Whole-heart 4D flow cardiac magnetic resonance in healthy dogs.
In cardiac magnetic resonance imaging (CMR), accurate flow measurements rely on perpendicular plane-alignment with flow direction. For 2D phase contrast (PC) cardiac magnetic resonance measurements, planes have to be defined during the examination of the heart, which is time consuming and error-prone. Collection of flow information of the entire volume of the heart by a 4D flow CMR postpones plane alignment to post-processing. Sampling of such a large amount of data requires acceleration of data acquisition with techniques such as SENSitivity Encoding (k-t SENSE) or Broad-use Linear Acquisition Speed-up Technique (k-t BLAST). Objectives of the study were to compare 4D flow CMR, accelerated with two different acceleration methods with the established 2D PC CMR based on assessment of stroke volume at all four cardiac valves. The values of stroke volume acquired with the 4D flow CMR SENSE did not differ significantly when compared to the 2D PC CMR SENSE at the left side of the heart (aortic and mitral valve). Significant differences between the techniques were seen at the pulmonic and tricuspid valves. Acceleration with k-t BLAST revealed significantly lower values of stroke volume at all cardiac valves, except at the mitral valve.


Iatrogenic intracranial aneurysms.
Intracranial aneurysms following head trauma are not uncommon. Few cases of iatrogenic intracranial aneurysm have been reported however. This type of lesion is illustrated by three cases. If these lesions have the same poor prognosis as that proposed for the usual traumatic aneurysm, their early diagnosis and treatment is important.


[Evaluation of hydroxyapatite-coated Schanz screws in the Heidelberg external fixation system (HEFS)].
The use of monolateral external fixation systems for the correction of limb length and/or axial anomalies involves the implantation of Schanz screws in the long bones for periods of weeks or months. The loosening rate, which increases with duration of implantation, is a problem. In animal experiments/superior fixation and a reduced infection rate have been reported for hydroxyapatite-coated screws in comparison with conventional screws. We report on the clinical application of 59 hydroxyapatite-coated Schanz screws in 15 external fixation mountings. The performance of the screws was evaluated by clinical and radiological criteria. Infection was seen in 15 screws, necessitating the early removal of 6 of them. In patients with a second fixation system/the infection rate was lower, with infection developing in only 1 of 12 screws.


Differential gene expression in peripheral blood lymphocytes of cancer patients treated with whole body hyperthermia and chemotherapy: a pilot study.
The effect of whole body hyperthermia (WBH) at 41.8-42 degrees C on the cellular immune system is still poorly investigated. The aim of this study was to identify genes that become upregulated in peripheral blood lymphocytes (PBLs) of cancer patients during a combined treatment with WBH and chemotherapy by generating complex arrays of cDNA. PBLs were obtained from four patients with different malignancies treated with WBH and varying cytostatic schedules before treatment and immediately thereafter. After constructing subtracted cDNA libraries, clones were screened for cDNA induction by dot-blot and semi-quantitative RT-PCR (sq-RT-PCR). Among 192 clones, 39 cDNAs were significantly upregulated. Sequencing revealed three groups of genes for which upregulation of mRNA was confirmed by sq-RT-PCR. The first group consisted of genes encoding for various heat shock proteins (HSP 60, 90a, 90b, 105). Further sq-RT-PCR demonstrated differential expression of HSP27 and HSP70 as well. The second group (calcyclin-binding-protein, haemoglobin-beta-chain) comprised genes without pre-specified association to hyperthermia. The cDNA encoding macrophage-inflammatory-protein-1-beta was also observed and may be associated with the pre-described activation of lymphocyte sub-populations during WBH. Treatment with WBH and chemotherapy elicits significant short-term effects on the expression of a variety of genes responsible for cellular integrity, stimulation and migration of immune effector cells. Further investigation is warranted to more clearly define the role of those genes for the clinical effect of WBH.


