Global Chronic Total Occlusion Crossing Algorithm: JACC State-of-the-Art Review.
The authors developed a global chronic total occlusion crossing algorithm following 10 steps: 1) dual angiography; 2) careful angiographic review focusing on proximal cap morphology, occlusion segment, distal vessel quality, and collateral circulation; 3) approaching proximal cap ambiguity using intravascular ultrasound, retrograde, and move-the-cap techniques; 4) approaching poor distal vessel quality using the retrograde approach and bifurcation at the distal cap by use of a dual-lumen catheter and intravascular ultrasound; 5) feasibility of retrograde crossing through grafts and septal and epicardial collateral vessels; 6) antegrade wiring strategies; 7) retrograde approach; 8) changing strategy when failing to achieve progress; 9) considering performing an investment procedure if crossing attempts fail; and 10) stopping when reaching high radiation or contrast dose or in case of long procedural time, occurrence of a serious complication, operator and patient fatigue, or lack of expertise or equipment. This algorithm can improve outcomes and expand discussion, research, and collaboration.


Induction of apoptosis in the murine liver with recombinant human activin A.
Recombinant human activin A, a member of the transforming growth factor-beta superfamily, induced significant cell loss in rodent livers and in primary hepatocyte cultures. Histologically and biochemically the hepatocyte death was mediated by apoptosis, a form of programmed cell death. Male mice were treated with 200 or 500 micrograms recombinant human activin A/kg body wt/day for up to 3 days by means of a subcutaneously implanted minipump. Livers were taken for light and electron microscopy, DNA isolation and in situ nick end-labeling. Primary cultures of rat hepatocytes were treated with 10 ng/ml recombinant human activin A for 24 hr before being harvested for electron microscopy and DNA isolation. Infusion of activin A evoked dose-dependent loss of liver mass due to the atrophy and death of hepatocytes around the central vein. Morphologically, the dying cells demonstrated all the characteristic nuclear and cytoplasmic features of apoptosis. Low molecular weight DNA isolated activin A-treated intact livers and primary cultures exhibited the typical oligosomal ladder. Nick end-labeling of DNA in situ confirmed that virtually all topographical apoptotic hepatocytes had fragmented DNA. The currently accepted criteria for apoptosis (i.e., specific morphological alterations and internucleosomal clipping of DNA) were evident in activin A-treated hepatocytes both in vitro and in vivo, leading to the conclusion that cell loss occurs mainly through apoptosis. These observations suggest that activin A may be important in hepatic homeostasis.


Construction of 3D lithium metal anode using bi-functional composite separator: a new approach for lithium battery.
With the increasing use of Li batteries for storage, their safety issues and energy densities are attracting considerable attention. The Li metal battery (LMB) with limited capacity in the Li metal anode is one of ideal high energy-density systems due to eliminating the use of traditional anode, elevating the energy density of battery and reducing production costs. However, the side reactions between the electrolyte and metallic Li and the irreversible loss of lithium resources caused by the generation of "dead Li" will directly lead to the loss of battery capacity during the cycling process. Therefore, the cycle life of the LMB with limited capacity in the Li metal anode faces significant challenges. Herein, a bi-functional manganese oxide (MnO)/polypropylene/Li1+xAlxTi2-x(PO4)3 (LATP) composite separator is designed to construct a stable three dimensional (3D) Li metal in the surface of Cu foil for LMB. The MnO can dissolve in electrolytes with low concentration, which can be reduced to produce Mn and Li2O, functioning as nucleating seeds to induce sheet-like Li deposition. The sustainably released MnO also involves in the formation of solid electrolyte interphase (SEI) layer, which can be repaired promptly once damaged by the volume expansion of Li. The LATP coating layer is in situ transferred onto the sheet-like Li, acting as an artificial SEI layer for further protection. The constructed 3D Li metal anode with limited capacity shows improved cycle stability in LiFePO4 cell, which shows a capacity retention of 94.5% after 150 cycles. Our strategy, constructing stable 3D Li metal anode with bi-functional composite separator, will bring a new inspiration for developing high energy density LMB.


Genetic inactivation of essential HSF1 reveals an isolated transcriptional stress response selectively induced by protein misfolding.
Heat Shock Factor 1 (Hsf1) in yeast drives the basal transcription of key proteostasis factors and its activity is induced as part of the core heat shock response. Exploring Hsf1 specific functions has been challenging due to the essential nature of the HSF1 gene and the extensive overlap of target promoters with environmental stress response (ESR) transcription factors Msn2 and Msn4 (Msn2/4). In this study, we constructed a viable hsf1∆ strain by replacing the HSF1 open reading frame with genes that constitutively express Hsp40, Hsp70, and Hsp90 from Hsf1-independent promoters. Phenotypic analysis showed that the hsf1∆ strain grows slowly, is sensitive to heat as well as protein misfolding and accumulates protein aggregates. Transcriptome analysis revealed that the transcriptional response to protein misfolding induced by azetidine-2-carboxylic acid is fully dependent on Hsf1. In contrast, the hsf1∆ strain responded to heat shock through the ESR. Following HS, Hsf1 and Msn2/4 showed functional compensatory induction with stronger activation of the remaining stress pathway when the other branch was inactivated. Thus, we provide a long-overdue genetic test of the function of Hsf1 in yeast using the novel hsf1∆ construct. Our data highlight that the accumulation of misfolded proteins is uniquely sensed by Hsf1-Hsp70 chaperone titration inducing a highly selective transcriptional stress response.


[Expression of CD(14) protein in liver sinusoidal endothelial cells during endotoxemia].
To observe the expression of CD(14) protein and CD(14) gene in liver sinusoidal endothelial cells (LSECs) of rats during endotoxemia and the role of CD(14) protein in the activation of lipopolysaccharide (LPS)-induced LSECs. Wistar rat endotoxemia model was established by injection of a dose of LPS (5 mg/kg, Escherichia coli O111:B4) via the tail vein of the rats, then sacrificed immediately, at 3, 6, 12, and 24 h, respectively. LSECs were isolated from normal and LPS-injected rats by the in situ collagenase perfusion technique. The isolated LSECs were incubated with anti CD(14) polyclonal antibody, then followed by staining with goat anti-rabbit IgG conjugated fluorescein isothiocyanate (FITC). The percentage and mean fluorescence intensity (MFI) of CD(14)-positive cells were detected by the flow cytometric analysis (FCM). LSECs were collected to measure the expression of CD(14) mRNA by the in situ hybridization analysis. The isolated LSECs from normal rats were divided into two groups. Group of LPS: LSECs were induced with different concentration of LPS (0, 0.01 microg/ml, 1 microg/ml, 10 microg/ml, and 100 microg/ml). Group of anti-CD(14) blockade: LSECs were pre-incubated for 30 min with CD(14) antibody before different concentrations of LPS were added. The supernatants of these cells were then collected for measuring the levels of tumor necrosis factor (TNF)- alpha and interleukin (IL)-6. In rats with endotoxemia, LSECs displayed a strong MFI distinct from that of control rats. The number of FITC-CD(14) positive LSECs was 54.32%, 65.83%, 85.61%, and 45.65% at 3, 6, 12, and 24 h, respectively, which increased markedly when compared to control rats (4.45%, P<0.01). The expression of CD(14) mRNA in LSECs was stronger than that in control rats. The levels of TNF-alpha were significantly increased in group of LPS (54.49 +/- 6.02 pg/ml, 84.65 +/- 10.16 pg/ml, 206.54 +/- 23.55 pg/ml, 349.87 +/- 39.47 pg/ml, and 365.76 +/- 40.31 pg/ml) than those in group of anti-CD(14) blockade (55.93 +/- 6.95 pg/ml, 63.32 +/- 7.81 pg/ml, 85.34 +/- 9.72 pg/ml, 112.75 +/- 13.54 pg/ml, and 198.66 +/- 21.54 pg/ml) (P<0.01). The levels of IL-6 also increased significantly in group of LPS (103.34 +/- 12.52 pg/ml, 187.39 +/- 20.31 pg/ml, 243.87 +/- 27.83 pg/ml, 289.51 +/- 30.15 pg/ml, and 298.53 +/- 31.94 pg/ml) than those in group of anti-CD(14) blockade (104.37 +/- 11.49 pg/ml, 125.02 +/- 13.58 pg/ml, 164.59 +/- 19.47 pg/ml, 183.47 +/- 20.17 pg/ml, and 221.76 +/- 26.43pg/ml) (P<0.01). LSEC can synthesize CD(14) protein and express CD(14) gene during endotoxemia. Anti CD(14) antibody can inhibit the production of TNF-alpha and IL-6 in LSECs induced by LPS. The expression of CD(14) protein may take an important part in the activation of LSECs induced by LPS.


Pulmonary Mycobacterium abscessus in an AIDS patient.
Mycobacterium abscessus is an unusual pathogen in HIV/AIDS patients. We report a case of M abscessus with review of the literature, which revealed 1 confirmed case in an HIV/AIDS patient. Preliminary diagnosis was presumed to be pulmonary tuberculosis secondary to positive acid-fast bacilli in sputum stain. After initial treatment failure, sputum stains were repeated, and the species was identified; therefore the antibiotic regimen was tailored for M abscessus. Early recognition and treatment of nontuberculous mycobacteria is vital in the reduction of complications and mortality in HIV/AIDS patients. M abscessus is a highly virulent and should be considered as a potential offending pathogen on differential diagnosis in an immunocompromised host.


Bayesian interpretation and analysis of research results.
From a computational perspective, Bayesian methods can be viewed as a natural extension of familiar confidence intervals and significance tests, which sheds light on their meaning. This viewpoint shows that no special software is required to compute Bayesian results, leaving the distinctions between conventional and Bayesian analyses in the conceptual realm. Key Bayesian concepts may be grasped more easily than those required for proper use of conventional methods. These concepts allow one to re-examine results from a Bayesian perspective, to complement and prevent misinterpretation of conventional results. Thus, even if frequentist results remain the norm for presentation, the inclusion of Bayesian perspectives in teaching and analysis is strongly recommended.


