Pulmonary actinomycosis followed by pericarditis and intractable pleuritis.
A case of pleuropericarditis caused by Actinomyces israelli is described. The patient first underwent left upper lobectomy because of pulmonary actinomycosis. Seven months later, cardiac tamponade developed. Culture of the bloody pericardial effusion resulted in positive growth of Actinomyces israeli. He was successfully treated with penicillin G, ampicillin, and minocyclin. However, right pleural effusion appeared two months later. Cultures of the effusion again yielded positive growth of the same bacteria. However, the strain had gained resistance to any antibiotics that had been effective before. Accordingly, pleurodesis with minocyclin was undertaken, which was fortunately effective for controlling the pleural effusion.


[Proinsulin C-peptide -- the bioactive peptide with a huge promise].
Proinsulin connecting peptide (C-peptide) has been initially regarded as deprived of biological functions other than correct scaffolding of insulin. This was caused by the lack of evident effect of C-peptide administration to healthy subjects or animals. At present, in view of numerous studies concerning its structure, membrane binding and biological functions, C-peptide seems to constitute a crucial role in the pathogenesis of complications in diabetes mellitus type 1 (DM1). Patients who maintain high remnant insulin secretion (and therefore also of C-peptide) develop complications such as nephropathy, neuropathy and later microangiopathy with a milder clinical course. In this article we have covered molecular and cellular aspects of C-peptide functioning, such as: activation of protein kinase C, Na+,K+- ATP-ase, nitric oxide synthase, MAP and ERK 1/2 kinases, improvement of nerve conduction velocity and interactions with exogenous and endogenous insulin. We also outline the clinical consequences of deficiency of this underestimated peptide along with its potential therapeutical possibilities in the primary and secondary prevention of DM1 complications.


Electromyographic analysis of the pectoralis major and deltoideus anterior in the inclined "flying" exercise with loads.
Due to a shortage of textbooks with specific data on muscular activity concerning physical conditioning and sports, we analysed electromyographically the muscles pectoralis major and deltoideus anterior, bilaterally, in inclined "flying" exercises, during the concentric and eccentric phases, with external loads of 25, 50, 75 and 100% of the maximum load. The electromyographic analysis was performed in eleven male volunteers with MEDI-TRACE-200 surface electrodes connected to a six-channel biologic signal acquisition module coupled to a PC/AT computer. The electromyographic signals were processed and the obtained effective values were normalized through maximum voluntary isometric contraction. Statistically, the results showed that all the muscles studied presented significant differences between the concentric and the eccentric phases, with higher electromyographic activity during the concentric phase. By analysing the different loads for each muscle in both phases, significant electromyographic activity was observed for all muscles. When the effect of each load on each muscle during the concentric phase was analysed, it was noticed that the muscles on the left were more active than those on the right side, while in the eccentric phase the muscles had different behavior.


Arabidopsis Lectin EULS3 Is Involved in ABA Signaling in Roots.
The Arabidopsis thaliana lectin ArathEULS3 is upregulated in particular stress conditions and upon abscisic acid (ABA) treatment. ABA is a plant hormone important for plant growth and stress responses. During stress ABA is perceived by PYR/PYL/RCAR receptors, inhibiting protein phosphatases PP2Cs thereby enabling SNRK2s kinases to start downstream phosphorylation cascades and signaling. PYL9, one of the ABA receptors was identified as an interacting partner for ArathEULS3. Promoter::GUS activity studies revealed the expression of ArathEULS3 in the central root cylinder and the cells flanking young lateral root primordia, and showed enhanced expression in root tips after ABA treatment. Transcript levels for ArathEULS3 increased after exposure to ABA and osmotic treatments. ArathEULS3 CRISPR KO mutants served as a tool to expand the knowledge on the role of ArathEULS3 in plant development. KO lines revealed a longer root system compared to WT plants, and showed reduced sensitivity to ABA, salt, and osmotic conditions. Additionally it was noted that the KO mutants had more emerged lateral roots when grown in high osmotic conditions. Together these data suggest that ArathEULS3 may be an important player in ABA responses in roots.


Allogeneic stem cell transplantation in paroxysmal nocturnal hemoglobinuria.
In the era of eculizumab, identifying patients with paroxysmal nocturnal hemoglobinuria who may benefit from allogeneic stem cell transplantation is challenging. We describe the characteristics and overall survival of 211 patients transplanted for paroxysmal nocturnal hemoglobinuria in 83 EBMT centers from 1978 to 2007. Next, we conducted a comparison with a cohort of 402 non-transplanted patients with paroxysmal nocturnal hemoglobinuria diagnosed between 1950 and 2005 in 92 French centers. We compared the occurrence of complications (i.e. thromboembolism and aplastic anemia) using either an individual or a stratum-matching procedure. After a median follow-up of 5 years, the 5-year overall survival rate ± standard error (%) was 68 ± 3 in the transplanted group (54 ± 7 in the case of thromboembolism, 69 ± 5 in the case of aplastic anemia without thromboembolism and 86 ± 6 in the case of recurrent hemolytic anemia without thromboembolism or aplastic anemia). Only thromboembolism as the indication for transplantation was associated with worse outcome (P=0.03). We identified 24 pairs of transplanted and non-transplanted patients with thromboembolism for the matched comparison, with worse overall survival for the transplanted patients (hazard ratio=10.0; 95% confidence interval, 1.3-78.1; P=0.007). This was confirmed by the global matching procedure (P=0.03). As regards aplastic anemia without thromboembolism, 30 pairs were identified for the matched comparison. It was not observed that transplanted patients had a significantly worse overall survival (hazard ratio=4.0; 95% confidence interval, 0.9-18.9; P=0.06). A global matching procedure was not feasible. Allogeneic stem cell transplantation is probably not a suitable treatment option for life-threatening thromboembolism in paroxysmal nocturnal hemoglobinuria.


[Ossiculoplasty with KURZ titanium prosthesis].
Report the functional and anatomic results of ossicular reconstruction by titanium prosthesis. Retrospective chart reviews were performed for 111 patients who had undergone titanium ossicular implants between November 1998 and 2002 (61 PORP, 50 TORP). The anatomical and audiometric data were analyzed on average at 3 and 20 months. At 20 months, the improvement of air-bone-gap mean was 12.7 dB with better results at low frequencies. The global success rate was 66% (PORP 77%, TORP 52%). It decreased significantly in the open techniques. Extrusion rate was low (2/111) and the labyrinthization rate was 3.6%. Twenty patients required a surgical revision (18%). In 9 patients, the prosthesis was too short. At long-term follow-up, the gains were stable in 60 patients, improved in 32 patients and worsened in 19 patients. The success rate is higher in the group of the PORP with the closed technique. The stability of the TORP in open technique still remains problematic. In all cases, the risk of extrusion requires a large cartilage graft recovering the plate of the prosthesis. The high rate of luxation (9/111 prosthesis too short) has led us to increase slightly the length of the prosthesis (+1.22 mm mean).


Urinary Excretion of Tetrodotoxin Modeled in a Porcine Renal Proximal Tubule Epithelial Cell Line, LLC-PK₁.
This study examined the urinary excretion of tetrodotoxin (TTX) modeled in a porcine renal proximal tubule epithelial cell line, LLC-PK₁. Time course profiles of TTX excretion and reabsorption across the cell monolayers at 37 °C showed that the amount of TTX transported increased linearly for 60 min. However, at 4 °C, the amount of TTX transported was approximately 20% of the value at 37 °C. These results indicate that TTX transport is both a transcellular and carrier-mediated process. Using a transport inhibition assay in which cell monolayers were incubated with 50 µM TTX and 5 mM of a transport inhibitor at 37 °C for 30 min, urinary excretion was significantly reduced by probenecid, tetraethylammonium (TEA), l-carnitine, and cimetidine, slightly reduced by p-aminohippuric acid (PAH), and unaffected by 1-methyl-4-phenylpyridinium (MPP+), oxaliplatin, and cefalexin. Renal reabsorption was significantly reduced by PAH, but was unaffected by probenecid, TEA and l-carnitine. These findings indicate that TTX is primarily excreted by organic cation transporters (OCTs) and organic cation/carnitine transporters (OCTNs), partially transported by organic anion transporters (OATs) and multidrug resistance-associated proteins (MRPs), and negligibly transported by multidrug and toxic compound extrusion transporters (MATEs).


