Epigenetic cancer prevention mechanisms in skin cancer.
Epigenetics is an important emerging area for study of mechanisms of cancer prevention. In recent years, it has been realized that cancer prevention agents, derived from natural dietary sources, impact cancer cell survival by modulating epigenetic processes. In the present manuscript, we review key epigenetic regulatory mechanisms and examine the impact of sulforaphane and green tea polyphenols on these processes. We also discuss available information on the epigenetics in the context of skin cancer. These studies indicate that diet-derived chemopreventive agents modulate DNA methylation status and histone modification via multiple processes and point to additional areas for study of epigenetic mechanisms in skin cancer.


Response and Disease Dynamics in Untreated Metastatic Colorectal Cancer With Bevacizumab-Based Sequential vs. Combination Chemotherapy-Analysis of the Phase 3 XELAVIRI Trial.
Early tumor shrinkage (ETS), depth of response (DpR), and time to DpR represent exploratory endpoints that may serve as early efficacy parameters and predictors of long-term outcome in metastatic colorectal cancer (mCRC). We analyzed these endpoints in mCRC patients treated with first-line bevacizumab-based sequential (initial fluoropyrimidines) versus combination (initial fluoropyrimidines plus irinotecan) chemotherapy within the phase 3 XELAVIRI trial. DpR (change from baseline to smallest tumor diameter), ETS (≥20% reduction in tumor diameter at first reassessment), and time to DpR (study randomization to DpR image) were analyzed. We evaluated progression-free survival and overall survival with ETS as stratification parameter according to treatment arm, molecular subgroup, and sex. In 370 patients analyzed, a higher rate of ETS (60.9% vs. 43.5%; p = 0.001) and significantly greater DpR (-40.0% vs. -24.7%; p < 0.001) were observed in the initial combination therapy arm. The improvement was pronounced in RAS/BRAF wild-type tumors. ETS correlated with improved survival irrespective of treatment arm (PFS: p < 0.001; OS: p = 0.012) and molecular subgroup (PFS: p < 0.001; OS: p < 0.001). Male patients in contrast to female patients with ETS had survival benefit (PFS: p < 0.001, HR 0.532; OS: p < 0.001, HR 0.574 vs. PFS: p = 0.107; OS: p = 0.965). Initial irinotecan-based combination therapy with bevacizumab improved ETS and DpR in mCRC patients with a particularly high irinotecan sensitivity of RAS/BRAF wild-type tumors. ETS seems to be a suitable prognostic marker for fluoropyrimidine- and bevacizumab-based combinations in mCRC. This finding was rather driven by male patients, potentially indicating that ETS might be less predictive of long-term outcome in an elderly, female population.


Phosphorylation of Ser232 directly regulates the transcriptional activity of the P protein of human respiratory syncytial virus: phosphorylation of Ser237 may play an accessory role.
The phosphoprotein P of human respiratory syncytial virus (RSV) was expressed in eukaryotic cells in phosphorylated form. Site-directed mutagenesis of the recombinant protein established Ser232 as the major site of phosphorylation in vivo. Phosphorylation of bacterially made P protein in vitro by purified casein kinase II (CKII) resulted in the phosphorylation of Ser237, whereas mainly Ser232 was phosphorylated by a crude cell extract. The P kinase activity in the cell extract exhibited properties characteristic of CKII. While the Ser232,237 to Ala double mutant was nearly completely defective for phosphorylation and transcription, phosphorylation at Ser232, through the use of appropriate P mutant or kinase, activated P protein. Phosphorylation of Ser237 restored activity only to the extent it facilitated phosphorylation of Ser232. Phosphate groups of P protein in RSV-infected cells were highly stable; inhibitors of protein serine phosphatases had no effect on the intracellular turnover of the phosphates. Highly purified viral polymerase L was transcriptionally active but devoid of P protein kinase activity. Thus, CKII-mediated phosphorylation of Ser232 appears to be the primary regulator of P protein activity while phosphorylation of Ser237 may be involved in a modulatory role under certain conditions.


[Immunological status and the condition of local defense factors in patients with various forms of chronic bronchitis treated by using performed physical factors].
Physiotherapeutic and other methods were employed for the treatment of patients with chronic nonobstructive bronchitis (CNB), chronic bronchitis with transient obstruction of the small bronchi of inflammatory genesis, chronic asthmatic bronchitis (CAB) and chronic obstructive bronchitis (COB). The level of secretory IgA and relative E-RFC number in the bronchial wash off, lysozyme concentration, the level of IgA and titer of heterophilic normal antibodies in the saliva were assessed. The content of T- and B-lymphocytes in the blood was studied. The results were assessed with a method of discrete-dynamic analysis. It was established that the incorporation of inductothermia with ethonium-electrophoresis and the magnetic field effect on the thyroid in CAB and inductothermia with ethonium-electrophoresis in COB in the complex of therapeutic measures produced a positive effect. In CNB (inactive phase) and COB patients inductothermia resulted in restoration of some interrelationships in the immune system whereas in CAB patients in their dysbalance. Different changes in the levels of interrelationships of certain parameters of the immune system were observed in the incorporation of sinusoidal modulated currents in the therapeutic complexes.


Prediction of individual genetic risk of complex disease.
Most common diseases are caused by multiple genetic and environmental factors. In the last 2 years, genome-wide association studies (GWAS) have identified polymorphisms that are associated with risk to common disease, but the effect of any one risk allele is typically small. By combining information from many risk variants, will it be possible to predict accurately each individual person's genetic risk for a disease? In this review we consider the lessons from GWAS and the implications for genetic risk prediction to common disease. We conclude that with larger GWAS sample sizes or by combining studies, accurate prediction of genetic risk will be possible, even if the causal mutations or the mechanisms by which they affect susceptibility are unknown.


Mutasynthesis of siderophore analogues by Pseudomonas aeruginosa.
The Gram-negative bacterium Pseudomonas aeruginosa produces the phenolic siderophore pyochelin. Salicylic acid is an intermediate in the pyochelin biosynthetic pathway, and mutants blocked in salicylic acid biosynthesis (Sal-) are able to incorporate exogenously supplied salicylic acid into pyochelin. A P. aeruginosa Sal- mutant was incubated with 13 salicylic acid analogues and was found to incorporate three (5-fluorosalicylic acid, 4-methylsalicylic acid, and 3-hydroxypicolinic acid) into pyochelin analogues, trivially designated as 5-fluoropyochelin, 4-methylpyochelin, and 6-azapyochelin. The structures of the mutasynthetic products were confirmed by 1H and 13C NMR and high-resolution fast atom bombardment mass spectrometry as being identical to pyochelin except for the expected changes in the aromatic ring. The biological activity of the three pyochelin analogues was determined in iron transport assays. In comparison to pyochelin, 4-methylpyochelin was more active in the assays whereas the activities of 5-fluoropyochelin and 6-azapyochelin were markedly decreased. In coincubation assays, 5-fluoropyochelin substantially inhibited iron transport by pyochelin; 4-methylpyochelin and 6-azapyochelin did not demonstrate this inhibitory effect.


Aortopulmonary Collateral Artery from the Proximal Ascending Aorta: A Rare Anatomical Finding.
Tetralogy of Fallot with pulmonary atresia and major aortopulmonary collateral arteries is a rare congenital heart lesion in which pulmonary blood supply may arise from different segments of the aorta. We report an unusual case of a newborn with a major collateral artery originating from the proximal ascending aorta. Successful reparative surgery was undertaken.


Salivary Microbiological and Gingival Health Status Evaluation of Adolescents With Overweight and Obesity: A Cluster Analysis.
Given the high prevalence of obesity in children and adolescents, the investigation of early markers is of clinical importance to better manage this condition. Thus, the aim was to evaluate the cross-sectional relationship between salivary microbiota, gingival health status, and excess weight in adolescents. A total of 248 students (14-17 y; 119 girls) were included, free of caries lesions and periodontal pockets. Physical examination included measures of height, weight, and body fat percentage (%BF). Oral examination was performed to gather information on dental (DMFT index) and gingival health status. Unstimulated saliva was submitted to qPCR reactions to quantify Streptococcus mutans, Porphyromonas gingivalis, Bifidobacteria, and Streptococcus pneumoniae percentages and the NFKappaB expression. Two-way ANOVA was applied considering group (normal-weight/overweight/obesity) and sex factors, in addition to cluster analysis. Group effect was significant for %S. mutans (partial eta2 = 0.20; p < 0.001) and %Bifidobacteria (partial eta2 = 0.19; p < 0.001), with overweight and obesity groups showing the highest levels compared to normal-weight ones, with no significant sex effect. There was no difference in the frequency of gingivitis, P. gingivalis, and S. pneumoniae percentages or NFKappaB expression between groups. Cluster analysis generated three clusters according to body fat accumulation: "Higher %BF," "Moderate %BF," and "Lower %BF." "Higher %BF" cluster was characterized by higher body fat percentage and higher salivary %Bifidobacteria, while cluster "Lower %BF" was characterized by lower body fat percentage and lower frequency of gingivitis ("Moderate %BF" cluster was the contrast). According to nutritional status, a difference in salivary S. mutans and Bifidobacteria percentages was found, with overweight or obesity adolescents showing the highest percentages than normal-weight ones. Besides, a positive relationship between body fat accumulation and Bifidobacteria count was observed, indicating a possible interaction between oral bacteria communities and weight gain.


Quantitative trait loci (QTL) analysis for rice grain width and fine mapping of an identified QTL allele gw-5 in a recombination hotspot region on chromosome 5.
Rice grain width and shape play a crucial role in determining grain quality and yield. The genetic basis of rice grain width was dissected into six additive quantitative trait loci (QTL) and 11 pairs of epistatic QTL using an F(7) recombinant inbred line (RIL) population derived from a single cross between Asominori (japonica) and IR24 (indica). QTL by environment interactions were evaluated in four environments. Chromosome segment substitution lines (CSSLs) harboring the six additive effect QTL were used to evaluate gene action across eight environments. A major, stable QTL, qGW-5, consistently decreased rice grain width in both the Asominori/IR24 RIL and CSSL populations with the genetic background Asominori. By investigating the distorted segregation of phenotypic values of rice grain width and genotypes of molecular markers in BC(4)F(2) and BC(4)F(3) populations, qGW-5 was dissected into a single recessive gene, gw-5, which controlled both grain width and length-width ratio. gw-5 was narrowed down to a 49.7-kb genomic region with high recombination frequencies on chromosome 5 using 6781 BC(4)F(2) individuals and 10 newly developed simple sequence repeat markers. Our results provide a basis for map-based cloning of the gw-5 gene and for marker-aided gene/QTL pyramiding in rice quality breeding.