A possible role for integrin signaling in diffuse axonal injury.
Over the past decade, investigators have attempted to establish the pathophysiological mechanisms by which non-penetrating injuries damage the brain. Several studies have implicated either membrane poration or ion channel dysfunction pursuant to neuronal cell death as the primary mechanism of injury. We hypothesized that traumatic stimulation of integrins may be an important etiological contributor to mild Traumatic Brain Injury. In order to study the effects of forces at the cellular level, we utilized two hierarchical, in vitro systems to mimic traumatic injury to rat cortical neurons: a high velocity stretcher and a magnetic tweezer system. In one system, we controlled focal adhesion formation in neurons cultured on a stretchable substrate loaded with an abrupt, one dimensional strain. With the second system, we used magnetic tweezers to directly simulate the abrupt injury forces endured by a focal adhesion on the neurite. Both systems revealed variations in the rate and nature of neuronal injury as a function of focal adhesion density and direct integrin stimulation without membrane poration. Pharmacological inhibition of calpains did not mitigate the injury yet the inhibition of Rho-kinase immediately after injury reduced axonal injury. These data suggest that integrin-mediated activation of Rho may be a contributor to the diffuse axonal injury reported in mild Traumatic Brain Injury.


Nutritional assessment in overweight and obese patients with metastatic cancer: does it make sense?
Obesity is causally related with tumor development, and thus, many cancer patients are overweight or obese at diagnosis. Whether these patients need regular nutritional assessment is not known. In the present study, we evaluated the utility of Mini Nutritional Assessment (MNA), a nutritional screening/assessment questionnaire, in overweight or obese patients with metastatic tumors. Overweight or obese patients referred for initiation of systemic therapy in three cancer centers were eligible. Basic demographics and clinical data were recorded. MNA was completed at baseline and patients were divided into three groups: A (well nourished), B (at risk), and C (malnourished). Survival data were subsequently collected. The prevalence of malnutrition and prognostic significance were evaluated. In total, 1469 patients with metastatic primaries were identified. Of them, 594 (41.9%) were overweight or obese and included in the analysis. According to MNA, almost 50% were at risk and around 12% were already malnourished at presentation. A significant difference in overall survival was found between groups [group A 17.8 (15.5-20.1) months, group B 8.2 (7.3-9.3) months, and group C 6.4 (3.2-9.6) months, P < 0.001]. Moreover, MNA was the only independent predictor of survival. Our findings support that a significant percentage of overweight or obese cancer patients may be at nutritional risk and this is moreover related with adverse prognosis. An MNA score could be used for the identification of this risk.


Dissociation of N(2) Gas-induced Monomeric Ribosomes and Functioning of the Derived Subunits in Protein Synthesis in Pea.
The dissociation of N(2) gas-induced monomeric ribosomes from the pea root was studied by varying the concentration of KCl (or NH(4)Cl) and MgCl(2) in the presence of dithiothreitol. These monoribosomes were shown to dissociate completely into subunits at 0.5m KCl or NH(4)Cl in the presence of 5 mm MgCl(2). The 40S subunits were more susceptible to structural change in KCl than were the 60S subunits. On the other hand, the 60S subunits appeared to be more labile to NH(4)Cl.The activity of the subunits relative to aminoacyl-tRNA binding and peptide bond formation was investigated using subunits derived from 0.5 m KCl (or NH(4)Cl) in the absence and presence of 5 mm MgCl(2). The 40S subunits were active in aminoacyl-tRNA binding only when dissociated in the presence of MgCl(2). The 40S and 60S subunits combined in the presence of poly U were active in incorporation of (14)C-phenylalanine from (14)C-phenylalanyl-tRNA only when dissociation was achieved in the presence of 5 mm MgCl(2). The KCl-dissociated subunits were much more active in protein synthesis than NH(4)Cl-dissociated subunits.


