Effects of counterstaining with DNA binding drugs on fluorescent banding patterns of human and mammalian chromosomes.
Pairs of fluorescent A-T specific dyes and nonfluorescent agents with similar or complementary base pair binding specificity were used to analyse the extent to which banding patterns in human chromosomes obtained by fluorescent staining can be modified by counterstaining. By testing a variety of different combinations of drugs, essentially three types of alterations were observed. Enhanced contrast of specific heterochromatic regions was obtained with pentamidine, or netropsin, in conjunction with the fluorescent stains Hoechst 33258, DAPI or DIPI, the resulting banding patterns being similar to that reported for distamycin A plus DAPI (DA-DAPI banding [21]. Uniform quenching of Hoechst 33258, DAPI or DIPI fluorescence was induced by counterstaining with stilbamidine or berenil. The combination of echinomycin with DAPI resulted in an improved contrast of DAPI banding on chromosome arms and pale fluorescence on major autosomal C band regions. In addition, a subdivision of the heterochromatic part of the Y chromosome may be discerned by this latter technique.


Role of chest X-ray in diagnosis of the first breast cancer relapse: a randomized trial.
Between May 1991 and December 1995, follow-up after primary therapy for 472 consecutive patients with localized breast cancer was randomly assigned to assess the efficacy of routine chest X-ray in detecting intrathoracic relapse as the first metastatic event. One group had regular chest X-rays while the other group had chest radiographs only when clinically needed (spontaneous). Patients were followed up until December 1999 or death. In the routine group, 243 patients had 1429 chest X-rays (mean 5.9 chest X-rays per patient). In the spontaneous group, 229 patients had 411 chest X-rays (mean 1.8 chest X-rays per patient). Both sensitivity and specificity were somewhat higher in the spontaneous arm compared to the routine arm. Patient sensitivity was 30% in the regular arm and 36% in the spontaneous arm. Film sensitivity was 11% in the regular arm and 20% in the spontaneous arm. Patient specificity was 85% in the regular arm and 86% in the spontaneous arm. The predictive values were practically the same in both arms. Patient positive predictive values were 22% in both arms and film positive predictive values were 21% in the regular and 22% in the spontaneous arm. Patient negative predictive values were 90% in the regular and 92% in the spontaneous arm. Film negative predictive values were 93% in the regular and 89% in the spontaneous arm. The differences in accuracy were not statistically significant between the arms. There were no significant differences in disease free survival or overall survival. The 5-year disease free survival was 86% in the regular and 89% in the spontaneous arm and the overall survival was 88 and 85% in the regular versus spontaneous arm, respectively. Routine chest X-ray in the follow-up of breast cancer patient is evidently of little use and is not likely to be of benefit to the patient in terms of disease free survival or overall survival as compared to the spontaneous schedule.


Loss of erythropoietin responsiveness in erythroid progenitors due to expression of the Evi-1 myeloid-transforming gene.
Inappropriate expression of the Evi-1 zinc-finger gene in hematopoietic cells has been associated with acute myelogenous leukemia and myelodysplastic syndromes in murine models and in humans. Consistent with this, previous studies have shown that aberrant expression of the Evi-1 gene in a myeloid progenitor cell line blocks granulocytic differentiation. Here we demonstrate that the aberrant expression of the Evi-1 gene impairs the normal response of erythroid cells or bone-marrow progenitors to erythropoietin. Erythroid differentiation has been shown to require the GATA-1 transcription factor that binds to a sequence contained within the consensus binding sequence identified for Evi-1. In the studies presented here we also show that Evi-1 can repress GATA-1-dependent transactivation in transient chloramphenicol acetyltransferase assays. Together the data support the hypothesis that inappropriate expression of the Evi-1 gene blocks erythropoiesis by repressing the transcription of a subset of GATA-1 target genes.


An implementation of dual energy CT scanning.
We have described a prereconstruction method for dual energy (PREDECT) analysis of CT scans. In theory, this method can (a) eliminate beam hardening and produce an accuracy comparable with monoenergetic scans and (b) provide the effective atomic number and electron density of any voxel scanned. Our implementation proves these statements and eliminates some of the objectionable noise. We constructed a phantom with a cylindrical sleeve-like compartment containing known amounts of high atomic number material simulating a removable skull. Conventional scans, with and without this beam hardener, were done of a water bath containing tubes of high electron and high atomic number material. Dual energy scans were then done for PREDECT. To increase the effective separation of the low and high energy beams by using more appropriate tube filtration, we fabricated a beam filter changer containing erbium, tungsten, aluminum, and steel. We used erbium, tungsten, and steel at high energy and aluminum, steel, and erbium at low energy for data acquisition. The reconstructions were compared visually and numerically for noise levels with the original steel only filtration. We found a decrease in noise down to approximately one-half the prior level when erbium/aluminum or tungsten/aluminum replaced the steel/steel filter. Erbium and tungsten were equally effective. Steel/erbium and steel/aluminum also significantly reduced image noise. The noise in the photoelectric (P) and Compton (C) images is negatively correlated. At any pixel, if the noise is positive in the P image, it is most probably negative in the C. Using this fact, the noise was reduced by postreconstruction processing.


[Changes in neurotransmitters uptake and their receptors binding after transplanting adrenal medullary tissue into central striatum in rats].
Unilateral nigrostriatal pathway of rats was destroyed by using injection of 6-hydroxydopamine (6-OHDA), presenting the rotative movement model and transplanting isogenous rat adrenal medullary tissues into their lesioned lateral caudate nucleus. After 2 months, the rotative movement almost abolished by 34% out of the total transplanted rats, and it was significantly reduced by 57% of the same rats. Taking the above rats brain synaptosome, we found the lesioned side, the uptake of tyrosine, dopamine and choline increased significantly, nevertheless, in another group which transplanted with adrenal medullary tissue, the uptake of same neurotransmitters recover to the normal level. In addition, we also found that dopamine (DA2) receptor binding increased remarkably but muscarinic and GABAA receptors binding decreased significantly in lesioned side brain synaptic membrane, while the transplanted group didn't shown such changes.


Changes in use of time across retirement: A longitudinal study.
This study aimed to investigate how daily use of time changes across the retirement transition and how these changes may differ according to socio-demographic characteristics. This longitudinal cohort study was based on interviews with 124 people at pre-retirement and at three, six and 12 months after retirement. The Multimedia Activity Recall for Children and Adults (MARCA), a computer-assisted telephone interview, measured use of time. Random effects mixed modelling (REMM) was used to examine time use changes across retirement, and ANCOVA to investigate the extent of the change by sex, education and health. Apart from the decrease in time spent in work across retirement (-122min/day, p<0.001), less time was also spent in both active and passive transport (-26min/day, p<0.001). There were significant increases in time spent on Chores (+55min/day, p<0.001), Screen time (+32min/day, p<0.001), Sleep (+32min/day, p<0.001), Quiet time (+17min/day, p=0.02), Self-care (+8min/day, p=0.01) and Physical activity (+7min/day, p=0.01). There was little variation in change between sex, education and health sub-groups. Most changes occurred at retirement, with time use patterns fairly stable between three and 12 months post-retirement. The small amount of time spent in physical activity, combined with less time spent in active transport and increased time spent watching television, indicate the need for a more active lifestyle.


The Effect of High-Quality Nursing Management on Thyroid Tumor Patients after Bipolar Coagulation.
To evaluate the effect of high-quality nursing on thyroid tumor patients after bipolar coagulation and its impact on nursing satisfaction. From January 2019 to January 2020, 90 patients with thyroid tumors treated with bipolar coagulation in our hospital were identified as the study objects and randomized to the control group (n = 45) and the experimental group (n = 45) random number table method. Both groups received conventional nursing, and the experimental group additionally adopted high-quality nursing. The incidence of postoperative complications and nursing satisfaction between the two groups was compared. The Exercise of Self-Care Agency Scale (ESCA) was used to assess the self-care ability of patients after the intervention, and the Generic Quality of Life Inventory-74 (GQOLI-74) was used to evaluate the quality of life of the two groups of patients after the intervention. The Hospital Anxiety and Depression (HAD) scale was adopted to evaluate the emotional state of the patient before and after the intervention, and the Numerical Rating Scale (NRS) was employed to evaluate the pain intensity of the patient after the intervention. Counting data was analyzed by the X2 test, and the measurement data was analyzed by t-test. After the intervention, the total incidence of postoperative complications in the experimental group was significantly lower than that in the control group (11.11% versus 33.33%, P < 0.05). The experimental group obtained remarkably higher nursing satisfaction (93.33% versus 71.11%), ESCA scores, and GQOLI-74 scores than the control group (P < 0.05). Lower HAD scores were observed in the experimental group than those of the control group (P < 0.001). Lower HAD scores were observed in the experimental group than those of the control group (P < 0.001). The NRS score of the experimental group was significantly lower than that of the control group 12 h and 24 h after the intervention (P < 0.001). High-quality nursing for patients with thyroid tumors can effectively alleviate the negative emotions, improve the quality of life, and contribute to a harmonious nurse-patient relationship, which is worthy of promotion and application.


Use of mouthrinses for professional indications.
In view of the relationship between supragingival and subgingival plaque, chemical agents which alter supragingival plaque may also alter subgingival plaque. As a result, a beneficial effect on gingival health may be anticipated. This article reviews the use of chemotherapeutic agents which reduce plaque and gingivitis. Indications for the use of these agents include patients with problems with mechanical plaque control, extensive splinting or fixed prostheses, intraoral fixation, orthodontic appliances, overdenture abutments and implants, and for patients in the immediate post-surgical period. Improvement of wound healing following periodontal surgery may represent one of the most valuable aspects of use of these agents. As mouthrinses, these agents cannot be expected to significantly alter subgingival plaque. However, for this purpose, their use in irrigation devices deserves further study. Since recent reports have suggested benefits of various mouthrinses when used as irrigants as compared to rinses may also reduce the bacterial back-spray associated with ultrasonic devices and high-speed handpieces, and thus provide a protective effect for dental personnel. The practitioner in the United States is encouraged to recommend products accepted by the American Dental Association's Council on Dental Therapeutics in order to insure both safety and efficacy.