Understanding family motivations and barriers to participation in community-based programs for overweight youth: one program model does not fit all.
Successful obesity intervention efforts depend on effective recruitment and retention, an ongoing challenge for community-based programs. We sought to provide insights into the most salient factors affecting family enrollment and retention in community-based programs for overweight youth and their families. We especially sought to understand potentially modifiable program factors affecting participation. : We conducted semistructured, in-depth, face-to-face interviews with parents of overweight children within 1 year of referral to a public health grant-funded community-based healthy lifestyle promotion program. Purposeful sampling was used to select participants across program sites, by level of program completion, and child age and sex. Transcribed interviews were coded independently by 2 staff with a structured codebook and then analyzed by themes through an iterative process using Atlas.ti. The Integrative Model of Behavior served as an orienting theoretical framework. Community-based child obesity intervention program in King County, Washington. Twenty-three parents from diverse socioeconomic backgrounds were interviewed, of which 10 completed the program, 9 did not complete, and 4 did not enroll. Parent-reported factors related to enrollment and retention. Key parent reasons for program enrollment included: (a) addressing both eating and activity, (b) concern about child's weight, (c) seeking help outside the family, and (d) structured parent-child time. Parents perceived a lack of child motivation to enroll; some youth initially opposed attending, which was overcome through positive program experience. All families described barriers to attending, and some identified specific strategies or skills they used to overcome barriers. No single program design emerged to address every family's needs. Instead, using the themes of accessibility and accountability, we present parent- recommended design options. To meet different families' needs, public health and health care agencies offering youth health promotion programs should consider providing program options that vary intensity level and weight loss emphasis.


Associations between genotypes at codon 171 and 136 of the prion protein gene and production traits in market lambs.
To determine whether selection for the homozygous A136 R171 genotype that confers resistance to classic scrapie infection negatively affects production traits in sheep. 996 commercial lambs obtained from 2 flocks at separate locations across 3 consecutive years. Procedures-Genotyping at codon 136 and 171 was performed by use of commercially available testing or a single-nucleotide polymorphism assay. Carcass data were collected without knowledge of genotype approximately 24 hours after slaughter by an experienced grader. The model to analyze associations between prion protein (PRNP) genotype and production traits was based on genotype, breed, or both as fixed effects and days on feed as a covariate. Average daily gain was significantly associated with only combined codons 136 and 171. In flock 1, weaning average daily gain was significantly greater in AA136 sheep than heterozygotes; the difference between QR171 and RR171 sheep, compared with QQ171 sheep, were not significant although QR171 and RR171 sheep had higher values. However, in flock 2, average daily gain was significantly greater in AV136 sheep than AA136 sheep and in QR171 sheep than QQ171 sheep. Findings suggest there is an advantage for average daily gain in lambs with an arginine allele at codon 171, but there were no other genotype effects on production traits. Thus, selection for the resistant arginine allele at codon 171 to comply with USDA scrapie eradication guidelines should not be detrimental to lamb production in commercial flocks. Effects of codon 136 on average daily gain were ambiguous.


Osmoregulation in Paramecium: in situ ion gradients permit water to cascade through the cytosol to the contractile vacuole.
In vivo K(+), Na(+), Ca(2+) and Cl(-) activities in the cytosol and the contractile vacuole fluid of Paramecium multimicronucleatum were determined in cells adapted to a number of external osmolarities and ionic conditions by using ion-selective microelectrodes. It was found that: (1) under standardized saline conditions K(+) and Cl(-) were the major osmolytes in both the cytosol and the contractile vacuole fluid; and (2) the osmolarity of the contractile vacuole fluid, determined from K(+) and Cl(-) activities only, was always more than 1.5 times higher than that of the cytosol. These findings indicate that excess cytosolic water crosses the contractile vacuole complex membrane osmotically. Substitution of choline or Ca(2+) for K(+) in the external solution or the external application of furosemide caused concomitant decreases in the cytosolic K(+) and Cl(-) activities that were accompanied by a decrease in the water segregation activity of the contractile vacuole complex. This implies that the cytosolic K(+) and Cl(-) are actively coimported across the plasma membrane. Thus, the osmotic gradients across both the plasma membrane and the membrane of the contractile vacuole complex ensure a controlled cascade of water flow through the cell that can provide for osmoregulation as well as the possible extrusion of metabolic waste by the contractile vacuole complex.


Genetic variegation of clonal architecture and propagating cells in leukaemia.
Little is known of the genetic architecture of cancer at the subclonal and single-cell level or in the cells responsible for cancer clone maintenance and propagation. Here we have examined this issue in childhood acute lymphoblastic leukaemia in which the ETV6-RUNX1 gene fusion is an early or initiating genetic lesion followed by a modest number of recurrent or 'driver' copy number alterations. By multiplexing fluorescence in situ hybridization probes for these mutations, up to eight genetic abnormalities can be detected in single cells, a genetic signature of subclones identified and a composite picture of subclonal architecture and putative ancestral trees assembled. Subclones in acute lymphoblastic leukaemia have variegated genetics and complex, nonlinear or branching evolutionary histories. Copy number alterations are independently and reiteratively acquired in subclones of individual patients, and in no preferential order. Clonal architecture is dynamic and is subject to change in the lead-up to a diagnosis and in relapse. Leukaemia propagating cells, assayed by serial transplantation in NOD/SCID IL2Rγ(null) mice, are also genetically variegated, mirroring subclonal patterns, and vary in competitive regenerative capacity in vivo. These data have implications for cancer genomics and for the targeted therapy of cancer.


Incidence and Geographical Distribution of Adrenocortical Carcinoma: Retrospective Analysis of a State Cancer Registry.
Adrenocortical carcinoma (ACC) is a rare malignancy without established association with environmental risk factors. ACC incidence is stable based on large surgical databases while referral centers data reported increasing number of cases seen. We studied ACC incidence and distribution at a county level to find potential ACC "hot spots" that could be linked to environmental exposures. A retrospective analysis of Texas Cancer Registry that included ACC patients diagnosed between 2000 and 2018. County-level heatmaps were created and compared with breast, prostate, and lung cancer. We identified 448 ACC cases during the study period. Cases were registered in 110 of the 254 counties (43.3%) in Texas, representing 92.74% of the total population. The median incidence was 23 new cases/y (range 14-33). The mean population-adjusted ACC incidence rate was 0.104 per 100 000 per year (standard deviation 0.005; 95% CI, 0.092-0.116). Seven counties (6.3%) accounted for 215 (48.0%) cases, with more than 10 cases each and median standardized incidence ratio (SIR) of 0.1 (range, 0.0-0.9). One hundred three counties (93.7%) accounted for the remaining 233 cases (52%), with fewer than 10 cases per county. The highest standardized incidence ratios were found in counties with a median population of fewer than 14 000 residents and with only one reported case. Our analysis is the first report to create ACC heatmap and could not detect any geographic clustering of ACC in Texas. The incidence of ACC remained stable and consistent with data from other large databases.


Diagnostic developments for quasicontinuous operation of the Wendelstein 7-X stellarator.
The stellarator Wendelstein 7-X will allow for quasicontinuous operation with the duration only being limited to two 30 min discharges per day, at a continuous heating power of 10 MW electron cyclotron resonance heating (ECRH) at 140 GHz, by the capacity of the cooling water reservoir. This will result in high thermal loads on all plasma facing components of 50-100 kW/m(2) from radiation alone and of up to about 500 kW/m(2) on components additionally exposed to convective loads. In high density scenarios toroidally varying ECRH stray radiation levels of 50-200 kW/m(2) need to be coped with, requiring careful material selection and different shielding and hardening techniques. Furthermore, a gradual buildup of coatings on plasma facing optical components, which without any measures being taken, would lead to high transmission losses already within a few days of long pulse operation (equivalent to about 1 year of operation in pulsed devices like JET or ASDEX-upgrade) and therefore needs to be prevented as much as possible. In addition in situ cleaning as well as absolute calibration techniques need to be developed for all plasma facing optical systems. Here we report about some of our efforts to find, for various types of diagnostics, ways to cope with these adverse effects. Moreover, we give a few examples for individual diagnostic specific issues with respect to quasicontinuous operation, such as the development of a special integrator for the magnetic diagnostics as well as special interferometer types which can cope with unavoidable vibrations and slow path length changes due to, e.g., thermal expansion of the plasma vessel.


Efficacy of a polyethylene glycol marker system in urine drug screening in an opiate substitution program.
Screening for concomitant drug consumption is necessary in opiate substitution therapy of opiate-dependent patients. Adulteration of samples is a common problem in this setting. A recently developed polyethylene glycol marker system allows reliable identification of urine samples. In this study, we aimed to compare the rates of drug detection in conventional and marker urine samples. This cross-sectional evaluation was performed in an ambulatory opiate substitution program. We studied 55 opiate-dependent patients (32 men, 23 women). In all patients we compared the rates of drugs detected in the marker urine with the most recent conventional urine control. Additionally we assessed the rate of marker urine manipulation. In the conventional urine controls, opiates and benzodiazepines were found in 3.6 and 27%, respectively, whereas in the marker urine controls, these rates were 33 and 40%, respectively. Signs of urine manipulation were present in 35%. The rates of concomitant consumption and urine manipulation were higher among the patients without than among those with take-home substitution. With the marker urine, an unexpectedly high prevalence of concomitant consumption can be found. Marker urine testing has a significantly higher sensitivity for the detection of concomitant drug use.