RANDOMIZED PROSPECTIVE STUDY ON THE TREATMENT OF FEMORO-PATELLAR OSTEOARTHRITIS USING BRACING.
To compare the effect of a brace designed to stabilize the patellofemoral joint to that of a patella-shaped neoprene sleeve with patella cut out in patients with patellofemoral osteoarthritis. Fifty-seven patients with femoro-patellar osteoarthritis were allocated to two groups: patients with femoro-patellar functional brace and those with a neoprene knee with a patellar orifice. Both groups underwent clinical treatment of osteoarthritis and used medications daily 1 month before and up to 3 months after brace placement. They were evaluated with the WOMAC and Lequesne questionnaires and performed five times sit to stand test, Timed Up and Go test, and six minutes walk test immediately before and 1 and 3 months after brace placement. Both groups had improved pain, stiffness, and function with no difference between groups. Drug use decreased in both groups in the first month but increased in the third month. Naproxen use was progressively higher in the control group. Both knee orthoses improved pain and function and altered drug use only in the first month. Functional knee brace provided analgesia without increased use of naproxen. Level of Evidence IB, Randomized clinical trial.


The impact of comorbidities on survival in oral cancer patients: a population-based, case-control study.
Comorbidities have shown to highly influence the outcome and risk of death of head and neck cancer patients. The purpose of this study was to examine the comorbidities among oral cavity squamous cell carcinoma (OSCC) patients, and to investigate the impact of comorbidities on overall survival (OS) and recurrence free survival (RFS). Patients diagnosed with OSCC in Eastern Denmark in the period 2000-2014 and treated with curative intend were included. Patients data were linked to the Danish National Patients Register to identify comorbidities based on the Charlson Comorbidity Index (CCI) at the time of diagnosis and five years after diagnosis. Each patient was age-and sex-matched in a 1:10 ratio with an age and sex matched reference group. A total of 1,183 patients and 11,830 controls were included. Overall this study found comorbidities to be more common among OSCC compared to the reference group both at the time of diagnosis and five years after. The 5-year OS among patients with a CCI score of zero, one, two, and three or above was 60%, 44%, 41%, and 40%, respectively. Similarly, the multivariate cox-regression analysis showed that patients with increasing CCI score also had an increasing risk of death compared to patients with no comorbidities. OSCC patients had significantly higher comorbidity burden at diagnosis and risk of developing additional comorbidities after diagnosis compared to the reference population. Survival outcomes decreased significantly with higher CCI.


[Shear stress-induced platelet aggregation in children with minimal change nephrotic syndrome].
Analysis of the hemostasis system using biochemical techniques in children with minimal change nephrotic syndrome (MCNS) has previously been restricted to in vitro assays. The recent introduction of measurement of shear stress-induced platelet aggregation (SIPA) using platelet-rich plasma (PRP) has facilitated detailed investigation of the hemostatic system in vivo. In order to further analyze the etiology of the thrombotic tendency exhibited by patients with childhood MCNS, we investigated SIPA at both low shear stress (L-SIPA) and high shear stress (H-SIPA) in 14 children with MCNS using PRP collected weekly after commencing prednisolone therapy. Seven patients were newly diagnosed cases of MCNS (ND) whereas the remainder had suffered a disease relapse (DR). Prior to prednisolone therapy L-SIPA, which was thought to be affected by fibrinogen (Fbg) levels, was significantly increased in both patient groups compared to normal controls (17.4 +/- 4.1% vs. 3.6 +/- 0.7%, ND vs control, p < 0.01: 11.7 +/- 3% vs. 2 +/- 0.7%, DR vs control, p < 0.01) with values declining at weekly intervals thereafter. Plasma Fbg levels in simultaneously collected samples followed a similar course. In contrast, H-SIPA, which was thought to be affected by von Willebrand factor (VWF), was significantly enhanced in MCNS patients after 1 week of prednisolone therapy compared to the controls (45 +/- 5.1% vs. 26.3 +/- 3.5%, ND vs normal, p < 0.05: 36.9 +/- 3.3% vs. 25.5 +/- 1.6%, DR vs. normal, p < 0.05). Plasma ristocetin cofactor and VWF antigen levels in simultaneously collected samples followed a similar course, whereas thrombin-antithrombin complex (TAT) levels remained constant. These results indicate that SIPA is enhanced in the acute stage of childhood MCNS, especially L-SIPA prior to the initiation of prednisolone therapy and H-SIPA after 1 week of prednisolone therapy, and that these phenomena may be affected by plasma Fbg and VWF levels, respectively. The enhanced SIPA may play an important thrombogenic role in the acute phase of childhood MCNS.


A recombinant AeDNA containing the insect-specific toxin, BmK IT1, displayed an increasing pathogenicity on Aedes albopictus.
The Aedes aegypti densovirus (AeDNV) has previously shown potential in mosquito control. To improve its efficacy as a biopesticide, the gene for an excitatory insect-specific toxin from Buthus martensii Karsch (BmK IT1) was inserted into the AeDNV genome and cloned into pUCA plasmid. The coding sequence for green fluorescent protein was ligated to the C-terminus of the BmK IT1 gene as a screening marker. Recombinant and helper plasmids were cotransfected into C6/36 cells; wild-type viruses were the controls. The recombinant viruses were identified and quantified by real-time polymerase chain reaction and exposed to Ae. albopictus larvae for the evaluation of its bioinsecticidal activity. LT(50) and LD(50) bioassays showed that the recombinant AeDNV had stronger and faster pathogenic effects on Ae. albopictus than the wild-type virus. This is the first report on the recombinant AeDNA containing the insect-specific toxin, BmK IT1, which may be used to develop a novel type of insecticide.


Seasonal variation in urocanic acid isomers in human skin.
Urocanic acid (UCA) is a major chromophore for UV in the skin and has been suggested to act as an initiator of UV-induced immunosuppression. It converts from the naturally occurring trans-isomer to the cis-isomer on UV exposure. Isomerization is dose dependent until the photostationary state is reached, and the seasonal variation in irradiance from the sun may lead to changes in the percentage of UCA present as cis-UCA throughout the year. Thirty young healthy subjects, skin types I-IV, were followed from early summer till spring. At each of six visits (June, July, August, October, December, March), pigmentation and the concentration of UCA isomers were measured at six body sites: forehead, upper chest, upper back, outer upper arm, inner upper arm and buttock. In exposed as well as unexposed regions a variation in pigmentation was found, peak values being recorded in August. Total UCA concentration was lower in July and August than in the rest of the year, irrespective of body site. In July, the percentage of cis-UCA was close to the maximal obtainable (50-60%) at all sites except the buttock. In the three winter months the percentage of cis-UCA was below 7% in all regions except for the forehead, where the mean cis-UCA was 18% in October and March. No consistent relationship was found between UCA isomers and pigmentation or skin type.


The novel use of commonly captured data to assess a district's diabetes service that encompasses both primary and secondary care.
To identify commonly captured data in the UK to look at the performance of a district's diabetes care that encompasses both primary and secondary care. Primary care quality outcomes framework (QOF) measures for diabetes, referral rates for first appointment for specialist secondary care and emergency admission rates for diabetes (Dr Foster/HES) were used to produce a performance index scoring system. Illustrative measures from QOF were total diabetes points, DM23 attainment of HbA1c <7% (53 mmol/mol) and its exemption rate (number of patients excluded from analysis). The performance index was used to study the effectiveness of the Medway district diabetes service and this was compared to another district (Guildford) within the same Strategic Health Authority and nationally. Medway has the highest prevalence of Diabetes (6.1%) of the 8 Primary Care Trusts examined, the lowest achievement of diabetes QOF points (96.1%) and the lowest achievement of an HbA1c level <7% (53 mmol/mol) (54.3%). Exemption reporting was the 3rd highest. SAR for first diabetes out-patient appointment to the hospital was low at 281 (predicted 576) 48% of expected. The emergency admission rate was high at 225 (predicted 168) 133% of expected. Thus primary care diabetes needs to raise performance and implement a lower threshold for OPD referral to prevent emergency admissions. It is possible to produce an assessment of diabetes care that transcends primary/secondary care that gives a true reflection of a district's performance which will be useful to plan future health service provision.


Pre and interdialytic acid-base balance in hemodialysis patients.
In an observational study, nine hemodialysis patients using 35 mmol/l bicarbonate dialysate were studied over a 44-hour interdialytic interval. Serum bicarbonate was measured at regular intervals at home and the mean time averaged concentration was 27.0+/-1.2 mmol/l. Seven of the nine patients showed a slow linear decline in bicarbonate whilst in two patients levels were unchanged. In 8 of 9 patients the average of the post and predialysis bicarbonate accurately predicted the time-averaged (area under the curve) bicarbonate concentration. In addition, predialysis serum bicarbonate was measured in 46 patients after both a 2 and 3-day interdialytic interval. The serum bicarbonate was significantly lower after the 3-day interdialytic interval (3-day, 22.1+/-0.6 vs 2-day, 23.0+/-0.5 mmol/l, p<0.05). The results from this study emphasize the importance of standardization of bicarbonate measurement in order to avoid spurious acidosis.


Antidepressant Use in Siblings of Children With Cancer: A Danish Population-Based Cohort Study.
Siblings of children with cancer experience severe stress early in life. Most studies of mental health problems in these siblings are limited by being small, cross-sectional, or self-reporting. In a population-based cohort study, we investigated the risk for antidepressant use by linking several nationwide, population-based registries comparing 6644 siblings of children diagnosed with cancer from 1991-2009 with 128 436 population-based sibling comparisons using the Cox proportional hazards model. Irrespective of cancer type, no increased risk of antidepressant use in siblings of children with cancer was found (hazard ratio = 1.00, 95% confidence interval = 0.91 to 1.11). However, data suggested that siblings being young at cancer diagnosis had an increased risk (2-sided P trend = .01). Interaction analyses showed no modifying effect of parental socioeconomic position or antidepressant use. Findings from this study with a very low risk of bias are reassuring and important for families facing childhood cancer and for clinicians counseling these families.


Generational differences in registered nurse turnover.
The chronic nature of the nursing workforce shortage in the United States is a continuing concern. As the nationwide gap between supply and demand grows, it remains unknown what impact turnover will have on nursing, access to care, and efforts to improve quality and safety of health care. It also remains unclear whether the recent turnover trends among new graduate registered nurses differ from past generational cohorts of new nurses. The aims of this study were to identify the reasons why registered nurses turnover by generational cohort (Veterans, Baby Boomers, and GenXMs) and to compare the length of time nurses were employed in their first five nursing positions by generational cohort. The findings suggest the three generational cohorts displayed similar reasons for leaving nursing positions with relocation, career advancement, and personal/family reasons reported most frequently. Except for the first nursing position, significant generational effects were found in the length of time Veterans, Baby Boomer, and GenXMs stayed employed in their nursing positions. It remains unknown why the GenXMs displayed a significantly shorter length of employment time in their second, third, fourth, and fifth nursing positions. The decline in length of employment time displayed in both the Baby Boomers and GenXMs may be an issue of concern requiring future research.