Enhanced development of Th2-like primary CD4 effectors in response to sustained exposure to limited rIL-4 in vivo.
Previous studies have established that cytokines regulate development of Th cell subsets from naive CD4 cells, suggesting promising therapeutic potential for cytokines that has not been fully realized, in part due to high dose toxicity. Here we examined effects of sustained delivery of low doses of rIL-4 on development of cytokine-secreting primary CD4 cells in vivo. Diffusion chambers injected with X63.Ag-653 plasmacytoma transfectants that constitutively produce rIL-4 were implanted s.c. in mice 24 to 48 h before immunization with keyhole limpet hemocyanin (KLH). Five days later at the peak of the response, KLH-specific CD4 cells from controls, which received chambers containing untransfected plasmacytoma cells, secreted primarily IL-2 and IL-4, with low levels of IFN-gamma and no IL-5 following Ag restimulation. Administration of rIL-4 enhanced IL-2 and IL-4 production by two- to fivefold, with a corresponding decrease in IFN-gamma. As frequencies of KLH-specific precursors that secreted IL-4 were unaltered, exogenous cytokine apparently affected the magnitude of IL-4 secretion by primed CD4 cells. Although IL-4 was undetectable in sera of mice carrying chambers, titers of KLH-specific IgG1 and IgG3 Ab were increased by rIL-4, whereas IgM, IgG2a, and IgG2b levels were unaltered. The results indicate that sustained delivery of low doses of cytokines at sites distant from Ag exposure can selectively potentiate development of CD4 subsets.


Chemoselective modifications for the traceless ligation of thioamide-containing peptides and proteins.
Thioamides are single-atom substitutions of canonical amide bonds, and have been proven to be versatile and minimally perturbing probes in protein folding studies. Previously, our group showed that thioamides can be incorporated into proteins by native chemical ligation (NCL) with Cys as a ligation handle. In this study, we report the expansion of this strategy into non-Cys ligation sites, utilizing radical initiated desulfurization to "erase" the side chain thiol after ligation. The reaction exhibited high chemoselectivity against thioamides, which can be further enhanced with thioacetamide as a sacrificial scavenger. As a proof-of-concept example, we demonstrated the incorporation of a thioamide probe into a 56 amino acid protein, the B1 domain of Protein G (GB1). Finally, we showed that the method can be extended to β-thiol amino acid analogs and selenocysteine.


Mononuclear cell dynamics in M. tuberculosis infection provide opportunities for therapeutic intervention.
Mycobacterium tuberculosis causes chronic infection of mononuclear phagocytes, especially resident (alveolar) macrophages, recruited macrophages, and dendritic cells. Despite the importance of these cells in tuberculosis (TB) pathogenesis and immunity, little is known about the population dynamics of these cells at the sites of infection. We used a combination of congenic monocyte adoptive transfer, and pulse-chase labeling of DNA, to determine the kinetics and characteristics of trafficking, differentiation, and infection of mononuclear phagocytes during the chronic, adaptive immune phase of M. tuberculosis infection in mice. We found that Ly6Chi monocytes traffic rapidly to the lungs, where a subpopulation become Ly6Clo and remain in the lung vascular space, while the remainder migrate into the lung parenchyma and differentiate into Ly6Chi dendritic cells, CD11b+ dendritic cells, and recruited macrophages. As in humans with TB, M. tuberculosis-infected mice have increased numbers of blood monocytes; this is due to increased egress from the bone marrow, and not delayed egress from the blood. Pulse-chase labeling of dividing cells and flow cytometry analysis revealed a T1/2 of ~15 hrs for Ly6Chi monocytes, indicating that they differentiate rapidly upon entry to the parenchyma of infected lungs; in contrast, cells that differentiate from Ly6Chi monocytes turn over more slowly, but diminish in frequency in less than one week. New cells (identified by pulse-chase labeling) acquire bacteria within 1-3 days of appearance in the lungs, indicating that bacteria regularly encounter new cellular niches, even during the chronic stage of infection. Our findings that mononuclear phagocyte populations at the site of M. tuberculosis infection are highly dynamic provide support for specific approaches for host-directed therapies directed at monocytes, including trained immunity, as potential interventions in TB, by replacing cells with limited antimycobacterial capabilities with newly-recruited cells better able to restrict and kill M. tuberculosis.


EZ-Root-VIS: A Software Pipeline for the Rapid Analysis and Visual Reconstruction of Root System Architecture.
If we want to understand how the environment has shaped the appearance and behavior of living creatures, we need to compare groups of individuals that differ in genetic makeup and environment experience. For complex phenotypic features, such as body posture or facial expression in humans, comparison is not straightforward because some of the contributing factors cannot easily be quantified or averaged across individuals. Therefore, computational methods are used to reconstruct representative prototypes using a range of algorithms for filling in missing information and calculating means. The same problem applies to the root system architecture (RSA) of plants. Several computer programs are available for extracting numerical data from root images, but they usually do not offer customized data analysis or visual reconstruction of RSA. We developed Root-VIS, a free software tool that facilitates the determination of means and variance of many different RSA features across user-selected sets of root images. Furthermore, Root-VIS offers several options to generate visual reconstructions of root systems from the averaged data to enable screening and modeling. We confirmed the suitability of Root-VIS, combined with a new version of EZ-Rhizo, for the rapid characterization of genotype-environment interactions and gene discovery through genome-wide association studies in Arabidopsis (Arabidopsis thaliana).