Effects of nitrogen fertilization and dried distillers grains supplementation: nitrogen use efficiency.
In a 3-yr study, 135 crossbred steers (330 ± 10 kg) were used in a randomized complete block design to evaluate corn dried distillers grains plus solubles (DDGS) fed to yearling steers as a substitute for forage and N fertilizer and its effect on N use efficiency in yearling steers grazing smooth bromegrass pastures. Steers were initially stocked at 6.8 animal unit months (AUM)/ha on nonfertilized smooth bromegrass pastures (CONT), at 9.9 AUM/ha on smooth bromegrass pastures fertilized with 90 kg of N/ha (FERT), or at 9.9 AUM/ha on nonfertilized smooth bromegrass pastures with 2.3 kg (DM) of DDGS supplemented daily per steer (SUPP). Paddock was the experimental unit, with 3 replications per treatment per year for 3 yr. Paddocks were strip-grazed, and put-and-take cattle were used to maintain similar grazing pressure among treatment paddocks during the 160-d grazing season. Steers consumed less forage (P < 0.01), but total N intake for SUPP was greater (P < 0.01) per steer and per hectare than for FERT, and both were greater (P < 0.01) than for CONT. Nitrogen retention for steers in the SUPP treatment was increased (P < 0.01) by 31% compared with N retention in the CONT and FERT treatments. Nitrogen retention per hectare for SUPP was 30 and 98% greater (P < 0.01) than N retention per hectare for FERT and CONT, respectively. Nitrogen excretion per steer and per hectare were also greater (P < 0.01) for SUPP than FERT, and both were increased (P < 0.01) compared with CONT. Animal N use efficiency was similar (P = 0.29) for steers in the CONT, FERT, and SUPP treatments. However, system-based N use improved (P < 0.01) by 144% for SUPP compared with FERT. The DDGS increased N intake and N excretion in yearling steers. However, because of improvements in BW gain and increases in stocking rate of pastures, DDGS can be a useful tool to increase the efficiency of N use in smooth bromegrass grazing systems.


Does malrotation of components correlate with patient dissatisfaction following secondary patellar resurfacing?
The aim of our study was to identify whether there was any correlation between the outcome of secondary patellar resurfacing and malrotation of either the femoral or tibial component. We identified patients that underwent secondary patellar resurfacing following previous primary total knee arthroplasty (TKA) at a single, large orthopaedic department. Patients were reviewed for range of movement, satisfaction, health status and knee function. CT scanning was performed, assessing rotational alignment of the components. Twenty-one patients (23 knees) were reviewed. Nine out of 21 (39%) were satisfied while 14 (61%) remained dissatisfied after the secondary patellar resurfacing. There were no complications after the secondary procedure. All knees were internally rotated. The mean femoral internal rotation in the satisfied group was 0.92°, and in the dissatisfied group was 2.88° of internal rotation. In the dissatisfied group eight out of 14 TKAs were in >3° femoral internal rotation compared with only one in nine TKAs in the satisfied group (p<0.05). Investigation for malrotation should be considered in patients with post-operative pain, especially anteriorly, causing significant dissatisfaction amongst patients following TKA. This is especially true if the patella has not been primarily resurfaced and secondary resurfacing is being considered. Patients with more than 3(°) of femoral internal rotation undergoing secondary patella resurfacing should be warned of the possibility of a poor outcome. It may well be that if the underlying problem is component malrotation, revision knee replacement may lead to a more satisfactory outcome than secondary resurfacing alone. Level of Evidence III.


G-Protein-Coupled Receptor 5 (LGR5) Overexpression Activates β-Catenin Signaling in Breast Cancer Cells via Protein Kinase A.
BACKGROUND Targeting cancer stem cells (CSCs) in breast cancer (BrCa) may improve treatment outcome and patient prognosis. Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) is a well-recognized adult stem cell and CRC marker, and previous reports have suggested the cancer-promoting role of LGR5 in breast cancer, but the mechanism remains unclear. MATERIAL AND METHODS Potential LGR5-associating genes were explored using STRING database, and LGR5 overexpression and knockdown was constructed in MCF-7 and MDA-MB-453 human BrCa cells, respectively. PKA catalytic subunit activation and PKA kinase activity in human BrCa cells was examined by Western blot and PKA kinase activity assay, respectively. Protein expression level or activation of β-catenin and GSK-3β in human BrCa cells was investigated by Western blot. Cell proliferation, colony formation, Transwell migration, cisplatin sensitivity, and in vivo tumor formation of human BrCa cells were examined. RESULTS LGR5 overexpression increased PKA activation and its kinase activity in human BrCa cells, which was decreased by LGR5 knockdown. LGR5 expression level or PKA kinase activity were correlated with β-catenin Ser 552 phosphorylation but inversely correlated with GSK-3β Ser9 phosphorylation in human BrCa cells in vitro. LGR5/PKA increased cell proliferation, colony formation, Transwell migration, and cisplatin resistance in vitro, as well as tumor formation in vivo, of human BrCa cells. CONCLUSIONS LGR5 activates the Wnt/β-catenin signaling pathway in human BrCa cells in vitro via PKA.


MiR-323b-5p acts as a novel diagnostic biomarker for critical limb ischemia in type 2 diabetic patients.
Type 2 diabetes mellitus (T2DM) is a major contributor to peripheral artery disease (PAD), especially in cases that advance to critical limb ischemia (CLI). Accumulating evidence indicates that miRNAs play an important role in the development of PAD and T2DM. Due to the limited value of current diagnostic methods for CLI in T2DM patients, we compared the miRNA expression profiles of Chinese T2DM patients with or without CLI to find out whether distinctive miRNAs could serve as potential diagnostic biomarkers. We statistically identified 7 miRNAs (hsa-miR-200b-3p, hsa-miR-2115-3p, hsa-miR-431-5p, hsa-miR-486-5p, hsa-miR-210-3p, hsa-miR-1264, hsa-miR-323b-5p) which were up-regulated in the CLI group, whereas other 4 miRNAs (hsa-miR-5579-3p, hsa-miR-665, hsa-miR-4285, hsa-miR-500a-3p) were down-regulated. Our validation test suggested a relatively high diagnostic accuracy of serum hsa-miR-323b-5p levels for the detection of CLI in T2DM patients, with a sensitivity of 62.67% and a specificity of 80.65%. The area under the curve (AUC) for miR-323b-5p + confounding risk factors was 0.94 (95% CI: 0.884-0.994, P < 0.001), which was higher than that for miR-323b-5p. Taken together, our results indicate that circulating hsa-miR-323b-5p could be a promising serum biomarker for the diagnosis of critical limb ischemia in type 2 diabetic patients.


[Russia and Halle reciprocity in medicine of the 18th century. Correspondence, scientific communication and reception].
In the history of the interrelations of Halle and Russia in medicine during the 18th century Francke's Foundations, the Faculty of Medicine and the Academia Naturae Curiosorum are important institutions. The correspondence of these three institutions with the partners in Russia became remarkable for the scientific communication and reception. The activities of the working teams which were embedded in these authoritative bodies were scarcely inferior in importance to the centres of enlightenment of that time working in other towns (for instance in Leipzig). In the field of medicine Halle occupied a leading position for the early knowledge about Russia.


Simulated low-dose computed tomography in oncological patients: a feasibility study.
Image quality of chest and abdominal computed tomographic (CT) scans was evaluated at different doses to assess the lowest value of x-ray dose at which the image quality was not being affected. Using multislice CT (MSCT), 29 patients who submitted to follow-up examinations were examined using a combined MSCT protocol of the chest and the abdomen on 4-raw MSCT (Siemens, Erlangen, Germany). For each examination, approximately 120 mL of contrast agent (Bracco-Altana, Konstanz, Germany) was applied intravenously. The raw data were transferred to an external personal computer equipped with an image reconstruction software (CardioRecon 6; Siemens, Forchheim, Germany) to simulate 5 different dose levels. To simulate them correctly, a milliampere second-dependent noise was added to every image, so that the changes in a current-time product could be imitated. The images were compared in consensus by 2 radiologists who were not informed about the technical scanning parameters, that is, dose parameters, and were graded in 4 different subcategories on a 1-to-5-point scale. For statistical analysis, the Friedman test was used. Additional evaluations for lesions smaller than 1.0 cm were performed and analyzed separately. For image noise, there was a significant change between 40 and 60 mA s. For lesion detection, there was no significant change. The contour of the small objects did not differ between 90, 60, and 40 mA s. However, a dose reduction to 30 mA s had a significant effect. The contrast did not differ between 90, 60, 40, and even down to 30 mA s. Only a maximal dose reduction to 20 mA s had a significant effect on the contrast. The level of noise was most sensitive to the current. Whereas a dose reduction to 60 mA s did not yet have a significant effect, there was a significant increase of noise at 40 mA s. The MSCT can be applied with a lower dose than that usually selected in examinations at present to follow-up and stage the oncological patients adequately.