Effects of forage source and particle size on chewing activity, ruminal pH, and saliva secretion in lactating Holstein cows.
The present study investigated the effects of dietary forage source (quality) and particle size on chewing activity, saliva secretion, and ruminal pH. Twelve multiparous lactating Holstein cows, four of which were ruminally cannulated, were used in a replicated 4 × 4 Latin square experimental design with a 2 × 2 factorial arrangement of treatments. Cows fed wild-rye hay diets had longer daily eating times than cows fed oaten hay diets. Treatments had no effect on ruminating time; therefore, resting time varied inversely to eating time. Neither the rate nor the amount of saliva secretion while eating, ruminating, or resting was affected by diet, resulting in similar total daily saliva secretions across treatments (231 L/day). Total volatile fatty acids (VFAs) in the ruminal fluid from animals fed oaten hay diets were higher than those from animals fed wild-rye hay diets; further, VFAs increased with decreasing forage particle size (FPS). Consistent with elevated VFA concentrations, reducing FPS and including oaten hay in the diet decreased mean ruminal pH and increased the daily time of ruminal pH under 5.8. Results of this study suggest that forage source and particle size affect ruminal pH might be via variations in VFA production rather than increased salivary recycling of buffering substrates.


Closed loop adaptive optics for microscopy without a wavefront sensor.
A three-dimensional wide-field image of a small fluorescent bead contains more than enough information to accurately calculate the wavefront in the microscope objective back pupil plane using the phase retrieval technique. The phase-retrieved wavefront can then be used to set a deformable mirror to correct the point-spread function (PSF) of the microscope without the use of a wavefront sensor. This technique will be useful for aligning the deformable mirror in a widefield microscope with adaptive optics and could potentially be used to correct aberrations in samples where small fluorescent beads or other point sources are used as reference beacons. Another advantage is the high resolution of the retrieved wavefont as compared with current Shack-Hartmann wavefront sensors. Here we demonstrate effective correction of the PSF in 3 iterations. Starting from a severely aberrated system, we achieve a Strehl ratio of 0.78 and a greater than 10-fold increase in maximum intensity.


Endoscopic Endonasal Transsphenoidal Approach From the Surgeon Point of View.
In February 2009, the authors' center formed a team of neurosurgeons, otolaryngologists, endocrinologists, and radiologists to perform pituitary surgery using the endoscopic endonasal transsphenoidal approach (EETSA). This paper reviews the authors' experience with the technique, pathological outcomes, hormone profiles, and postoperative complications. Between February 2009 and December 2015, 535 patients underwent the EETSA with 2-nostrils/4-hands surgery. All of the patients had preoperative neurophthalmological and endocrinological assessments and neuroimaging. Patients were followed for at least 6 months with otolaryngological evaluations. The most common pathology treated was pituitary adenomas, with 390 (72.9%) patients. Of these, 287 (73.6%) were nonfunctioning adenomas. As the surgical method, the conventional 2-nostrils/4-hands technique was performed in 77 patients (14.4%), a right conventional nasoseptal flap and left modified nasoseptal rescue flap technique was used in 135 patients (25.2%), and bilateral modified nasoseptal rescue flaps were used in 323 patients (60.4%). Postoperative complications occurred in 46 patients (8.6%). The most common complications were vascular injury or hematoma (10 patients, 1.9%), and the most common postoperative sinonasal complaints were hyposmia or anosmia. Olfactory function was significantly decreased according to the Connecticut Chemosensory Clinical Research Center test (P <0.001) and Cross-Cultural Smell Identification Test scores (P <0.001) evaluated 6 months postoperatively. Skull-base tumor surgery via an EETSA with a team approach was performed for various extended tumors. It is important to consider postoperative sinonasal dysfunction, such as hyposmia or anosmia, and to have this followed by an otolaryngologist.


Image-guided percutaneous drainage of an emphysematous bulla with a fluid level.
We report here a case of a large emphysematous bulla with a fluid level that was managed successfully by percutaneous catheter drainage in a 50 year-old man with chronic obstructive airway disease.


VKORC1 -1639G>A and CYP2C9*3 are the major genetic predictors of phenprocoumon dose requirement.
Phenprocoumon, similar to other coumarin-derived anticoagulants, is associated with a large variation in the individual dose requirement to achieve stable anticoagulation. Polymorphisms in the vitamin K epoxide reductase complex subunit 1 (VKORC1) and the liver enzyme cytochrome P450 2C9 (CYP2C9) effectively account for the variability in warfarin and acenocoumarol response but are less well-defined pharmacogenetic predictors in phenprocoumon therapy. A retrospective study was performed on 185 outpatients attending anticoagulation clinics in Austria and Germany. These patients were genotyped for the VKORC1 -1639G>A and 3730G>A polymorphisms as well as for the CYP2C9 *2 and *3 polymorphisms using a reverse hybridisation-based teststrip assay. The VKORC1 -1639A allele, which was present at a frequency of 41.4% in the study cohort, significantly reduced the mean weekly phenprocoumon dose by 3 mg (19%) in the heterozygous and by 6.7 mg (43%) in the homozygous state compared to wild-type carriers (15.5 +/- 6.8 mg, p < 0.0001). A stepwise multiple regression analysis revealed that VKORC1 -1639G>A, age and CYP2C9*3 were the major independent determinants of phenprocoumon dose, accounting for 14.2, 9.1 and 4.7% of its variability, respectively (p </= 0.0007). The CYP2C9*2 polymorphism had a marginal influence (1.4%) and failed to reach statistical significance (p = 0.062). The VKORC1 3730G>A genotype had no additional predictive power for individual dose variability. Similar to warfarin and acenocoumarol, the VKORC1 -1639G>A polymorphism had the highest impact on the maintenance dose of phenprocoumon. The factor age was the second most important predictor and explained a greater percentage of the variability than CYP2C9 genotype.


Targeting RAS-driven human cancer cells with antibodies to upregulated and essential cell-surface proteins.
While there have been tremendous efforts to target oncogenic RAS signaling from inside the cell, little effort has focused on the cell-surface. Here, we used quantitative surface proteomics to reveal a signature of proteins that are upregulated on cells transformed with KRASG12V, and driven by MAPK pathway signaling. We next generated a toolkit of recombinant antibodies to seven of these RAS-induced proteins. We found that five of these proteins are broadly distributed on cancer cell lines harboring RAS mutations. In parallel, a cell-surface CRISPRi screen identified integrin and Wnt signaling proteins as critical to RAS-transformed cells. We show that antibodies targeting CDCP1, a protein common to our proteomics and CRISPRi datasets, can be leveraged to deliver cytotoxic and immunotherapeutic payloads to RAS-transformed cancer cells and report for RAS signaling status in vivo. Taken together, this work presents a technological platform for attacking RAS from outside the cell.


Infectious Agents Trigger Trophic Cascades.
Most demonstrated trophic cascades originate with predators, but infectious agents can also cause top-down indirect effects in ecosystems. Here we synthesize the literature on trophic cascades initiated by infectious agents including parasitoids, pathogens, parasitic castrators, macroparasites, and trophically transmitted parasites. Like predators, infectious agents can cause density-mediated and trait-mediated indirect effects through their direct consumptive and nonconsumptive effects respectively. Unlike most predators, however, infectious agents are not fully and immediately lethal to their victims, so their consumptive effects can also trigger trait-mediated indirect effects. We find that the frequency of trophic cascades reported for different consumer types scales with consumer lethality. Furthermore, we emphasize the value of uniting predator-prey and parasite-host theory under a general consumer-resource framework.


Evaluation of ergonomic adjustments of catering carts to reduce external pushing forces.
An existing standard catering cart was compared with two prototypes for pushbar and castor design. The first objective of this study was to find out which cart was accompanied with the lowest manually exerted external forces in pushing in a straight way and in pushing a 90 turn. The second objective was to explore effects of the pushbar and castor design of the carts. In the initial and ending phase, the prototypes were accompanied with higher exerted forces compared with the standard catering cart. In pushing straight. the reversed start position of the bigger castors of the prototypes hampered a fluent acceleration and caused higher initial forces. In decelerating, the lower rolling friction of the bigger castors required higher forces to stop the prototypes compared to the standard cart. During the sustained phase, the prototype carts were more favourable. Effects of pushbar and castor design were studied during a turn. The vertical pushbars of the prototypes resulted in lower time-integrated pushing forces. Providing an axis of rotation for turning activities by means of a fixed wheel was proven to be advantageous.


[Effect of protein synthesis inhibitors on DNA replication. I. Effect of the short-term action of cycloheximide on cell permeability for thymidine in vitro].
The effect of protein synthesis inhibitors on DNA replication was studied on L cells. After a 10 minutes' action of the inhibitors, protein synthesis was seen to be completely blocked, and DNA synthesis decreased by 85%. Four hours after a 20-minutes' cycloheximide treatment, the cells completely restored their ability to protein synthesis and DNA replication and even surpass the control level, due, probably, to a partial cell synchronization in S period. The short action of cycloheximide did not interfere with thymidine uptake by the cells. The rate of the exogenous precursor uptake was even higher than that in the control, apparently, because of its much reduced utilization in the inhibited DNA synthesis.


Gastric meal accommodation studied by ultrasound in diabetes. Relation to vagal tone.
Disturbed gastric meal accommodation may cause abdominal symptoms in patients with functional dyspepsia and diabetes mellitus who have poor vagal control of gastric motility. In the present study we aimed to explore the relation between gastric meal accommodation and vagal tone in diabetic patients with vagal neuropathy. Twenty patients with diabetes (DM) (insulin-dependent type; 10 men and 10 women, aged 35.3 +/- 7.6 years) and 20 healthy controls (HC) (10 men and 10 women; aged 34.7 +/- 10.7 years) were studied. Proximal gastric size was assessed with ultrasound in a sagittal area and a frontal diameter. Distal gastric (antrum) size was assessed in a sagittal area. Vagal tone was assessed non-invasively by recording of respiratory sinus arrhythmia (RSA) in beats per minute. Proximal sagittal area was significantly (P = 0.03) smaller in DM (18.5 +/- 5.5 cm2) than in HC (22.2 +/- 4.6 cm2). Proximal frontal diameter did not differ significantly (P = 0.60) between DM and HC (5.9 +/- 1.1 cm versus 5.7 +/- 0.8 cm). Antral area, too, did not differ significantly (P = 0.59) between DM and HC (14.5 +/- 4.1 cm2 versus 13.6 +/- 5.8 cm2). Proximal/distal meal distribution ratio, defined as proximal sagittal area/distal sagittal area, was significantly (P = 0.05) smaller in DM (6.8 +/- 0.6) than in HC (9.9 +/- 5.5). Vagal tone was significantly (P = 0.03) lower in DM (4.5 +/- 1.9 beats/min) than in HC (6.3 +/- 2.7 beats/min). Vagal tone tended (r = 0.33, P = 0.06) to correlate with proximal sagittal area in DM and HC pooled. Vagal tone correlated (r = 0.34, P = 0.05) with proximal frontal diameter in DM and HC pooled. A significant negative correlation (r = -0.39, P = 0.03) was observed between vagal tone and antral area in DM and HC pooled. Patients with diabetes and low vagal tone have an impaired postprandial gastric meal distribution characterized by a small proximal stomach and a small proximal/distal meal distribution ratio.


