 6 months after surgery. This occurred in 13 out of 41 operated patients. The follow-up study revealed that 11 such patients have been free of any signs of cancer relapse up until the time of the follow-Up examination, i.e. for 12-28 months, mean 19 months. In contrast, only 4 out of 28 patients who remained positive for the excessive antibody longer than 2 months after surgery are at present free of the disease. The high antibody levels which persist more than 6 months after surgery are almost always associated with cancer recurrences or metastases. This was true for 21 out of 22 such patients. The high levels of the antibody preceded other signs of cancer relapse, including increased concentrations of CEA in about 40% of the operated patients.


Projections of the carotid sinus nerve to the medulla in the dog.
The afferent and efferent projections of the carotid sinus nerve were examined within the medulla of the dog with axonal transport of horseradish peroxidase (HRP), and compared with the projections of the glossopharyngeal nerve. The carotid sinus nerve was identified electrophysiologically prior to injection of tracer. Carotid sinus nerve afferent fibers entered the medulla as part of the glossopharyngeal nerve root near the caudal limits of the cochlear nuclei. Labeled axons entered the solitary tract and ran caudally to about 3 mm anterior to the obex, where they began to enter the nucleus tractus solitarii (nTS). Carotid sinus afferent fibers and presumptive terminals were discretely localized within limited portions of the ipsilateral dorsal, medial, and lateral nTS as far as 3 mm caudal to the obex. A few fibers entered the dorsolateral area postrema ipsilateral to HRP injection. Labeled fibers in the commissural nTS crossed the midline and entered the contralateral medial nTS. Efferent neurons were observed only in half of the cases, and were limited to one to three labeled perikarya in the periphery of the retrofacial nucleus. Comparison of the carotid sinus distribution with the previously described vagal afferent projections to the canine nTS revealed partially overlapping, but clearly distinctive patterns, which support a viscerotopic organization of the nTS.


A novel three-dimensional printed vacuum bell for pectus excavatum treatment: a preliminary study.
Conservative treatment with a vacuum bell (VB) for pectus excavatum (PE) has now been gradually popularized as an alternative to surgery. We describe our initial experience with a novel three dimensional (3D) printed VB device. Prospectively collected data of all patients who started using a 3D printed VB in 2018 at our institution were analyzed. Linear and logistic regressions were used to identify factors associated with effectiveness of device usage. In total, forty-two patients with a median age of 3.6 years were treated with the device. The median follow-up duration was 11.1 months and the mean initial Depth Ratio (DR) was 0.129. There were no permanent sequelae from side effects. Thirty patients with at least one follow-up body scan data showed varying improvement (z = - 4.569, p = 0.0000). Linear regression suggested that longer usage improved outcomes (R2 = 0.235, p = 0.014). By logistic regression there was a trend of younger ages and less initial DR for better improvement though neither was statistically significant (p = 0.086, 0.078, respectively). Our initial experience has shown the 3D printed VB may be as effective as other conventional VBs and could be used as an alternative to surgical treatment for selected patients with PE. More experience and studies with this type of VB are needed to demonstrate its superiority with regard to the 3D printing design and optimal timing and indication for use.


In vitro differences in lymphocyte subpopulation reactivity in lung cancer patients: purified protein derivative-specific suppressor T lymphocytes in patients who have received Bacillus Calmette-Guerin.
Antigen-specific responses of lymphocyte to purified protein derivative (PPD) were studied in seven patients with non-small cell lung cancer who had undergone complete resection and received postoperative intrapleural Bacillus Calmette-Guerin. In addition, one patient with unresected lung cancer and reactive tuberculin skin test (PPD +) and five normal PPD- individuals were also studied. Lung cancer patients had significantly fewer responsive peripheral blood lymphocytes, unfractionated T cells, and T cells bearing Fc-IgG receptors (TG + populations) than normal controls. These deficits were most pronounced in the group who had received intrapleural Bacillus Calmette-Guerin but who had failed to develop reactive tuberculin skin tests. In contrast, the TG-populations (FC-IgG receptor-negative T cells) from all patients responded to PPD. TG + cells specifically inhibited TG- -cell responses to PPD in both proliferation and immunoglobulin secretion. Radiosensitive suppressor monocytes were found in other patients. This study shows interesting immune deficits in early lung cancer patients. These patients appear to have PPD-specific suppressor TG + cells which may contribute to the immune deficits in these patients.


Lymphocytes as cell model to study apoptosis in Alzheimer's disease: vulnerability to programmed cell death appears to be altered.
Recent evidence indicates that programmed cell death (apoptosis) may contribute to neuronal death in Alzheimer's disease (AD). In situ data derived from post mortem brain tissue indicate that DNA fragmentation which represents an important and typical apoptotic feature is markedly increased in brain cells of AD patients compared to controls. Furthermore, in vitro studies demonstrate that the peptide beta-amyloid (A beta) and its fragments induce apoptosis in neuronal cell cultures. One possible mechanism initiating apoptosis could be free radical generation by the peptide leading to oxidative stress. In a wide range of cell types common morphological and molecular events occur during apoptosis and several genes appear to be involved. Particularly in lymphocytes, apoptosis plays an important physiological role. Our data demonstrate that similar oxidative stressors induce apoptosis in mature human lymphocytes as in neurons. In addition, first evidence indicates that susceptibility to apoptosis is altered in lymphocytes from AD patients compared to non-demented controls. Our preliminary findings suggest that changes of the individual sensitivity to undergo cellular apoptosis are already detectable in lymphocytes from AD patients, probably as a consequence of genetic as well as other risk factors. Therefore, this biochemical marker might have the potential for identifying individuals at risk of the diseases.