Sports Medicine: Fractures, Sprains, and Other Musculoskeletal Injuries.
Family physicians commonly treat athletes with simple fractures and other musculoskeletal injuries that require temporary immobilization. Certain fractures (eg, intraarticular, multiple, open, associated with dislocations or tendon injury) typically are managed by orthopedic subspecialists. During the healing process, a custom-molded or prefabricated orthopedic support, known as an orthosis, may be used to support the injured area and prevent reinjury. To reduce the risk of complications that may develop from orthosis use, timely follow-up is required. Proficiency in specific orthotic applications, such as splint application and cast making, requires continued skill maintenance. Patients with suspected scaphoid bone fractures should initially undergo splinting or bracing in a thumb spica device until fracture is definitively diagnosed or ruled out. Injuries to the extensor tendons of the finger are managed with continuous extension splinting for 4 to 6 weeks. Patients with grade I and II medial collateral ligament injuries heal well with use of a hinged knee brace for 4 to 6 weeks. There is no good evidence for use of a brace after anterior cruciate ligament repair. Lateral ankle sprains are common, and bracing is an integral component of functional rehabilitation and injury prevention. There are specific requirements related to reimbursement for orthoses prescriptions.


Risk Perception and Willingness to Work Among Doctors and Medical Students of Karachi, Pakistan During the COVID-19 Pandemic: A Web-Based Cross-Sectional Survey.
During the timeline of twenty years, several epidemics and pandemics have occurred. Yet, a consistent feature of these public health crises is the surge in the demand for healthcare services exceeds the availability. A cross-sectional web-based survey was conducted in the month of June and July 2020 in Karachi, Pakistan. The study participants included doctors and medical students residing in Karachi. Out of 187 doctors, 74.3% were working during the COVID-19 pandemic, of which 58.3% were willing to work. Out of 200 medical students, 93.5% were not volunteering during the COVID-19 pandemic, of which 46% were willing to volunteer. Doctors strongly agreed that they would be willing to work during the COVID-19 pandemic if they were healthy and able to do so (57.2%), if they were provided personal protective equipment (PPE) (51.3%), and if they were guaranteed coverage of treatment cost if they get infected while working (57.8%). Medical students strongly agreed that they would be willing to volunteer during the COVID-19 pandemic if they were provided PPE (49.0%), and if their parents were supportive of their decision to volunteer (44.5%). Most doctors (54.5%) felt that they were extremely likely to get infected while working during the COVID-19 pandemic and 59.4% felt that in turn, they were extremely likely to infect their families as well. Most medical students (40.5%) felt that they were somewhat likely to get infected while volunteering during the COVID-19 pandemic and 55.5% felt that in turn, they were extremely likely to infect their family as well. In the event of infection with COVID-19, 51.3% doctors and 42.0% medical students felt that they would recover without hospitalization. Since future pandemics are likely, we encourage health-care policymakers to utilize the findings of this study to create a sustainable pandemic response.


[Papillary fibroelastoma in the cardiologist's practice].
The article presents a clinical case of diagnosis and treatment of a rare disease, multiple papillary fibroelastoma associated with a relapse and a complication in the form of cardioembolic stroke. The authors stressed difficulties in diagnostics of this disease and a special role of the physician-patient interaction.


Proliferative cell nuclear antigen in postradiotherapy prostate biopsies.
To determine if staining for proliferative cell nuclear antigen (PCNA) can distinguish between biologically active and inactive "residual tumor" in postradiotherapy prostate biopsies by correlating PCNA staining with clinical outcome. Since July 1990 all patients treated at the General Division of the Ottawa Regional Cancer Center with radical external beam radiotherapy for prostate cancer have had systematic transrectal ultrasound and transrectal ultrasound-guided biopsies beginning 12 months postradiotherapy. One hundred sixty-two patients have had 278 transrectal ultrasounds with four to seven biopsy specimens per examination. All biopsies were stained for prostate specific antigen and prostatic acid phosphatase. Keratin 903 was used to distinguish radiation atypia in benign glands from residual cancer. PCNA staining was done on all suspicious biopsies. Stage distribution was 31 T1b, 35 T2a, 61 T2b, and 35 T3-4. Median follow-up was 32 months (range 13-74). Negative biopsies have been obtained in 83% of T1b and T2a tumors and 70% of T2b and T3-4. Twenty-six tumors have recurred locally (T1b: 10%, T2a: 3%, T2b: 21%, T3-4: 26%), six with concurrent distant metastases. Of these 26 local failures, 23 had positive PCNA (mean 15.4 nuclei per 100) and three could not be determined (insufficient tissue). In 34 patients showing residual carcinoma at the first postradiotherapy biopsy, subsequent negative biopsies were obtained at a median of 25 months. Proliferative cell nuclear antigen staining could be performed in 23 of these 34 patients. Sixty-five percent (15/23) were negative on the first biopsy, indicating a nonproliferative state. In those with PCNA positive residual on initial biopsy, none retained PCNA staining on subsequent negative biopsies. One patient with an initial PCNA negative biopsy has failed locally. Proliferative cell nuclear antigen staining is useful in postradiotherapy prostate biopsies. Negative PCNA in a positive biopsy predicts (83-97%) for eventual resolution of tumor. Positive PCNA correlates with local failure (49-79%), but when present in an early biopsy (12-18 months), may still disappear.


Morphological Characteristics and Phylogenetic Trends of Trematode Cercariae in Freshwater Snails from Nakhon Nayok Province, Thailand.
The prevalence of cercarial infection in freshwater snails and their evolutionary trends were studied in Nakhon Nayok province, Thailand. A total of 2,869 individual snails were examined for parasitic infections. The results showed that 12 snail species were found to host larval stages of trematodes with an overall prevalence of 4.7%. The infected specimens included 7 types at the cercarial stage; cercariae, megalurous cercariae, echinostome cercariae, furcocercous cercariae, parapleurolophocercous cercariae, virgulate cercariae, and xiphidiocercariae. Regarding molecular identification, ITS2 sequence data of each larval trematode were analyzed, and a dendrogram was constructed using the neighbor-joining method with 10,000 replicates. The dendrogram was separated into 6 clades (order/family), including Echinostomatida/Echinostomatidae, Echinostomatida/Philophthalmidae, Opisthorchiida/Heterophyidae, Plagiorchiida/Prosthogonimidae, Plagiorchiida/Lecithodendriidae, and Strigeatida/Cyathocotylidae. These findings were used to confirm morphological characteristics and evolutionary trends of each type of cercariae discovered in Nakhon Nayok province. Furthermore, this investigation confirmed that the ITS2 data of cercariae could be used to study on phylogenetic relationships or to determine classification of this species at order and/or family level when possible.


Saliva: its role in health and disease.
Saliva serves many functions in the upper digestive tract, with its roles in esophageal physiology, digestion, and gastric cytoprotection having been documented by many studies in the recent literature. Understanding the multiple functions of saliva and the consequences of its absence is of paramount importance to gastroenterologists. We present a clinically oriented review of the literature on the role of saliva in the upper gastrointestinal tract and review the many problems associated with lack of saliva. We also discuss the management of xerostomia.


Post-stroke depression, executive dysfunction and functional outcome.
The early diagnosis of vascular cognitive impairment has been challenged and executive control function has been suggested to be a rational basis for the diagnosis of vascular dementia. We sought to examine the correlates of executive dysfunction in a well-defined stroke cohort. A group of 256 patients from a consecutive cohort of 486 patients with ischaemic stroke, aged 55-85 years, was subjected to a comprehensive neuropsychological examination 3-4 months after ischaemic stroke and 188 of them in addition to detailed psychiatric examination. Basic and complex activities of daily living (ADLs) (bADLs and cADLs) post-stroke were assessed. The DSM-III-R criteria were used for the diagnosis of the depressive disorders. Altogether 40.6% (n=104) of the patients had executive dysfunction. The patients with executive dysfunction were older, had lower level of education, were more often dependent, did worse in bADLs and cADLs, had more often DSM-III dementia, had worse cognition as measured by Mini Mental State Examination (MMSE) and were more depressed as measured by the BECK depression scale, but not with the more detailed psychiatric evaluation. They had more often stroke in the anterior circulation and less often in the posterior circulation. The independent correlates of executive dysfunction were cADLs (OR 1.1, 95% CI 1.03-1.16), each point of worsening in cognition by MMSE (OR 1.7, 95% CI 1.42-1.97) and stroke in the posterior circulation area (OR 0.4, 95% CI 0.18-0.84). Clinically significant executive dysfunction is frequent after ischaemic stroke and is closely connected with cADLs and to overall cognitive status but could be distinguished from depression by detailed neuropsychological examination. Executive measures may detect patients at risk of dementia and disability post-stroke.