Interactions between an entomopathogenic microsporidium and the endoparasitoid Glyptapanteles liparidis within their host, the gypsy moth larva.
Interactions in the host-parasitoid-pathogen system, Lymantria dispar L. (Lep., Lymantriidae)-Glyptapanteles liparidis (Bouché) (Hym., Braconidae)-Vairimorpha sp. (Protista, Microspora), were investigated. Host selection experiments revealed that G. liparidis females did not discriminate between infected and uninfected host larvae for oviposition. Transmission of the microsporidium from infected to uninfected hosts by stinging female wasps could not be ascertained. Females that developed in infected L. dispar larvae did not transmit the pathogen via oviposition. Vairimorpha infection of the host negatively affected the performance of the braconid, when inoculation took place either before or after parasitization. Microsporidiosis of the host caused delayed development, reduced pupation and adult eclosion, reduction in size and weight, and reduction of adult longevity of G. liparidis. Parasitoids themselves were not systemically infected by Vairimorpha sp., but braconid larvae did ingest microsporidian spores at the end of their endoparasitic development and accumulated the undigested and ungerminated spores in the blind midgut. Negative effects of host infection on parasitoid larvae were detectable from the beginning of parasitoid larval development. Lethal time was reduced when L. dispar larvae were infected and parasitized, often at the expense of the parasitoid when G. liparidis were unable to complete endoparasitic development before the host died. Intensity of infection, measured as number of spores produced per milligram fresh weight of L. dispar larva, was slightly higher in parasitized and infected hosts than in unparasitized and infected hosts.


Seedling growth, mitochondrial characteristics, and alternative respiratory capacity of corn genotypes differing in cold tolerance.
Four maize (Zea mays L.) inbreds representing genetic differences in seedling cold tolerance were used to determine the effect of growth temperatures on dry weight accumulation and mitochondrial properties, especially the alternative oxidase capacity. Seedlings were grown in darkness at 30 degrees C (constant), 14 degrees C (constant), and 15 degrees C for 16 hours and 8 degrees C for 8 hours. Inbreds B73 and B49 were characterized as cold tolerant while G50 and G84 were cold sensitive. Shoot growth rate of cold-sensitive inbreds in the lower temperatures was slower relative to the tolerant inbreds. Mesocotyl tissue was particularly sensitive to low temperatures during growth after germination. There were no significant differences in relative rates of mitochondrial respiration in the cold-tolerant compared to cold-sensitive inbreds measured at 25 degrees C. Mitochondria from all seedlings grown at all temperatures had the ability to phosphorylate as indicated by the observation of respiratory control. This result indicated that differences in low temperature growth were probably not related to mitochondrial function at low temperatures. Alternative oxidase capacity was higher in mitochondria from seedlings of all inbreds grown at 14 degrees C compared to 30 degrees C. Capacities in seedlings of 14 degrees C-grown B73 and G50 were higher than in B49 and G84. Capacities in seedlings grown for 16 hours at 15 degrees C and 8 hours at 8 degrees C were similar to those from 14 degrees C-grown except in G50 which was lower and similar to those grown at 30 degrees C. Mesocotyl tissue was the most responsive tissue to low growth temperature. Coleoptile plus leaf tissue responded similarly but contained lower capacities. Antibody probing of western blots of mitochondrial proteins confirmed that differences in alternative oxidase capacities were due to differences in levels of the alternative oxidase protein. Male sterile lines of B73 were also grown under the three different temperature regimes. These lines grew equally as well as the normal B73 at all temperatures and the response of alternative oxidase capacity and protein to low growth temperature was similar to normal B73.


Cooperative education of respiratory therapy students.
Cooperative education (coop), applied to respiratory care students at Northeastern University in Boston, Massachusetts since 1974, is designed to enhance self-realization and direction by integrating classroom study with experience in educational, vocational, and cultural learning situations outside the classroom. Achievement of this goal requires a curriculum that allows paid work periods at intervals in the program and acceptance by the institution of responsibility for finding work positions for the students. For students coop education gives reality to learning, increases educational motivation, provides financial aid, and provides useful employment contacts. For the employer it provides a source of labor, facilitates recruitment and retention, and permits better utilization of personnel. For the University it permits more effective use of the physical plant, encourages greater community support, and provides benefits to the faculty. The cooperative education plan offers advantages for respiratory therapy training on both the Association and Baccalaureate level. Successful implementation of the program requires the institution to assume responsibility for integrating the experiential phase into the education process.


Neurobehavioral Differences of Valproate and Risperidone on MK-801 Inducing Acute Hyperlocomotion in Mice.
The glutamate system plays a major role in the development of neuropsychiatric disorders such as addiction, epilepsy, dementia, and psychosis. MK-801 (dizocilpine), an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, could increase locomotor activity and stereotyped neurobehaviors mimicking schizophrenic-like features in the mouse model. The study would explore the neuropharmacological differences of risperidone and valproic acid on the MK-801-induced neurobehavioral changes. The subjects were male C57BL/6J mice obtained from the National Laboratory Animal Center. Drug effects were assessed using the open field with a video-tracking system and gaiting tests. After habitation, risperidone (0, 0.1 mg/kg) or valproic acid (0, 200 mg/kg) was injected and ran locomotion for 30 mins. Sequentially, mice were followed by intraperitoneal injection (i.p.) with MK-801 (0, 0.2 mg/kg) and ran locomotion for 60 mins. Gaiting behaviors such as step angles, stride lengths, and stance widths were measured following the study drugs. The results showed that risperidone and valproic acid alone could not alter the locomotor activities. Following the MK-801 injection, the travelled distance and speed in the entire open field dramatically increased. The dose 0.1 mg/kg of risperidone could totally inhibit the MK-801-induced hyperlocomotion compared with that of the saline-injected group (p < 0.001). The valproic acid (200 mg/kg) partially suppressed the hyperlocomotion which is induced by MK801. The more dominant effect of risperidone to rescue MK-801 induced hyperlocomotion compared with that of valproic acid. The partial suppression of valproic acid may imply the psychopharmacological evidence as adjuvant effect to treat psychotic patients through tuning glutamatergic neurotransmission.


[Study on MSO/GO-based determination method for trace amount of aqueous Hg2+].
To establish a highly sensitive fluorometric nanobiosensor for determination of aqueous mercury ions (Hg(2+)) using optimized mercury-specific oligonucleotide (MSO) probes and graphene oxide (GO). The nanobiosensor was assembled by attaching the self-designed MSO(1) (5' end labeled with fluorophore carboxyfluorescein (FAM), denoted as FAM-MSO(1)) and MSO(2) to the surface of GO through strong non-covalent bonding forces. Upon the addition of Hg(2+), the formation of the T-Hg(2+)-T configuration desorbed the FAM-MSO(1) and MSO(2) from the surface of GO, resulting in a restoration of the fluorescence of FAM-MSO(1). Using the specific mispairing of T-Hg(2+)-T and the changes in fluorescent signals in solutions, quantitative analysis of Hg(2+) could be performed. The average thickness of the prepared GO sheets was only 1.4 nm. For the Hg(2+) nanobiosensor, the optimum concentrations of FAM-MSO(1) and MSO(2) were both 1 µmol/L, the optimum volume of 0.5 g/L GO was 5 µL, and the limit of detection was 10 pmol/L; it had low cross-reactivity with 10 other kinds of non-specific metal ions; the fluorescence recovery efficiency was up to 65% in the re-determination of Hg(2+) after addition of Na(2)S(2)O(3). The MSO/GO-based nanobiosensor is convenient to operate, highly sensitive, highly specific, highly accurate, and reusable. It can be applied to determine trace amount of Hg(2+) in aqueous solutions.


Experimental Analysis and Simulation of Novel Technical Textile Reinforced Composite of Banana Fibre.
The use of natural fibres allows reducing environmental impact, due to their natural renewable origin and the lower energy needed for their production and processing. This work presents the mechanical characterization of a newly developed technical textile, with banana fibre treated by enzymes, comparing experimental results with numerical simulation based on the definition of the unit cell at micromechanical level. The experimental test shows that the composite with the fabric of banana fibre presents worse mechanical behaviour than the one with commercial flax fibre. The presence of wool, necessary for producing the yarn, reduces the mechanical properties of the banana textile. The numerical simulation had an acceptable error compared with the experimental results, with a global average error of 9%, showing that the predictive modelling based on the multiscale method is suitable for the design process of this kind of composite.


Klippel-Feil anomaly with Sprengel anomaly, omovertebral bone, thumb abnormalities, and flexion-crease changes: novel association or syndrome?
We report on a family with Klippel-Feil anomaly (KF), Sprengel anomaly, omovertebral bone, thumb abnormalities, and flexion-crease abnormalities. This combination of abnormalities does not fit into Holt-Oram syndrome, Wildervanck syndrome, oculo-auriculo-vertebral (Goldenhar) anomaly, or the VATER complex. Clinical aspects of a KF classification are discussed. The state of molecular research on KF is briefly reported. We conclude that this set of anomalies is a novel combination, probably representing pleiotropy of a single Mendelian gene.


[The present and future of providing iodinated salt to the population].
Iodine content was estimated in 401 samples of table salt (out of which 365 from the distribution network and 101 from households). The values of 85.5% of samples from the distribution network were in normal range (i.e. 25 +/- 10 mg KI/kg) while 9.8% of samples showed the values below that range. The samples from households showed lower values, only 70.2% being in normal range and 28.6% below that which was 3 times more than in those from the distribution network. Such difference may be explained by the loss of iodine from the salt during the storage due to the effects of moisture, temperature and light. However, less satisfactory iodine levels were found in the salt imported from Poland (9 of 28 samples below the normal range, i.e. 32%), Austria (5 from 9 samples below normal range, i.e. 55%) and in the sea salt (7 from 11 samples below normal range, i.e. 63%), while satisfactory values were found in the salt from Germany (all 5 samples examined were in normal range). From 1126 samples from the distribution network examined during 1981-1986 were 63.6 in normal range, while 88.4% out of 612 samples examined during the period 1987-1990 hat their iodine levels in normal range. Present data show satisfactory iodine content in the salt which justifies the assumption of satisfactory iodine intake in the population of Slovakia. (Tab. 2, Ref. 6.).