Incarcerated congenital transmesenteric hernia in an adult: a case report.
Transmesenteric hernia is a rare cause of bowel obstruction and strangulation. It can be due to iatrogenic injury, trauma, inflammatory and less likely congenital. We present a case of true congenital transmesenteric hernia in a 26-year-old male with no previous surgical history or trauma. The patient presented acutely with no prior symptoms. Investigations provided limited information towards the diagnosis of the hernia, but suggestive of mid-gut volvulus. Emergency laparotomy was performed to find >75% of small bowel herniating through a proximal jejunal mesenteric defect leading to incarceration and early strangulation. No resection was required and patient recovered well. This case presents yet another rare pathology and highlights the importance of keeping a low threshold for operative intervention in uncertain cases.


[Analysis of FOXL2 gene mutation and genotype-phenotype correlation in a Chinese pedigree affected with blepharophimosis-ptosis-epicanthus inversus syndrome].
To detect FOXL2 gene mutation in a Chinese pedigree affected with blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) type I, and to explore its genotype-phenotype correlation. Peripheral blood samples were obtained from 3 patients and 19 healthy members from the pedigree for the isolation of genomic DNA. All exons and flanking sequences of the FOXL2 gene were amplified by PCR with 7 pairs of overlapping primers and sequenced. DNA sequencing indicated that the BPES phenotype in this pedigree was caused by a hotspot c.843_859dup17 mutation. The same mutation was not found among the healthy members of the pedigree. The c.843_859dup17 frameshift mutation probably underlies the BPES type I in this Chinese pedigree, which may manifest as either BEPS type I or type II.


Role of induced abortion in attaining reproductive goals in Kyrgyzstan: a study based on KRDHS-1997.
Estimates indicate that about 42 million pregnancies are voluntarily terminated every year at the global level, of which more than 80% occur in developing countries. Abortion has been one of the major reproductive health concerns in post-Soviet nations, especially when it is commonly used as a means of fertility regulation. On average, every woman has had around 1.6 abortions in Kyrgyzstan. This paper attempts to measure the role of abortion in fertility regulation using data from the Kyrgyz Republic Demographic and Health Survey (KRDHS), 1997. The analysis reveals that Kyrgyzstan can attain replacement level fertility in the absence of induced abortion by raising the contraceptive prevalence to 70% at the current level of effectiveness. The study also shows that women's attitude towards becoming pregnant and their partner's perception about abortion are significantly associated with the propensity to opt for an induced abortion. Reproductive health programmes need to address these issues, including the enhancement of male involvement in family planning.


Highly Stable Fluorescent-Traffic-Light Sensor for Point-of-Care Detection of Tetracycline.
Fluorescent point-of-care (POC) sensors have found great utility in fields like clinical diagnosis, food testing, and environmental monitoring. Herein, we developed a highly stable POC sensor that enabled the visual detection of tetracycline (TC) in a distinct fluorescent-traffic-light manner. In the sensor, a composite material of copper nanoclusters and metal-organic framework (CuNCs@MOF-5) prepared with a facile one-pot synthetic strategy was employed as the core element for target recognition and signal transduction. As evidenced by experiments, the as-prepared CuNCs@MOF-5 exhibited significantly improved fluorescence properties in terms of emission enhancement (about 28-fold) and stability improvement (over 110 days) compared to the CuNCs without confining and protection by MOF-5. More importantly, it was found that TC could uniquely interact with Zn(II) to trigger the disassembly of CuNCs@MOF-5, resulting in green fluorescence emission from the TC-Zn(II) complex and red fluorescence weakening of CuNCs. On the basis of this finding, a simple and stable sensor was proposed for POC detection of TC, which demonstrated high sensitivity, selectivity, and reproducibility. In addition to homogeneous visual detection in a 96-well plate, a CuNCs@MOF-5-contained agarose gel array was easily fabricated to achieve direct detection of TC in milk without any pretreatment, thanks to the size-sieving effect of the gel. Moreover, a test paper array was also put forward for low-cost TC detection, which indicates the extensibility and practicability of this sensing strategy.


A Content Analysis of Organ Donation Stories Printed in U.S. Newspapers: Application of Newsworthiness.
The current study applied a theory of newsworthiness to the topic of organ donation. Specifically, content analysis of newspaper stories published in the United States (N = 1,988) was performed to identify whether deviance and significance of a story predicted story prominence, measured as story length and placement in the newspaper. Results indicated support for study hypotheses: Longer stories and front-page stories pertaining to organ donation were more deviant and more significant in content. Analyses also indicated stories more negative in nature were more likely given front-page coverage, represented international events, and were high on deviance and significance. Higher circulating newspapers were more likely to publish stories recounting negative events in organ donation. Results indicated organ donation coverage represents a valid application of newsworthiness theory, and implications of study findings are discussed in relation to the agenda-setting function of news stories.


Mitochondrial disease: when the powerhouse goes awry.
Knowledge of and interest in mitochondrial disease is relatively recent. The first diagnosis of a mitochondrial cytopathy occurred in 1962. Since then, researchers have elucidated hundreds of types of mutant mitochondrial DNA and mapped their repercussions. This article walks the reader through the basics of mitochondrial function--normal and mutant. Mitochondrial cytopathies appear first in organs with high-energy needs; once a threshold of mutant mitochondrial DNA is exceeded, manifestations can be single or multisystem conditions. Although these conditions are currently incurable, some therapies aimed at enhancing mitochondrial function or scavenging free radicals may help individual patients. Certain nonpharmacological therapies should be employed in all patients. Research findings suggest that mitochondrial functioning may have a greater role in other pathologies than previously assumed.


Dual blockade of the renin-angiotensin system compared with a 50% increase in the dose of angiotensin-converting enzyme inhibitor: effects on proteinuria and blood pressure.
Several publications in the past 2 years have demonstrated that combined angiotensin-converting enzyme inhibitors (ACEI) and angiotensin-II receptor antagonist (AIIRA) are more effective in reducing blood pressure and proteinuria in patients with chronic renal disease than ACEI or AIIRA alone. This study compares the effect of increasing the ACEI dose by 50% with that of adding an AIIRA to a standard ACEI dose. This study was designed as part of a previous comparison of ACEI with ACEI plus candesartan. Directly after completion of the randomized intervention periods of that study, the dose of ACEI was increased by 50% in all patients. Proteinuria and blood pressure were compared in both groups of patients in the three periods, on standard ACEI, on ACEI plus candesartan and on a dose of ACEI increased by 50%. No significant differences in the primary end-point proteinuria or secondary end-points were observed when the ACEI dose was increased by 50%. Proteinuria was 1.8 g in 24 h on candesartan and ACEI and 2.4 g in 24 h when the ACEI dose was increased by 50% (P<0.02). Systolic blood pressure was 126.6 mmHg on candesartan and ACEI and 134.47 mmHg when the ACEI dose was increased by 50% (P<0.002). Diastolic blood pressure, serum creatinine, urea and potassium were not different between groups. Standard ACEI plus candesartan is more effective in reducing systolic blood pressure and proteinuria than a 50% increase in ACEI dose. This has implications for the prevention of renal failure in chronic renal disease.


Gardnerella vaginalis bacteremia from pulmonary abscess in a male alcohol abuser.
A case of Gardnerella vaginalis bacteremia is reported. This bacteremia occurred in a male alcohol abuser who developed definite signs of pulmonary abscess and empyema. Streptococcus milleri grew from another blood culture, but Gardnerella vaginalis was also isolated from a bronchoscopic aspirate and pleural drainage sample as part of mixed flora containing anaerobes, Streptococcus species, Neisseria sicca, and a Haemophilus sp. We discuss the possible pathogenic character of G. vaginalis outside the genital tract from a review of the literature.


Utility of teacher-report assessments of autistic severity in Japanese school children.
Recent studies suggest that many children with milder autism spectrum disorder (ASD) are undiagnosed, untreated, and being educated in mainstream classes without support and that school teachers might be the best persons to identify a child's social deviance. At present, only a few screening measures using teacher ratings of ASD have been validated. The aim of this study was to examine the utility of teacher ratings on the Social Responsiveness Scale (SRS), a quantitative measure of ASD. We recruited 130 participants aged 4 to 17 years from local schools or local pediatric outpatient clinics specializing in neurodevelopmental disorders that included 70 children with ASD. We found that the teacher-report SRS can be reliably and validly applied to children as a screening tool or for other research purposes, and it also has cross-cultural comparability. Although parent-teacher agreement was satisfactory overall, a discrepancy existed for children with ASD, especially for girls with ASD. To improve sensitivity in children at higher risk, especially girls, we cannot overstate the importance of using standardized norms specific to gender, informant, and culture.


Evaluation of the Feasibility and Utility of a Pharmacist-Centered Collaborative Drug Therapy Management Program for Oncology-Based Symptom Management.
Collaborative drug therapy management (CDTM) is a practice agreement between a pharmacist and a physician, which allows the pharmacist to assume responsibility of drug therapy management. There has been limited documentation of CDTM practices in the oncology setting. Therefore, a CDTM program in the gynecology oncology clinic at Roswell Park Cancer Institute (RPCI) was initiated to establish the feasibility and utility of CDTM and its effects on patient care and physician satisfaction. Primarily, 3 symptoms were managed by the CDTM pharmacists, namely chemotherapy-induced nausea and vomiting (CINV), chemotherapy-induced peripheral neuropathy (CIPN), and women's health. The CDTM program showed favorable results after a short 4-month period. The CDTM pharmacists were referred a total of 12 consultations for CDTM purposes; 8 patients enrolled in the CIPN CDTM protocol, 3 in the CINV protocol, and 1 in the women's health protocol. The CDTM pharmacists were able to perform a total of 54 consultations, with a mean time of 16.9 minutes spent with each patient per consultation. Additionally, the CDTM pharmacists made 70 interventions and identified 6 medication-related adverse effects. The patient and physician satisfaction survey demonstrated the value of the CDTM pharmacists, and respondents were supportive of the program.