The Drosophila splicing regulator sex-lethal directly inhibits translation of male-specific-lethal 2 mRNA.
Male-specific expression of the protein male-specific-lethal 2 (MSL-2) controls dosage compensation in Drosophila. msl-2 gene expression is inhibited in females by Sex-lethal (SXL), an RNA binding protein known to regulate pre-mRNA splicing. An intron present at the 5' untranslated region (UTR) of msl-2 mRNA contains putative SXL binding sites and is retained in female flies. Here we show that SXL plays a dual role in the inhibition of msl-2 expression. Cotransfection of Drosophila Schneider cells with an SXL expression vector and a reporter containing the 5' UTR of msl-2 mRNA resulted in retention of the 5' UTR intron and efficient accumulation of the unspliced mRNA in the cytoplasm, where its translation was blocked by SXL, but not by the intron per se. Both splicing and translation inhibition by SXL were recapitulated in vitro and found to be dependent upon SXL binding to high-affinity sites within the intron, showing that SXL directly regulates these events. Our data reveal a coordinated mechanism for the regulation of msl-2 expression by the same regulatory factor: SXL enforces intron retention in the nucleus and subsequent translation inhibition in the cytoplasm.


Fixation of the femoral head prosthesis with methylmethacrylate.
The techniques used in fixation of the femoral prosthesis in total hip replacement are often based on empiricism and raise questions about: venting the medullary canal with a catheter during the insertion of cement; the inclusion of blood into cement during insertion with possible deleterious effects; recementing a prosthesis; increased strength imparted to an endoprosthesis by cement itself. Biological variables are minimized by the use of paired wet formalin preserved femurs; one acting as control. A single static load was applied until failure. The results show trends and gross differences and are not statistically evaluated. The methylmethacrylate-bone-metal system consistently produces good results with reasonable but not careless variations in technique. A hemiprosthesis is presented which can easily be converted to a standard Charnley prosthesis by using a small amount of fresh cement.


An Analysis of Patient Safety Incident Reports Associated with Electronic Health Record Interoperability
Background: With the widespread use of electronic health records (EHRs) for many clinical tasks, interoperability with other health information technology (health IT) is critical for the effective delivery of care. While it is generally recognized that poor interoperability negatively impacts patient care, little is known about the specific patient safety implications. Understanding the patient safety implications will help prioritize interoperability efforts around architectures and standards. Objectives: Our objectives were to (1) identify patient safety incident reports that reflect EHR interoperability challenges with other health IT, and (2) perform a detailed analysis of these reports to understand the health IT systems involved, the clinical care processes impacted, whether the incident occurred within or between provider organizations, and the reported severity of the patient safety events. Methods: From a database of 1.735 million patient safety event (PSE) reports spanning multiple provider organizations, 2625 reports that were indicated as being health IT related by the event reporter were reviewed to identify EHR interoperability related reports. Through a rigorous coding process 209 EHR interoperability related events were identified and coded. Results: The majority of EHR interoperability PSE reports involved interfacing with pharmacy systems (i.e. medication related), followed by laboratory, and radiology. Most of the interoperability challenges in these clinical areas were associated with the EHR receiving information from other health IT systems as opposed to the EHR sending information to other systems. The majority of EHR interoperability challenges were within a provider organization and while many of the safety events reached the patient, only a few resulted in patient harm. Conclusions: Interoperability efforts should prioritize systems in pharmacy, laboratory, and radiology. Providers should recognize the need to improve EHRs interfacing with other health IT systems within their own organization.


Shifting set about task switching: behavioral and neural evidence for distinct forms of cognitive flexibility.
Task switching is an important aspect of cognitive control and understanding its underlying mechanisms is the focus of considerable research. In this paper, we contrast two different kinds of task switching paradigms and provide evidence that different cognitive mechanisms underlie switching behavior depending on whether the switch is between sets of rules (rule switch) or sets of features presented simultaneously (perceptual switch). In two experiments, we demonstrate that behavioral effects (Experiment 1) and neural recruitment (Experiment 2) vary with the type of switch performed. While perceptual switch costs occurred when the alternative feature set was physically present, rule switch costs were observed even in their absence. Rule switching was also characterized by larger target repetition effects and by greater engagement of the dorsolateral prefrontal cortex. In contrast, perceptual switching was associated with greater recruitment of the parietal cortex. These results provide strong evidence for multiple forms of switching and suggest the limitations of generalizing results across shift types.


Impact of solar background radiation on the accuracy of wind observations of spaceborne Doppler wind lidars based on their orbits and optical parameters.
Due to the quantum properties of light, solar background radiation (SBR) is the main source of noise in daytime wind observations of spaceborne Doppler wind lidars (DWLs). In previous works, the impact of SBR on the observation accuracy of spaceborne lidars was assessed mainly using the default or worst-case scenarios. We assessed the impact of SBR on the observations of spaceborne DWLs using the global distributions of SBR in summer and winter, which were obtained based on their orbit parameters, view geometry and optical parameters. Three experiments illustrate that the uncertainty in wind observations increases with an increase in the quantiles of SBR. The uncertainties of the whole profiles of wind are greater than 2 m s-1 in the troposphere and 3 m s-1 in the stratosphere when the quantile of the SBR is greater than 85% in summer and 95% in winter, which do not satisfy the accuracy expectations of the European Space Agency (ESA) for spaceborne DWLs. The facts indicate that the impact of SBR cannot be negligible for the observations of spaceborne DWLs. Based on the orbit parameters, view geometry, and optical parameters of new spaceborne DWLs, engineers can assess the impact of SBR on the accuracy of wind observations from a global perspective using the method proposed in this paper.


Methodological and clinical aspects of alloimmunization after granulocyte transfusion in patients undergoing allogeneic stem cell transplantation.
In allogeneic hematopoietic stem cell transplantation (HSCT), granulocyte transfusions (GT) may be required in immunocompromised, neutropenic patients. In this context, alloimmunization against alloantigens may occur and affect HSCT outcome. Anti-human leukocyte antigen (HLA) and -MHC class I chain related antigens A (MICA) antibody response after the administration of GT in 29 patients undergoing allogeneic HSCT (n = 27) encompassing 109 sera was investigated by multianalyte microbead assay before and up to 6 month after HSCT. Anti-HLA class I and II antibodies emerged de novo in 11 (38%) and 4 (14%) patients, respectively. Similarly, preformed antibodies were observed in four cases (14%) for anti-HLA class I and also four patients for anti-HLA class II antibodies. Anti-MICA antibodies were observed in eight granulocyte recipients of which three patients developed anti-MICA antibodies after GT, whereas preformed antibodies were seen in five patients. The conversion to positivity for any of the investigated antibodies did not significantly affect overall survival or the incidence of GVHD. GT-associated alloantibody conversion observed did not significantly correlate with outcome. Thus, surveillance of anti-HLA antibodies in the course of GT in the context of HSCT may not be required routinely. The role of MICA antibodies in HSCT and GT, however, requires further study.


Risk factors and novel predictive models for metastatic neuroblastoma in children.
Neuroblastoma (NB) with distant metastasis (DM) is a high-risk condition with a poor prognosis. Early identify the risk and prognostic differences of DM in children, which is helpful for the development of clinical diagnosis and treatment. The study cohort included patients with NB in surveillance, epidemiological, and final outcome databases between 2010 and 2018. To identify the risk and prognostic factors for DM, both univariate and multivariate logistic and Cox regression analyses were conducted. In addition, we created and verified three online clinical prediction models. Finally, we assess the performance of the proposed predictive model. Among the 1224 children with NB included in the study, 599 developed DM. Primary site is the most important factor affecting metastasis and prognosis. The training and validation groups of the diagnostic nomograms had area under curves (AUC) values of 0.872 and 0.824, respectively. In addition, in the training group, the AUC values at 12, 36, and 60 months were 0.68, 0.71, and 0.75 for the OS nomogram and 0.70, 0.72, and 0.75 for the CSS nomogram. In the validation group, the AUC values at 12, 36, and 60 months were 0.68, 0.72, and 0.70 for the OS nomogram and 0.67, 0.71, and 0.69 for the CSS nomogram, respectively. Calibration curve and decision curve analyses revealed good performance of the nomogram. The nomogram developed in this study could appropriately predict DM and assess its prognosis in patients with NB.