Applying a Midwifery Lens to Indigenous Health Care Delivery: The Contribution of Campus Learning and Rural Placements to Effecting Systemic Change.
Increasing cultural safety in health settings is essential to address stark health disparities between Indigenous and non-Indigenous Australians. Respect for cultural knowledge, better communication, and recognition of racism as a determinant of health are required for improved service delivery. How this knowledge is acquired in health professional training and translated to clinical settings is poorly understood. Impacts of an innovative Indigenous health unit and remote clinical placements on knowledge acquisition and attitude change were explored among midwifery students to inform cultural competency initiatives in health professional training. A multiphased, mixed methods research design used surveys, observations, and interviews. Qualitative analysis was strengthened through triangulation with quantitative data. A unit conceived with substantial Indigenous Australian input and which privileged these voices enhanced knowledge and shifted attitudes in a positive direction; however, immediate gains diminished over time. Remote placements had a profound effect on student learning. Exposure to Indigenous Australians in classrooms and communities, and the self-reflection generated, helped dispel stereotypes and challenge assumptions based on limited cultural knowledge and contact. Optimization of receptivity to Indigenous Australian content and opportunities for remote placements contributed to students' developing cultural capabilities with implications for all health professional training. Whether this heightened awareness is enough to address institutional racism identified in health service delivery remains unanswered. The focus must include those established health practitioners and administrators who influence organizational culture if real systemic change is to occur. Given appropriate on-going support, graduates can play a vital role in expediting this process.


Anti-Inflammatory and Antioxidant Effects of Carvacrol on N-Methyl-N'-Nitro-N-Nitrosoguanidine (MNNG) Induced Gastric Carcinogenesis in Wistar Rats.
Carvacrol is a dietary polyphenol from Lamiaceae plants that has been shown to possess a wide range of biological activities including antioxidant and antitumor effects. This study aimed to investigate its anti-inflammatory and antioxidant effects on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) induced gastric carcinogenesis in Wistar rats. Forty-nine rats were randomly assigned to four treatment and three control groups. Over 60 days, MNNG (200 mg/kg BW) was orally applied to animals of groups 1-5 while the rats in groups 2-5 also received different doses of carvacrol (10, 25, 50, and 100 mg/kg BW, respectively) until the end of the experiment. Group 6 rats were treated with 100 mg/kg BW carvacrol and no MNNG whereas group 7 was the control group without any treatment. After the euthanasia of all rats, the inflammatory cytokines and oxidative stress parameters were assessed in the blood and tissues. The expression of caspase 9, Bax, and Bcl-2 proteins in the stomach tissues were investigated through histopathological examinations. Statistically significant differences were observed in the body weight, oxidative stress, and inflammation parameters of groups 1 to 6 compared to group 7 (p ≤ 0.001). Animals in MNNG groups 2 and 3 treated with the low dose carvacrol (10 and 25 mg/kg BW) showed significantly reduced oxidative stress, inflammation, and apoptotic effect compared to animals of the MNNG groups receiving increased doses of carvacrol (50 and 100 mg/kg BW) or no carvacrol. Rats exposed to MNNG exhibited gastric cancer cells in several areas. In the MNNG group receiving 100 mg/kg BW carvacrol, the inflammatory cell infiltration was observed in gastric mucosal and submucosal areas whereas MNNG rats supplemented with 10 and 25 mg/kg BW carvacrol showed no pathological alterations of the gastric cells. The results of this study indicate that significant antioxidant and anti-inflammatory effects induced by carvacrol at doses of 10 and 25 mg/kg BW interfered with gastric carcinogenesis induced by MNNG in Wistar rats as well as provide hepatoprotection. However, high doses of carvacrol (50 and 100 mg/kg BW) increased oxidative stress, inflammation, and apoptosis.