From progressive nonfluent aphasia to corticobasal syndrome: a case report of corticobasal degeneration.
In a previous report, we presented longitudinal clinical, cognitive and anatomical data of a right-handed woman, whose clinical picture evolved from progressive nonfluent aphasia with apraxia of speech to corticobasal syndrome (CBS) in the last stage of the disease. The patient died at age 57 and pathological examination revealed severe atrophy in the left frontal operculum and left premotor area. On histological examination, there was diffuse tau-positive pathology in gray and white cortical hemispheric gray and white matter, basal ganglia and substantia nigra, compatible with corticobasal degeneration (CBD). This case demonstrates the clinical overlap between frontotemporal lobar degeneration and CBD. In this case, early motor speech impairment predicted earlier and more accurately than CBS the presence of underlying tau-pathology and CBD.


Effects of bilateral vestibular deafferentation in rat on hippocampal theta response to somatosensory stimulation, acetylcholine release, and cholinergic neurons in the pedunculopontine tegmental nucleus.
Vestibular dysfunction has been shown to cause spatial memory impairment. Neurophysiological studies indicate that bilateral vestibular loss (BVL), in particular, is associated with an impairment of the response of hippocampal place cells and theta rhythm. However, the specific neural pathways through which vestibular information reaches the hippocampus are yet to be fully elucidated. The aim of the present study was to further investigate the hypothesised 'theta-generating pathway' from the brainstem vestibular nucleus to the hippocampus. BVL, and in some cases, unilateral vestibular loss (UVL), induced by intratympanic sodium arsanilate injections in rats, were used to investigate the effects of vestibular loss on somatosensory-induced type 2 theta rhythm, acetylcholine (ACh) release in the hippocampus, and the number of cholinergic neurons in the pedunculopontine tegmental nucleus (PPTg), an important part of the theta-generating pathway. Under urethane anaesthesia, BVL was found to cause a significant increase in the maximum power of the type 2 theta (3-6 Hz) frequency band compared to UVL and sham animals. Rats with BVL generally exhibited a lower basal level of ACh release than sham rats; however, this difference was not statistically significant. The PPTg of BVL rats exhibited significantly more choline-acetyltransferase (ChAT)-positive neurons than that of sham animals, as did the contralateral PPTg of UVL animals; however, the number of ChAT-positive neurons on the ipsilateral side of UVL animals was not significantly different from sham animals. The results of these studies indicate that parts of the theta-generating pathway undergo a significant reorganisation following vestibular loss, which suggests that this pathway is important for the interaction between the vestibular system and the hippocampus.


How to Evaluate Fibrosis in IBD?
In this review, we will describe the importance of fibrosis in inflammatory bowel disease (IBD) by discussing its distinct impact on Crohn's disease (CD) and ulcerative colitis (UC) through their translation to histopathology. We will address the existing knowledge on the correlation between inflammation and fibrosis and the still not fully explained inflammation-independent fibrogenesis. Finally, we will compile and discuss the recent advances in the noninvasive assessment of intestinal fibrosis, including imaging and biomarkers. Based on the available data, none of the available cross-sectional imaging (CSI) techniques has proved to be capable of measuring CD fibrosis accurately, with MRE showing the most promising performance along with elastography. Very recent research with radiomics showed encouraging results, but further validation with reliable radiomic biomarkers is warranted. Despite the interesting results with micro-RNAs, further advances on the topic of fibrosis biomarkers depend on the development of robust clinical trials based on solid and validated endpoints. We conclude that it seems very likely that radiomics and AI will participate in the future non-invasive fibrosis assessment by CSI techniques in IBD. However, as of today, surgical pathology remains the gold standard for the diagnosis and quantification of intestinal fibrosis in IBD.


Bone loss and its management in long-term survivors from allogeneic stem cell transplantation.
Recently, great efforts have been made to understand the pathogenesis of bone loss after allogeneic stem cell transplant (allo-SCT) and possible treatments. A literature search of the MEDLINE database was performed to find articles in English using the search terms "allogeneic stem cell transplant" or "bone marrow transplant," in combination with "bone loss," "osteoporosis treatment," "osteoblast," "cytokines," or "osteoprotegerin." Reference lists from the articles retrieved were also evaluated for relevant information. Bone mineral density at the lumbar spine, but not at the femur, can improve or even recover several years after SCT. Multiple risk factors for posttransplant bone loss have been recently identified: abnormalities in the immune system function and their treatments, reduced production of growth factors, osteoclast activation by increased cytokine release, and decreased number and function of osteoblast precursors within the stromal stem cell compartment. Pamidronate was partially successful in preventing posttransplant bone loss, whereas both oral and parenteral bisphosphonates had beneficial effects on documented osteoporosis in long-term survivors. There is clear evidence that transplant-related bone loss is a multifactorial, early, and possibly long-lasting disorder. All patients who have already received allo-SCT should be evaluated as to their bone status and treated with appropriate supportive measures and specific treatments as soon as abnormalities are detected. Although preventive antiresorptive treatments are only partially effective, they should be started in all patients before or at the time of allo-SCT, regardless of their bone mineral density values, and continued at least for the first year after transplant.


Simultaneous feeding of calcium butyrate and tannin extract decreased the incidence of diarrhea and proinflammatory markers in weaned piglets.
This study was conducted to investigate the effect of associating calcium butyrate with tannin extract, compared to an antimicrobial on the growth performance, incidence of diarrhea, intestinal histology, immune-expression of cyclooxygenase-2 (COX-2) and tumor necrosis factor α (TNF-α) in piglets. Seventy-two piglets (36 barrows and 36 gilts) weaned at 28±2 d and initial body weight of 7.17±1.07 kg were allocated to 3 treatments in a randomized complete block design with 8 replicates per treatment and 3 animals per experimental unit. Treatments were composed of NC, negative control: basal diet without additives; PC, positive control: basal diet + 40 mg/kg of colistin sulfate; or BT, basal diet + calcium butyrate + tannin extract. The butyrate and tannin inclusion levels were 0.15% in the pre-starter phase and 0.075% in the starter phase. Incidence of diarrhea was monitored daily, and on d 14 and 35 of experiment, 1 animal from each experimental unit was slaughtered to collect intestinal samples. No significant differences were observed for growth performance. The butyrate-and tannin-based additive resulted in reduced (p<0.05) incidence of diarrhea in piglets during d 1 to 14 and d 1 to 35 in comparison with the other treatments. Piglets that consumed the diet containing the calcium-butyrate and tannin showed a lower (p<0.05) crypt depth in the duodenum than those receiving the NC treatment at 14 d of experimentation. The BT treatment provided a lower (p<0.05) immune-expression of COX-2 at 14 d and TNF-α at 35 d in the duodenum. Association between calcium butyrate and tannin extract resulted in a significant decrease in the incidence of diarrhea and inflammatory process in the duodenum of piglets. Therefore, calcium-butyrate combined with tannin could be a part of an alternative program to reduce the use of antimicrobials in the diet of weaned piglets.


Development of New Thiazole Complexes as Powerful Catalysts for Synthesis of Pyrazole-4-Carbonitrile Derivatives under Ultrasonic Irradiation Condition Supported by DFT Studies.
In this study, we are interested in preparing Fe(III), Pd(II), and Cu(II) complexes from new thiazole derivatives. All syntheses were elaborately elucidated to estimate their molecular and structural formulae, which agreed with those of mononuclear complexes. The square-planer geometry of Pd(II) complex (MATYPd) was the starting point for its use as a heterocatalyst in preparing pyrazole-4-carbonitrile derivatives 4a-o using ultrasonic irradiation through a facile one-pot reaction. The simple operation, short-time reaction (20 min), and high efficiency (97%) were the special advantages of this protocol. Furthermore, this green synthesis strategy was advanced by examination of the reusability of the catalyst in four consecutive cycles without significant loss of catalytic activity. The new synthesis strategy presented remarkable advantages in terms of safety, simplicity, stability, mild conditions, short reaction time, excellent yields, and use of a H2O solvent. This catalytic protocol was confirmed by the density functional theory (DFT) study, which reflected the specific characteristics of such a complex. Logical mechanisms have been suggested for the successfully exerted essential physical parameters that confirmed the superiority of the Pd(II) complex in the catalytic role. Optical band gap, electrophilicity, and electronegativity features, which are essential parameters for the catalytic behavior of the Pd(II) complex, are based mainly on the unsaturated valence shell of Pd(II).


Metalloproteomics: principles, challenges and applications to neurodegeneration.
Trace elements are required for a variety of normal biological functions. As our understanding of neurodegenerative disease advances we are identifying a number of metalloenzymes involved in disease process. Thus, the future of metals in neurobiology will rely more on detailed information regarding what metalloenzymes are present and how they are involved in the pathophysiology of disease. To gain this detailed information, we will rely less on bulk measures of the amount of a trace elements in a particular tissue and turn to metalloproteomic techniques to help elucidate both metalloprotein structure and function. Recent advances in metalloproteomics will translate to a richer understanding of the mechanism and precise role of metalloenzymes and proteins in the brain.


Sonographic evaluation of the fetal stomach: significance of nonvisualization.
The stomach was successfully visualized in 1051 (98%) of 1071 consecutive sonograms obtained in 995 fetuses after 14 weeks gestational age. All patients were studied prospectively. Stomach nonvisualization was associated with an abnormal outcome in 55% of the fetuses studied after 14 weeks and in 100% of the fetuses studied after 19 weeks. Fetal abnormalities included gastrointestinal and CNS malformations. Oligohydramnios was often present. The absence of a stomach on fetal sonograms obtained after 14 weeks gestational age strongly suggests fetal abnormality. Repeat sonograms should be obtained in all such cases.


The Development and Psychometric Evaluation of a Supplementary Index Score of the Neuropsychological Assessment Battery Screening Module that is Sensitive to Traumatic Brain Injury.
This study examines the validity of the NAB Screening Module (screening module of the neuropsychological assessment battery, S-NAB) in an acute traumatic brain injury (TBI) inpatient population and provides psychometric evaluation of an original index sensitive to TBI impairment. The utility of the S-NAB as a TBI screen was examined using a between groups design. One-hundred and four patients with mild complicated to severe TBI were recruited from a consecutive cohort of patients admitted as inpatients to a UK Major Trauma Centre. Ninety-eight control participants were selected from the S-NAB normative sample. All TBI patients completed the S-NAB during their inpatient stay. Control participants scored significantly higher than TBI participants on the Total Screening index (t = 3.626, p < 0.01), The Attention index (t = 7.882, p < 0.01), and the Executive index (t = 5.577, p < 0.01). A briefer TBI Impairment index of six subtests was constructed which accurately discriminated TBI patients from normative controls (t = 9.9, p < 0.01; Cohen's d = 1.54). The TBI index had excellent classification accuracy (AUC = 0.83), superior to that of the standard S-NAB indices. The TBI Index, Attention Index, and Total Screening Index demonstrated increasing impairment with increased severity of injury. The S-NAB TBI index is a robust, reliable screening index for use with acute TBI patients, which is sensitive to the effects of acute TBI. It affords a briefer cognitive screen than the S-NAB and demonstrates a dose response relationship to TBI severity.