Intra-operative detection of motor pathways using a simple electrode provides safe brain tumor surgery.
Preservation of motor function is very important in patients who require resection of tumors adjacent to the primary motor cortex and pyramidal tract. Resection of tumors in the white matter adjacent to motor cortices routinely requires electrical stimulation of the tumor cavity. However, efforts to detect the pyramidal tract often result in postoperative neurological deterioration. To overcome this problem, a novel bipolar needle electrode was developed which enabled the identification of motor pathways by inserting it into the white matter. Motor-evoked potentials were induced by electrical stimulation with this electrode when it was inserted toward the estimated motor pathway from the resected tumor cavity. The scale on the needle indicated the approximate distance from the tumor cavity wall to the pyramidal tract. We conclude that the motor pathways can be preserved by detecting them neurophysiologically before they are destroyed by tumor resection.


Failure of two distinct anti-apoptotic approaches to reduce mortality in experimental cerebral malaria.
Cerebral malaria is responsible for a high proportion of mortality in human Plasmodium falciparum infection. Previous studies have reported the presence of apoptosis in endothelial cells, astrocytes, neurons, and glial cells in experimental murine cerebral malaria caused by infection with Plasmodium berghei ANKA. Using this model, we tested two strategies, which have been shown to improve survival in murine models of sepsis: 1) treatment with z-VAD, a pancaspase inhibitor; and 2) overexpression of Bcl-2 using transgenic mice expressing human Bcl-2 (which prevents the release of apoptotic mediators from the mitochondria) from a myeloid cell promoter. Neither of these anti-apoptotic strategies, previously shown to provide therapeutic benefit in sepsis, improved survival in experimental cerebral malaria.


1997 SCVIR Gary J. Becker Young Investigator Award paper. A transluminally created abdominal aortic aneurysm model.
To develop a stable, transluminally created abdominal aortic aneurysm (AAA) within a live animal model. Eight mongrel dogs were utilized to evaluate a new, catheter-based technique for the creation of an AAA. With use of a standard angioplasty balloon and a balloon-expandable intravascular metallic stent, the infrarenal abdominal aorta was overdilated to twice its measured diameter into a fusiform shape AAA in eight dogs. At 30 days, aortography was performed, the dogs were killed, and the aorta was resected and evaluated for histopathology. Seven of the eight dogs that underwent transluminal AAA creation survived the initial procedure. A stable, fusiform AAA was successfully created in these seven dogs. At 30 days, repeat angiography and histologic examination confirmed that the seven AAAs were still twice the diameter of the normal aorta (a four-fold increase in luminal area), that the branch arteries remained patent, and that the lumen was endothelialized. One of the eight dogs was killed 9 hours after the procedure because of inability to awaken from anesthesia. Gross and histopathologic results in this one dog also demonstrated an intact aorta containing an AAA. A stable, infrarenal AAA model can be successfully created in the canine species with use of standard catheter-based techniques and equipment. This model can be used to test emerging endovascular treatments of AAA.


Characterization of K+ and Cl- conductances in apical membrane vesicles from stimulated rabbit oxyntic cells.
K+ and Cl- conductance pathways in apical membrane vesicles (SA vesicles) of stimulated oxyntic cells have been characterized. SA vesicles were prepared from rabbit fundic mucosa after stimulation of acid secretion with histamine. Conductive K+ and Cl- fluxes were assayed by several methods: by their effects on pH gradient formation by endogenous H(+)-K(+)-ATPase, by the protonophore-induced dissipation of preformed pH gradients, and by the effects of channel blockers. pH gradient formation by H(+)-K(+)-ATPase required K+ and was greatly reduced when the permeant anion chloride was replaced by gluconate or sulfate. In the presence of 75 mM K+, 1 mM Cl- was sufficient for generation of near maximal pH gradients, as was 5 mM K+ in the presence of 75 mM Cl-. At all K+ and Cl- concentrations tested, the ATP-generated formation of pH gradients was inhibited and the dissipation of these pH gradients stimulated by the protonophore tetrachlorosalicylanilide (TCS). Similar effects of TCS were also seen when Cl- was replaced by impermeant anions. Both processes were blocked by the K+ channel inhibitor Ba2+. The Ki for Ba2+ inhibition of pH gradient formation was 1.5 microM at 5 mM K+ and was proportional to the 3rd power of the K+ concentration. At 75 mM K+ the Cl- channel blocker diphenylamine-2-carboxylate inhibited ATP-dependent pH gradient formation when the Cl- concentration was 1 mM; however, when the Cl- concentration was greater than 5 mM no inhibition was observed. The membrane potential-sensitive dye DISC (5) was used to measure membrane potential generated by K+ gradients.(ABSTRACT TRUNCATED AT 250 WORDS)


Ironing Out Genes in the Environment: An Experimental Study of the DNA-Goethite Interface.
DNA fate in soil plays an important role in the cycling of genetic information in the environment. Adsorption onto mineral surfaces has great impact on this function. This study probes the kinetics, equilibrium behavior and bonding mechanisms associated with adsorption of DNA onto goethite, a common soil mineral. Surface sensitive ATR-FTIR and XPS approaches are applied to directly characterize the DNA-goethite interface. Adsorption kinetics follow a pseudo-first-order model, suggesting adsorption rate is surface limited. Adsorption rate constants increase with DNA concentration, ranging from 3.29 × 10-3 to 3.55 × 10-1 min-1. Equilibrium adsorption, as monitored by ATR-FTIR and XPS, follows the Langmuir model, with a high affinity of DNA for goethite observed (K = 1.25 × 103 and 9.48 × 102 mL/mg for ATR-FTIR and XPS, respectively). ATR-FTIR and XPS characterization of the structure of surface adsorbed DNA demonstrates inner-sphere coordination between backbone phosphate groups of DNA and goethite. Furthermore, adsorbed DNA retains a B-form, suggesting the DNA helix adsorbs on goethite without degradation or alteration to helical structure, despite binding of backbone phosphate groups. This work advances our understanding of the environmental behavior of DNA by characterizing the mechanism of adsorption onto a prominent soil mineral.


Overexpression of B-cell lymphoma 6 alters gene expression profile in a myeloma cell line and is associated with decreased DNA damage response.
B-cell lymphoma 6 (BCL6) attenuates DNA damage response (DDR) through gene repression and facilitates tolerance to genomic instability during immunoglobulin affinity maturation in germinal center (GC) B cells. Although BCL6 expression is repressed through normal differentiation of GC B cells into plasma cells, a recent study showed the ectopic expression of BCL6 in primary multiple myeloma (MM) cells. However, the functional roles of BCL6 in MM cells are largely unknown. Here, we report that overexpression of BCL6 in a MM cell line, KMS12PE, induced transcriptional repression of ataxia telangiectasia mutated (ATM), a DDR signaling kinase, which was associated with a reduction in γH2AX formation after DNA damage. In contrast, transcription of known targets of BCL6 in GC B cells was not affected, suggesting a cell type-specific function of BCL6. To further investigate the effects of BCL6 overexpression on the MM cell line, we undertook mRNA sequence analysis and found an upregulation in the genomic mutator activation-induced cytidine deaminase (AID) with alteration in the gene expression profile, which is suggestive of de-differentiation from plasma cells. Moreover, interleukin-6 exposure to KMS12PE led to upregulation of BCL6 and AID, downregulation of ATM, and attenuation of DDR, which were consistent with the effects of BCL6 overexpression in this MM cell line. Taken together, these results indicated that overexpression of BCL6 alters gene expression profile and confers decreased DDR in MM cells. This phenotypic change could be reproduced by interleukin-6 stimulation, suggesting an important role of external stimuli in inducing genomic instability, which is a hallmark of MM cells.


New Doppler techniques for the evaluation of regurgitant and shunt volumes.
The aim of this review is to highlight some relatively new applications of Doppler echocardiography in children. Recent observations of flow dynamics through a restricted orifice have revealed that flow through an opening converges toward the orifice in a series of proximal isovelocity hemispheric surfaces. The flow convergence region can be demonstrated by Doppler echocardiography as a color mosaic on the ventricular side of the mitral valve in the presence of mitral regurgitation and on the left-ventricular side of a ventricular septal defect with left-to-right shunting. The continuity principle dictates that regurgitant flow rate can be calculated as the product of the hemispheric surface area of the flow convergence region and the velocity at that hemispheric surface. Using this principle, investigators have made quantitative flow measurements of mitral regurgitation, ventricular septal defect flow and aortic regurgitation. These studies demonstrate that this new technique of noninvasive quantification has the potential of providing direct measures of regurgitant and shunt flow. However, further validation in the pediatric population is needed before it can be incorporated into routine clinical practice.