Endoscopic transnasal sphenoidotomy with or without ethmoidectomy.
We evaluated endoscopic transnasal sphenoidotomy (ETNS) with or without ethmoidectomy in patients with inflammatory sphenoid sinus disease (ISSD). A retrospective review was conducted in 42 patients (17 males, 25 females; mean age 41 years; range 17 to 67 years) who underwent ETNS with (n=37) or without (n=5) ethmoidectomy for ISSD. The disase was staged according to our staging system based on computed tomography findings. Postnasal drainage was the most common symptom (n=37, 88.1%). Chronic rhinosinusitis was accompanied by sinonasal polyps in 25 patients (59.5%). Five patients (11.9%) had isolated sphenoid disease and 16 patients (38.1%) had unilateral disease. Five patients (11.9%) had stage 1, 15 patients (35.7%) had stage 2, and 22 patients (52.4%) had stage 3 disease. Surgery involved 68 sides. Ethmoidectomy was used in 63 sides of 37 patients, eight of whom required a supplementary procedure. At least one complication was seen in eight patients (19%), including severe perioperative hemorrhage (n=2), early postoperative hemorrhage (n=2), minor injuries to the lamina papyracea (n=4), and synechiae (n=5). In patients with isolated ISSD, the direct approach to the sphenoid sinus by ETNS without ethmoidectomy is a favorable technique, whereas ETNS with ethmoidectomy is necessary for patients with concurrent disease in other paranasal sinuses.


Identification of AHNAK as a novel autoantigen in systemic lupus erythematosus.
To identify candidate autoantigens associated with arthritis, a rat chondrocyte cDNA library was immunoscreened with serum from a patient with rheumatoid arthritis. One isolated cDNA encoded part of AHNAK, a 700-kDa phosphoprotein with DNA binding properties, that appears to be involved in several signal transduction pathways. Immunoreactivity against an in vitro translated human AHNAK fragment was detected in 4.6% (5/109) of patients with rheumatoid arthritis, 29.5% (18/61) of patients with systemic lupus erythematosus (SLE), and 1.2% (2/172) of blood donors. Anti-AHNAK antibodies reacted with a recombinant human AHNAK fragment and with native AHNAK from C32 cell lysates. In vitro translated AHNAK fragment could be cleaved by granzyme B and caspase-3. Anti-AHNAK positive SLE patients had a higher frequency of homogeneous antinuclear antibody staining patterns and a lower frequency of recent mucosal ulcerations. This is the first report that AHNAK can be targeted by the immune system in autoimmune disease.


Lyme meningoencephalitis: report of a severe, penicillin-resistant case.
Although Lyme disease frequently attacks the central nervous system, this involvement is rarely severe, and high-dose intravenous penicillin usually is adequate treatment. The patient we describe developed severe Lyme meningoencephalitis despite receiving a full course of penicillin, and his condition continued to deteriorate after reinstitution of this treatment. Intravenous chloramphenicol was used successfully and resulted in a substantial improvement.


Silencing of integrated human papillomavirus-16 oncogenes by small interfering RNA-mediated heterochromatization.
Double-stranded RNAs or small interfering RNAs (siRNA) targeting the promoters of genes are known to cause gene knockdown by a process known as transcriptional gene silencing (TGS). We screened multiple siRNAs homologous to one of the NF-1 binding sites in the human papillomavirus-16 (HPV-16) enhancer and identified one siRNA which causes specific TGS of the HPV-16 oncogenes E6 and E7 when transfected into two HPV-16-positive cell lines siHa and CaSki. This phenomenon was specific to the HPV-16 enhancer with no effect on the HPV-18 enhancer. TGS was associated with heterochromatization of the targeted region of the enhancer but no DNA methylation was noted during the time period studied. The choice of target in the enhancer was important as siRNAs differing by one or two bases showed no suppression of downstream gene expression. A low copy number enhancer-associated transcript was detected in the cell lines studied and its level decreased significantly after treatment with the siRNA that caused TGS. This supports the RNA:RNA model described previously for TGS. This siRNA which causes simultaneous silencing of E6 as well as E7 oncogenes by an epigenetic mechanism might be useful as a therapeutic modality for HPV-16-positive cervical and other epithelial cancers.