Sabbatical policies and their implementation at United States dental schools.
An ad hoc Committee on Sabbaticals created by the Council of Faculties of the AADS surveyed sabbatical policies and their implementation at dental schools in the United States. Data from a questionnaire completed by 56 of 60 members of the Council of Faculties reveal that a majority of U.S. dental schools have sabbatical policies but that dental educators are less likely to apply for or to be awarded sabbaticals than educators from other parts of the university, except perhaps the medical school. Information was also obtained on the regulations governing sabbaticals--interval between leaves, rates of remuneration, and rules defining how the leave may be spent. Finally, suggestions are made as to how this important benefit of academic life might be made more available to dental educators.


Afterload reduction and cardiac output in patients after mitral valve surgery.
Thirteen patients who had mitral valve surgery were studied within 3 hours after operation. The patients were divided into 2 groups: group A with initial low cardiac index (1.70 +/- 0.25), elevated left atrial pressure (16.5 +/- 6.7) and high peripheral vascular resistance (2623 +/- 789); group B with initial normal cardiac index (3.71 +/- 0.54), normal left atrial pressure (13 +/- 3.5) and normal peripheral vascular resistance (1223 +/- 303). In both groups the mean arterial pressure was elevated (98 +/- 8.8, 96 +/0 15.8). An infusion of nitroprusside to reduce the mean arterial pressure to either 80 mmHg or 10% below the initial value had different effects in each group. In group A, cardiac index (CI) increased by 23%, left atrial pressure (LAP) decreased by 20%, pulmonary artery pressure (PAP) by 35%, and peripheral vascular resistance (PRV) by 32%. In group B, CI decreased by 8%, LAP by 32%, PAP by 30% and PVR by 13%. When LAP returned to initial values after an infusion of blood with continued infusion of nitroprusside, CI increased in both groups (27%, 11%) and the PVR remained lower (40%, 29%). The study demonstrates the favorable effect on cardiac output of vasodilator therapy on patients with elevated blood pressure, impaired by left ventricular function and high LAP, after surgery on mitral valve. The optimal effect is achieved by keeping the LAP within normal limits.


Peripheral signals in the control of satiety and hunger.
Food intake is critical for survival and is a complex behavior with multiple levels of control. Short-term, meal-related signals arise from many sources including the gastrointestinal tract, the environment, and higher centers in the brain. As described in this review, inputs from the gastrointestinal tract can exert potent effects on meal initiation, meal termination, and meal frequency. The complex array of signals generated from the gastrointestinal system and from adipose tissue, which participate in the regulation of food intake, and specifically how these signals relate to satiety and hunger, is the focus of this review. Literature on the role of the well-studied gastrointestinal peptide, cholecystokinin, in satiety, in addition to its interaction with long-term adiposity signals in mediating food intake will be reviewed. In addition, literature on the gastrointestinal hormones glucagon-like-peptide 1, apolipoprotein A-IV and peptide YY, and how they may act to regulate satiety, is described. Finally, the newly discovered hormone, ghrelin, and how it relates to meal initiation and hunger is discussed. A better understanding of these systems and how they relate to body adiposity will prove to have important clinical applications. The available data suggest that interventions directed at multiple targets in the energy homeostasis system may be necessary to achieve and maintain weight loss.


Impaired plasma viscosity via increased cholesterol levels in peripheral occlusive arterial disease [correction of disase].
The aim of this study was to investigate the relationship between plasma viscosity and lipoprotein and apolipoprotein pattern in normo- and hypercholesterolemic patients with peripheral occlusive arterial disease (POAD). 40 patients with POAD have been selected (8 females and 32 males, mean age: 54+/-3.2 years) with clinically evident superficial femoral occlusive artery disease. They were separated into two groups as normocholesterolemic (plasma total cholesterol <200 mg/dl) and hypercholesterolemic (plasma total cholesterol >200 mg/dl). Plasma total cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides, total protein, and albumin levels were determined by enzymatic methods using commercial kits. Levels of apolipoprotein AI (apo AI), and apolipoprotein B (apo B) were measured using a immunoturbidometric method. Plasma viscosity (PV) was measured by capillary viscometer. Classifying the patients with PAOD according to the cholesterol levels; hypercholesterolemic (mean total-cholesterol: 227.90+/-26.97 mg/dl) patients had significantly higher LDL-C, PV and triglyceride levels compared with nornocholesterolemic patients (p<0.001, p<0.001, p<0.001, respectively). HDL-C and apo B were significantly lower in hypercholesterolemic patients than in normocholesterolemic patients (p<0.001, p<0.001, respectively). PV was positively correlated with total cholesterol (r=0.485, p<0.05), atherogenic index (r=0.624, p<0.01), total-C/HDL-C ratio (r=0.624, p<0.05), and LDL-C/HDL-C ratio (r=0.707, p<0.001) in hypercholesterolemic patients with POAD. PV was higher in hypercholesterolemic patients with POAD than in normocholesterolemic patients with POAD. We suggest that POAD patients should be regarded as a heterogenous group with lipid and lipoprotein parameters in order to assess the microcirculation in the affected limb. In case of dyslipidemia in POAD patients an elevated plasma viscosity should be considered as coexisting risk factor.


Quasi-free-standing epitaxial graphene on SiC obtained by hydrogen intercalation.
Quasi-free-standing epitaxial graphene is obtained on SiC(0001) by hydrogen intercalation. The hydrogen moves between the (6 square root(3) x 6 square root(3))R30 degrees reconstructed initial carbon layer and the SiC substrate. The topmost Si atoms which for epitaxial graphene are covalently bound to this buffer layer, are now saturated by hydrogen bonds. The buffer layer is turned into a quasi-free-standing graphene monolayer with its typical linear pi bands. Similarly, epitaxial monolayer graphene turns into a decoupled bilayer. The intercalation is stable in air and can be reversed by annealing to around 900 degrees C.


Incisional administration of local anesthetic provides satisfactory analgesia following port access heart surgery.
To evaluate the new method of postoperative pain relief following port access (PA) heart surgery. Patients scheduled for PA heart surgery under cardioplegic arrest were enrolled in the study. At the end of the operation an epidural catheter was placed in the surgical wound. Analgesia was started with a bolus of 20 mL 0.75% ropivacaine through the catheter followed by 0.15% ropivacaine administered via patient control analgesia pump. Metamizol was also given to the patient every 12 hours intravenously (IV), and, in the case of inadequate analgesia, the rescue analgetic piritramid IV was used. The variables recorded were the visual analogue scale (VAS), the number of bolus applications of local anesthetic, and the number of bolus applications of rescue analgetic piritramid. The pain control at the end of the operation was satisfactory with all patients who were extubated on the table. In the first 24 hours the mean VAS pain score was 2.5, the number of bolus applications of local anesthetic was 2.0, and the number of applications of rescue medication was 1.5. There were no wound infections related to the catheter and no complications related to local anesthetic. The incisional administration of local anesthetic provides satisfactory pain control after PA heart surgery.


[Dangerous aquaria].
World trends for a home breeding of exotic freshwater and marine fishes did not miss Poland. There are almost all species of aquarium fishes available in Polish pet shops, but there is not enough information about threat given to customers. In some fish, there are masses of one-cell glands, mainly serous, in the proximity of the spines. In others, those one-cell glands may be grouped in larger aggregates of cells called venom glands, that may form organs resembling multicellular glands of terrestrial animals. They are usually located around the spines or hard rays of the fins. Even if covered with a connective tissue sheath, the aggregates of the venom cells do not have any common outlet; they are not, therefore, proper multicellular glands. The venom glands of the catfish are covered with a thin sheath and they release their contents when the fin ray is pressed. Spines are derived from fin rays. When the spine penetrates the body of its prey, it presses its base against the cells, squashes them and squeezes the venomous contents into the wound. Catfish, lionfish and stonefish have the venom glands producing secretion which could be dangerous. The eels and morays blood is also dangerous, as well as slime of reduced squamae. Poison information centers noted several cases of fishes' stings in Poland.


Quality assurance in cervical cancer screening: results of a proficiency testing scheme for cytology laboratories in the north west Thames region.
To examine the effectiveness of introducing External Quality Assessment (EQA) into all laboratories which undertake gynaecological cytopathology. To assess pathologists and cytotechnologists regularly for their competence to screen cervical smears, regardless of their standing in the laboratory hierarchy or their experience of gynaecological cytopathology. Each participant was asked to screen and report on 10 slides during a 2 h period. The assessment was carried out by a facilitator under the direction of a specially appointed EQA Committee. A maximum score of 20 points was awarded for a completely correct set of answers. A minus score was awarded for a missed abnormal smear. Seventeen pathology laboratories in North West Thames Regional Health Authority participated; 146 cytologists were assessed. A pilot and four rounds of EQA have been completed and a total 5350 smears examined. Out of 2568 dyskaryotic (abnormal) smears screened, 0.7% were not identified correctly. Of the 146 cytologists taking part in the assessment, 95% achieved a score of 17 or more. Three participants were identified who did not reach an acceptable level of competence and appropriate remedial action was taken. The EQA scheme detected unacceptable levels of performance which can be quickly rectified. Participation of 100% has been maintained on a voluntary basis, and 4 years experience of the scheme confirms that a very high standard of screening prevails in the Region. The study illustrates that voluntary self-regulation is acceptable in the NHS, and the introduction of similar EQA schemes on a national scale will go a long way to establishing confidence in the cervical cancer screening programme.


Fast structure-based virtual ligand screening combining FRED, DOCK, and Surflex.
A protocol was devised in which FRED, DOCK, and Surflex were combined in a multistep virtual ligand screening (VLS) procedure to screen the pocket of four different proteins. One goal was to evaluate the impact of chaining "freely available packages to academic users" on docking/scoring accuracy and CPU time consumption. A bank of 65 660 compounds including 49 known actives was generated. Our procedure is successful because docking/scoring parameters are tuned according to the nature of the binding pocket and because a shape-based filtering tool is applied prior to flexible docking. The obtained enrichment factors are in line with those reported in recent studies. We suggest that consensus docking/scoring could be valuable to some drug discovery projects. The present protocol could process the entire bank for one receptor in less than a week on one processor, suggesting that VLS experiments could be performed even without large computer resources.