Correctors promote maturation of cystic fibrosis transmembrane conductance regulator (CFTR)-processing mutants by binding to the protein.
The most common cause of cystic fibrosis (CF) is defective folding of a cystic fibrosis transmembrane conductance regulator (CFTR) mutant lacking Phe(508) (DeltaF508). The DeltaF508 protein appears to be trapped in a prefolded state with incomplete packing of the transmembrane (TM) segments, a defect that can be repaired by expression in the presence of correctors such as corr-4a, VRT-325, and VRT-532. To determine whether the mechanism of correctors involves direct interactions with CFTR, our approach was to test whether correctors blocked disulfide cross-linking between cysteines introduced into the two halves of a Cys-less CFTR. Although replacement of the 18 endogenous cysteines of CFTR with Ser or Ala yields a Cys-less mutant that does not mature at 37 degrees C, we found that maturation could be restored if Val(510) was changed to Ala, Cys, Ser, Thr, Gly, Ala, or Asp. The V510D mutation also promoted maturation of DeltaF508 CFTR. The Cys-less/V510A mutant was used for subsequent cross-linking analysis as it yielded relatively high levels of mature protein that was functional in iodide efflux assays. We tested for cross-linking between cysteines introduced into TM6 and TM7 of Cys-less CFTR/V510A because cross-linking between TM6 and TM7 of P-glycoprotein, the sister protein of CFTR, was inhibited with the corrector VRT-325. Cys-less CFTR/V510A mutant containing cysteines at I340C(TM6) and S877C(TM7) could be cross-linked with a homobifunctional cross-linker. Correctors and the CFTR channel blocker benzbromarone, but not P-glycoprotein substrates, inhibited cross-linking of mutant I340C(TM6)/S877C(TM7). These results suggest that corrector molecules such as corr-4a interact directly with CFTR.


Gbvdr6, a Gene Encoding a Receptor-Like Protein of Cotton (Gossypium barbadense), Confers Resistance to Verticillium Wilt in Arabidopsis and Upland Cotton.
Verticillium wilt is a soil-borne disease that can cause devastating losses in cotton production. Because there is no effective chemical means to combat the disease, the only effective way to control Verticillium wilt is through genetic improvement. Therefore, the identification of additional disease-resistance genes will benefit efforts toward the genetic improvement of cotton resistance to Verticillium wilt. Based on screening of a BAC library with a partial Ve homologous fragment and expression analysis, a V. dahliae-induced gene, Gbvdr6, was isolated and cloned from the Verticillium wilt-resistant cotton G. barbadense cultivar Hai7124. The gene was located in the gene cluster containing Gbve1 and Gbvdr5 and adjacent to the Verticillium wilt-resistance QTL hotspot. Gbvdr6 was induced by Verticillium dahliae Kleb and by the plant hormones salicylic acid (SA), methyl jasmonate (MeJA) and ethephon (ETH) but not by abscisic acid (ABA). Gbvdr6 was localized to the plasma membrane. Overexpression of Gbvdr6 in Arabidopsis and cotton enhanced resistance to V. dahliae. Moreover, the JA/ET signaling pathway-related genes PR3, PDF 1.2, ERF1 and the SA-related genes PR1 and PR2 were constitutively expressed in transgenic plants. Gbvdr6-overexpressing Arabidopsis was less sensitive than the wild-type plant to MeJA. Furthermore, the accumulation of reactive oxygen species and callose was triggered at early time points after V. dahliae infection. These results suggest that Gbvdr6 confers resistance to V. dahliae through regulation of the JA/ET and SA signaling pathways.


Symmetry controlled spin polarized conductance in au nanowires.
The fact that the resistance of propagating electrons in solids depends on their spin orientation has led to a new field called spintronics. With the parallel advances in nanoscience, it is now possible to talk about nanospintronics. Many works have focused on the study of charge transport along nanosystems, such as carbon nanotubes, graphene nanoribbons, or metallic nanowires, and spin dependent transport properties at this scale may lead to new behaviors due to the manipulation of a small number of spins. Metal nanowires have been studied as electric contacts where atomic and molecular insertions can be constructed. Here we describe what might be considered the ultimate spin device, namely, a Au thin nanowire with one Co atom bridging its two sides. We show that this system has strong spin dependent transport properties and that its local symmetry can dramatically change them, leading to a significant spin polarized conductance.


Chiral [Mo8O26]4- Polyoxoanion-Induced Three-Dimensional Architectures With Homochiral Eight-Fold Interpenetrated Metal-Organic Frameworks.
A pair of novel chiral compounds based on homochiral 8-fold interpenetrated metal-organic frameworks (MOFs) and chiral polyoxometalates (POMs), formulated as d-[Cu(4,4'-bipy)1.5]4[Mo8O26] (d-1) and l-[Cu(4,4'-bipy)1.5]4[Mo8O26] (l-1) (4,4'-bipy = 4,4'-bipyridine), have been successfully synthesized and characterized by single crystal X-ray diffraction, infrared, thermogravimetric analysis, elemental analysis, and solid circular dichroism spectra. Structural analysis indicates that two compounds are enantiomers. The connection of copper cations and 4,4'-bipy ligands generates helical infinite chains, while adjacent chains are further linked by Cu-N bonds to form a three-dimensional interpenetrating framework with a (10,3)-a topology. Interestingly, the chiral [Mo8O26]4- polyanions are encapsulated in the chiral MOFs via sharing the oxygen atoms. Both d- and l-[Cu(4,4'-bipy)1.5]4[Mo8O26] crystallize in chiral space group C2221. Additionally, two compounds represent new examples of chiral self-assembly.


Electrostatic relaxation and hydrodynamic interactions for self-diffusion of ions in electrolyte solutions.
The concentration dependence of self-diffusion of ions in solutions at large concentrations has remained an interesting yet unsolved problem. Here we develop a self-consistent microscopic approach based on the ideas of mode-coupling theory. It allows us to calculate both contributions which influence the friction of a moving ion: the ion atmosphere relaxation and hydrodynamic interactions. The resulting theory provides an excellent agreement with known experimental results over a wide concentration range. Interestingly, the mode-coupling self-consistent calculation of friction reveal a nonlinear coupling between the hydrodynamic interactions and the ion atmosphere relaxation which enhances ion diffusion by reducing friction, particularly at intermediate ion concentrations. This rather striking result has its origin in the similar time scales of the relaxation of the ion atmosphere relaxation and the hydrodynamic term, which are essentially given by the Debye relaxation time. The results are also in agreement with computer simulations, with and without hydrodynamic interactions.


Meta-analysis on the long-term effectiveness of psychological and medical treatments for binge-eating disorder.
Long-term effectiveness is a critical aspect of the clinical utility of a treatment; however, a meta-analytic evaluation of psychological and medical treatments for binge-eating disorder (BED), including weight loss treatments, is outstanding. This meta-analysis sought to provide a comprehensive evaluation of the long-term effectiveness in diverse treatments for BED regarding a range of clinically relevant outcomes. Based on a systematic search up to February 2018, 114 published and unpublished randomized-controlled (RCTs), nonrandomized, and uncontrolled treatment studies, totaling 8,862 individuals with BED (DSM-IV, DSM-5), were identified and analyzed using within-group random-effect modeling. Effectiveness (regarding binge-eating episodes and abstinence, eating disorder and general psychopathology) up to 12 months following treatment was demonstrated for psychotherapy, structured self-help treatment, and combined treatment, while the results regarding body weight reduction were inconsistent. These results were confirmed in sensitivity analyses with RCTs on the most common treatments-cognitive-behavioral therapy and self-help treatment based on this approach. Follow-up intervals longer than 12 months were rarely reported, mostly supporting the long-term effectiveness of psychotherapy. Few follow-up data were available for pharmacotherapy, and behavioral and self-help weight loss treatment, while follow-up data were lacking for pharmacological and surgical weight loss treatment. Study quality varied widely. This comprehensive meta-analysis demonstrated the medium-term effectiveness of psychotherapy, structured self-help treatment, and combined treatment for patients with BED, and supported the long-term effectiveness of psychotherapy. The results were derived from uncontrolled comparisons over time. Further long-term high quality research on psychological and medical treatments for BED is required.