Linking the content to demographic reach of online advertising of electronic nicotine delivery systems.
Recent studies have separately examined the content and demographic reach of the advertising of electronic nicotine delivery systems (ENDS). No study to our knowledge has linked the two in investigating whether racial/ethnic groups are differentially exposed to the comparative messages conveyed in online ENDS advertisements. 932 unique ENDS advertisements (6311 total), which were posted on 3435 websites between December, 2009 and October, 2015, were categorized as either comparative or non-comparative with respect to the traditional cigarette. The race/ethnicity of website visitors was obtained from a proprietary source and used in constructing variables for racial/ethnic viewership. The variables for advertising content and website racial/ethnic viewership were then linked yielding a final sample of 551 unique ENDS advertisements (2498 total) on 1206 websites. A two-level hierarchical generalized linear model, used in estimating website racial/ethnic viewership as a predictor of comparative advertising, accounted for the nesting of advertisements (level 1) within 152 ENDS brands (level 2). In contrast to racial/ethnic minorities, a greater proportion of non-Hispanic whites visited websites with ENDS advertisements than the overall proportion of nonHispanic white U.S. Internet users. Yet, it was the advertisements on websites that appealed to Hispanics that had greater odds of comparing ENDS to traditional cigarettes. The lower exposure to ENDS advertising among racial/ethnic minorities versus non-Hispanic whites is consistent with survey data. Yet, the greater odds of comparative advertising of ENDS on websites that appeal to racial/ethnic minorities (ie, Hispanics) could impact the longterm health of minority smokers. This study's findings have important implications for the uptake of ENDS among minority smokers. If the comparative advertising yields greater interest and eventual use of ENDS, then minority smokers could either benefit from smoking cessation because they switch to ENDS, or adopt dual tobacco use. The fate of comparative advertising of ENDS versus the traditional cigarette will depend on the Food and Drug Administration enforcement of its deeming rules and the ensuing changes in the ENDS marketplace.


Determinants of attenuation in the envelope protein of the flavivirus Alfuy.
Murray Valley encephalitis virus (MVEV) is a mosquito-borne flavivirus endemic to Australia and Papua New Guinea. Most strains of MVEV cause potentially fatal cases of encephalitis in humans and horses, and have been shown to be highly neuroinvasive in weanling mice. In contrast, the naturally occurring subtype Alfuy virus (ALFV) has never been associated with human disease, nor is it neuroinvasive in weanling mice, even at high doses. To identify viral factors associated with ALFV attenuation, a chimeric infectious clone was constructed containing the structural genes premembrane (prM) and envelope (E) of ALFV swapped into the MVEV genome. The resulting virus (vMVEV/ALFVstr) was no longer neuroinvasive in mice, suggesting that motifs within prM-E of ALFV confer attenuation. To define these motifs further, mutants were constructed by targeting divergent sequences between the MVEV and ALFV E proteins that are known markers of virulence in other encephalitic flaviviruses. MVEV mutants containing a unique ALFV sequence in the flexible hinge region (residues 273-277) or lacking the conserved glycosylation site at position 154 were significantly less neuroinvasive in mice than wild-type MVEV, as determined by delayed time to death or increased LD(50). Conversely, when the corresponding MVEV sequences were inserted into the vMVEV/ALFVstr chimera, the mutant containing the MVEV hinge sequence was more neuroinvasive than the parental chimera, though not to the same level as wild-type MVEV. These results identify the hinge region and E protein glycosylation as motifs that contribute to the attenuation of ALFV.