Neutrophilic inflammation promotes SARS-CoV-2 infectivity and augments the inflammatory responses in airway epithelial cells.
In response to viral infection, neutrophils release inflammatory mediators as part of the innate immune response, contributing to pathogen clearance through virus internalization and killing. Pre-existing co- morbidities correlating to incidence of severe COVID-19 are associated with chronic airway neutrophilia. Furthermore, examination of COVID-19 explanted lung tissue revealed a series of epithelial pathologies associated with the infiltration and activation of neutrophils, indicating neutrophil activity in response to SARS- CoV-2 infection. To determine the impact of neutrophil-epithelial interactions on the infectivity and inflammatory responses to SARS-CoV-2 infection, we developed a co-culture model of airway neutrophilia. SARS-CoV-2 infection of the airway epithelium alone does not result in a notable pro-inflammatory response from the epithelium. The addition of neutrophils induces the release of proinflammatory cytokines and stimulates a significantly augmented pro-inflammatory response subsequent SARS-CoV-2 infection. The resulting inflammatory response is polarized with differential release from the apical and basolateral side of the epithelium. Additionally, the integrity of the epithelial barrier is impaired with notable epithelial damage and infection of basal stem cells. This study reveals a key role for neutrophil-epithelial interactions in determining inflammation and infectivity in response to SARS-CoV-2 infection.


Cytomorphological patterns of tubercular lymphadenitis and its comparison with Ziehl-Neelsen staining and culture in eastern up. (Gorakhpur region): Cytological study of 400 cases.
Tuberculous lymphadenitis is most common cause of lymphadenopathy in developing countries. Although enormous literature is available on various aspects of the disease including cytological patterns and its incidence in others parts of India and in other countries, only limited literature is available regarding its incidence and morphological spectrum on cytology in eastern parts of Uttar Pradesh in Gorakhpur region. The present study was undertaken to estimate the incidence of tuberculous lymphadenitis in our settings along with its morphological spectrum on cytology as well as to determine the utility of culture of fine needle aspirates in addition to cytology and Ziehl-Neelsen (ZN) staining. Four hundred cases of superficial lymphadenopathy were subjected to fine needle aspiration cytology (FNAC), and in case, smears were stained with Hematoxylin and eosin (H and E), Giemsa, and ZN stain and categorized into three cytomorphological patterns. All the aspirates were inoculated on two sterile Lowenstein Jensen (LJ) medium. Out of 400 cases of consecutive lymph nodes aspirated, 180 cases (45%) showed features of tuberculous lymphadenitis. Smears revealed epithelioid granulomas with caseous necrosis in maximum cases (40%). On statistical analysis, difference between group I and group II was found to be significant (P < 0.05); while comparison between groups II and III as well as between groups I and III was found to be statistically insignificant. Overall, acid fast bacilli positivity was seen in 51.6% of the cases. FNAC has been proved very safe, highly sensitive, and first line investigation in diagnosing tubercular lymphadenitis. The sensitivity can be further be increased by complementary cytomorphology with acid fast staining. Diagnostic accuracy can further be increased by culture.


Variation in subsurface seawater temperature off Discovery Bay, Jamaica and the U.S. Virgin Islands.
Long-term, high accuracy seawater temperature data sets are essential in studies assessing environmental changes that may alter coral reef communities. Located at the approximately the same latitude, the subsurface seawater temperature (S3T) off Discovery Bay, Jamaica (DBJ) and the U.S. Virgin Islands (USVI) had the same overall mean temperature. The USVI S3T during the winter months is approximately 0.5 degrees C warmer than DBJ, while May - July at DBJ is approximately 1 degrees C warmer than USVI S3T. With the passing of tropical storms in 1995 and 1997 in the USVI S3T dropped as much as 1.5 degrees C within a 20 hr period and did not revert to the previous temperature during that calendar year. Mean monthly S3T during 2000 and 2001 in the USVI was > 0.5 degrees C warmer than during similar periods in the early 1990s. Mean monthly S3T during 1999-2002 at DBJ was 0.27 degrees C cooler than during 1994-1995.


Agonist-stimulated and basal phosphatidylethanol formation in neutrophils from alcoholics.
Phospholipase D has been shown to be a key enzyme in the signal transduction systems involved in neutrophil activation. In the presence of ethanol, the enzyme catalyzes a transphosphatidylation reaction through which phosphatidylethanol is formed instead of the normal product phosphatidic acid. The effects of ethanol on the formation of phosphatidylethanol and phosphatidic acid was studied in neutrophils from human alcoholics in vitro. Neutrophils were isolated and cellular lipids were labeled with [3H]oleate, whereafter the cells were preincubated with cytochalasin B. Subsequently, cells were stimulated with the chemotactic peptide formyl-Met-Leu-Phe in the presence of ethanol concentration ranging from 0 to 200 mM. In the presence of ethanol, both neutrophils from alcoholics and controls produced phosphatidylethanol, with a concomitant reduction of the production of phosphatidic acid. The amounts of phosphatidyl-ethanol and phosphatidic acid formed were dependent on the concentration of ethanol. In neutrophils from alcoholics, a higher apparent Km for the phospholipase D-mediated transphosphatidylation reaction was noted (58 mM ethanol compared with 28 mM in controls). The in vivo mass of phosphatidylethanol in recently drinking alcoholics was also analyzed in neutrophils. Measurable phosphatidyl-ethanol levels (average 5.6 pmol/10(8) neutrophils) were found in alcoholics up to 23 hr after the last intake of ethanol. Thus, in addition to the ethanol-induced changes in the normal production of phosphatidic acid, phosphatidylethanol accumulated in vivo in alcoholics may be expected to influence neutrophil function.


Common pathogens isolated in diabetic foot infection in Bir Hospital.
Foot ulcers are a frequent complication of patients suffering with diabetes mellitus, accounting for up to 20% of diabetes-related hospital admission . Secondary infection of these ulcers is by far the leading cause of amputation of feet and legs and the polymicrobial nature of diabetic foot infection has been well documented in the literature. The present study sought to reveal the bacterial etiology of diabetic foot ulcer in patients presenting to Bir Hospital. A 1 year retrospective study was carried out to analyse the bacterial isolates of all patients admitted with diabetic foot infection presented with Wagner grade 2 -5 ulcers. Bacteriological diagnosis and antibiotic sensitivity profiles were carried out and analysed using standard procedures. Diabetic polyneuropathy was found to be common in (51.1%) and gram positive bacteria were isolated more often than gram-negative ones in the patients screened. The most frequent bacterial isolate were Staphylococcus aureus (38.4%), Pseudomonas aeruginosa (17.5%), and Proteus (14%). Imipenem was the most effective agent against gram-negative organisms. Vancomycin was found to be most effective against gram-positive organisms. Staph aureus and Pseudomonas aeruginosa were the most common causes of diabetic foot infections in Bir Hospital. Theses wounds require use of combined antimicrobial therapy for initial management, repeated dressing and wound debridements were done.


Expression of vascular endothelial growth factor and transforming growth factor alpha in rat testis during chronic renal failure.
Vascular endothelial growth factor (VEGF) is known to influence testis function. Transforming growth factor alpha (TGF-α) is expressed in the postnatal testis, and has been demonstrated to stimulate testis development. Systemic diseases such as chronic renal failure (CRF) interfere with hypothalamic-pituitary-gonadal axis, which may cause defective steroidogenesis and gonadal functions. The aim of this study was to investigate the expression and localization of VEGF and TGF-α in testicular tissues of experimental CRF model. Experimental CRF was induced in rats by the resection of more than 85% of renal mass. The expression of VEGF and TGF-α in testicular tissues were assessed by immunohistochemistry on paraffin sections of control, CRF-nondialysed and CRF-dialysed rats. The microscopic evaluation of the testicular structure showed that CRF did not affect testicular histology. Immunohistochemical evaluation showed that VEGF was expressed in the cytoplasm of primary and secondary spermatocyte series as well as the early spermatids. Staining intensity was lower in spermatocytes going through the first meiotic division. TGF-α was expressed in the nuclei of spermatogonia and primary spermatocytes with stronger staining intensity in spermatogonia. The intensity of VEGF staining was similar in control and experimental animals, however, TGF-α expression was lower in the CRF group. The continuous expression of VEGF in spermatocytes and spermatids suggests that the applied model of CRF does not directly disrupt morphology of seminiferous epithelium, thus also spermiogenesis. However, difference between control rats and CRF group in TGF-α immunopositivity, which was localised in spermatogonial mitosis step, may suggest the interference of CRF with early stages of spermatogenesis.


Prosthetic restoration following removal of chondrosarcoma in the premaxillary region: a case presentation and follow-up for 16 years.
The present report describes a relatively simple but effective prosthodontic treatment following removal of a moderately well differentiated osteogenic chondrosarcoma in the premaxillary region. Following removal of a rare tumor, a young man was treated with gold crowns on three molars and a metal-ceramic crown on a first premolar, with attachments in the areas facing the defect for esthetic reasons. A removable partial denture was retained by the attachments and conventional cast retentive circumferential clasps, including a hollow obturator filling the defect. The restoration has served the patient for 16 years, seemingly without discomfort, and it has not required any maintenance. The patient has kept up with his oral hygiene, using conventional methods for the teeth and prosthesis, with periodic flushing with chlorhexidine solution. He has lived a normal family life and finished his university education. The problem-free use of the appliance can be at least partly explained by the patient taking oral hygiene measures seriously from the beginning. This report explains how relatively uncomplicated prosthodontic measures can enormously affect quality of life.


[Primary ciliary dyskinesia complicated by male infertility: An update].
Primary ciliary dyskinesia (PCD) is an autosomal recessive genetic disease. Gene mutation leads to ciliary structural abnormalities or functional defects, resulting in respiratory diseases. Male patients with PCD are prone to infertility, which pathogenically may be attributed to gene mutation-induced dysfunction of respiratory cilia and sperm flagella. This reviews focuses on the research progress in microtubule structure, gene mutation and outcomes of assisted reproduction relating to PCD complicated by male infertility.