Relaxation dynamics of photoexcited calcium deposited on argon clusters: theoretical simulation of time-resolved photoelectron spectra.
Relaxation dynamics following photoexcitation of a calcium atom deposited on an icosahedral-like argon cluster Ar(n) (n approximately = 55) is investigated through theoretical simulations. Based on ab initio calculations of the CaAr molecule, a diatomics-in-molecules model is set up to efficiently describe the electronic excited states of the system. The excited state dynamics is studied using molecular dynamics with electronic transitions (Tully, J. C. J. Chem. Phys. 1990, 93, 1061). The signature of this dynamics in the time-resolved photoelectron spectra is investigated, to assess the possibility of detecting competing vibrational and electronic relaxations through pump-probe experiments. The vibrational relaxation, influenced by nonadiabatic transitions, can clearly be seen in the time-resolved photoelectron spectra. The details of the electronic relaxation, as well as the possible ejection of the chromophore, are found to be sensitive to the local environment of the calcium atom deposited on the argon cluster.


Synthesis and Biological Evaluation of Mutual Prodrugs of Carboxylic Group Containing Some Non-Steroidal Anti-Inflammatory Drugs and Propyphenazone.
The use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) is not up to its potential because of their gastrointestinal side effects. Significant attention has been focused on the growth of bio-reversible derivatives, such as mutual prodrugs, to momentarily mask the acidic group of NSAIDs as a promising means of decreasing or eliminating the GI side effects. The aims of this paper are to synthesize the mutual prodrugs of selected NSAIDs (Ketorolac, niflumic acid, tolfenamic acid) with propyphenazone, a study on their several physicochemical characters, hydrolysis kinetics, antiinflammatory, analgesic activity and ulcerogenicity. Mutual prodrugs were synthesized and their structures were confirmed and characterized using IR, 1H NMR, 13C NMR, mass spectroscopy and their purity was established by elemental analysis. Synthesized prodrugs were subjected for pharmacokinetic studies, analgesic, anti-inflammatory activities and ulcerogenic index. In vitro hydrolysis study of synthesized prodrugs in enzyme-free simulated intestinal fluid (SIF, pH 7.4) and 80% human plasma showed encouraging hydrolysis rate following first order kinetics while found stable in simulated gastric fluid (SGF, pH 1.2). Considerable decrease in ulcerogenic index and better anti-inflammatory activities were found in most of the cases as compared to their parent drugs. Among all prodrugs, viz. KE and NG showed excellent pharmacological response. A very less irritation to gastric mucosal was observed with the synthesized prodrugs than their parent drugs and can be considered for sustained drug release. Encouraging hydrolysis rate in SIF and 80% human plasma, improved analgesic and anti-inflammatory activities and reduced ulcerogenic liabilities of synthesized prodrugs revealed enhancement in the therapeutic index of the parent drugs. On the basis of above observation, it is concluded that mutual prodrugs approach can be applied to obtain synergistic effect for analgesic and anti inflammatory activities as well as to minimize gastrointestinal toxicity of the drug.


[Chemoembolization therapy of hepatocellular carcinoma-antitumor effect and side effect].
Chemoembolization therapy with arterial injection of a mixture of various anticancer agents (CDDP, ADR, MMC) and Lipiodol along with gelfoam particles was carried out on 158 cases of hepatocellular carcinoma between January 1985 and July 1987. In two groups using CDDP the tumor regressed 50% or more in higher percentage than in the groups without CDDP. The antitumor effect was more significant in the group using CDDP and ADR than in the group using CDDP alone. No significant side effect was noted in any case.


On neuropsychoanalytic metaphysics.
Neuropsychoanalysis focuses on the neural counterparts of psychoanalytically interesting phenomena and has left the difference in the metaphysical presuppositions between neuroscience and psychoanalysis unexamined. The authors analyse the logical possibilities concerning the relation between the brain and the mental unconscious in terms of the serial, parallel, epiphenomenalist and Kantian conceptions, and conclude that none of them provides a satisfactory ground for neuropsychoanalysis. As far as psychoanalytic explanations refer to the mental unconscious, they cannot be verified with the help of neuroscience. Neither is it possible to form a picture of how a neuro-viewpoint might be of help for psychoanalytic theorizing. Neuropsychoanalysis has occasionally been seen as a reductionist affair, but the authors suggest that neuropsychoanalysts themselves lean on the hybrid conception, which combines neuroscientific and psychoanalytic viewpoints. The authors state arguments in favour of the interfield conception of neuropsychoanalysis that takes seriously the metaphysical tensions between neuroscience and psychoanalysis.


Infusion of hypertonic saline into the lung parenchyma during radiofrequency ablation of the lungs with multitined expandable electrodes: results using a porcine model.
The present study was performed to clarify the effect of hypertonic saline infusion into the lung parenchyma on radiofrequency ablation (RFA) of the lungs. A total of 20 ablation zones were created in 3 pigs. The ablation zones were divided into 3 groups. Group 1 (n=6) consisted of ablation zones created by applying smaller radiofrequency (RF) power without saline infusion; group 2 (n=5) zones were created by applying greater RF power without saline infusion;and group 3 (n=9) zones were created by applying greater RF power with saline infusion. The techniques of saline infusion included administration of hypertonic saline 1 ml before RFA, followed by continuous administration at a rate of 1 ml/min during the first 2 min after the initiation of RFA. The ablation parameters and coagulation necrosis volumes were compared among the groups. Group 3 had a tendency toward smaller mean impedance than group 1 (p=0.059) and group 2 (p=0.053). Group 3 showed significantly longer RF application time than group 2 (p=0.004) and significantly greater maximum RF power than group 1 (p=0.001) and group 2 (p=0.004). Group 3 showed significantly larger coagulation necrosis volume (mean, 1,421mm3) than group 2 (mean, 858 mm3, p=0.039) and had a tendency toward larger necrosis volume than group 1 (mean, 878 mm3, p=0.077). Although this small study had limited statistical power, hypertonic saline infusion during RFA appeared to enlarge coagulation necrosis of the lung parenchyma.


Carboplatin + epirubicin +VP-16 + lenograstim followed by radiotherapy + carboplatin as radiosensitizer in limited small cell lung cancer. A multicenter phase II study.
A phase II trial was undertaken to test the activity and toxicity of carboplatin (300 mg/m2, i.v. day 1) + epirubicin (75 mg/m2, i.v. day 1) + VP-16 (100 mg/m2, i.v. days 1 to 3) + lenograstim (5 mcg/kg, s.c. days 6 to 15) administered every 3 weeks for 4 cycles and subsequent chest irradiation (50 Gy) + daily carboplatin (25 mg/m2) in the first-line treatment of adults affected by limited small cell lung cancer (SCLC). A single-stage phase II design was used; the complete response (CR) rate after chest radiotherapy was the primary end-point. Twenty-three CRs were required out of 38 patients to consider the treatment worthy of further study. Prophylactic cranial irradiation (PCI) was planned in case of CR. Patients aged < or = 70 were eligible if they had limited SCLC, a performance status not worse than 2 by the ECOG scale and no prior chemotherapy or radiotherapy. From January 1995 to April 1999, 33 patients were enrolled; the median age was 60 years. All the patients started chemotherapy; 23 patients received chest irradiation and concurrent daily carboplatin; 11 patients also received PCI. Toxicity was generally mild. Sixteen CRs (48.5%, 95% CI: 30.8-66.5) were recorded; the objective response rate was 72.7% (95% CI: 54.5-86.7). The median time-to-progression was 7.9 months (95% CI: 6.5-10.4). The median-survival was 10.7 months (95% CI: 9.2-16.1). Induction chemotherapy with carboplatin + epirubicin + VP-16 followed by chest irradiation plus concurrent daily carboplatin is well-tolerated but not sufficiently active to warrant further study in the treatment of patients with limited SCLC.


The elusive matching bias effect in the disjunctive selection task.
When reasoning with conditional statements (i.e., if [not] p then [not] q), for example when solving Wason's selection task, subjects tend to display matching bias: Options which match the entities named in the rule tend to be selected irrespective of whether this is logically appropriate. Recently, there have been suggestions that the underlying causes of matching bias reflect a general phenomenon that applies to many types of logical rule, not just conditionals. A study is reported in which performance is investigated for selection tasks with categorical or disjunctive rules. Although matching bias was clearly present for categorical rules, inverted matching bias was identified for disjunctive rules, calling into question the generality of the phenomenon and its explanations. In addition, performance at one task was not correlated with performance at the other, calling into question recent cognitive capacity accounts of selection task performance.


Safety and efficacy of oral physostigmine in the treatment of Alzheimer disease.
Results of therapeutic trials with physostigmine in the treatment of Alzheimer disease (AD) have been inconsistent and controversy persists concerning safety and efficacy. In a double-blind, placebo-controlled, crossover study, patients received 6 weeks of oral physostigmine (OP) and placebo in random order. Twenty-nine patients with AD received as much as 16 mg/day of OP and were assessed with neuropsychological and functional measures. No significant cardiac side effects were noted, though other systemic adverse effects were noted, requiring dose reduction in four patients. There was a slight but significant improvement (12%) in performance on the selective reminding test with physostigmine and the memory performance was correlated with dosage. This improvement compares favorably with the 15% decrease in scores seen in an untreated comparison cohort followed for an equivalent time period. There was a trend toward an improvement in communication and a reduction in memory complaint. These results suggest that oral physostigmine is safe and may improve memory in AD.


Metabolic Alteration in Cancer Cells by Therapeutic Carbon Ions.
Carbon-ion radiotherapy has strong antitumor effects in X-ray-resistant tumors. However, the mechanisms underlying the strong antitumor effect, especially on metabolic alterations, are not fully elucidated. This study aimed to determine the effect of therapeutic carbon ions on metabolic alterations in cancer cells. Five human cancer cell lines were used in this study. The change in 333 metabolite levels in response to carbon ions was analyzed using gas chromatography-mass spectrometry. Fifty-two metabolites were commonly detected in all cell lines. The levels of five metabolites significantly changed in four or more cell lines. Three of the five metabolites (i.e., 2-ketoglutaric acid, fumaric acid and 2-hydroxyglutaric acid) were associated with the TCA cycle. TCA cycle intermediates and the downstream oncometabolite 2-hydroxyglutaric acid were up-regulated by carbon ions. We demonstrated for the first time that TCA cycle intermediates and 2-hydroxyglutaric acid are up-regulated after carbon-ion irradiation.


A regional plan of the Emilia-Romagna regional bureau for Aedes albopictus control--year 2008.
Following the outbreak of Chikungunya virus fever occurred in the summer 2007 in Emila Romagna (an administrative region located along the Adriatic (East) coast of Italy) a regional plan for Aedes albopicus control has been implemented. The major items of the plan are here reported and discussed.