Protein carbonylation in a murine model for early alcoholic liver disease.
Hepatic oxidative stress and subsequent lipid peroxidation are well-recognized consequences of sustained ethanol consumption. The covalent adduction of nucleophilic amino acid side-chains by lipid electrophiles is significantly increased in patients with alcoholic liver disease (ALD); a global assessment of in vivo protein targets and the consequences of these modifications, however, has not been conducted. In this article, we describe the identification of novel protein targets for covalent adduction in a 6-week murine model for ALD. Ethanol-fed mice displayed a 2-fold increase in hepatic TBARS, while immunohistochemical analysis for the reactive aldehydes 4-hydroxynonenal (4-HNE), 4-oxononenal (4-ONE), acrolein (ACR), and malondialdehyde (MDA) revealed a marked increase in the staining of modified proteins in the ethanol-treated mice. Increased protein carbonyl content was confirmed utilizing subcellular fractionation of liver homogenates followed by biotin-tagging through hydrazide chemistry, where approximately a 2-fold increase in modified proteins was observed in microsomal and cytosolic fractions. To determine targets of protein carbonylation, a secondary hydrazide method coupled to a highly sensitive 2-dimensional liquid chromatography tandem mass spectrometry (2D LC-MS/MS or MuDPIT) technique was utilized. Our results have identified 414 protein targets for modification by reactive aldehydes in ALD. The presence of novel in vivo sites of protein modification by 4-HNE (2), 4-ONE (4) and ACR (2) was also confirmed in our data set. While the precise impact of protein carbonylation in ALD remains unknown, a bioinformatic analysis of the data set has revealed key pathways associated with disease progression, including fatty acid metabolism, drug metabolism, oxidative phosphorylation, and the TCA cycle. These data suggest a major role for aldehyde adduction in the pathogenesis of ALD.


Effects of anterior compartment fasciotomy on intramuscular compartment pressure in patients with chronic exertional compartment syndrome.
Patients with chronic exertional compartment syndrome (CECS) have pain during exercise that usually subsides at rest. Diagnosis is usually confirmed by measurement of intramuscular compartment pressure (IMCP) following exclusion of other possible causes. Management usually requires fasciotomy but reported outcomes vary widely. There is little evidence of the effectiveness of fasciotomy on IMCP. Testing is rarely repeated postoperatively and reported follow-up is poor. Improved diagnostic criteria based on preselection and IMCP levels during dynamic exercise testing have recently been reported. (1) To compare IMCP in three groups, one with classical symptoms and no treatment and the other with symptoms of CECS who have been treated with fasciotomy and an asymptomatic control group. (2) Establish if differences in IMCP in these groups as a result of fasciotomy relate to functional and symptomatic improvement. Twenty subjects with symptoms of CECS of the anterior compartment, 20 asymptomatic controls and 20 patients who had undergone fasciotomy for CECS were compared. All other possible diagnoses were excluded using rigorous inclusion criteria and MRI. Dynamic IMCP was measured using an electronic catheter wire before, during and after participants exercised on a treadmill during a standardised 15 min exercise challenge. Statistical analysis included t-tests and analysis of variance. Fasciotomy results in reduced IMCP at all time points during a standardised exercise protocol compared with preoperative cases. In subjects responding to fasciotomy, there is a significant reduction in IMCP below that of preoperative groups (P<0.001). Postoperative responders to fasciotomy have no significant differences in IMCP from asymptomatic controls (P=0.182). Fasciotomy reduces IMCP in all patients. Larger studies are required to confirm that the reduction in IMCP accounts for differences in functional outcomes and pain reductions seen in postoperative patients with CECS.


Uroporphyrinogen 3 cosynthetase activity in the fox squirrel (Sciurus niger).
The activity of uroporphyrinogen III cosynthetase in hemolyzates and tissue extracts from fox squirrels is much less than in similar preparations from gray squirrels. Low activity of this enzyme explains the production of large amounts of uroporphyrin I by the fox squirrel. Members of this species thus provide a small-animal model for studies of congenital erythropoietic porphyria, a hereditary disease of man and cattle which is associated with a similar partial deficiency of uroporphyrinogen III cosynthetase.