Occupational health in the Russian Federation.
Occupational health and safety in Russia has a long history, starting in 1866. Preventive and curative services are offered all over the country. Due to rapid, intense, and deep political changes, social and economic reforms led to democracy and a market economy. During this transition in the 1990s, the rate of industrial growth was negative, and the overall health of the working population decreased significantly. Although the economy began to recover, many workers are still exposed to occupational hazards at levels that exceed strict hygienic standards. Occupational health and safety practice has been adjusted to the new social economic system, but to be efficient, it needs essential restructuring, with special attention to health protection, health promotion, and prevention of injuries and diseases.


Musical training facilitates the neural discrimination of major versus minor chords in 13-year-old children.
Music practice since childhood affects the development of hearing skills. An important classification in Western music is the chords' major-minor dichotomy. Its preattentive auditory discrimination was studied here using a mismatch negativity (MMN) paradigm in 13-year-olds with active hobbies, music-related (music group) or other (control group). In a context of root major chords, root minor chords and inverted major chords were presented infrequently. The interval structure of inverted majors differs more from root majors than the interval structure of root minors. However, the identity of the chords is the same in inverted and root majors (major), but different in root minors. The deviant chords introduced no new frequencies to the paradigm. Hence, an MMN caused by physical deviance was prevented. An MMN was elicited by the minor chords but not by the inverted majors. The MMN amplitude in the music group was larger than in the control group. Thus, the conceptual discrimination skills are present already in the preattentive processing level of the auditory cortex, and musical training can advance these skills.


Patients with coronary slow flow phenomenon demonstrate normal myocardial blood flow and arterial wave reflection between acute episodes.
Patients with coronary slow flow (CSF) present with a syndrome (often recurrent) of resting angina with no significant coronary stenoses. The nature of myocardial blood flow (MBF), MBF reserve and systemic arterial characteristics may contribute to symptoms in these patients but this has not been examined previously. This study sought to measure MBF, arterial stiffness and wave reflection in patients with CSF and controls. Ten patients with angiographically proven CSF and 20 controls underwent dipyridamole-exercise stress myocardial contrast echocardiography and arterial waveform analysis. MBF was quantified off-line from 10 mid and apical segments with calculation of myocardial blood volume (A), red cell velocity (beta) and their product, MBF, at rest and post-stress. MBF reserve was calculated as the ratio of peak stress to resting MBF. Central arterial pressure waveforms were derived by radial tonometry, with arterial wave reflection expressed by augmentation index. Arterial stiffness was determined by aortic and brachial pulse wave velocities. There was no significant difference between CSF and control groups in mean resting beta (0.56+/-0.24 versus 0.59+/-0.26), A (7.9+/-1.4 versus 7.9+/-5.2), MBF (4.3+/-1.8 versus 4.4+/-3.6), MBF reserve (3.7+/-2.0 versus 4.0+/-2.0), augmentation index (26+/-12 versus 23+/-9%), aortic (7.4+/-1.8 versus 7.4+/-1.5 m/s) or brachial (8.0+/-0.8 versus 8.1+/-1.3) pulse wave velocity (p>0.4 for all). Similarly, there were no significant haemodynamic differences between groups after exercise (p>0.2 for all). MBF, large artery stiffness and arterial wave reflection characteristics are normal in CSF patients between their acute episodes.


Women's experiences of, and preferences for, postpartum contraception counselling.
The lack of access to and uptake of postpartum contraception is a key contributor to an estimated 121million unintended pregnancies worldwide. Research on counselling and women's preferences for postpartum contraception is scarce in Australia. We therefore aimed to explore Australian women's experiences of, and preferences for, accessing postpartum contraceptive counselling. In this qualitative study, English-speaking women of reproductive age (18-40years) with at least one child under the age of 5years were recruited via social media to participate in a semi-structured telephone interview. Interviews focussed on women's experiences of, and preferences for, postpartum contraception. The interviews were audio-recorded, transcribed, coded and thematically analysed. Twenty women participated. Most did not receive in-depth contraceptive counselling antenatally or postnatally, though had brief discussions with their GPs or obstetricians at the 6-week postnatal check. Participants felt some counselling throughout their antenatal and postnatal care would have been useful, particularly those who experienced medical complications perinatally. Most participants expressed a general preference for their GP or a midwife to provide such counselling, rather than an obstetrician or nurse, and they noted characteristics such as compassion, trust and care as being particularly important. The provision of postpartum contraceptive counselling could be enhanced in Australia. Contraceptive uptake in the postpartum period may be promoted by ensuring consistent and routine provision of contraceptive counselling for women antenatally and postnatally by their maternity carers.


Far-lateral approach to the craniocervical junction.
The far-lateral approach is an extension of the standard suboccipital approach, designed to maximize exposure of the lateroventral craniocervical junction. Following a basic principle of cranial base surgery, the angle of view is increased by bone removal. Bone removal involves the most lateral part of the inferior occipital squama and the posterior arch of C1. Drilling of various portions of the occipital condyle further increases the exposure. Transposition of the vertebral artery is seldom required. The far-lateral approach allows a tangential, unobstructed view of the lateroventral cervicomedullary area and can be applied effectively to manage with a heterogeneous spectrum of pathological lesions involving this area. The technical aspects of the procedure are briefly illustrated in this report.


An X1X1X2X2/X1X2Y mechanism of sex determination in a South American rodent, Deltamys kempi (Rodentia, Cricetidae).
Chromosome studies on 14 specimens of Deltamys kempi disclosed six males with 2n = 37, NF = 38, six females with 2n = 38, NF = 38, and two females with 2n = 37, NF = 38. G- and C-band analyses revealed a Y-autosome translocation in the males leading to a multiple chromosome system of sex determination of the type X1X1X2X2/X1X2Y, this being the second case of such a mechanism described in rodents. At meiosis the males presented a trivalent in which C-banding studies showed an alternate orientation of the sex chromosomes due to end-to-end association of the X1 and Y chromosomes, the Y and the X2 being held together by interstitial chiasmata. At metaphase II both n = 17 + Y and n = 18 + X1 are regularly observed. The two females with 2n = 37, NF = 38, are heterozygous for an autosomal centric fusion involving chromosomes 1 and 13. The product of the Y-autosome translocation constitutes the largest element of the karyotype (9.4% of the haploid set); the X1 chromosome amounts to 7.8% of this set, including a large heterochromatic block. When only its euchromatic region is considered, this percentage decreases to 4.6%. From two to seven NORs were observed at the telomeres, with a mean of 4.4 +/- 1.1 per cell.


Impact of stress hyperglycemia ratio on mortality in patients with critical acute myocardial infarction: insight from american MIMIC-IV and the chinese CIN-II study.
Among patients with acute coronary syndrome and percutaneous coronary intervention, stress hyperglycemia ratio (SHR) is primarily associated with short-term unfavorable outcomes. However, the relationship between SHR and long-term worsen prognosis in acute myocardial infarction (AMI) patients admitted in intensive care unit (ICU) are not fully investigated, especially in those with different ethnicity. This study aimed to clarify the association of SHR with all-cause mortality in critical AMI patients from American and Chinese cohorts. Overall 4,337 AMI patients with their first ICU admission from the American Medical Information Mart for Intensive Care (MIMIC)-IV database (n = 2,166) and Chinese multicenter registry cohort Cardiorenal ImprovemeNt II (CIN-II, n = 2,171) were included in this study. The patients were divided into 4 groups based on quantiles of SHR in both two cohorts. The total mortality was 23.8% (maximum follow-up time: 12.1 years) in American MIMIC-IV and 29.1% (maximum follow-up time: 14.1 years) in Chinese CIN-II. In MIMIC-IV cohort, patients with SHR of quartile 4 had higher risk of 1-year (adjusted hazard radio [aHR] = 1.87; 95% CI: 1.40-2.50) and long-term (aHR = 1.63; 95% CI: 1.27-2.09) all-cause mortality than quartile 2 (as reference). Similar results were observed in CIN-II cohort (1-year mortality: aHR = 1.44; 95%CI: 1.03-2.02; long-term mortality: aHR = 1.32; 95%CI: 1.05-1.66). In both two group, restricted cubic splines indicated a J-shaped correlation between SHR and all-cause mortality. In subgroup analysis, SHR was significantly associated with higher 1-year and long-term all-cause mortality among patients without diabetes in both MIMIC-IV and CIN-II cohort. Among critical AMI patients, elevated SHR is significantly associated with and 1-year and long-term all-cause mortality, especially in those without diabetes, and the results are consistently in both American and Chinese cohorts.


Influence of Parenting Guilt on the Mental Health among Single-Parent Women: Multiple Additive Moderating Effect of Economic Well-Being and Level of Education.
This study explored how the core problems (e.g., parenting, economy, and education level) of single-parent women affect their mental health. Although parenting guilt, economic well-being, and level of education are important variables that affect the mental health of single parents, there is no study that examines the interaction effect between them together. Therefore, this study examined the moderating effects of economic well-being and level of education on the relationship between parenting guilt and mental health in 419 single-parent women. In addition, it was verified whether there was a multiple additive modulation effect when they were put in at the same time. As a result, the higher the parenting guilt and the lower the economic well-being, the higher the level of mental health pain, but the level of education had no statistical significance. However, the interaction term between parenting guilt and education level had statistical significance, while the interaction term between parenting guilt and economic well-being did not produce significant results. These findings suggest the importance of education for single-parent women's mental health as well as the need to establish policies that allow them to have sufficient time and room for child rearing.


New C20-diterpenoid alkaloids from Aconitum vilmorrianum and structural revision of 2-O-acetylorochrine and orochrine.
Three new C20-diterpenoid alkaloids vilmorrianines E (1), F (2), and G (3) were isolated from the whole plants of Aconitum vilmorrianum, along with one artifact N-chloromethyl vilmorrianine E hydrochloride (4), as well as two known alkaloids hemsleyaconitines F (5) and G (6). The structures of 1-4 were established by HR-ESI-MS, 1D-, 2D-NMR (HMQC, HMBC, and NOESY), and single-crystal X-ray diffraction analysis. In addition, the structures of naturally occurring 2-O-acetylorochrine (7) and orochrine (8) were revised to be the known alkaloids heterophylloidine (9) and deacetyl heterophylloidine (10), respectively, on the basis of consideration of transannular effect and chemical correlations.