[Advances in genetyping of Toxoplasma gondii].
Toxoplasma gondii is a nucleated cell obligate parasite, and can cause severe toxoplasmosis. The genetypes of Toxoplasma gondii isolates of different host infections have significant differences, and the pathogenicity and sensitivity to drugs of different genotypes of Toxoplasma gondii isolates are also significantly different. At present, the analysis of Toxoplasma gondii genotypes is performed by using PCR-RFLP, PCR of highly repetitive sequences, multiple PCR and nested PCR techniques, and the multiple loci of amplification are usually B1, SAG2, HSP70, GRA6 and other genetic markers. There are main 3 traditional genotypes of Toxoplasma gondii, and along with the deepening and extension of research, more and more genotypes are found. This paper reviews the advances in the research of Toxoplasma gondii genotypes.


Heat shock cognate protein 70 controls Borna disease virus replication via interaction with the viral non-structural protein X.
Borna disease virus (BDV) is a non-segmented, negative-sense RNA virus and has the property of persistently infecting the cell nucleus. BDV encodes a 10-kDa non-structural protein, X, which is a negative regulator of viral polymerase activity but is essential for virus propagation. Recently, we have demonstrated that interaction of X with the viral polymerase cofactor, phosphoprotein (P), facilitates translocation of P from the nucleus to the cytoplasm. However, the mechanism by which the intracellular localization of X is controlled remains unclear. In this report, we demonstrate that BDV X interacts with the 71kDa molecular chaperon protein, Hsc70. Immunoprecipitation assays revealed that Hsc70 associates with the same region of X as P and, interestingly, that expression of P interferes competitively with the interaction between X and Hsc70. A heat shock experiment revealed that BDV X translocates into the nucleus, dependent upon the nuclear accumulation of Hsc70. Furthermore, we show that knockdown of Hsc70 by short interfering RNA decreases the nuclear localization of both X and P and markedly reduces the expression of viral genomic RNA in persistently infected cells. These data indicate that Hsc70 may be involved in viral replication by regulating the intracellular distribution of X.


Maternal excessive gestational weight gain as a risk factor for autism spectrum disorder in offspring: a systematic review.
Abnormal gestational weight gain (GWG) is a prenatal complication that may contribute to long-term behavioral and neurodevelopmental differences in offspring. This systematic review summarizes research on the association between maternal GWG and risk of autism spectrum disorder (ASD) in offspring. Google and electronic databases, including PubMed, SCOPUS, Embase, Cochrane Library and Google Scholar, were searched for original human studies published in English through June 2020. Articles that examined the association between GWG and risk of ASD in offspring were included. Duplicate and irrelevant studies were removed; and data were obtained through critical analysis. Of 96 articles searched, eight studies were included in the final review. All studies (n = 7) investigating the association of maternal excessive GWG with risk of ASD in offspring indicated that high GWG was independently associated with an increased risk of ASD. Of five studies investigating the association of inadequate GWG with the risk of ASD, four indicated that low GWG was not associated with an increased risk of ASD. Of seven studies examining the association of maternal pre-pregnancy BMI or weight with the risk of ASD, five reported that maternal pre-pregnancy BMI or weight did not appear to be independently associated with risk of ASD. The GWG-ASD association is independent of maternal BMI and child's intellectual disability, but offspring's genetic susceptibility connection to the GWG-ASD association remains a topic of debate. The findings suggest that maternal excessive GWG may be associated with increased risk of ASD in offspring. However, insufficient GWG does not appear to have such association.


Cornelia de Lange syndrome case due to genomic rearrangements including NIPBL.
Cornelia de Lange syndrome (CdLS) is a rare multisystem congenital anomaly disorder characterized by growth and developmental delay, distinctive facial dysmorphism, limb malformations and multiple organ defects. Approximately 60-65% of the CdLS subjects have mutation in one of three cohesin proteins, a main regulator of cohesin-associated protein, NIPBL, and two components of the cohesin ring structure SMC1A and SMC3. A prominent role for cohesin is to control chromosome segregation during cell divisions. We have performed MLPA analysis in a group of 11 children with the CdLS but without identifiable point mutations in the NIPBL and SMC1A genes. In a single patient, we identified a large deletion encompassing exons 35 to 47 of the NIPBL gene. Our finding was validated by aCGH and further characterized by long-range PCR and DNA sequencing of the breakpoint junction.


Behavioral effects of delayed timeouts from reinforcement.
Timeouts are sometimes used in applied settings to reduce target responses, and in some circumstances delays are unavoidably imposed between the onset of a timeout and the offset of the response that produces it. The present study examined the effects of signaled and unsignaled timeouts in rats exposed to concurrent fixed-ratio 1 fixed-ratio 1 schedules of food delivery, where each response on one lever, the location of which changed across conditions, produced both food and a delayed 10-s timeout. Delays of 0 to 38 s were examined. Delayed timeouts often, but not always, substantially reduced the number of responses emitted on the lever that produced timeouts relative to the number emitted on the lever that did not produce timeouts. In general, greater sensitivity was observed to delayed timeouts when they were signaled. These results demonstrate that delayed timeouts, like other delayed consequences, can affect behavior, albeit less strongly than immediate consequences.


Bmi-1 promotes the invasion and migration of colon cancer stem cells through the downregulation of E-cadherin.
Metastasis and recurrence are the challenges of cancer therapy. Recently, mounting evidence has suggested that cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT) are critical factors in tumor metastasis and recurrence. The oncogene, Bmi-1, promotes the development of hematologic malignancies and many solid tumors. The aim of the present study was to elucidate the mechanisms through which Bmi-1 promotes the invasion and migration of colon CSCs (CCSCs) using the HCT116 colon cancer cell line. Sphere formation medium and magnetic‑activated cell sorting were used to enrich and screen the CCSCs. CD133 and CD44 were regarded as markers of CCSCs and they were found to be co-expressed in the HCT116 colon cancer cell line. Colony formation assay, cell proliferation assay and viability assay using the Cell Counting Kit-8, and transplantation assay using nude mice injected with CCSCs were used to examine the CCSCs. The CD133+CD44+ HCT116 cells exhibited greater cloning efficiency, an enhanced proliferative ability, increased cell viability and stronger tumorigenicity; these cells were used as the CCSCs for subsequent experiments. In addition, the invasive and migratory abilities of the CD133+CD44+ HCT116 cells were markedly decreased when Bmi-1 was silenced by small interfering RNA (siRNA). The results of RT-qPCR and western blot analysis suggested that Bmi-1 had a negative effect on E-cadherin expression. On the whole, our findings suggest that Bmi-1 promotes the invasion and migration of CCSCs through the downregulation of E-cadherin, possibly by inducing EMT. Our findings thus indicate that Bmi-1 may be a novel therapeutic target for the treatment of colon cancer.


[50 years ago: documentation of the Bernburg "euthanasia" action program (II)].
The history of the "euthanasia" action programme began at Bernburg in 1940 and finished in 1943. It passed under regional peculiarities. In this second part of the report the organisational details of criminal actions were analysed and additionally the development of the physicians who took part in.


Chinese Consensus Report on Family-Based Helicobacter pylori Infection Control and Management (2021 Edition).
Helicobacter pylori infection is mostly a family-based infectious disease. To facilitate its prevention and management, a national consensus meeting was held to review current evidence and propose strategies for population-wide and family-based H. pylori infection control and management to reduce the related disease burden. Fifty-seven experts from 41 major universities and institutions in 20 provinces/regions of mainland China were invited to review evidence and modify statements using Delphi process and grading of recommendations assessment, development and evaluation system. The consensus level was defined as ≥80% for agreement on the proposed statements. Experts discussed and modified the original 23 statements on family-based H. pylori infection transmission, control and management, and reached consensus on 16 statements. The final report consists of three parts: (1) H. pylori infection and transmission among family members, (2) prevention and management of H. pylori infection in children and elderly people within households, and (3) strategies for prevention and management of H. pylori infection for family members. In addition to the 'test-and-treat' and 'screen-and-treat' strategies, this consensus also introduced a novel third 'family-based H. pylori infection control and management' strategy to prevent its intrafamilial transmission and development of related diseases. H. pylori is transmissible from person to person, and among family members. A family-based H. pylori prevention and eradication strategy would be a suitable approach to prevent its intra-familial transmission and related diseases. The notion and practice would be beneficial not only for Chinese residents but also valuable as a reference for other highly infected areas.


Surface roughness of opalescent porcelains after polishing.
Intraoral porcelain polishing is an important consideration in many restorative and esthetic procedures. Several porcelain polishing systems as well as improved ceramics are now commercially available. This study evaluated the efficacy of eight different intraoral polishing techniques on three opalescent porcelains. The surface roughness (Ra) of the opalescent porcelains were measured before and after the polishing procedures with a profilometer. These results were then compared to self-glazed and overglazed control groups. Five of the techniques tested produced surfaces smoother than glazing. The use of a 30-fluted carbide bur before diamond polishing paste produced the smoothest surfaces.


Transcutaneous bilirubin nomograms in African neonates.
The use of transcutaneous bilirubin (TcB) as a screening tool, based on relevant population-specific nomogram, or proxy for total serum bilirubin (TSB) levels in assessing the risk of subsequent hyperbilirubinemia is supported by several clinical guidelines on the management of neonatal hyperbilirubinemia. However, while TcB has been found to significantly over-estimate TSB in neonates of African-American ancestry, with variations across TcB devices, no nomogram has been specifically reported for this racial group. This study therefore set out to develop TcB nomograms for healthy late pre-term and term black African neonates derived from two widely used bilirubinometers. A retrospective analysis of 12,377 TcB measurements obtained from 6,373 neonates in the first postnatal week, over a period of 48 months using Bilichek and JM-103 bilirubinometers. TcB percentiles were computed from hour-specific TcB values and nomograms developed for each of the screening devices. Predictive ability of the 75th and 95th percentiles to detect significant hyperbilirubinemia was evaluated between 24-96 hours of age. The 95th percentile curve was compared with those from other populations. The velocity of TcB rise at 75th and 95th percentiles was generally higher with JM-103 than Bilichek. Both percentiles also peaked at higher TcB levels with JM-103. The 95th percentile for both instruments showed a downward trend as from approximately 114 hours. Both instruments had high negative predictive values across the selected time-epochs and lower discriminatory ability than reported in non-black populations. The predictive utility of TcB as a potential screening tool varies across devices in black African neonates with or without risk of significant hyperbilirubinemia, and lower than levels reported in non-black populations. Equipment-specific nomograms should be considered for TcB monitoring in this racial population where TSB is not routinely available.