Tobacco control policy and socio-economic inequalities in smoking in 27 European countries.
Higher Tobacco Control Scale (TCS) scores, in the early 2000s were associated with higher smoking cessation rates across Europe, both among lower and higher educated people. We aimed to assess if this association held in recent years. Repeated cross-sectional Eurobarometer surveys were used, in 27 European countries from 2006 to 2012 (study sample=73,617 adults). We used multilevel regression to model associations between the TCS (ranging from 0 to 100, quantifying: tobacco price, smoke-free laws, mass-media campaigns, advertising bans, warning labels, and cessation support) and both smoking cessation and cigarettes smoked per day. We modelled associations according to respondents' education and occupation, with adjustment for age, sex, and survey-wave. We found no association between the TCS and smoking cessation for lower or middle educated respondents, but we did find an association for higher educated respondents (OR: 1.13, 95%CI: 1.08 to 1.19). For smoking intensity, we observed no associations with the TCS for lower educated respondents (beta: 0.04, 95%CI: -0.33 to 0.41) but we did observe significant associations for middle (beta: -0.25, 95%CI: -0.47 to -0.03) and higher educated respondents (beta: -0.27, 95%CI: -0.55 to -0.01). Associations were observed for both manual and non-manual classes, but not for those not working for pay. Of the TCS domains, none were associated with smoking cessation for lower educated respondents, but five were for higher educated respondents. Associations between tobacco control policies and smoking cessation were found mostly among higher socioeconomic groups. This underlines the need for specific tobacco control policies that explicitly focus on reaching low socio-economic groups.


Proposal for a national diagnostics action plan for the United States.
Providing a definitive diagnostic test in a disease emergency is critical to limit pathogen spread, develop and deploy medical countermeasures, and mitigate the social and economic harms of a serious epidemic. While major accomplishments have accelerated test development, expanded laboratory testing capacity, and established widespread point-of-care testing, the United States does not have a plan to rapidly respond, to develop, manufacture, deploy, and sustain diagnostic testing at a national scale. To address this gap, we are proposing a National Diagnostics Action Plan that describes the steps that are urgently needed to prepare for future infectious disease emergencies, as well as the actions we must take at the first signs of such' events. These recommendations require substantial collaboration between the US government (USG) and the private sector to solve a series of challenges now, as well as to prepare for the massive and rapid scale-up of laboratory and point-of-care test development and testing capacity in future emergencies. The recommendations include establishing pre-event contracts; ensuring rapid access to clinical samples; creating a permanent public-private testing coordinating body to allow for rapid information sharing and improved cooperation among the USG, test developers, and clinical laboratories; and accelerating testing rollout at the beginning of an event-and thus, the effective public health management of a disease crisis.


Clinical response, drug survival, and predictors thereof among 548 patients with psoriatic arthritis who switched tumor necrosis factor α inhibitor therapy: results from the Danish Nationwide DANBIO Registry.
To describe the frequency of treatment switching and outcomes among patients with psoriatic arthritis (PsA) who switched tumor necrosis factor α inhibitor (TNFi) agents in routine care. We conducted an observational cohort study based on the Danish nationwide DANBIO registry. Treatment outcomes were evaluated using the American College of Rheumatology criteria for 20% improvement (ACR20)/ACR50/ACR70, European League Against Rheumatism (EULAR) response criteria for good response, and the 28-joint count Disease Activity Score (DAS28) (remission). Kaplan-Meier and regression analyses were used for drug survival analyses and to identify predictors of outcome after treatment switching. Of 1,422 patients starting TNFi agents, 548 patients (39%) switched to a second biologic drug during up to 10 years of followup. Median followup was 2.3 years (interquartile range [IQR] 1.0-4.3 years). Switchers were more frequently women (56% versus 45%), had a shorter disease duration (3 versus 4 years), a higher median Health Assessment Questionnaire (HAQ) score (1.1 [IQR 0.6-1.6] versus 0.9 [IQR 0.5-1.4]), DAS28 (4.8 [4.0-5.7] versus 4.4 [3.6-5.2]), pain score on a visual analog scale (VAS) (65 mm [46-77] versus 62 mm [40-75]), and fatigue score on a VAS (69 mm [50-83] versus 64 mm [42-80] mm) (all P < 0.05 at start of first TNFi). During the first and second treatment, HAQ, DAS28, and VAS scores and C-reactive protein levels had decreased after 6 months (all P < 0.05), and median drug survival was 2.2 versus 1.3 years (P < 0.001). Lower fatigue score increased survival of the second TNFi. After switching, the proportions of patients achieving a sustained ACR20, ACR50, ACR70, EULAR good response, and DAS28 remission after 3-6 months were 22% (number needed to treat [NNT] 4.5), 13% (NNT 7.9), 5% (NNT 20), 19% (NNT 5.3), and 34% (NNT 2.9), respectively. Response rates were lower during the second treatment (all P < 0.01 versus first TNFi). At the 2-year visit, 47% of switchers had achieved an ACR20 response. No differences between drug-drug combinations were found. Thirty-nine percent of the patients with PsA switched TNFi agents. Response rates and drug survival were lower after switching; however, half of the switchers had an ACR20 response 2 years after starting the first TNFi.


Organocatalytic domino reaction of cyanosulfones: access to complex cyclohexane systems with quaternary carbon centers.
When ε-nitro-α,β-unsaturated esters are added to conjugated cyanosulfones in the presence of a bifunctional thiourea catalyst, a highly stereoselective domino reaction occurs to generate complex cyclohexanes with up to four stereogenic centers, one of which is quaternary in nature. Therefore, it is demonstrated that, like nitro compounds, sulfones can undergo an asymmetric intramolecular conjugate addition to α,β-unsaturated esters in the presence of a bifunctional organocatalyst.


Newborn infants with severe defects: a survey of paediatric attitudes and practices in the United Kingdom.
This article reports the first results of a survey, by mail questionnaire, of the attitudes and practices of paediatricians with respect to the nontreatment of newborn infants with severe defects. Questionnaires were sent to 500 paediatricians in senior positions throughout the United Kingdom. 263 questionnaires (52.6%) were completed and returned. The survey was an attempt to identify areas of consensus amongst paediatric specialists, and to discover some of the factors which influence their practice. A preliminary analysis of the data has revealed variations in attitudes and practices in some areas, and a broad consensus in others. The following report is not an endorsement of any particular point of view.


Reconciling semiclassical and Bohmian mechanics. VI. Multidimensional dynamics.
In previous articles [J. Chem. Phys. 121, 4501 (2004); J. Chem. Phys. 124, 034115 (2006); J. Chem. Phys. 124, 034116 (2006); J. Phys. Chem. A 111, 10400 (2007); J. Chem. Phys. 128, 164115 (2008)] an exact quantum, bipolar wave decomposition, psi=psi(+)+psi(-), was presented for one-dimensional stationary state and time-dependent wavepacket dynamics calculations, such that the components psi(+/-) approach their semiclassical WKB analogs in the large action limit. The corresponding bipolar quantum trajectories are classical-like and well behaved, even when psi has many nodes or is wildly oscillatory. In this paper, both the stationary state and wavepacket dynamics theories are generalized for multidimensional systems and applied to several benchmark problems, including collinear H+H(2).


Molecular genetic analysis of TGF beta1 in breast cancer.
Conflicting data suggest that TGF-beta1 can either inhibit or promote the progression of breast cancer. To determine the biological role of TGF beta1 in mammary carcinoma, in this study we examined the gene structure, expression and localization of TGF-beta1 using paraffin-embedded samples from 32 (27 IDC, 1 ILC, 1 DCIS, 1 ADH) breast lesions. Gene mutations in the region coding for the active protein were investigated by PCR-SSCP of exons 5, 6, and 7. mRNA -TGF-beta1 expression and distribution was examined by NISH using cDNA probes generated by RT-PCR and immunohistochemistry. We detected two mutations in exon 6 TGF-beta1 from IDC; and TGF beta1 mRNA and proteins in 28 (87%) of the tumors. Invasive breast carcinomas had more intense TGF-beta1 activity than CIS and than normal tissue adjacent to tumor. TGF beta1 mRNA and proteins were higher at the edge of the tumor than in the center and were also higher in less differentiated breast neoplasms. TGF-beta1 mRNA transcription and protein levels did not correlate either with TGF-beta1 exon 6 mutation or type and grade of differentiation of breast tumors. These observations suggest that TGF beta1 mutations in breast neoplasms might cause loss or inactivation of the growth inhibitory effects of TGF-beta1. They also support the proposed role of TGF-beta1 in the pathogenesis of breast cancer.


Anopheles gambiae, Anoga-HrTH hormone, free and bound structure--a nuclear magnetic resonance experiment.
The spread of malaria by the female mosquito, Anopheles gambiae, is dependent, amongst other things, on its ability to fly. This in turn, is dependent on the adipokinetic hormone, Anoga-HrTH (pGlu-Leu-Thr-Phe-Thr-Pro-Ala-Trp-NH2). No crystal structure of this important neuropeptide is available and hence NMR restrained molecular dynamics was used to investigate its conformational space in aqueous solution and when bound to a membrane surface. The results showed that Anoga-HrTH has an almost cyclic conformation that is stabilized by a hydrogen bond between the C-terminus and Thr3. Upon docking of the agonist to its receptor, this H-bond is broken and the molecule adopts a more extended structure. Preliminary AKHR docking calculations give the free energy of binding to be -47.30 kJ/mol. There is a close correspondence between the structure of the docked ligand and literature structure-activity studies. Information about the 3D structure and binding mode of Anoga-HrTH to its receptor is vital for the design of suitable mimetics which can act as insecticides.


Seasonal variations in the effect of zinc pyrithione and copper pyrithione on pelagic phytoplankton communities.
The relationship between environmental factors, community composition and the sensitivity of pelagic phytoplankton to the antifouling agents zinc pyrithione (ZPT) and copper pyrithione (CPT) was studied using phytoplankton communities collected from March until August 2001 in Roskilde fjord, Denmark. Sensitivity to ZPT and CPT was measured as EC50 values obtained from dose-response curves of photosynthesis to ZPT and CPT. EC50 for ZPT and CPT varied between 2 and 60 nM and 4 and 25 nM, respectively. Changes in sensitivity throughout the season were related to changes in phytoplankton community composition and density, and to nutrient levels. It was found that the variation in sensitivity of ZPT and CPT was related to the abundance of the groups Cryptophyceae, Bacillariophycaea and Dinophyceae when they were dominating the community. Furthermore, the sensitivity to ZPT was increased at low concentrations of phosphate per cell (<0.2 nmol/cell). For CPT there was a negative correlation between toxicity and phosphate concentration in the water. Consequently, in aquatic environments where phytoplankton is phosphate limited the effect of ZPT and CPT may be enhanced.