[Imaging the tear film and in vivo cornea. Initial results with a modified confocal laser scanning ophthalmoscope].
As the slit-lamp technique is an restrictive method for the in-vivo examination and documentation of the multi-layer structure and the dynamics of the tear film and the cornea, e.g. during wound-healing processes, our aim was to find out whether it is possible to change the confocal laser scanning ophthalmoscope (CLSO; Zeiss) into a high-resolution confocal laser scanning microscope (CLSM) for the visualization of the anterior segments of the eye and the tear film by adapting a special objective system. In order to gain information concerning the function of such a cornea microscope we examined selected patients with erosion or pterygium before and after operation and subsequent phototherapeutic keratectomy (PTK), as well as some in-vitro corneal surfaces after photorefractive keratectomy (PRK). We developed an objective adapter for the CLSO in order to focus the laser beam onto anterior segments of the eye to visualize the tear film and the layer structure of the cornea. By combining the long-distance objective or a contract objective with different zoom-optic lenses it was possible to alter the scan field size and so the magnification of the CLSM by a factor of up to 1000. The CLSM provides a new method for the in-vivo examination of the tear film and its dynamics as well as the thin layers of the cornea in real-time imaging technique with high contrast and resolution in non-contact or contact procedures. This system is a unique took for evaluating and monitoring the effect of excimer laser ablation after PTK and PRK on the corneal surface and the dynamics of the tear film. The application of this method causes no pain for the patient.


Unusual cystic neoplasms in the pancreas: radiologic-pathologic correlation.
Cystic neoplasms in the pancreas encompass a broad spectrum of benign, borderline, and malignant lesions that either are primarily cystic or result from the cystic degeneration of solid tumors. Although these lesions show different histologic findings, the overlap of the radiologic findings for many pancreatic cystic lesions makes differentiation difficult, and the clinical manifestations can also overlap. Therefore, some of the pancreatic cystic lesions, especially uncommon lesions, can cause diagnostic confusion, and this may result in unnecessary surgery or inappropriate follow-up. In this article, we discuss and illustrate the radiologic features of unusual cystic neoplasms and the unusual findings of the relatively common cystic neoplasms in the pancreas. We also correlate the radiologic findings with the findings on pathologic analysis.


Experimental characterization of entanglement dynamics in noisy channels.
We experimentally characterize the bipartite entanglement under one-sided open system dynamics and verify the recently formulated entanglement factorization law [Nature Phys. 4, 99 (2008)]. The one-sided open system dynamics is realized by implementing a phase damping and an amplitude decay channel, respectively, acting on one of the qubits, by an all-optical setup. Our results greatly simplify the characterization of entanglement dynamics and will play an important role in the construction of complex quantum networks.


Spondylolysis and isthmic spondylolisthesis: impact of vertebral hypoplasia on the use of the Meyerding classification.
Spondylolysis and isthmic spondylolisthesis are common multifactorial disorders. The extent of slipping of the spondylolytic vertebra is considered a major predicator for prognosis and further follow-up. Vertebral hypoplasia is a common finding associated with spondylolysis. The purpose of this study is to evaluate the incidence of hypoplastic vertebral bodies in patients with spondylolysis and in the general population and to analyse the impact of the findings on the measurement and grading of spondylolisthesis. 140 patients with 141 levels of spondylolysis identified by MRI were included in this study. The slippage of the spondylolytic vertebral body and the size in the midline sagittal image were measured and correlated. In addition, a randomised control group was evaluated to test the hypothesis that shortened, hypoplastic vertebral bodies can also be found in the general population. Shortened, hypoplastic vertebrae were found in 50 patients with spondylolysis and none was found in the control group. These shortened vertebrae mimicked spondylolisthesis and in 19 patients the slippage equalled the shortening, thus mimicking spondylolisthesis, although only spondylolysis was present. Sagittal shortening of the spondylolytic vertebra is common and may mimic spondylolisthesis. In order to define and measure spondylolisthesis the shortening of the spondylolytic vertebra has to be taken into account.


Binding affinity prediction of S. cerevisiae 14-3-3 and GYF peptide-recognition domains using support vector regression.
Proteins interact with other proteins and bio-molecules to carry out biological processes in a cell. Computational models help understanding complex biochemical processes that happens throughout the life of a cell. Domain-mediated protein interaction to peptides one such complex problem in bioinformatics that requires computational predictive models to identify meaningful bindings. In this study, domain-peptide binding affinity prediction models are proposed based on support vector regression. Proposed models are applied to yeast bmh 14-3-3 and syh GYF peptide-recognition domains. The cross validated results of the domain-peptide binding affinity data sets show that predictive performance of the support vector based models are efficient.


Monte Carlo modeling of geminate recombination in polymer-polymer photovoltaic devices.
A Monte Carlo model is used to examine geminate pair dissociation in polymer-polymer photovoltaic devices. It is found that increasing one or both carrier mobilities aids geminate separation yield eta(GS) particularly at low fields. This, in turn, leads to improved maximum power output from polymer-polymer blend photovoltaics, even when carrier mobilities are unbalanced by a factor of 10. The dynamic behaviors of geminate charges that eventually separate and recombine are examined for the first time. It is shown that geminate pairs in a bilayer become effectively free when separated by approximately 4 nm, which is far smaller than the thermal capture radius of 16 nm here. This may lead one to expect that eta(GS) would not be limited by the separation allowed by the morphology once the domain size has increased above 4 nm. In fact it is found that eta(GS) in a blend improves continuously as the average domain size increases from 4 to 16 nm. We show that although a small degree of separation may be available in a blend, the limited number of possible routes to further separation makes charge pairs in blends more susceptible to recombination than charge pairs in a bilayer.


Improving estimation and prediction in linear regression incorporating external information from an established reduced model.
We consider a situation where there is rich historical data available for the coefficients and their standard errors in a linear regression model describing the association between a continuous outcome variable Y and a set of predicting factors X, from a large study. We would like to use this summary information for improving inference in an expanded model of interest, Y given X,B. The additional variable B is a new biomarker, measured on a small number of subjects in a new dataset. We formulate the problem in an inferential framework where the historical information is translated in terms of nonlinear constraints on the parameter space and propose both frequentist and Bayes solutions to this problem. We show that a Bayesian transformation approach proposed by Gunn and Dunson is a simple and effective computational method to conduct approximate Bayesian inference for this constrained parameter problem. The simulation results comparing these methods indicate that historical information on E(Y|X) can improve the efficiency of estimation and enhance the predictive power in the regression model of interest E(Y|X,B). We illustrate our methodology by enhancing a published prediction model for bone lead levels in terms of blood lead and other covariates, with a new biomarker defined through a genetic risk score.


Anti-CD8 monoclonal antibody protects against spontaneous IgA nephropathy in ddY mice.
We investigated the effects of anti-CD4 monoclonal antibody (mAb) and/or anti-CD8 mAb in ddY mice, an animal model of spontaneous IgA nephropathy. Female ddY mice were treated with 18 intravenous injections of anti-CD4 and/or anti-CD8 mAb at 2-week intervals. This was based on our observation that a single injection of anti-CD4 mAb or anti-CD8 mAb caused a selective depletion in CD4+ T cells for 2 weeks and CD8+ T cells for 4 weeks, respectively. The level of proteinuria, serum IgA, and changes in the histopathological features of renal tissue samples were assessed in treated mice between the age of 4 and 40 weeks. The level of proteinuria increased with age, but there was not significant difference among the groups. No animal developed microhematuria throughout the study. Treatment with anti-CD4 mAb produced a mild to moderate level of mesangial hypertrophy at 20 and 40 weeks, similar to the results in untreated mice. The lowest degree of mesangial hypertrophy occurred in mice treated with anti-CD8 mAb up to the age of 40 weeks. Treatment with a combination of anti-CD4 and anti-CD8 mAbs produced effects that were similar to those observed on treatment with anti-CD8 mAb alone. Our results suggest that CD8+ T cells mediate mesangial proliferation and the progression of nephropathy in ddY mice.


A Case of Metastatic Pancreatic Adenocarcinoma in Complete Remission Using Chemotherapy and Immunotherapy.
Among the various types of cancer, pancreatic cancer is considered to have a particularly grim prognosis. Treatment includes surgery, chemotherapy, or both. While the role of immunotherapy is well-studied in many types of cancer, such is not the case with pancreatic cancer. A 49-year-old female presented to the oncology clinic following a biopsy of a pancreatic mass. CT-guided needle biopsy of the mass demonstrated moderately differentiated pancreatic adenocarcinoma. Positive emission tomography-computed tomography (PET-CT) revealed metastases to the liver. She was started on chemotherapy with FOLFIRINOX (leucovorin calcium, 5-fluorouracil, irinotecan hydrochloride, oxaliplatin) and demonstrated over 60% reduction in the size of liver metastases within three months. PET-CT four months after initiation of chemotherapy revealed no focal avid fluorodeoxyglucose (FDG) uptake in the liver, and the pancreatic body mass was stable in size at 3.0 cm with stable standardized uptake value (SUV) max at 2.4, only slightly elevated from 1.9 on the previous scan. Further treatment with chemotherapy was halted after 18 cycles due to side effects. With the patient's tumor being epidermal growth factor receptor (EGFR) negative, mismatch repair (MMR) negative, 3% tumor cells PD-L1 positive with 10% tumor-associated immune cells positive, treatment with pembrolizumab was started. Follow-up PET-CTs over the next several months confirmed the patient was in complete remission from metastatic pancreatic cancer. At the time of the report, the patient had a durable response of three years. We report a rare case of complete remission of metastatic pancreatic adenocarcinoma treated with chemotherapy, followed by immunotherapy. With emerging targets for modification of tumor microenvironment, immunotherapy must be further explored in the treatment of pancreatic cancer.


Chronic neuropathologies of single and repetitive TBI: substrates of dementia?
Traumatic brain injury (TBI) has long been recognized to be a risk factor for dementia. This association has, however, only recently gained widespread attention through the increased awareness of 'chronic traumatic encephalopathy' (CTE) in athletes exposed to repetitive head injury. Originally termed 'dementia pugilistica' and linked to a career in boxing, descriptions of the neuropathological features of CTE include brain atrophy, cavum septum pellucidum, and amyloid-β, tau and TDP-43 pathologies, many of which might contribute to clinical syndromes of cognitive impairment. Similar chronic pathologies are also commonly found years after just a single moderate to severe TBI. However, little consensus currently exists on specific features of these post-TBI syndromes that might permit their confident clinical and/or pathological diagnosis. Moreover, the mechanisms contributing to neurodegeneration following TBI largely remain unknown. Here, we review the current literature and controversies in the study of chronic neuropathological changes after TBI.