Developmental regulation and tissue distribution of the liver transcription factor LFB1 (HNF1) in Xenopus laevis.
The transcription factor LFB1 (HNF1) was initially identified as a regulator of liver-specific gene expression in mammals. It interacts with the promoter element HP1, which is functionally conserved between mammals and amphibians, suggesting that a homologous factor, XLFB1, also exists in Xenopus laevis. To study the role of LFB1 in early development, we isolated two groups of cDNAs coding for this factor from a Xenopus liver cDNA library by using a rat LFB1 cDNA probe. A comparison of the primary structures of the Xenopus and mammalian proteins shows that the myosin-like dimerization helix, the POU-A-related domain, the homeo-domain-related region, and the serine/threonine-rich activation domain are conserved between X. laevis and mammals, suggesting that all these features typical for LFB1 are essential for function. Using monoclonal antibodies, we demonstrate that XLFB1 is present not only in the liver but also in the stomach, intestine, colon, and kidney. In an analysis of the expression of XLFB1 in the developing Xenopus embryo, XLFB1 transcripts appear at the gastrula stage. The XLFB1 protein can be identified in regions of the embryo in which the liver diverticulum, stomach, gut, and pronephros are localized. The early appearance of XLFB1 expression during embryogenesis suggests that the tissue-specific transcription factor XLFB1 is involved in the determination and/or differentiation of specific cell types during organogenesis.


Recent diversification rates in North American tiger beetles estimated from a dated mtDNA phylogenetic tree.
Species-level phylogenies derived from DNA sequence data provide a tool for estimating diversification rates and how these rates change over time, but to date there have been few empirical studies, particularly on insect groups. We use a densely sampled phylogenetic tree based on mitochondrial DNA to investigate diversification rates in the North American tiger beetles (genus Cicindela). Using node ages estimated from sequence data and calibrated by biogeographical evidence, we estimate an average per-lineage diversification rate of at least 0.22 +/- 0.08 species/Myr over the time interval since the most recent colonization that led to a radiation within the continent. In addition, we find evidence for a weak, recent increase in the net diversification rate. This is more consistent with a late Pleistocene increase in the speciation rate than with a constant rate of background extinction, but the results are sensitive to the dating method and taxon sampling. We discuss practical limitations to phylogenetic studies of diversification rates.


Anastomotic aneurysms--20-years of experience from one center.
Anastomotic aneurysms may develop after any type of vascular surgery, in different areas of the arterial system, and require reoperation. The frequency of occurrence of the above-mentioned is estimated at 1-5%. During the period between 1989 and 2010, 180 patients with 230 anastomotic aneurysms were subject to surgical intervention at the Department of General and Thoracic Surgery, Warsaw Medical University. The study group comprised 21 (11.7%) female and 159 (88.3%) male patients, aged between 30 and 87 years (mean age - 62.8 years). In relation to the number of anastomoses aneurysms were diagnosed in 2.1% of cases. Twenty-four (10.4%) patients were diagnosed with recurrent aneurysms. Surgical procedures performed were as follows: artificial prosthesis implantation (119), reanastomosis (40), patch plasty (25), graftectomy (19), prosthesis replacement (9), and stent-graft (7) implantation. 195 (84.8%) aneurysms were subject to planned surgery, while 35 (15.2%) required emergency intervention. 77.8% of patients were diagnosed with aseptic aneurysms, while the remaining 22.2% with infected perioperative aneurysms. Good treatment results were obtained in 149 (82.8%) patients. Limb amputations were performed in 19 (10.5%) cases. Twelve (6.7%) patients died as a consequence of infection and general complications. Vascular reoperations are a difficult clinical problem and are burdened with a high rate of complications. The above-mentioned often require complex treatment, in order to improve therapeutic results.


Benzalacetone synthase. A novel polyketide synthase that plays a crucial role in the biosynthesis of phenylbutanones in Rheum palmatum.
Benzalacetone synthase (BSA) is a novel plant-specific polyketide synthase that catalyzes a one step decarboxylative condensation of 4-coumaroyl-CoA with malonyl-CoA to produce the C6-C4 skeleton of phenylbutanoids in higher plants. A cDNA encoding BAS was for the first time cloned and sequenced from rhubarb (Rheum palmatum), a medicinal plant rich in phenylbutanoids including pharmaceutically important phenylbutanone glucoside, lindleyin. The cDNA encoded a 42-kDa protein that shares 60-75% amino-acid sequence identity with other members of the CHS-superfamily enzymes. Interestingly, R. palmatum BAS lacks the active-site Phe215 residue (numbering in CHS) which has been proposed to help orient substrates and intermediates during the sequential condensation of 4-coumaroyl-CoA with malonyl-CoA in CHS. On the other hand, the catalytic cysteine-histidine dyad (Cys164-His303) in CHS is well conserved in BAS. A recombinant enzyme expressed in Escherichia coli efficiently afforded benzalacetone as a single product from 4-coumaroyl-CoA and malonyl-CoA. Further, in contrast with CHS that showed broad substrate specificity toward aliphatic CoA esters, BAS did not accept hexanoyl-CoA, isobutyryl-CoA, isovaleryl-CoA, and acetyl-CoA as a substrate. Finally, besides the phenylbutanones in rhubarb, BAS has been proposed to play a crucial role for the construction of the C6-C4 moiety of a variety of natural products such as medicinally important gingerols in ginger plant.


The prognostic value of CXC subfamily ligands in stage I-III patients with colorectal cancer.
To investigate the value of CXC subfamily ligands in stage I-III patients with colorectal cancer, in order to find a new predictor for CRC patients. We used Gene Expression Omnibus (GEO) database to collect the gene expression of CXC subfamily ligands and corresponding clinical data. The survival analysis was performed by "survival" package of Rsoftware. The CRC patients' DFS and the relationship between the expression levels of CXC subfamily ligands were evaluated by the univariate Cox regression analysis. By using microarray data, there were 14 CXC subfamily ligands identified from dataset GSE39582. Seven CXC subfamily ligands were significantly correlated with DFS in CRC patients. (p<0.05),including CXCL1, CXCL3, CXCL9, CXCL10, CXCL11, CXCL13, and CXCL14. From multivariate Cox regression analyze, four CXC subfamily ligands (CXCL9, CXCL10, CXCL11, and CXCL13) were significantly associated with CRC patients' DFS (all p<0.05). Three CXC subfamily ligands (CXCL10, CXCL11, and CXCL13) were significantly associated with CRC patients' Overall survival (OS) (all p<0.05). Both CXCL11 and CXCL13 had the similar prediction values for DFS and OS. There were seven CXC subfamily ligands were significantly correlated with DFS in CRC patients. Different expression level of four CXC subfamily ligands (CXCL9, CXCL10, CXCL11, and CXCL13) and Three CXC subfamily ligands (CXCL10, CXCL11, and CXCL13) were related to CRC patients' DFS and OS. There are still needs more experiments to confirm our conclusions. Next step we will make animal experiment about the genes in order to verified the predictive value of the CXC subfamily ligands.


Betaine Accumulation and [C]Formate Metabolism in Water-stressed Barley Leaves.
Barley (Hordeum vulgare L.) plants at the three-leaf stage were water-stressed by flooding the rooting medium with polyethylene glycol 6000 with an osmotic potential of -19 bars, or by withholding water. While leaf water potential fell and leaf kill progressed, the betaine (trimethylglycine) content of the second leaf blade rose from about 0.4 micromole to about 1.5 micromoles in 4 days. The time course of betaine accumulation resembled that of proline accumulation. Choline levels in unstressed second leaf blades were low (<0.1 micromole per blade) and remained low during water stress. Upon relief of stress, betaine-like proline-remained at a high concentration in drought-killed leaf zones, but betaine did not disappear as rapidly as proline from viable leaf tissue during recovery.When [methyl-(14)C]choline was applied to second leaf blades of intact plants in the growth chamber, water-stressed plants metabolized 5 to 10 times more (14)C label to betaine than control plants during 22 hours. When infiltrated with tracer quantities of [(14)C]formate and incubated for various times in darkness or light, segments cut from water-stressed leaf blades incorporated about 2- to 10-fold more (14)C into betaine than did segments from unstressed leaves. In segments from stressed leaves incubated with [(14)C]formate for about 18 hours in darkness, betaine was always the principal (14)C-labeled soluble metabolite. This (14)C label was located exclusively in the N-methyl groups of betaine, demonstrating that reducing equivalents were available in stressed leaves for the reductive steps of methyl group biosynthesis from formate. Incorporation of (14)C from formate into choline was also increased in stressed leaf tissue, but choline was not a major product formed from [(14)C]formate.These results are consistent with a net de novo synthesis of betaine from 1- and 2-carbon precursors during water stress, and indicate that the betaine so accumulated may be a metabolically inert end product.


[Cascade genetic testing of familial hypercholesterolemia A new opportunity for prevention].
Familial hypercholesterolemia (FH) is a genetic disorder associated with an increased risk of early-onset cardiovascular events. Because lifestyle interventions and lipid-lowering drugs can strongly reduce cardiovascular risk, the early diagnosis of FH is important. Indeed, given the autosomal dominant transmission of the pathogenic variant, a genetic cascade screening program of first-degree relatives from an index case could identify patients at high cardiovascular risk. In Switzerland, genetic testing for FH is rarely used, because it is not reimbursed by health insurance companies. To test the usefulness of cascade genetic testing for FH, the CATCH study is currently ongoing in all linguistic part of Switzerland.


Significance of Interleukin (IL)-4 and IL-13 in Inflammatory Arthritis.
Interleukin (IL)-4 and IL-13 belong to the T helper 2 (Th2) cytokine family, along with IL-3, IL-5, and IL-9. These cytokines are key mediators of allergic inflammation. They have important immunomodulatory activities and exert influence on a wide variety of immune cells, such as B cells, eosinophils, basophils, monocytes, fibroblasts, endothelial cells, airway epithelial cells, smooth muscle cells, and keratinocytes. Recent studies have implicated IL-4 and IL-13 in the development of various autoimmune diseases. Additionally, these cytokines have emerged as potential players in pathogenesis of inflammatory arthritis. Recent findings suggest that the IL-4 and IL-13 might play a significant role in the downregulation of inflammatory processes underlying RA pathology, and beneficially modulate the course of the disease. This review summarizes the biological features of the IL-4 and IL-13 and provides current knowledge regarding the role of these cytokines in inflammatory arthritis.