A re-examination of ambient air ozone monitor interferences.
Attaining the National Ambient Air Quality Standard (NAAQS) for ozone (O3) could cost billions of dollars nationwide. Attainment of the NAAQS is judged on O3 measurements made by the Federal Reference Method (FRM), ethylene chemiluminescence, or a Federal Equivalent Method (FEM), predominantly ultraviolet (UV) absorption. Starting in the 1980s, FRM monitors were replaced by FEMs so that today virtually all monitoring in the United States uses the UV methodology. This report summarizes a laboratory and collocated ambient air monitoring study of interferences in O3 monitors. Potential interferences examined in the laboratory included water vapor, mercury, o-nitrophenol, naphthalene, p-tolualdehyde, and mixed reaction products from smog chamber simulations of urban atmospheric photochemistry. UV absorption O3 monitors modified for humidity equilibration were also collocated with UV FEM O3 monitors at six sites in Houston, TX, during the 2007 summer O3 season. The results suggest that humidity and interfering species can positively bias (overestimate) O3 measured by FEM monitors used to determine compliance with the O3 standards. The results also suggest that humidity equilibration can mitigate this bias.


Membrane vesicles released by intestinal epithelial cells infected with rotavirus inhibit T-cell function.
Rotavirus (RV) predominantly replicates in intestinal epithelial cells (IEC), and "danger signals" released by these cells may modulate viral immunity. We have recently shown that human model IEC (Caco-2 cells) infected with rhesus-RV release a non-inflammatory group of immunomodulators that includes heat shock proteins (HSPs) and TGF-β1. Here we show that both proteins are released in part in association with membrane vesicles (MV) obtained from filtrated Caco-2 supernatants concentrated by ultracentrifugation. These MV express markers of exosomes (CD63 and others), but not of the endoplasmic reticulum (ER) or nuclei. Larger quantities of proteins associated with MV were released by RV-infected cells than by non-infected cells. VP6 co-immunoprecipitated with CD63 present in these MV, and VP6 co-localized with CD63 in RV-infected cells, suggesting that this viral protein is associated with the MV, and that this association occurs intracellularly. CD63 present in MV preparations from stool samples from 36 children with gastroenteritis due or not due to RV were analyzed. VP6 co-immunoprecipitated with CD63 in 3/8 stool samples from RV-infected children, suggesting that these MV are released by RV-infected cells in vivo. Moreover, fractions that contained MV from RV-infected cells induced death and inhibited proliferation of CD4(+) T cells to a greater extent than fractions from non-infected cells. These effects were in part due to TGF-β, because they were reversed by treatment of the T cells with the TGF-β-receptor inhibitor ALK5i. MV from RV-infected and non-infected cells were heterogeneous, with morphologies and typical flotation densities described for exosomes (between 1.10 and 1.18 g/mL), and denser vesicles (>1.24 g/mL). Both types of MV from RV-infected cells were more efficient at inhibiting T-cell function than were those from non-infected cells. We propose that RV infection of IEC releases MV that modulate viral immunity.


School and household tuberculosis contact investigations in Swaziland: Active TB case finding in a high HIV/TB burden setting.
Investigation of household contacts exposed to infectious tuberculosis (TB) is widely recommended by international guidelines to identify secondary cases of TB and limit spread. There is little data to guide the use of contact investigations outside of the household, despite strong evidence that most TB infections occur outside of the home in TB high burden settings. In older adolescents, the majority of infections are estimated to occur in school. Therefore, as part of a project to increase active case finding in Swaziland, we performed school contact investigations following the identification of a student with infectious TB. The Butimba Project identified 7 adolescent TB index cases (age 10-20) with microbiologically confirmed disease attending 6 different schools between June 2014 and March 2015. In addition to household contact investigations, Butimba Project staff worked with the Swaziland School Health Programme (SHP) to perform school contact investigations. At 6 school TB screening events, between May and October 2015, selected students underwent voluntary TB screening and those with positive symptom screens provided sputum for TB testing. Among 2015 student contacts tested, 177 (9%) screened positive for TB symptoms, 132 (75%) produced a sputum sample, of which zero tested positive for TB. Household contact investigations of the same index cases yielded 40 contacts; 24 (60%) screened positive for symptoms; 19 produced a sputum sample, of which one case was confirmed positive for TB. The odds ratio of developing TB following household vs. school contact exposure was significantly lower (OR 0.0, 95% CI 0.0 to 0.18, P = 0.02) after exposure in school. School-based contact investigations require further research to establish best practices in TB high burden settings. In this case, a symptom-based screening approach did not identify additional cases of tuberculosis. In comparison, household contact investigations yielded a higher percentage of contacts with positive TB screens and an additional tuberculosis case.


Stereochemistry specifies the regiochemistry of phosphorylation in two cAMP-dependent protein kinase substrates.
The substrate specificity of the cAMP-dependent protein kinase has been assessed with peptides bearing threoninol diastereomers. The threoninol residue contains both a primary alcohol and a secondary alcohol, either of which may serve as a site of phosphorylation. The enzyme-catalyzed phosphorylation of Gly-Arg-Thr-Gly-Arg-Arg-Asn-(2R,3R)-threoninol furnishes a Km of 498 +/- 39 microM and a Vmax of 7.8 +/- 0.2 mumol/min-mg, whereas the phosphorylation of Gly-Arg-Thr-Gly-Arg-Arg-Asn-(2S,3S)-threoninol provides a Km of 16.3 +/- 0.8 microM and a Vmax of 16.0 +/- 0.4 mumol/min-mg. Mass spectral analysis of the phosphopeptide reaction products revealed that each species is phosphorylated only once. 1H-coupled 31P NMR experiments unequivocally demonstrated that the (2R,3R)-isomer is specifically phosphorylated at the secondary alcohol, whereas the (2S,3S)-isomer is exclusively phosphorylated at the primary alcohol. This regiospecificity appears to be a consequence of the stereochemistry at C-2 in the threoninol residues. The structural attributes of the protein kinase that appear to be responsible for the observed differentiation between the C-2 stereoisomers is discussed.


Appraisal of the causal effect of plasma caffeine on adiposity, type 2 diabetes, and cardiovascular disease: two sample mendelian randomisation study.
To investigate the potential causal effects of long term plasma caffeine concentrations on adiposity, type 2 diabetes, and major cardiovascular diseases. Two sample mendelian randomisation study. Genome-wide association study summary data for associations of two single nucleotide polymorphisms associated with plasma caffeine at the genome-wide significance threshold (rs2472297 near the CYP1A2 gene and rs4410790 near the AHR gene) and their association with the outcomes. Primarily individuals of European ancestry participating in cohorts contributing to genome-wide association study consortia. Outcomes studied were body mass index, whole body fat mass, whole body fat-free mass, type 2 diabetes, ischaemic heart disease, atrial fibrillation, heart failure, and stroke. Higher genetically predicted plasma caffeine concentrations were associated with lower body mass index (beta -0.08 standard deviation (SD) (95% confidence interval -0.10 to -0.06), where 1 SD equals about 4.8 kg/m2 in body mass index, for every standard deviation increase in plasma caffeine) and whole body fat mass (beta -0.06 SD (-0.08 to -0.04), 1 SD equals about 9.5 kg; P<0.001) but not fat-free mass (beta -0.01 SD (-0.02 to -0.00), 1 SD equals about 11.5 kg; P=0.17). Higher genetically predicted plasma caffeine concentrations were associated with a lower risk of type 2 diabetes in two consortia (FinnGen and DIAMANTE), with a combined odds ratio of 0.81 ((95% confidence interval 0.74 to 0.89); P<0.001). Approximately half (43%; 95% confidence interval 30% to 61%) of the effect of caffeine on type 2 diabetes was estimated to be mediated through body mass index reduction. No strong associations were reported between genetically predicted plasma caffeine concentrations and a risk of any of the studied cardiovascular diseases. Higher plasma caffeine concentrations might reduce adiposity and risk of type 2 diabetes. Further clinical study is warranted to investigate the translational potential of these findings towards reducing the burden of metabolic disease.


Increased risk of lung cancer among male professional drivers in urban but not rural areas of Sweden.
To study the risk of lung cancer in different subgroups of professional drivers in urban and rural areas of Sweden. Information on occupation and geographical region was obtained from the Swedish census of 1970 and data on the incidence of lung cancer between 1971 and 1984 from the National Swedish Cancer Registry. Professional drivers were separated into bus, taxi, and long and short distance lorry drivers. Comparisons of cumulative incidence of lung cancer were made between each particular group of drivers and gainfully employed men in the same region. Taxi drivers, and long and short distance lorry drivers in Stockholm County showed increased relative risks (RRs) of lung cancer with the highest risk among the short distance lorry drivers (RR 2.0, 95% confidence interval (95% CI) 1.5 to 2.6). These categories of drivers also showed increased risks in the other two large conurbations in Sweden. In the rest of the country (mainly rural areas) there were no increased RRs for any category of driver. The RR for bus drivers was not increased in any region. After adjustment for assumed differences in smoking habits the RRs remained significantly increased for lorry drivers in Stockholm but not for other groups of drivers in other areas. However, the RRs remained numerically higher in large conurbations than in rural regions for all groups of drivers. These findings suggest that some factors present in the urban environment play a substantial part in the excess of lung cancer among short distance lorry drivers in urban areas of Sweden. Exposure to motor exhaust fumes may have contributed to this excess.


Morphological features of the left atrial appendage in consecutive coronary computed tomography angiography patients with and without atrial fibrillation.
The majority of intracardiac thrombi form in the left atrial appendage (LAA). Enlargement of this structure, together with certain morphological features, may indicate a predisposition to the formation of thrombi and subsequent cardioembolic stroke. Thus far, studies on LAA morphology have largely focused on those patients with atrial fibrillation (AF). Taking a different approach, we investigated the variation in LAA morphology in a consecutive patient population with and without AF. We evaluated 808 consecutive patients (529 females; mean age 52.5±9.9 years) who underwent coronary artery computed tomography angiography (CCTA), the majority of whom (749) had no history of AF. We assessed the length, lobe number, and morphological classification of their LAAs. Demographic data and medical histories were collated from medical records and then correlated with LAA morphology. The proportions of each of the four morphological classes of LAA for the overall vs. non-AF population were: WindSock, 62.3/61.5%; Cactus, 18.6/18.8%; ChickenWing, 10.0/10.0%; and CauliFlower, 9.2/9.6%. Age (p<0.001; r = 0.156) and female gender (p<0.001) were both found to be associated with an increased body surface area (BSA)-related LAA length. Male patients were more likely to manifest multi-lobed (p = 0.003) LAAs, and overweight patients with a greater number of multi-lobed LAA morphological classes (p = 0.010). No associations with morphological LAA features could be found for patients with diabetes, hypertension, or dyslipidemia. Nor did the size of the left atrium exhibit any correlation with BSA-related LAA length. In the overall and non-AF populations, aging and female gender were associated with longer BSA-indexed LAAs.