A supertree pipeline for summarizing phylogenetic and taxonomic information for millions of species.
We present a new supertree method that enables rapid estimation of a summary tree on the scale of millions of leaves. This supertree method summarizes a collection of input phylogenies and an input taxonomy. We introduce formal goals and criteria for such a supertree to satisfy in order to transparently and justifiably represent the input trees. In addition to producing a supertree, our method computes annotations that describe which grouping in the input trees support and conflict with each group in the supertree. We compare our supertree construction method to a previously published supertree construction method by assessing their performance on input trees used to construct the Open Tree of Life version 4, and find that our method increases the number of displayed input splits from 35,518 to 39,639 and decreases the number of conflicting input splits from 2,760 to 1,357. The new supertree method also improves on the previous supertree construction method in that it produces no unsupported branches and avoids unnecessary polytomies. This pipeline is currently used by the Open Tree of Life project to produce all of the versions of project's "synthetic tree" starting at version 5. This software pipeline is called "propinquity". It relies heavily on "otcetera"-a set of C++ tools to perform most of the steps of the pipeline. All of the components are free software and are available on GitHub.


Changes in colorectal cancer during a 20-year period: an extended report from the multi-institutional registry of large bowel cancer, Japan.
This study was designed to examine trends of colorectal cancer in relation to age, gender, site, and survival during the past 20 years. The multi-institutional registry of the Japanese Society for Cancer of the Colon and Rectum offered 87,695 surgical cases with invasive adenocarcinoma during 1978 to 1997 for analysis. We calculated survival rates and used the Cox's proportional hazard model for cases during 1978 to 1994. The number of cases showed a 2.5-fold increase with consistent male predominance confined to the distal colon and the rectum. Colon cancer in the last five-year period was more likely right-sided for females (odds ratio, 1.26; 95 percent confidence interval, 1.16-1.38) and males (odds ratio, 1.16; 95 percent confidence interval, 1.06-1.25) compared with the first period. Cancers in younger patients were more likely at Stage III to IV in the late 1990s if the cancers were in the distal colon, the rectum (for both genders), or the proximal colon (for females). Survival was improved except for cases with proximal colon cancer of Stage IV. In the multivariate analysis, hazard ratios for death in the postoperative five years were 0.77, 0.59, and 0.66 for proximal colon, distal colon, and rectal cancers, respectively, in the last period as compared with those in the first period [corrected]. Reduced hazard ratio for females was the largest for proximal colon cancer with Stage I to II. Although surgical outcome was largely improved, delayed presentation or diagnosis in younger patients remained a problem. Preferential localization in the proximal colon and survival benefit for females should be investigated.


Validation of the criteria of transcatheter arterial chemoembolization failure or refractoriness in patients with advanced hepatocellular carcinoma proposed by the LCSGJ.
Transcatheter arterial chemoembolization (TACE) failure or refractoriness is an indication for sorafenib therapy in patients with advanced hepatocellular carcinoma. The study evaluated the validity of the definition of TACE failure or refractoriness as proposed by the Liver Cancer Study Group of Japan (LCSGJ) through a retrospective analysis of sorafenib treatment. Out of 265 patients with advanced hepatocellular carcinoma who were treated with sorafenib at our hospital, 45 experienced TACE failure or refractoriness and were included in this study and retrospectively analyzed. Multivariate analysis only identified the number of ineffective TACE procedures performed before starting sorafenib treatment as significant factors. Overall survival (OS) after starting sorafenib was statistically longer in patients treated with ≤2 consecutive ineffective TACE procedures before sorafenib administration than in patients treated with ≥3 consecutive ineffective TACE procedures (p < 0.005). This result matched the LCSGJ criteria. In patients treated with sorafenib, OS was extended with ≤2 consecutive ineffective TACE procedures compared to that with ≥3 consecutive ineffective TACE procedures. Thus, if tumors are uncontrolled, TACE should not be repeated. The result of this study supports the definition of TACE failure or refractoriness proposed by the LCSGJ.


Winged scapula in patients with myotonic dystrophy type 1.
We report two patients with myotonic dystrophy type 1 (DM1) showing winged scapula in a single family. Genomic analysis revealed a marked expansion of CTG repeats in the 3' untranslated region; 1100 in patient 1 and 667 in patient 2. Muscle MRI revealed marked atrophy in the serratus anterior muscle in both patients. Muscle biopsy findings showed central nuclei and variations in fiber size. One of the patients showed ragged red fibers in muscles of the biceps brachii. To our knowledge, this is the first report of typical winged scapula in DM1.


[Promoting hepatitis B elimination and laying emphasis on its economics evaluation].
WHO has developed and issued global hepatitis B elimination program. Continuing hepatitis B immunization and conducting community based antiviral treatment for chronic hepatitis B are the most important strategies for hepatitis B elimination. According to the estimation of related cost by WHO, the cost of antiviral therapy would be very high. Great achievement has been made in hepatitis B immunization in China, but the prevalence of chronic hepatitis B is high. Elimination of hepatitis B needs a large amount of public resource, posing serious challenge to public health policy making. Economics research on hepatitis B prevention and treatment can provide evidence and technical support for hepatitis B elimination. In this column "Economic evaluations of hepatitis B" , the related articles in this issue summarize the progress in this research field, which is inspiring and encouraging.


Preparation and Use of Retroviral Vectors for Labeling, Imaging, and Genetically Manipulating Cells.
Retroviral vectors are a powerful technology for achieving long-term genetic manipulation. This introduction provides some background on replication-deficient retroviral vectors based on Moloney murine leukemia virus and lentivirus. Details, examples, and associated protocols are provided for using these vectors to fluorescently label, genetically alter, and image both live and fixed murine brain tissue.


Genome wide expression analysis in HPV16 cervical cancer: identification of altered metabolic pathways.
Cervical carcinoma (CC) is a leading cause of death among women worldwide. Human papilloma virus (HPV) is a major etiological factor in CC and HPV 16 is the more frequent viral type present. Our aim was to characterize metabolic pathways altered in HPV 16 tumor samples by means of transcriptome wide analysis and bioinformatics tools for visualizing expression data in the context of KEGG biological pathways. We found 2,067 genes significantly up or down-modulated (at least 2-fold) in tumor clinical samples compared to normal tissues, representing ~3.7% of analyzed genes. Cervical carcinoma was associated with an important up-regulation of Wnt signaling pathway, which was validated by in situ hybridization in clinical samples. Other up-regulated pathways were those of calcium signaling and MAPK signaling, as well as cell cycle-related genes. There was down-regulation of focal adhesion, TGF-beta signaling, among other metabolic pathways. This analysis of HPV 16 tumors transcriptome could be useful for the identification of genes and molecular pathways involved in the pathogenesis of cervical carcinoma. Understanding the possible role of these proteins in the pathogenesis of CC deserves further studies.


Epinephrine inhalers in emergency sets of patients with anaphylaxis.
Emergency sets are prescribed to allow patients with anaphylaxis to treat themselves before professional aid arrives. The need for epinephrine in this setting is well-accepted, but how it should be administered is still controversial. Epinephrine preparations can be administered orally, subcutaneously, intramuscularly or as aerosols. Primatene Mist is one epinephrine inhaler, which is approved for asthma treatment in the USA, and InfectoKrupp Inhal is another one approved to support the treatment of acute laryngo-tracheitis and of allergic reactions with a nebulizer. Both are possible components of the emergency set for patients with anaphylaxis. The following review article summarizes data currently available on the use of epinephrine preparations in first-aid treatment of anaphylaxis. Studies have shown that the plasma concentrations needed for hemodynamic stabilization cannot be reached with epinephrine inhalers. Since most cases of hypotension in anaphylaxis cannot be effectively treated with epinephrine inhalers, the prescriber should be aware of this before including them in an emergency pack.


Machine Learning Prediction Algorithm for In-Hospital Mortality following Body Contouring.
Body contouring is a common procedure, but it is worth attention because of concern for a variety of complications, and even the potential for death. As a result, the purpose of this study was to determine the key predictors following body contouring and create models for the risk of mortality using diverse machine learning (ML) models. The National Inpatient Sample database from 2015 to 2017 was queried to identify patients undergoing body contouring. Candidate predictors, such as demographics, comorbidities, personal history, postoperative complications, and operative features, were included. The outcome was in-hospital mortality. Models were compared by area under the curve, accuracy, sensitivity, specificity, positive and negative predictive values, and decision curve analysis. Overall, 8214 patients undergoing body contouring were identified, among whom 141 (1.72%) died in the hospital. Variable importance plot demonstrated that sepsis was the variable with greatest importance across all ML algorithms, followed by Elixhauser Comorbidity Index, cardiac arrest, and so forth. The naive Bayes model had a higher predictive performance (area under the curve, 0.898; 95% CI, 0.884 to 0.911) among these eight ML models. Similarly, in the decision curve analysis, the naive Bayes model also demonstrated a higher net benefit (ie, the correct classification of in-hospital deaths considering a tradeoff between false-negatives and false-positives) compared with the other seven models across a range of threshold probability values. The ML models, as indicated by this study, can be used to predict in-hospital death for patients at risk who undergo body contouring.