The 2.15 A crystal structure of CG-16, the developmentally regulated homodimeric chicken galectin.
Differential developmental regulation of expression, fine-specificity differences in ligand recognition and disparate capacity for homodimerization are characteristics of the two currently known proto-type chicken galectins. The X-ray crystal structure of the first avian galectin, the homodimeric agglutinin from chicken liver (CG-16), has been solved in the absence of ligand in two crystal forms. Although the arrangement of lectin dimers in the two crystals is different, the structure of the monomers and their association into the extended beta-sandwich that characterises the dimer are virtually identical. The fold establishes a beta-sandwich motif composed of a five-stranded and a six-stranded beta-sheet evocative of proto-type mammalian galectins. The carbohydrate-binding site is occupied by six water molecules that take the place of the sugar in the complex. They help to stabilise in the absence of the ligand the spatial arrangement of the amino acid side-chains involved in sugar recognition. Docking of N-acetyllactosamine into the binding site reveals that three of these water molecules, which are in direct contact with the protein, occupy positions equivalent to the key sugar hydroxyl groups, namely the hydroxyls at positions 4 and 6 of the galactose unit and at position 3 of the N-acetylglucosamine unit. Crystallographic data are fully consistent with the binding features in solution previously derived from chemical mapping with deoxy, fluoro and O-methyl derivatives and laser photo-CIDNP (chemically induced dynamic nuclear polarisation) studies. The possible molecular basis for the monomeric character of the chicken intestinal galectin as well as potential mechanisms of oxidative inactivation by disulphide bridging are evaluated on the basis of the given structural information concerning the CG-16 dimer interface and the cysteine residues, respectively.


Macrophage migration inhibitory factor receptor CD74 mediates alphavirus-induced arthritis and myositis in murine models of alphavirus infection.
Arthrogenic alphaviruses such as Ross River virus (RRV) and chikungunya virus (CHIKV) circulate worldwide. This virus class causes debilitating illnesses that are characterized by arthritis, arthralgia, and myalgia. In previous studies, we identified macrophage migration inhibitory factor (MIF) as a critical inflammatory factor in the pathogenesis of alphaviral diseases. The present study was undertaken to characterize the role of CD74, a cell surface receptor of MIF, in both RRV- and CHIKV-induced alphavirus arthritides. Mouse models of RRV and CHIKV infection were used to investigate the immunopathogenesis of arthritic alphavirus infection. The role of CD74 was assessed using histologic analysis, real-time polymerase chain reaction, flow cytometry, and plaque assay. In comparison to wild-type mice, CD74-/- mice developed only mild clinical features and had low levels of tissue damage. Leukocyte infiltration, characterized predominantly by inflammatory monocytes and natural killer cells, was substantially reduced in the infected tissue of CD74-/- mice, but production of proinflammatory cytokines and chemokines was not decreased. CD74 deficiency was associated with increased monocyte apoptosis, but had no effect on monocyte migratory capacity. Consistent with these findings, alphaviral infection resulted in a dose-dependent up-regulation of CD74 expression in human peripheral blood mononuclear cells, and serum MIF levels were significantly elevated in patients with RRV or CHIKV infection. CD74 appears to regulate immune responses to alphaviral infection through its effects on cellular recruitment and survival. These findings suggest that both MIF and CD74 play a critical role in mediating alphaviral disease, and blocking these factors with novel therapeutic agents could substantially ameliorate the pathologic manifestations.


Corrections and clarifications.
In Christopher Anderson's News & Comment article "Rocky road for Federal Research Inc." (22 Oct., p. 496), a comment from National Institutes of Health neuroscientist Michael Rogawski regarding Cooperative Research and Development Agreement (CRADA) delays did not refer to his own CRADA experiences, which he says were not characterized by inordinate delays. Rogawski was referring to the effect on scientists in general of the delays inherent in what he considers appropriate scientific and administrative review.


Preparation of Three-Dimensional Mo2C/NC@MXene and Its Efficient Electromagnetic Absorption Properties.
The positively charged MoO3/PDA microspheres are obtained by stacking and assembly of the sheet structure, and the negatively charged MXene nanosheets are wrapped on the surface through the principle of electrostatic self-assembly. After annealing, a nitrogen-doped carbon composite and a MXene-coated Mo2C wave absorber are obtained. The formation of the wrinkled surface provides a complex pore structure, and the multiple interface reflections between the nanosheets enhance the absorption performance. The existence of heterogeneous interfaces and the uneven distribution of space charges accumulated between the interfaces effectively reduce the minimum reflection loss (RLmin). This work explores the effects of the ratio between MoO3/PDA and MXene nanosheets and loading amount on the microwave absorption properties. Mo2C/NC@MXene-2 obtained when the ratio of the two is 3:1 has the best absorption performance under 25% loading. The RLmin is -59.36 dB, and the corresponding effective absorption bandwidth (EAB) is 4.6 GHz at 2.5 mm. This work expands the new applications of MXene-based and Mo2C-based materials and has a guiding significance for the design of electrostatic self-assembly materials.


Reptile freeze tolerance: metabolism and gene expression.
Terrestrially hibernating reptiles that live in seasonally cold climates need effective strategies of cold hardiness to survive the winter. Use of thermally buffered hibernacula is very important but when exposure to temperatures below 0 degrees C cannot be avoided, either freeze avoidance (supercooling) or freeze tolerance strategies can be employed, sometimes by the same species depending on environmental conditions. Several reptile species display ecologically relevant freeze tolerance, surviving for extended times with 50% or more of their total body water frozen. The use of colligative cryoprotectants by reptiles is poorly developed but metabolic and enzymatic adaptations providing anoxia tolerance and antioxidant defense are important aids to freezing survival. New studies using DNA array screening are examining the role of freeze-responsive gene expression. Three categories of freeze responsive genes have been identified from recent screenings of liver and heart from freeze-exposed (5h post-nucleation at -2.5 degrees C) hatchling painted turtles, Chrysemys picta marginata. These genes encode (a) proteins involved in iron binding, (b) enzymes of antioxidant defense, and (c) serine protease inhibitors. The same genes were up-regulated by anoxia exposure (4 h of N2 gas exposure at 5 degrees C) of the hatchlings which suggests that these defenses for freeze tolerance are aimed at counteracting the injurious effects of the ischemia imposed by plasma freezing.


Modulation of drug release from glyceryl palmitostearate-alginate beads via heat treatment.
Diclofenac calcium alginate (DCA) beads containing glyceryl palmitostearate (GPS) were prepared by ionotropic gelation method. The effect of GPS amount and heat treatment on characteristics of the DCA beads was investigated. Incorporation of GPS into the DCA beads increased particle size and entrapment efficiency of diclofenac sodium (DS), but decreased water uptake in distilled water, and DS release rate. The heat treatment caused the DCA beads to be irregular shape particles and to possess higher water uptake. A slower release rate of DS in distilled water was found because of interaction of DS and alginate polymer matrix, and a restriction of water sorption into the inside region of the beads, which caused by the shrinkage of the beads after heating. However, the heat treatment did not affect particle shape and water uptake in distilled water of the 3%GPS-DCA beads. Differential scanning calorimetric study showed that GPS in the DCA beads was resolidified to different polymorph after cooling. Furthermore, the micro-Raman spectra indicated the existence of DS in the GPS matrix particles in the beads due to the partition of DS into the melted GPS during heat treatment. This led to a decrease in release rate of DS in pH 6.8 phosphate buffer and a change in DS release pattern in distilled water. Thus, not only the calcium alginate matrix, but also the resolidified GPS matrix in the alginate beads controlled the DS release from the 3%GPS-DCA beads with heat treatment.


Mental and self-rated health of bakery workers in Lebanon: A national study.
The relationship between poverty and health has been well addressed in public health research. The health effects of social and economic inequalities on working groups have also drawn the attention of occupational health scholars. Research addressing workers in low-paying jobs showed increased risks for poor health. This research examined the psychosocial factors associated with poor mental health and self-rated health among low-income bakery workers performing demanding tasks. Face-to-face interviews in 504 randomly selected bakeries in Lebanon provided data on socio-demographics, perception of the workplace environment, job security, job satisfaction, general health, and mental health. In total, 16.5% of bakery workers reported poor self-rated health, and 45% reported poor mental health. Workers with a chronic illness were almost three times more likely to report poor self-rated health (OR = 2.86; 95% CI = 1.44-5.67), and those with musculoskeletal pain reported poor self-rated health five times as often (OR = 5.34; 95% CI = 2.9-9.80). Those with a chronic illness and musculoskeletal pain were twice as likely to report poor mental health (OR = 1.94; 95% CI = 1.07-3.50 and OR = 2.07; 95% CI = 1.32-3.23, respectively); and those dissatisfied with their job reported poorer self-rated health (OR = 2.18; 95% CI = 1.12-4.23) and mental health (OR = 2.57; 95% CI = 1.54-4.26). In addition, workers reporting job insecurity had poor mental health twice as often (OR = 1.93; 95% CI = 1.24-2.99). Low socioeconomic indicators showed a gradient association with both poor self-rated health and mental health. Reporting job dissatisfaction and insecurity, musculoskeletal pain, and chronic illness were associated with poor mental and self-rated health among bakery workers. Interventions to improve the working conditions of bakery workers are timely and essential. This research provided evidence for policy to guide occupational health practice and safeguard the health of bakery workers.


Chest illnesses and the decline of FEV1 in steelworkers.
This study relates the impact of various medical conditions to clinically important forced expiratory volume in 1 second (FEV1) declines in a cohort of steelworkers evaluated cross-sectionally and longitudinally. Medical records of 1171 randomly chosen steelworkers were obtained from the medical department of a steel company. We reviewed the medical records for information regarding demographic parameters, smoking status, spirometry indexes, job history, and the worker's respiratory health. These workers had performed annual spirometry from 1980 to 1991 at least once and up to 12 times. We compared the prevalence of medical conditions in 203 male never-smoking steelworkers in this group of 1171 workers by separating workers into three groups on the basis of final predicted FEV1 values (< 65%, between 65% and 79%, and > or = 80%). We also evaluated the prevalence of medical conditions and the association between these conditions and the rate of annual decline in FEV1 in 475 steelworkers who had at least three valid tests and at least 5 years separating the first and last test by multiple logistic regression analysis. Of the 475 steelworkers, 121 were categorized as rapid decliners (an annual rate of decline in FEV1 exceeding the 75th percentile of the slope distribution), whereas the remaining workers served as controls. Three of 203 and 17 of the remaining 200 in the cross-sectional survey had final predicted FEV1 values < 65% or between 65% and 79%, respectively. Among these 20 never-smokers, the accelerated rate of decline could be reasonably explained by factors independent of dust and age in all but two. In the 203 never-smokers, hay fever and trauma occurred more frequently in those with a decreased predicted FEV1. In the longitudinal study of 475 workers, the prevalence of pneumonia was significantly greater in the rapid decliners, whereas the prevalence of allergy, asthma or hay fever, and trauma approached a significant excess in number. Logistic regression models demonstrated that aging, weight gain, smoking, trauma, pneumonia, and a history of allergy, asthma, or hay fever were independently related to the risk of a clinically important decline of FEV1 in this group. In summary, there are multiple risk factors for an accelerated rate of decline in workers with dust exposure. An accurate assessment of the causes for an excessive rate of lung function decline in an individual worker within a population requires an understanding of the relationship between environmental exposures, lung function decline, and the individual worker's underlying health. In addition to the three traditionally recognized variables--age, smoking, and dust exposure--the medical conditions of trauma, pneumonia, and allergy, asthma, or hay fever were related to a clinically important decline of FEV1 in this industrial population.