The effects of triceps surae fatigue on the torque and electromyographic parameters in athletes compared with non-athletes.
The common description of muscular fatigue is the failure of muscle in maintaining a target force. Even in sustained contraction, when muscle force is held at a stable level, physiological, biomechanical and electromyographic changes can occur. The purpose of this study is to compare the effects of triceps surae (TS) fatigue on the torque, falling slope and electromyographic (EMG) parameters between athletes and non-athletes. Nineteen healthy women (10 non-athletes and 9 basketball players) participated in this study. After warm-up, subjects performed one maximum voluntary contraction (MVC) followed by fatigue test including sustained maximum isometric contraction of TS until the peak torque (PT) decreased to 50% of maximum value. Immediately after the test, subjects were asked to perform one MVC; then, root mean square (RMS), median frequency (MDF), median frequency slope (MDF slope), PT, falling slope (FSL) and the amount of pain were measured. In both groups shift of MDF slope to negative values, significant decrease of MDF and RMS occurred at the end of the fatigue test (P < 0.05). Immediately after the test, PT decreased significantly in both groups (P < 0.05), however, decrease of FSL was significant in non-athletes (P < 0.05) but not in athletes. After fatigue test, increase in Pain was significant in both groups (P < 0.05). Before fatigue test, at the end, and immediately after the test, MDF of non-athletes was more than athletes. There was no significant difference in RMS between the two groups. Our findings suggest that TS fatigue affects EMG parameters, PT and pain in athletes and non-athletes similarly.


A hybrid discrete-continuous model of in vitro spheroid tumor growth and drug response.
Anti-cancer therapy efficacy in solid tumors mainly depends on drug transportation through the vasculature system and the extracellular matrix, on diffusion gradients and clonal heterogeneity within the tumor mass, as well as on the responses of the individual tumor cells to drugs and their interactions with each other and their local microenvironment. In this work, we develop a mathematical predictive model for tumor growth and drug response based on 3D spheroids experiments that possess several in vivo features of tumors and are considered better for drug screening. The model takes into account the diffusion gradients of both oxygen and drug through the tumor volume, describes the tumor population at cell level and assumes a simple underlying cellular dose-response curve that is translated to a cell death probability. The model shows that although the endpoint tumor regression can be well approximated, the effects of the drug on cell fate necessitate a more sophisticated model to explain the temporal evolution of tumor regression and more quantitative information regarding the number and topology of dead and living cells, which is highly important for in vivo clinical relevant predictions. The model is built in a way that can be constrained by experimentally derived set of parameters and is capable of accommodating cell heterogeneity, sub-cellular regulatory mechanisms and drug-induced signaling cascades, as well as additional mechanisms of adapted resistance.


Influence of patient mispositioning on SAR distribution and simulated temperature in regional deep hyperthermia.
Patient positioning plays an important role in regional deep hyperthermia to obtain a successful hyperthermia treatment. In this study, the influence of possible patient mispositioning was systematically assessed on specific absorption rate (SAR) and temperature distribution. With a finite difference time domain approach, the SAR and temperature distributions were predicted for six patients at 312 positions. Patient displacements and rotations as well as the combination of both were considered inside the Sigma-Eye applicator. Position sensitivity is assessed for hyperthermia treatment planning -guided steering, which relies on model-based optimization of the SAR and temperature distribution. The evaluation of the patient mispositioning was done with and without optimization. The evaluation without optimization was made by creating a treatment plan for the patient reference position in the center of the applicator and applied for all other positions, while the evaluation with optimization was based on creating an individual plan for each position. The parameter T90 was used for the temperature evaluation, which was defined as the temperature that covers 90% of the gross tumor volume (GTV). Furthermore, the hotspot tumor quotient (HTQ) was used as a goal function to assess the quality of the SAR and temperature distribution. The T90 was shown considerably dependent on the position within the applicator. Without optimization, the T90 was clearly decreased below 40 °C by patient shifts and the combination of shifts and rotations. However, the application of optimization for each positon led to an increase of T90 in the GTV. Position inaccuracies of less than 1 cm in the X-and Y-directions and 2 cm in the Z-direction, resulted in an increase of HTQ of less than 5%, which does not significantly affect the SAR and temperature distribution. Current positioning precision is sufficient in the X (right-left)-direction, but position accuracy is required in the Y-and Z-directions.


Purinergic signaling in the pancreas and the therapeutic potential of ecto-nucleotidases in diabetes.
It is widely accepted that purinergic signaling is involved in the regulation of functions of all known tissues and organs. Extracellular purines activate two classes of receptors, P1-adenosine receptors and P2-nucleotide receptors, in a concentration-dependent manner. Ecto-enzymes metabolizing nucleotides outside the cell are involved in the termination of the nucleotide signaling pathway through the release of ligands from their receptors. The pancreas is a central organ in nutrient and energy homeostasis with endocrine, exocrine and immunoreactive functions. The disturbances in cellular metabolism in diabetes mellitus lead also to changes in concentrations of intra- and extracellular nucleotides. Purinergic receptors P1 and P2 are present on the pancreatic islet cells as well as on hepatocytes, adipocytes, pancreatic blood vessels and nerves. The ATP-dependent P2X receptor activation on pancreatic β-cells results in a positive autocrine signal and subsequent insulin secretion. Ecto-NTPDases play the key role in regulation of extracellular ATP concentration. These enzymes, in cooperation with 5'-nucleotidase can significantly increase ecto-adenosine concentration. It has been demonstrated that adenosine, through activation of P1 receptors present on adipocytes and pancreatic islets cells, inhibits the release of insulin. Even though we know for 50 years about the regulatory role of nucleotides in the secretion of insulin, an integrated understanding of the involvement of purinergic signaling in pancreas function is still required. This comprehensive review presents our current knowledge about purinergic signaling in physiology and pathology of the pancreas as well as its potential therapeutic relevance in diabetes.


Internet-based cognitive-behavioural therapy for tinnitus: secondary analysis to examine predictors of outcomes.
The current study examined predictors of outcomes of internet-based cognitive-behavioural therapy (ICBT) for individuals with tinnitus. Secondary analysis of intervention studies. Internet-based guided tinnitus intervention provided in the UK. 228 individuals who underwent ICBT. ICBT. The key predictor variables included demographic, tinnitus, hearing-related and treatment-related variables as well as clinical factors (eg, anxiety, depression, insomnia), which can have an impact on the treatment outcome. A 13-point reduction in Tinnitus Functional Index (TFI) scores has been defined as a successful outcome. Of the 228 subjects who were included in the study, 65% had a successful ICBT outcome. As per the univariate analysis, participants with a master's degree or above had the highest odds of having a larger reduction in tinnitus severity (OR 3.47; 95% CI 1.32 to 12.51), compared with the participants who had education only up to high school or less. Additionally, the baseline tinnitus severity was found to be a significant variable (OR 2.65; 95% CI 1.50 to 4.67) contributing to a successful outcome with the intervention. Both linear and logistic regression models have identified education level and baseline tinnitus severity to be significant predictor variables contributing to a reduction in tinnitus severity post-ICBT. As per the linear regression model, participants who had received disability allowance had shown a 25.3-point lower TFI reduction compared with those who did not experience a decrease in their workload due to tinnitus after adjusting for baseline tinnitus severity and their education level. Predictors of intervention outcome can be used as a means of triaging patients to the most suited form of treatment to achieve optimal outcomes and to make healthcare savings. Future studies should consider including a heterogeneous group of participants as well as other predictor variables not included in the current study.ClinicalTrial.gov Registration: NCT02370810 (completed); NCT02665975 (completed).


Reproductive toxicity studies of rentiapril.
(2R,4R)-2-(o-Hydroxyphenyl)-3-(3-mercaptopropionyl)-4- thiazolidinecarboxylic acid (rentiapril, SA 446), an orally active inhibitor of angiotensin converting enzyme, was examined for effects upon general reproductive performance, for embryofoetal toxicity and for peri- and postnatal toxicity in the rat at dosages of 0, 20, 100 and 500 mg/kg/d. Embryofoetal toxicity was also examined in the New Zealand White rabbit at dosages of 0, 1, 2 and 4 mg/kg/d. The compound was administered by gastric intubation. Prolonged treatment at 100 and 500 mg/kg/d during the fertility study was associated with some slight depression of body weight gain of males. Body weight gain of females during gestation was significantly depressed at 500 mg/kg/d. There was salivation in both sexes at 500 mg/kg/d and also in males receiving 100 mg/kg/d. Following this prolonged treatment in the fertility study. Fo male and female kidney weights were increased at all dosages. Although there was no obvious effect upon fertility there was an increased incidence of total litter loss at 500 mg/kg/d and mean pup weights to day 21 post partum were reduced at this dosage and at 100 mg/kg/d with delays in the attainment of some of the developmental landmarks. In the rat treatment at 500 mg/kg/d from day 7 to 17 of pregnancy did not adversely effect embryofoetal development. Subsequent development and reproductive performance of the F1 offspring was also unimpaired. During this treatment period signs of salivation were seen at 500 mg/kg/d. Slight retardation of maternal body weight gain was noted at 500 mg/kg/d and at 100 mg/kg/d but not at 20 mg/kg/d.(ABSTRACT TRUNCATED AT 250 WORDS)


Guidelines for using posts in the restoration of endodontically treated teeth.
A review of the literature was done to determine when posts are required for restoring endodontically treated teeth and to give guidance on preparation of post space, design of posts, and use of luting agents. Posts were deemed to be unnecessary when adequate coronal tooth structure was present to retain a core. It was found that tooth structure should not be removed to construct a stronger post. The thinnest post with adequate strength was recommended. For best retention, it was found that post surfaces should not be smooth. When resin reinforced glass ionomer cements were used, they were found to be potentially harmful to restored teeth. Remaining coronal tooth structure was found to have the highest correlation in regard to success of the final restoration of endodontically treated teeth.


Skin necrosis at the injection site induced by low-molecular-weight heparin: case report and review.
Heparin-induced skin necrosis at the injection site is a rare adverse effect, more commonly associated with standard heparins than with low-molecular-weight heparins (LMWH) and its mechanism remains unclear. We report a case of LMWH-induced skin necrosis in a female during prophylactic treatment with LMWH after a surgical procedure. Determination of heparin-platelet-factor-4(PF4)-induced antibodies was positive. This case describes the occurrence of LMWH-induced skin necrosis and antibodies to heparin-PF4 complex, suggesting that this effect is more frequent than previously suspected.