Construction, purification, and evaluation of multivalent DNA vaccine against Schistosoma japonicum.
DNA vaccine encoding a multivalent antigen is a novel approach of protective immunization. Four Schistosoma japonicum candidate antigen genes, glyceraldehyde-3-phosphate dehydrogenase (SjGAPDH), 23 kDa transmembrane protein (Sj23), 14 kDa fatty-acid binding protein (SjFABP) and 26 kDa glutathione-S-transferase (Sj26), are recombined into two pieces of fusion genes SjFABP.Sj23 and Sj26.SjGAPDH, respectively. Tetravalent DNA vaccine pVIVO2-SjFABP.Sj23/Sj26.SjGAPDH is constructed by co-expressing these two fusion genes. The super-coiled DNA vaccines for large-scale clinic application were purified by sequential chromatographies including group separation chromatography and affinitive chromatographies. The purified DNA vaccines were evaluated for in vivo and in vitro transfection assay. The immunoprotective properties of the different kinds of constructed DNA vaccines were appraised by pharmacological trials. The pharmacological trials results showed that tetravalent DNA vaccine has higher protective efficiency than other tested DNA vaccines.


Analysis of lactase processing in rabbit.
The proteolytic processing of rabbit intestinal lactase-phlorizin-hydrolase (LPH) was studied by pulse-chase and continuous labeling experiments in organ culture from 15-day-old rabbits in the presence of glycosylation and processing inhibitors. Monensin and brefeldin A inhibited the two proteolytic cleavages of the precursor indicating that they are post-Golgi events as previously reported for the unique cleavage of LPH in man. The inhibition was not related to a concomitant alteration glycosylation; in fact, if trimming was blocked by MDNM the abnormal glycosylated precursor was proteolytically processed normally. Finally the use of the anti-microtubular drug colchicine strongly inhibited both cleavages and caused accumulation of the complex-glycosylated precursor form the brush border fraction indicating that proteolytic events depend on intact microtubule (transport).


Influence of toll-like receptor 4, CD14, tumor necrosis factor, and interleukine-10 gene polymorphisms on clinical outcome in Japanese critically ill patients.
The innate recognition of microbial components and subsequent activation of cytokine network are important in the pathophysiology of sepsis. Recently, functional gene polymorphisms in molecules associated with these responses were demonstrated. On the other hand, it has been claimed that there are ethnic differences in genetic polymorphisms. This study investigated toll-like receptor (TLR) 4, CD14, tumor necrosis factor (TNF)-alpha and -beta, and interleukin (IL)-10 gene polymorphisms in 197 Japanese critically ill patients and 214 healthy control subjects to evaluate the influence of these polymorphisms on clinical outcome. No Japanese participant carrying TLR4Asp299Gly or Thr399Ile was detected. No association of CD14-159C/T polymorphisms with genotype frequency or sepsis mortality was observed. Frequency of TNF-alpha-308 GA genotype was significantly higher in the sepsis group than in the control group and TNF-alpha-308GA and IL-10-592CC genotypes were related to poor outcome of sepsis. Ethnic differences in genetic variations are very important issues and the frequencies in this study differ from those previously reported in Caucasians. In conclusion, this study may indicate that TNF-alpha-308G/A and IL-10-592C/A polymorphisms involved in subsequent activation of cytokine network had a larger effect on clinical outcome in patients with sepsis than TLR4Asp299Gly, Thr399Ile, and CD14-159C/T polymorphisms associated with the initial host-microbial interaction.


[Influences of the genotypes of HBV and HBeAg regarding their response to PEG-IFN in chronic hepatitis B patients].
To study the effects of genotypes of HBV and HBeAg on the response to PEG-interferon alpha (PEG-IFN) in chronic hepatitis B (CHB) patients. PCR-RFLP and S gene sequencing were conducted in 42 CHB patients. The sustained response (SR) rates were 66.7% in genotype B and 27.3% in genotype C group. The P value was 0.039 by the Pearson Chi-square test, while it was 0.06 by the Fisher's exact test. The results suggested a trend that patients with genotype B HBV compared to genotype C had better SR to PEG-IFN therapy, although the difference was not significant. Results also showed that SR rate in patients with HBeAg-negative CHB (7/8 87.5%) was significantly higher than that in HBe+ CHB patients (8/21 38.1%, P < 0.05). Our results indicate that HBV genotype and HBeAg, especially the later, are main factors for predicting PEG-IFN therapy response in CHB patients.