Efficacy and effectiveness of anti-digoxin antibodies in chronic digoxin poisonings from the DORA study (ATOM-1).
We hypothesized that in chronic digoxin toxicity, anti-digoxin antibodies (Fab) would be efficacious in binding digoxin, but this may not translate into improved clinical outcomes. This study aims to investigate changes in free digoxin concentrations and clinical effects on heart rate and potassium concentrations in chronic digoxin poisoning when anti-digoxin Fab are given. This is a prospective observational study. Patients were recruited if they have been treated with anti-digoxin Fab for chronic digoxin poisoning. Data was entered into a standardised prospective form, supplemented with medical records. Their serum or plasma was collected, analysed for free and bound digoxin and free anti-digoxin Fab concentrations. From September 2013 to February 2015, 36 patients (median age, 78 years; 22 females) were recruited from 18 hospitals. Median heart rate (HR) was 49 beats/min. Initial median digoxin and potassium concentrations were 4.7 nmol/L (3.6 μg/L) (range: 2.3-11.2 nmol/L) and 5.3 mmol/L (range: 2.9-9.2 mmol/L) respectively. Beta-blockers (n = 18), calcium antagonists (n = 6), spironolactone and/or angiotensin blocking agents (n = 24) were also used concomitantly. Renal impairment and gastrointestinal symptoms were present in 31 (86%) and 22 (63%) patients respectively. Five patients died from conditions unrelated to digoxin toxicity. Median change in HR was 8 beats/min post-Fab with no effect on blood pressure; they were 4, 10 and 17 beats/min for the 1, 2 and ≥3 vials of anti-digoxin Fab groups respectively. Concomitant treatments with potassium lowering agents (12/36) and inotropic drugs (7/36) were used. Gastrointestinal effects resolved in all 22 patients. The median decrease for potassium was 0.3 mmol/L. Digoxin concentration reduced from 3.8 to 0 nmol/L post-Fab. There was a rebound observed in the free digoxin concentration in 25 patients but none had associated clinical deterioration. One to two vials of anti-digoxin Fab initially bound all free digoxin confirming Fab efficacy. However, this was associated with only a moderate improvement in HR and potassium, suggesting bradyarrhythmia and hyperkalaemia may be from other co-morbidities.


Budgetary impact of treatment with adjuvant imatinib for 1 year following surgical resection of Kit-positive localized gastrointestinal stromal tumors.
Imatinib mesylate, an orally administered kinase inhibitor that targets the Kit (CD117) protein, currently has 10 approved indications including treatment of chronic myelogenous leukemia and metastatic gastrointestinal stromal tumors (GIST). Treatment with adjuvant imatinib following surgical resection of localized Kit-positive GIST, the most recent FDA-approved indication (December 2008), has been shown to significantly improve recurrence-free survival (RFS) compared with surgical resection alone. Although adjuvant imatinib has proven effective in clinical trials, it is important to consider the economic impact to health plans of introducing imatinib in accordance with its new labeled indication. To evaluate the budgetary impact over a 3-year time horizon of treating patients with localized Kit-positive GIST with 1 year of adjuvant imatinib following surgical resection. A Markov model was developed to predict patients' transitions across health states defined by initial treatment (surgical resection followed by adjuvant imatinib 400 milligrams [mg] daily versus surgical resection alone), recurrence, and progression. Treatments for a first recurrence were (a) imatinib 400 mg daily for recurrences following resection only or after completion of 1 year of treatment with imatinib 400 mg daily and (b) imatinib 800 mg daily for recurrence during active treatment with imatinib 400 mg daily. Treatments for further progression were imatinib 800 mg daily, sunitinib, or best supportive care (BSC) following imatinib 400 mg per day, and sunitinib or BSC following imatinib 800 mg daily. Recurrence rates were derived from the American College of Surgeons Oncology Group (ACOSOG) Z9001 clinical trial, which compared 1 year of adjuvant imatinib following surgical resection with surgical resection only. The total number of patients with localized and surgically resected GIST (incidence rate of 0.36 per 100,000) was estimated from epidemiologic studies of GIST. Uptake of treatment with imatinib was estimated from unpublished data from qualitative market research funded by the study sponsor. The uptake rate assumptions reflected both (a) the percentage of patients with Kitpositive disease and (b) the percentage of clinically eligible patients who would use imatinib. Costs were estimated by combining unit costs from published sources with expected resource utilization based on the clinical trial publication and National Comprehensive Cancer Network guidelines on the treatment of patients with GIST. To obtain estimates of the budgetary impact, we compared estimated health care costs with versus without adjuvant imatinib, where health care costs with imatinib reflected the costs of treatment minus cost offsets associated with delayed or avoided recurrence or progression. All "with" scenarios assumed no additional uses other than surgically resected localized Kit-positive GIST (i.e., no change in off-label use of imatinib). The budgetary impact was estimated for the first 3 years after the introduction of adjuvant imatinib in accordance with its new labeled indication in a hypothetical plan population of 10 million persons. Results were calculated both as total budgetary impact and as per member per month (PMPM) cost in 2009 dollars. Sensitivity analyses were performed to test the robustness of model results to changes in parameter estimates. The model predicted 36 incident resected GIST cases per year in a health plan of 10 million members. The estimated counts of cases treated with adjuvant imatinib were 10.8, 16.2, and 21.6 in the first, second, and third years after introduction, respectively, with the annual increases attributable to changes in the proportion of patients with resected GIST assumed to use imatinib (30% in year 1, rising to 45% in year 2 and 60% in year 3). The model predicted that treatment of these cases with imatinib will increase pharmacy costs by an additional $505,144 in the first year, $757,717 in the second year, and $1,010,289 in the third year. Increased resource use associated with monitoring patients during and after treatment with adjuvant imatinib would cost an additional $21,564, $38,145, and $56,605 in the first, second, and third years, respectively. Recurrence would be avoided or delayed in 7 patients over the 3-year period. Avoided or delayed recurrences would result in cost offsets of $61,583 in the first year, $156,702 in the second year, and $233,849 in the third year. The net budgetary impact was estimated to be $465,126 in the first year (less than $0.01 PMPM), $639,159 in the second year ($0.01 PMPM), and $833,044 in the third year ($0.01 PMPM). Results of sensitivity analyses indicated that the budgetary impact in the third year is most sensitive to changes in the price of adjuvant imatinib and recurrence rates. The model predicted that the introduction of adjuvant imatinib for treatment of surgically resected, localized, Kit-positive GIST will lead to a net budgetary impact of $0.01 PMPM in the third year after introduction assuming change in use only in accordance with the new labeled indication. Approximately 11.7%-21.9% of the cost of adjuvant imatinib is offset by the reduction in costs associated with GIST recurrence.


Hepatic fibrosis as a predictor of hepatic regenerative activity after partial hepatectomy in the rat.
Liver regeneration is an essential component of the recovery period after partial hepatectomy. Unfortunately, tests that accurately predict regenerative activity in the postoperative period have yet to be described. This study was designed to determine whether the extent of hepatic fibrosis correlates with liver regeneration activity after partial hepatectomy in rats with carbon tetrachloride-induced liver disease. Two groups of adult male Sprague-Dawley rats (12 to 30/group) were treated for 20 to 22 wk with weekly intragastric doses of carbon tetrachloride or vehicle. All rats then underwent 70% hepatectomy while under ether anesthesia. Liver regeneration activity was determined at 24 and 48 hr by [3H]thymidine incorporation into DNA. Hepatic fibrosis was calculated at the time of partial hepatectomy by automated image analysis on Van Gieson-stained liver tissue. Although a significant inverse correlation was found between the extent of hepatic fibrosis and DNA synthesis when all rats were considered (carbon tetrachloride-treated and vehicle-treated) at 24 and 48 hr after partial hepatectomy (r = -0.4943 and -0.7396, respectively; p < 0.05), no such correlation existed when carbon tetrachloride-treated rats were considered independently (r = -0.3231 and -0.0910 at 24 and 48 hr, respectively). In conclusion, we believe that in diseased livers, preoperative quantitation of hepatic fibrosis on automated image analysis does not serve as a useful predictor of liver regeneration activity.


Personalized computed tomography - Automated estimation of height and weight of a simulated digital twin using a 3D camera and artificial intelligence.
The aim of this study was to develop an algorithm for automated estimation of patient height and weight during computed tomography (CT) and to evaluate its accuracy in everyday clinical practice. Depth images of 200 patients were recorded with a 3D camera mounted above the patient table of a CT scanner. Reference values were obtained using a calibrated scale and a measuring tape to train a machine learning algorithm that fits a patient avatar into the recorded patient surface data. The resulting algorithm was prospectively used on 101 patients in clinical practice and the results were compared to the reference values and to estimates by the patient himself, the radiographer and the radiologist. The body mass index was calculated from the collected values for each patient using the WHO formula. A tolerance level of 5 kg was defined in order to evaluate the impact on weight-dependent contrast agent dosage in abdominal CT. Differences between values for height, weight and BMI were non-significant over all assessments (p > 0.83). The most accurate values for weight were obtained from the patient information (R² = 0.99) followed by the automated estimation via 3D camera (R² = 0.89). Estimates by medical staff were considerably less precise (radiologist: R² = 0.78, radiographer: R² = 0.77). A body-weight dependent dosage of contrast agent using the automated estimations matched the dosage using the reference measurements in 65 % of the cases. The dosage based on the medical staff estimates would have matched in 49 % of the cases. Automated estimation of height and weight using a digital twin model from 3D camera acquisitions provide a high precision for protocol design in computer tomography. · Machine learning can calculate patient-avatars from 3D camera acquisitions.. · Height and weight of the digital twins are comparable to real measurements of the patients.. · Estimations by medical staff are less precise.. · The values can be used for calculation of contrast agent dosage.. · Geissler F, Heiß R, Kopp M et al. Personalized computed tomography - Automated estimation of height and weight of a simulated digital twin using a 3D camera and artificial intelligence. Fortschr Röntgenstr 2021; 193: 437 - 445.