Vitamin D supplementation for patients with alopecia areata: A protocol for systematic review and meta-analysis.
Several studies have reported an association between low Vitamin D (VD) levels and Alopecia areata (AA), and suggested VD preparations as a potential therapy. VD has immunomodulatory function closely associated with a variety of skin diseases, but there is no conclusive evidence to support VD supplementation for patients with AA. Therefore, we will conduct a meta-analysis to collect and evaluate the efficacy and safety of VD supplementation in the treatment of AA. We will search the following databases according to the developed strategy: Cochrane Library, PubMed, Web of Science, EMBASE, Scopus, Google scholar for Randomized controlled trials related to VD supplementation for AA. The retrieval time is from the establishment of each database to July 2022. Two reviewers will independently complete the literature search and screening, risk of bias assessment and data extraction. Severity of Alopecia Tool, Alopecia Density and Extent, Lesional area and senstivity (score) will be the primary results. RevMan V.5.3 will be used for data analysis and synthesis. For dichotomous outcomes and the continuous outcomes, we will calculate risk ratio with 95% Confidence intervals and mean differences or standardized mean differences with 95% Confidence intervals respectively. The reporting bias will be investigated using funnel plots, and the asymmetry of the funnel plots will be explained using the Harbord modified test or the Egger's regression test. The results of the study expect to provide a high-quality, evidence-based recommendation on VD supplementation in the treatment of AA for clinicians. The study will provide scientific and useful evidence for better use of VD supplementation in treating AA.


Evolution of nanocrystallinity in periodic mesoporous anatase thin films.
Herein we report the first kinetic study of the intrachannel wall phase-transition of amorphous titania to nanocrystalline anatase for periodic mesoporous titania thin films, monitored by time-resolved in situ high-temperature X-ray diffraction. Structural transformations associated with the phase transition are further probed by high-resolution scanning electron microscopy and transmission electron microscopy. The model found to be most consistent with the kinetic data involves 1D diffusion-controlled growth of nanocrystalline anatase within the spatial confines of the channel walls of the mesostructure. The observation of anisotropic, rod-shaped anatase nanocrystals preferentially aligned along the channel axis implies that the framework of the liquid-crystal-templated mesostructure guides the crystal growth.


Needle track seeding following percutaneous procedures for hepatocellular carcinoma.
Neoplastic seeding may arise after diagnostic or therapeutic percutaneous procedures for hepatocellular carcinoma. The true incidence of seeding with hepatocellular carcinoma is difficult to assess precisely, but a significant risk of seeding exists and is greater when performing diagnostic biopsy as compared to therapeutic percutaneous procedures [radiofrequency ablation, radiofrequency ablation (RFA); percutaneous ethanol injection, Percutaneous ethanol injection (PEI)]. Whenever liver transplantation is feasible, diagnostic needle biopsies should be avoided, but RFA and PEI are often needed as "bridge" treatments. The role of adjuvant treatments in reducing the incidence of seeding following RFA or PEI requires further evaluation.


Health physics technician injury reduction.
As part of a safety summit sponsored by Fluor Hanford Occupational Health and Safety, it was noted that Health Physics Technicians (HPTs) have one of the highest injury rates at Hanford. A multi-disciplined team made up of HPTs, health physics professionals, health physics management, indostrial hygienists, and medical personnel was established to determine causes and corrective actions. Committee activities included reviewing and characterizing occupational injuries and illnesses, assessing areas affecting the health of HPTs, soliciting field input, performing field evaluations of tasks, and making recommendations for improvements to senior management. Five areas showed a need for immediate improvement: manmachine interface (human factors and ergonomics), work environment, procedures, people, and communications. A key area of risk identified is the lack of ergonomic design considerations of the survey instruments currently used. There are several cases of cumulative trauma disorder requiring surgery. These cases are directly related to use of health physics instrumentation and/or survey techniques. The committee has made ergonomics and instrument redesign/modification its key initiative for 2001. The committee is encouraging vendor support and is seeking feedback from other health physics organizations regarding their experience and any recommendations they would like to make. Some success has already been achieved through an ergonomics-training program aimed at all HPTs and their supervisors. In addition, there have been several changes made to the way surveys are conducted, survey frequencies have been reduced, and the way modifications have been made to existing instrumentation. This is a long-term initiative with broad support within the Hanford HPT community. This document reports the progress made thus far on the initiative.


Problems in intracellular membrane traffic.
Eukaryotic cells operate an extensive and well regulated traffic of membrane-bound vesicles to: (a) transport intracellularly, and eventually discharge by exocytosis, macromolecular products; (b) take up by endocytosis molecules and particles from the environment; (c) transport macromolecules across epithelial barriers; and (d) move membranes from their site of assembly to their final locations. Vesicular transport appears to be the equivalent of a discontinuous circulatory system in which vesicles recycle between the termini of each transport pathway, so that balanced membrane distribution is maintained among cell compartments and the cell's surface. Although the general outline of the process is reasonably clear, much remains to be learned about the number and types of pathways, the types and quantities of membranes, and the rates of vesicular movement. Since each vesicular carrier finds its specific terminus (and fuses with it), vesicular traffic is strictly controlled. By analogy with the control of intracellular protein traffic, it may be assumed that vesicular traffic is regulated by the mutual recognition of protein signals and receptors affixed, in this case, with appropriate asymmetry to the surface of the interacting membranes. Since vesicular transport operates without loss of specific chemistry and function of various cellular membranes, cells can counteract effectively the randomization of membrane proteins and lipids, which becomes possible whenever two membranes establish continuity of their fluid bilayers, and when membrane is removed from one or both termini of a recycling pathway. Specific selection of termini and prevention of randomization among membrane components are major unsolved problems in vesicular transport. Their solution in terms of molecular interactions requires further work.


Multi target analysis of putrefactive specimens by liquid chromatography-tandem mass spectrometry to prove multiple poisonings by hypnotics and muscle relaxants.
The muscle relaxant rocuronium and the hypnotics etomidate, diazepam and midazolam were candidate poisons in a case of a suspected series of fatal intoxications in a hospital. A robust, specific and sensitive multi-target screening procedure was established to identify unequivocally the parent compounds and diagnostic metabolites and artefacts in putrefied specimens, obtained from exhumed bodies. The analytical findings of relevant compounds could be traced partially back to authorised therapeutic measures, whereas the identification of rocuronium proved potentially lethal intoxications in 13 (of a total number of 42) cases. Moreover, the detection of certain hypnotics revealed an improper administration of these compounds in another nine cases, which suggested manipulation but was not indicative of fatal intoxications. Quantitative estimations of substance concentrations were highly correlated with the post-mortem time intervals and did not reveal any information on doses, initial serum concentrations or toxicological effects.


Genetic diversity of Xanthoceras sorbifolium bunge germplasm using morphological traits and microsatellite molecular markers.
Xanthoceras sorbifolium Bunge has great potential for producing biodiesel. In order to select and evaluate appropriate germplasm to produce biodiesel, we analyzed the genetic diversity of Xanthoceras sorbifolium Bunge germplasm based on morphological traits and simple sequence repeats (SSRs) in this study. Fifty-six germplasm samples were evaluated using nine morphological traits and 23 SSR loci. Significant differences among germplasms were observed in eight morphological characters. The SSR markers analysis showed high genetic diversity among the germplasms. All SSRs had polymorphisms, and we detected 77 alleles in total. The number of alleles at each locus ranged from two to six, averaging 3.35 per marker. The polymorphic information content values ranged from 0.36 to 0.61, averaging 0.49. Expected heterozygosity, observed heterozygosity, and Shannon's information index calculations detected large genetic variations among germplasms. The high average number of alleles per locus and the allelic diversity observed in the set of genotypes analyzed indicated that the genetic base of this species is relatively wide. Thus, microsatellite markers can be used to efficiently distinguish Xanthoceras sorbifolium Bunge germplasms and assess their genetic diversity. Hundred-grain weight and lateral diameter were positively correlated with monounsaturated fatty acids and depended on genotype. These results suggest that seeds with higher hundred-grain weight and lateral diameter could be more suitable to produce biodiesel. Our data will lay a foundation for selecting appropriate germplasm to produce biodiesel based on seed phenotype and will contribute to the conservation and management of this important plant genetic resource.


Peer-to-peer mentoring for individuals with early inflammatory arthritis: feasibility pilot.
To examine the feasibility and potential benefits of early peer support to improve the health and quality of life of individuals with early inflammatory arthritis (EIA). Feasibility study using the 2008 Medical Research Council framework as a theoretical basis. A literature review, environmental scan, and interviews with patients, families and healthcare providers guided the development of peer mentor training sessions and a peer-to-peer mentoring programme. Peer mentors were trained and paired with a mentee to receive (face-to-face or telephone) support over 12 weeks. Two academic teaching hospitals in Toronto, Ontario, Canada. Nine pairs consisting of one peer mentor and one mentee were matched based on factors such as age and work status. Mentee outcomes of disease modifying antirheumatic drugs (DMARDs)/biological treatment use, self-efficacy, self-management, health-related quality of life, anxiety, coping efficacy, social support and disease activity were measured using validated tools. Descriptive statistics and effect sizes were calculated to determine clinically important (>0.3) changes. Peer mentor self-efficacy was assessed using a self-efficacy scale. Interviews conducted with participants examined acceptability and feasibility of procedures and outcome measures, as well as perspectives on the value of peer support for individuals with EIA. Themes were identified through constant comparison. Mentees experienced improvements in the overall arthritis impact on life, coping efficacy and social support (effect size >0.3). Mentees also perceived emotional, informational, appraisal and instrumental support. Mentors also reported benefits and learnt from mentees' fortitude and self-management skills. The training was well received by mentors. Their self-efficacy increased significantly after training completion. Participants' experience of peer support was informed by the unique relationship with their peer. All participants were unequivocal about the need for peer support for individuals with EIA. The intervention was well received. Training, peer support programme and outcome measures were demonstrated to be feasible with modifications. Early peer support may augment current rheumatological care. NCT01054963, NCT01054131.


Presenting ADAMTS13 antibody and antigen levels predict prognosis in immune-mediated thrombotic thrombocytopenic purpura.
Immune-mediated thrombotic thrombocytopenic purpura (TTP) is a life-threatening disorder caused by antibodies against ADAMTS13. From the United Kingdom TTP registry, we undertook a prospective study investigating the impact of the presenting anti-ADAMTS13 IgG antibody and ADAMTS13 antigen on mortality. A total of 312 episodes involving 292 patients over 87 months were included; 68% were female, median age 46 (range, 11-88 years), and median presenting ADAMTS13 of <5% (range, <5%-18%). The mortality rate was 10.3% (n = 32); 68% of patients had a raised troponin at presentation conferring a sixfold increase in mortality compared with those with normal troponin levels (12.1% vs 2.0%, P = .04). Twenty-four percent had a reduced Glasgow Coma Score (GCS) at presentation with a ninefold increase in mortality (20% vs 2.2% for normal GCS at presentation, P < .0001). Mortality increased with higher anti-ADAMTS13 antibody levels and lower ADAMTS13 antigen levels. Those with antibody levels in the upper quartile (antibody >77%) had a mortality of 16.9% compared with 5.0% for the lowest quartile (antibody <20%) (P = .004). Those with an antigen level in the lowest quartile (antigen <1.5%) had a mortality of 18% compared with 3.8% for the highest quartile (antigen >11%) (P = .005). The synergistic effect of anti-ADAMTS13 IgG antibody in the upper quartile and ADAMTS13 antigen in the lowest quartile had the highest mortality of 27.3%. We conclude that both anti-ADAMTS13 IgG antibody and ADAMTS13 antigen levels correlate with outcome in TTP with increased cardiac and neurological involvement and increased mortality.


Detection of lipopolysaccharides by ethidium bromide staining after sodium dodecyl sulfate-polyacrylamide gel electrophoresis.
A rapid and easy method for staining lipopolysaccharides with ethidium bromide is described. Lipopolysaccharides could be visualized by ethidium bromide with almost the same sensitivity as found with the silver-staining method in less than 30 min. The ethidium bromide-staining method was particularly suitable for staining lipopolysaccharides possessing acidic O-specific polysaccharides, which were poorly visualized by silver staining.


Clinico-electrographic characteristics and classification of genetic generalized epilepsy in Oman.
There is a lack of information on the annual incidence of genetic generalized epilepsy (GGE) in the Arab countries, especially Oman. Ascertaining the true burden of illness has crucial implications for health policies and priorities. We aim to study the clinico-electrographic characteristics, classification, and annual incidence of GGE in Oman. Using the cross-sectional data of EEGs obtained from all patients with GGE who presented to Sultan Qaboos University hospital (major referral center for epilepsy in Oman) from January 2007 to June 2014. Analyses were performed using univariate statistics. Approximately 10,423 patients had EEG studies during the study period of which 376 patients (3.6 %) had EEG abnormalities suggestive of GGE. Forty two percent of the 376 GGE patients were male with ages ranging from 3 to 58 years. We were able to classify 273 patients to one of the GGE syndromes. Forty-three percent of 130 patients had a positive family history of epilepsy in their first or second-degree relatives. The generalized tonic-clonic seizure was the most common seizure type observed in 242 patients (64 %; 95 %CI: 59.2 %-68.9 %). Juvenile myoclonic epilepsy was the most common epilepsy syndrome (41 % of the total GGE patients) encountered in our region. A significant female predominance (9.7 % vs 2.5 %; p = 0.016) was observed in juvenile absence epilepsy. Certain interictal focal EEG abnormalities did not exclude a diagnosis of GGE. An average annual GGE incidence of 2.9 % (95 % CI: 2.6 %-3.2 %) was observed during the study period. This hospital-based study is the first of its kind in the Arabian Gulf region, classifying the different subcategories of GGE. Our results indicate that GGE is a common epilepsy subtype in Oman. A prospective population-based epidemiological study is required to estimate the precise frequency of GGE in Oman.


MXenes and Their Applications in Wearable Sensors.
MXenes, a kind of two-dimensional material of early transition metal carbides and carbonitrides, have emerged as a unique class of layered-structured metallic materials with attractive features, as good conductivity comparable to metals, enhanced ionic conductivity, hydrophilic property derived from their hydroxyl or oxygen-terminated surfaces, and mechanical flexibility. With tunable etching methods, the morphology of MXenes can be effectively controlled to form nanoparticles, single layer, or multi-layer nanosheets, which exhibit large specific surface areas and is favorable for enhancing the sensing performance of MXenes based sensors. Moreover, MXenes are available to form composites with other materials facilely. With structure design, MXenes or its composite show enhanced mechanical flexibility and stretchability, which enabled its wide application in the fields of wearable sensors, energy storage, and electromagnetic shielding. In this review, recent progress in MXenes is summarized, focusing on its application in wearable sensors including pressure/strain sensing, biochemical sensing, temperature, and gas sensing. Furthermore, the main challenges and future research are also discussed.


Case of cannabinoid hyperemesis syndrome with long-term follow-up.
Long-term cannabis use may be associated with attacks of severe nausea and vomiting, and a characteristic learned behavior of compulsive hot bathing, termed cannabinoid hyperemesis syndrome (CHS). Long-term follow-up and prognosis of CHS have not been reported previously. A 44-year-old Caucasian man with a long history of addiction to marijuana presented with chronic abdominal pain complicated by attacks of uncontrollable vomiting for 16 years. He had a compulsion to take scalding hot showers, as many as 15 times a day, to relieve his symptoms. All previous therapies had been ineffective. However, abstinence from marijuana led to rapid and complete resolution of all symptoms and his compulsive hot showering behavior. He has been followed for nine years, and is still doing well without recurrence of symptoms. Physicians should have a high index of suspicion for this under-recognized condition, as excellent long-term prognosis of CHS can be achieved when abstinence is maintained.


Three-dimensional structure of Escherichia coli branched-chain amino acid aminotransferase at 2.5 A resolution.
The X-ray crystallographic structure of the branched-chain amino acid aminotransferase from Escherichia coli was determined by means of isomorphous replacement using the selenomethionyl enzyme as one of the heavy atom derivatives. The enzyme is a homo hexamer with D3 symmetry, and the polypeptide chain of the subunit is folded into two domains (small and large domains). The coenzyme, pyridoxal 5'-phosphate, resides at the domain interface, its re-face facing toward the protein. The active site structure shows that the following sites can recognize branched-chain amino acids and glutamate as substrates: (1) a hydrophobic core formed by Phe36, Tyr164, Tyr31*, and Val109* for a branched-chain; (2) Arg97 for an acidic side chain of glutamate; and (3) Tyr95 and two main chain NH groups of Thr257 and Ala258 for the alpha-carboxylate of substrates. Although the main chain conformation of the active site is homologous to that of D-amino acid aminotransferase, many of the active site residues are different between them.


Attachment of Treponema denticola strains to monolayers of epithelial cells of different origin.
The attachment of 10 different Treponema denticola strains to monolayers of 4 types of epithelial cells derived from rat palatal epithelium, guinea pig ear, human buccal epithelium and human corneal epithelium was screened microscopically. Most T. denticola strains were able to attach to all four types of epithelial cells. The T. denticola strains seemed to attach better to epithelial cells derived from primary cultured material. The T. denticola strains showed different degrees of attachment. Scanning electron microscopy studies revealed that the attachment of T. denticola was not only tip-associated but occurred also at random points in close contact with microvilli of the epithelial cells. Attached spirochetes were non-uniformly distributed over the monolayers, indicating the presence of receptive subpopulations of epithelial cells in the monolayers.


Role of neurogenic inflammation in pancreatitis and pancreatic pain.
Pain arising from pancreatic diseases can become chronic and difficult to treat. There is a paucity of knowledge regarding the mechanisms that sensitize neural pathways that transmit noxious information from visceral organs. In this review, neurogenic inflammation is presented as a possible amplifier of the noxious signal from peripheral organs including the pancreas. The nerve pathways that transmit pancreatic pain are also reviewed as a conduit of the amplified signals. It is likely that components of these visceral pain pathways can also be sensitized after neurogenic inflammation.


Freeze-etch study of Pseudomonas aeruginosa: localization within the cell wall of an ethylenediaminetetraacetate-extractable.
A freeze-etch study of normal cells of Pseudomonas aeruginosa and of cells after incubation with ethylenediaminetetraacetate (EDTA) and tris(hydroxymethyl)aminomethane (Tris) was performed. When cells were freeze-etched without a cryoprotective agent, a smooth outer cell wall layer, which showed a regular array of subunits, and the presence of flagella and pili were observed. These features were not observed in cells freeze-etched after cryoprotection with glycerol. Four fracture surfaces, which resulted from splitting down the center of the outer wall membrane and of the inner cytoplasmic membrane, were revealed in freeze-etched glycerol-protected cells. The murein layer was seen in profile between the outer cell wall membrane and the cytoplasmic membrane. Spherical units and small rods composed of the spherical units were observed in the inner layer of the outer cell wall membrane. These spherical units appeared to be attached to, or embedded in, the inner face of the outer layer of the outer cell wall membrane. These spherical units were removed from cells on exposure to EDTA-Tris, resulting in cells that were osmotically fragile. The spherical units were detected via electron microscopy of negatively stained preparations in the supernatant fluid of cellular suspensions treated with EDTA-Tris. Upon addition of Mg(2+), the spherical units were reaggregated into the inner layer of the outer cell wall membrane and the cells were restored to osmotic stability. The spherical units were shown to consist primarily of protein. These data are thought to represent the first ultrastructural demonstration of reaggregation of cell wall components within a living cell system.


Selective lysis of the autologous tumor by delta TCS1+ gamma/delta+ tumor-infiltrating lymphocytes from human lung carcinomas.
Two distinct non-overlapping populations of TcR1+ (gamma/delta) T cells have been described: the first, bearing the disulfide-linked gamma/delta heterodimer, is predominant in the peripheral blood; the second, expressing the non-disulfide-linked form of TcR1, is mostly confined to epithelial tissues (lung, gut, skin). TcR1+ lymphocytes may be cytotoxic and could be involved in anti-tumor immunity, especially against tumors at epithelial sites. Freshly derived tumor-infiltrating lymphocytes (TIL) obtained from two patients with lung cancer were enriched in CD3+WT31- cells. The percentage of this subset substantially increased upon culture in the presence of interleukin 2. These cells were TcR1+ as demonstrated by immunofluorescence and immunoprecipitation. In one case only 40% of this population reacted with delta TCS1 mAb, that recognizes the non-disulfide-linked form of TcR1, and co-expressed the CD8 antigen. Cultured TcR1+ TIL were able to kill fresh autologous tumor cells, K-562 and, to a lesser extent, some natural killer-resistant cell lines and allogeneic lung tumor cells in 4-h 51Cr-release cytotoxicity assays. The fractionated delta TCS1+ TIL lysed only autologous tumor cells and K-562, whereas the lytic activity against all the other targets was confined to the delta TCS1- subset. Moreover, the autotumor cytotoxicity was inhibited by anti-HLA class I but not by anti-CD1c or anti-LFA-1 mAb, suggesting that killing of the autologous tumor cells and non-major histocompatibility complex-restricted cytotoxicity are mediated by different mechanisms.


Degradation of salicylic acid by Fusarium graminearum.
Fusarium head blight (FHB) is a major cereal crop disease, caused most frequently by the fungus Fusarium graminearum. We have previously demonstrated that F. graminearum can utilize SA as sole source of carbon to grow. In this current study, we further characterized selected four fungal SA-responsive genes that are predicted to encode salicylic acid (SA)-degrading enzymes and we used a gene replacement approach to characterize them further. These included two genes predicted to encode a salicylate 1-monooxygenase, FGSG_03657 and FGSG_09063, a catechol 1, 2-dioxygenase gene, FGSG_03667, and a 2, 3-dihydroxybenzoic acid decarboxylase gene, FGSG_09061. For each gene, three independent gene replacement strains were assayed for their ability to degrade salicylic acid in liquid culture. Salicylate 1-monooxygenase FGSG_03657 and catechol 1, 2-dioxygenase FGSG_03667 were shown to be essential for SA degradation, while a loss of 2, 3-dihydroxybenzoic acid decarboxylase FGSG_09061 caused only a partial reduction of SA degradation and a loss of salicylate 1-monooxygenase FGSG_09063 had no effect when compared to wild type culture. Salicylate 1-monooxygenase FGSG_03657 and catechol 1, 2-dioxygenase FGSG_03667 were identified as the first two key enzyme steps of SA degradation via catechol in the β-ketoadipate pathway. Expression profiles for all four genes were also determined in liquid culture and in planta. Salicylate 1-monooxygenase FGSG_03657 and catechol 1, 2-dioxygenase FGSG_03667 were co-expressed and their expression was substrate dependent in liquid culture; however their expression was uncoupled in planta. Disruption of the gene for catechol 1, 2-dioxygenase FGSG_03667 was shown to have no effect on fungal virulence on wheat. Our results with 2, 3-dihydroxybenzoic acid decarboxylase FGSG_09061 raise the possibility of an alternate non-oxidative decarboxylation pathway for the conversion of SA to catechol via 2, 3-dihydrozybenzoic acid and for a connection between the oxidative and the non-oxidative decarboxylation pathways for SA conversion.


[Rehabilitative treatment of patients with primary and secondary spinal cord neoplasms].
The Authors present their studies concerning rehabilitation treatment in primary and secondary spinal cord tumors. They examine the problems inherent in this complex pathology. Rehabilitation was initiated in the acute phase of the illness with the aim of preventing secondary and tertiary damage that could jeopardize successive functional recuperation. The Authors believe that rehabilitation treatment, when used early enough, improves the day life for patients with spinal cord tumors.


Activity changes in cranberry bean (Phaseolus vulgaris) alpha-amylase inhibitor by chemical modification and enzymatic digestion.
An alpha-amylase inhibitor was prepared from cranberry bean (Phaseolus vulgaris). The alpha-amylase inhibitor was composed of three different subunits not linked by disulfide bridges and only one of them contained carbohydrate. Although the inhibitor was stable at pH 3 to 7, it was heat labile at pH 3 and 5. Chemical modification of the amino groups and the guanido groups in cranberry bean alpha-amylase inhibitor molecule resulted in rapid loss of the inhibitory activity, respectively. Oxidation of the tryptophan residues also led to loss of the activity. On the other hand, reductive methylation of the amino groups scarcely affected the activity. The inhibitor was quite resistant to the proteolytic digestions by pepsin and trypsin, while it was relatively susceptible to the action of chymotrypsin.


Most stomatal closure in woody species under moderate drought can be explained by stomatal responses to leaf turgor.
Reduced stomatal conductance (gs ) during soil drought in angiosperms may result from effects of leaf turgor on stomata and/or factors that do not directly depend on leaf turgor, including root-derived abscisic acid (ABA) signals. To quantify the roles of leaf turgor-mediated and leaf turgor-independent mechanisms in gs decline during drought, we measured drought responses of gs and water relations in three woody species (almond, grapevine and olive) under a range of conditions designed to generate independent variation in leaf and root turgor, including diurnal variation in evaporative demand and changes in plant hydraulic conductance and leaf osmotic pressure. We then applied these data to a process-based gs model and used a novel method to partition observed declines in gs during drought into contributions from each parameter in the model. Soil drought reduced gs by 63-84% across species, and the model reproduced these changes well (r(2) = 0.91, P < 0.0001, n = 44) despite having only a single fitted parameter. Our analysis concluded that responses mediated by leaf turgor could explain over 87% of the observed decline in gs across species, adding to a growing body of evidence that challenges the root ABA-centric model of stomatal responses to drought.


Awareness and attitude towards sex health education and sexual health services among youngsters in rural and urban settings of Sindh, Pakistan.
To assess attitudes and awareness regarding sexual health education and services among young individuals in Pakistan. A cross-sectional survey was conducted in urban and semi-urban districts of Sindh, Pakistan, in 2010. A self-administered questionnaire was distributed in-hand among 200 young people aged 16-25 years; who were selected on the basis of convenience sampling. Of the questionnaires distributed, 165 (82%) were returned. After checking for quality and consistency, 150 (75%) forms were found good enough to be used for categorical analysis, using PASW Statistics 18 for Mac 2008 version. Of the 150 participants, 94 (63%) were males and 56 (37%) were females. A quarter of them (n = 38; 25.3%) said sexual health services were available too far away from their area. Besides, they also found the staff to be 'not competent.' Almost one-third (n = 49; 32.7%) reported of not having matching gender choice (male or female) of professionals with whom they could feel comfortable sharing their sexual health concerns. Majority of the participants (n = 101; 67.3%) considered trained health professionals as the primary source of sexual health education, whereas, 90 (60%), 75 (50%), and 59 (39.3%) also reported to have secondary sources, including internet, parents and telephone helpline respectively. Sexual health education and services for the young are barely enough or satisfactory in terms of quantity and quality in Pakistan, suggesting a case for having curriculum-based sex education implemented in academic institutions.


Explaining women's employment patterns: 'orientations to work' revisited.
Explanations of the persisting differences in the structure of men's and women's employment have long been debated in the social sciences. Sociological explanations have tended to stress the continuing significance of structural constraints on women's employment opportunities, which persist despite the removal of formal barriers. Neo-classical economists, in contrast, have emphasized the significance of individual choice, an argument which has been recently endorsed by Hakim who suggests that patterns of occupational segregation reflect the outcome of the choices made by different 'types' of women. In this paper, a previous debate relating to the explanatory utility of men's 'orientations to work' is used to argue that employment structures are the outcome of both choice and constraint, and that this is the case for women, as well as men. The argument is illustrated with evidence from cross-nationally comparative biographical interviews carried out in five countries.


Pregnancy-Related Coronary Artery Dissection: Recognition of a Life Threatening Process.
Pregnancy-related spontaneous coronary artery dissection (P-SCAD) is a rare but life-threatening condition of the peripartum and postpartum mother. The gold standard of diagnosing P-SCAD is a left cardiac catheterization; however, this diagnostic tool may not be used early because myocardial infarction is not typically a top differential diagnosis for women and especially young pregnant women presenting with acute chest pain. Providers and registered nurses, particularly those in the prehospital setting, the emergency department, and labor and delivery units, should be aware of signs, symptoms, potential risk factors, and diagnostic results that could indicate P-SCAD and initiate early and appropriate treatment to improve maternal outcomes.


Transient ETV2 Expression Promotes the Generation of Mature Endothelial Cells from Human Pluripotent Stem Cells.
Differentiation protocols are used for induced pluripotent stem cells (iPSCs) in in vitro disease modeling and clinical applications. Transplantation of endothelial cells (ECs) is an important treatment strategy for ischemic diseases. For example, in vitro generated ECs can be used to provide the vascular plexus to regenerate organs such as the liver. Here, we demonstrate that the E-twenty-six (ETS) transcription factor ETV2 alone can directly convert iPSCs into vascular endothelial cells (iPS-ETV2-ECs) with an efficiency of over 90% within 5 d. Although the stable overexpression of ETV2 induced the expression of multiple key factors for endothelial development, the induced ECs were less mature. Furthermore, doxycycline-inducible transient ETV2 expression could upregulate the expression of von Willebrand factor (vWF) in iPS-ETV2-ECs, leading to a mature phenotype. The findings of this study on generation of mature iPS-ETV2-ECs provide further insights into the exploration of cell reprogramming from iPSCs. Here, we provide a new protocol for differentiation of iPSCs, thus providing a new source of ECs for in vitro disease modeling and clinical applications.


Application of multivariate time-series model for high performance computing (HPC) fault prediction.
Aiming at the high reliability demand of increasingly large and complex supercomputing systems, this paper proposes a multidimensional fusion CBA-net (CNN-BiLSTAM-Attention) fault prediction model based on HDBSCAN clustering preprocessing classification data, which can effectively extract and learn the spatial and temporal features in the predecessor fault log. The model can effectively extract and learn the spatial and temporal features from the predecessor fault logs, and has the advantages of high sensitivity to time series features and sufficient extraction of local features, etc. The RMSE of the model for fault occurrence time prediction is 0.031, and the prediction accuracy of node location for fault occurrence is 93% on average, as demonstrated by experiments. The model can achieve fast convergence and improve the fine-grained and accurate fault prediction of large supercomputers.


Role of Epoxide Hydrolases and Cytochrome P450s on Metabolism of KZR-616, a First-in-Class Selective Inhibitor of the Immunoproteasome.
KZR-616 is an irreversible tripeptide epoxyketone-based selective inhibitor of the human immunoproteasome. Inhibition of the immunoproteasome results in anti-inflammatory activity in vitro and based on promising therapeutic activity in animal models of rheumatoid arthritis and systemic lupus erythematosus KZR-616 is being developed for potential treatment of multiple autoimmune and inflammatory diseases. The presence of a ketoepoxide pharmacophore presents unique challenges in the study of drug metabolism during lead optimization and clinical candidate profiling. This study presents a thorough and systematic in vitro and cell-based enzymatic metabolism and kinetic investigation to identify the major enzymes involved in the metabolism and elimination of KZR-616. Upon exposure to liver microsomes in the absence of NADPH, KZR-616 and its analogs were converted to their inactive diol derivatives with varying degrees of stability. Diol formation was also shown to be the major metabolite in pharmacokinetic studies in monkeys and correlated with in vitro stability results for individual compounds. Further study in intact hepatocytes revealed that KZR-616 metabolism was sensitive to an inhibitor of microsomal epoxide hydrolase (mEH) but not inhibitors of cytochrome P450 (P450) or soluble epoxide hydrolase (sEH). Primary human hepatocytes were determined to be the most robust source of mEH activity for study in vitro. These findings also suggest that the exposure of KZR-616 in vivo is unlikely to be affected by coadministration of inhibitors or inducers of P450 and sEH. SIGNIFICANCE STATEMENT: This work presents a thorough and systematic investigation of metabolism and kinetics of KZR-616 and related analogs in in vitro and cell-based enzymatic systems. Information gained could be useful in assessing novel covalent proteasome inhibitors during lead compound optimization. These studies also demonstrate a robust source in vitro test system that correlated with in vivo pharmacokinetics for KZR-616 and two additional tripeptide epoxyketones.


Molecular and electronic structure of square planar complexes [PdII(tbpy)(L N,O IP)]0, [PdII(tbpy)(LN,O ISQ)](PF6), and [PdII(tbpy)(L N,O IBQ)](PF6)(BF4).2CH2Cl2: an o-iminophenolato based ligand centered, three-membered redox series.
Three Pd(II) complexes which are members of the same electron-transfer series have been synthesized. Refluxing of the reaction mixture containing equimolar amounts of PdCl(2), 2-(2-trifluoromethyl)anilino-4,6-di-tert-butylphenol (H(2)L(N,O)), 4,4'-di-tert-butyl-2,2'-dipyridyl ((t)bpy), and 3 equiv of triethylamine in MeOH under an argon atmosphere followed by exposure to air and addition of KPF(6) after cooling to room temperature yields reddish brown crystals of paramagnetic (S = 1/2) [Pd(L(N,O)(ISQ))((t)bpy)](PF6) (2). Reaction of 2 with one equiv of [CoCp2] in dry and degassed CH(2)Cl(2) using anaerobic conditions gives diamagnetic [Pd(L(N,O)(IP))((t)bpy)] (1), which is the one-electron reduced form of 2. One-electron oxidation of 2 in CH(2)Cl(2) under argon with one equiv of NOBF4 affords diamagnetic [Pd(L(N,O)(IBQ))((t)bpy)](PF6)(BF4).2CH(2)Cl(2) (3). Complexes 1, 2, and 3 constitute three members of the same electron-transfer series. They are ideally suited to distinctly distinguish the geometrical and spectroscopic features of the N,O-coordinated, closed-shell, diamagnetic o-iminophenolate (L(N,O)(IP))2-, the corresponding open-shell pi-radical o-iminobenzosemiquinonate (L(N,O)(ISQ))1-.(S(rad) = 1/2), and the closed-shell o-iminobenzoquinone (L(N,O)(IBQ))0 forms. All complexes were characterized by X-ray crystallography (100 K), cyclic voltammetry, EPR, and UV-vis spectroscopy. Complex 2 exhibits three reversible electron transfer waves in the cyclic voltammogram. Structural characterization of complex 3 reveals an interesting strong ion pairing between the BF4 anion and the complex dication with a short C-F distance of 2.7 A.


[Tea polyphenols reduces the apoptosis of spermatogenic cells in rats with experimental varicocele].
To study the effect of tea polyphenols (TP) on the apoptosis of germ cells in rats with experimental varicocele. Thirty-two adolescent male Wistar rats were randomly and equally divided into groups A (sham-operation), B (high-dose TP), C (low-dose TP), and D (experimental left varicocele). Experimental varicocele was induced by partial ligation of the left renal vein in the latter three groups of rats. The animals in groups A and D were fed with normal saline, while those in B and C with TP at 40 and 10 mg per kg per d, respectively, all for 4 weeks. Then, all the rats were sacrificed and the left testes harvested for determination of the expression of HIF-1, Bcl-2, Bax, CytC, and caspase-3 by immunohistochemistry and measurement of the apoptosis index (AI) of spermatogenic cells. The expression of Bcl-2 was higher in groups B and C than in D but lower than in A (P < 0.05), and lower in C than in B (P < 0.05). However, the expressions of HIF-1, Bax, CytC, and caspase-3 were lower in groups B and C than in D but higher than in A (P < 0.05), and higher in C than in B (P < 0.05). The AI of spermatogenic cells was the lowest in group A, higher in D than in the other groups but lower in B than in C (P < 0.05). TP can reduce the apoptosis of spermatogenic cells in a dose-dependent manner in varicocele rats.


The Story of MedCom.
This chapter describes the development of the electronic communication in Denmark and the background behind the Danish project organisation MedCom. Since 1996, there has been an IT-strategy in the healthcare sector by the Danish government, which has been under constant development. These strategies have laid the foundation for MedCom, which was established in 1994 in order to build a Danish Healthcare Data Network. Today, the Healthcare Data Network forms an integral part of the everyday work of the Danish healthcare sector, since the dissemination and use of it has risen sharply since it was established.


Eculizumab in the treatment of membranoproliferative glomerulonephritis.
A major shift in our understanding of the membranoproliferative glomerulonephritis (MPGN) lesion is the focus on which components of the complement pathway are involved in mediating renal injury. Hence, MPGN is no longer classified solely by ultrastructural findings on biopsy but instead divided into immune complex-mediated lesions versus complement-mediated lesions. This emphasis on complement, in turn, leads to interest in therapies that target complement as potential disease-modifying agents. Eculizumab, the first available anticomplement therapy, blocks at the level of C5 and has revolutionized the treatment of complement-mediated diseases such as paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome. Whether this agent will work equally well for the far more heterogeneous complement-mediated MPGN lesions, also known as C3 glomerulopathy, remains unclear. To date, the experience and published data on using eculizumab in MPGN suggests this agent will work for some, but not all, patients with this pathologic lesion.


Prognostic value of microRNAs in lung cancer: A systematic review and meta-analysis.
Lung cancer is one of the leading causes of cancer-associated mortality throughout the world. The prognosis of the disease depends on many factors including the stage and type of cancer. Many studies have identified various microRNAs (miRNAs) that affect the prognosis of lung cancer. In order to systemically analyze the available clinical data, the present study performed a meta-analysis to examine all evidence on the potential role of miRNAs as novel predictors of survival in lung cancer. Literature published in English prior to February 1st, 2018 was searched through PubMed to review all of the associations between individual miRNAs and groups of miRNAs with the prognosis of lung cancer. Data was extracted using standard forms and pooled odds ratios with 95% confidence intervals (CIs) were calculated. A total of 15 eligible studies were included in the meta-analysis. These represented 1,753 lung cancer patients and 20 miRNAs. A total of 8 downregulated miRNAs were associated with poorer overall survival (OS) [hazard ratio (HR)=0.59, 95% CI: 0.47-0.75, P<1×10-4], while 10 upregulated miRNAs were associated with poorer OS (HR=1.76, 95% CI: 1.31-2.35, P<1×10-4). Additionally, low miRNA expression was associated with lymph node metastasis [LNM; relative risk (RR)=0.53, 95% CI: 0.46-0.61, P<1×10-4]. The expression of miRNAs was not associated with lung cancer stage (RR=1.07, 95% CI: 0.94-1.22, P=0.23). Expression levels of different miRNAs were associated with the OS and LNM of patients with lung cancer. These miRNAs may be applied as potential prognostic markers in lung cancer.


Effective Approach to Promoting the Proton Conductivity of Metal-Organic Frameworks by Exposure to Aqua-Ammonia Vapor.
We explored the proton conductivities of two 3D CoII metal-organic frameworks (MOFs), {[Co3(m-ClPhIDC)2(H2O)6]·2H2O}n [1; m-ClPhH3IDC = 2-(m-chlorophenyl)imidazole-4,5-dicarboxylic acid] and {[Co3(p-ClPhHIDC)3(H2O)3]·6H2O}n (2; p-ClPhH3IDC = 2-(p-chlorophenyl)imidazole-4,5-dicarboxylic acid), under water and aqua-ammonia vapors, respectively. The experimental results revealed that the proton conductivities of 1 and 2 at aqua-ammonia vapor were 2.89 × 10-2 and 4.25 × 10-2 S/cm, respectively, and approximately 2 orders of magnitude greater than those at water vapor. On the basis of the activation energy, water and ammonia vapor absorption, and powder X-ray diffraction patterns, their proton-conduction mechanisms have been discussed. We believe that this is a novel approach to drastically improving the proton conductivity of MOFs.


Expression of protein tyrosine kinase pp60v-src variants in Dictyostelium discoideum.
We achieved production of v-Src of the low-oncogenic PRC and its variant proviral structure H19 in Dictyostelium discoideum, an emerging host system suitable for synthesis of heterologous proteins. To accomplish their expression, the first six codons of the N-terminus of v-src had to be changed according to the D. discoideum codon preference. Alternatively, N-terminal fusions of 6xHis-tag or GFP were sufficient to overcome the incompatibility in codon usage. D. discoideum-expressed v-Src kinases of the expected molecular weight were recognized by Src-specific antibodies; GFP-PRC was distributed uniformly in the cytosol. In contrast to other lower eukaryotes, where the accumulation of v-Src leads to growth inhibition, D. discoideum cells silenced the kinase activity of PRC-derived v-Src and showed no developmental or growth defects.


Hereditary gingival fibromatosis: characteristics and novel putative pathogenic mechanisms.
Hereditary gingival fibromatosis (HGF) is a rare condition that can occur as an isolated disease or as part of a syndrome or chromosomal abnormality. In severe cases, the gingival enlargement may cover the crowns of teeth and cause severe functional and esthetic concerns. Histological and cell culture studies have uncovered some of the molecular and cellular changes associated with HGF. However, the pathogenesis of the disease is still largely unknown. Recent studies about the genetic characteristics of HGF have provided novel clues about the potential pathogenic mechanisms. In particular, mutation in the son-of-sevenless (SOS-1) gene has been associated with one form of the disease. However, HGF displays genetic heterogeneity, and mutations in other genes are also likely involved. This review outlines the current knowledge about the histological, cellular, and genetic characteristics of HGF. In addition, the potential role of the SOS-1 molecule and related novel intracellular signaling pathways in the pathogenesis of HGF will be discussed.