Prediction model for best focus, power, and spherical aberration of the cornea: Raytracing on a large dataset of OCT data.
To analyse corneal power based on a large optical coherence tomography dataset using raytracing, and to evaluate corneal power with respect to the corneal front apex plane for different definitions of best focus. A large OCT dataset (10,218 eyes of 8,430 patients) from the Casia 2 (Tomey, Japan) was post-processed in MATLAB (MathWorks, USA). Using radius of curvature, corneal front and back surface asphericity, central corneal thickness, and pupil size (aperture) a bundle of rays was traced through the cornea. Various best focus definitions were tested: a) minimum wavefront error, b) root mean squared ray scatter, c) mean absolute ray scatter, and d) total spot diameter. All 4 target optimisation criteria were tested with each best focus plane. With the best-fit keratometer index the difference of corneal power and keratometric power was evaluated using a multivariate linear model. The mean corneal powers for a/b/c/d were 43.02±1.61/42.92±1.58/42.91±1.58/42.94±1.59 dpt respectively. The root mean squared deviations of corneal power from keratometric power (nK = 1.3317/1.3309/1.3308/1.3311 for a/b/c/d) were 0.308/0.185/0.171/0.209 dpt. With the multivariate linear model the respective RMS error was reduced to 0.110/0.052/0.043/0.065 dpt (R² = 0.872/0.921/0.935/0.904). Raytracing improves on linear Gaussian optics by considering the asphericity of both refracting surfaces and using Snell's law of refraction in preference to paraxial simplifications. However, there is no unique definition of best focus, and therefore the calculated corneal power varies depending on the definition of best focus. The multivariate linear model enabled more precise estimation of corneal power compared to the simple keratometer equation.


Dynamics of the rhomboid-like protein RHBDD2 expression in mouse retina and involvement of its human ortholog in retinitis pigmentosa.
The novel rhomboid-like protein RHBDD2 is distantly related to rhomboid proteins, a group of highly specialized membrane-bound proteases that catalyze regulated intramembrane proteolysis. In retina, RHBDD2 is expressed from embryonic stages to adulthood, and its levels show age-dependent changes. RHBDD2 is distinctly abundant in the perinuclear region of cells, and it localizes to their Golgi. A glycine zipper motif present in one of the transmembrane domains of RHBDD2 is important for its packing into the Golgi membranes. Its deletion causes dislodgment of RHBDD2 from the Golgi. A specific antibody against RHBDD2 recognizes two forms of the protein, one with low (39 kDa; RHBDD2(L)) and the other with high (117 kDa; RHBDD2H) molecular masses in mouse retinal extracts. RHBDD2(L) seems to be ubiquitously expressed in all retinal cells. In contrast, RHBDD2H seems to be present only in the outer segments of cone photoreceptors and may correspond to a homotrimer of RHBDD2(L). This protein consistently co-localizes with S- and M-types of cone opsins. We identified a homozygous mutation in the human RHBDD2 gene, R85H, that co-segregates with disease in affected members of a family with autosomal recessive retinitis pigmentosa. Our findings suggest that the RHBDD2 protein plays important roles in the development and normal function of the retina.


Ethics rounds: An appreciated form of ethics support.
Ethics rounds are one way to support healthcare personnel in handling ethically difficult situations. A previous study in the present project showed that ethics rounds did not result in significant changes in perceptions of how ethical issues were handled, that is, in the ethical climate. However, there was anecdotal evidence that the ethics rounds were viewed as a positive experience and that they stimulated ethical reflection. The aim of this study was to gain a deeper understanding of how the ethics rounds were experienced and why the intervention in the form of ethics rounds did not succeed in improving the ethical climate for the staff. An exploratory and descriptive design with a qualitative approach was adopted, using individual interviews. A total of 11 healthcare personnel, working in two different psychiatry outpatient clinics and with experience of participating in ethics rounds, were interviewed. The study was based on informed consent and was approved by one of the Swedish Regional Ethical Review Boards. The participants were generally positive about the ethics rounds. They had experienced changes by participating in the ethics rounds in the form of being able to see things from different perspectives as well as by gaining insight into ethical issues. However, these changes had not affected daily work. A crucial question is whether or not increased reflection ability among the participants is a good enough outcome of ethics rounds and whether this result could have been measured in patient-related outcomes. Ethics rounds might foster cooperation among the staff and this, in turn, could influence patient care. By listening to others during ethics rounds, a person can learn to see things from a new angle. Participation in ethics rounds can also lead to better insight concerning ethical issues.


Genotoxic effects of anesthetic agents.
Preliminary research results indicate that exposure to anesthetics affects health. To provide, with evidence-based knowledge, the answer to the question: What are the genotoxic effects threatening people exposed to anesthetics? A systematic review of scientific literature. A systematic search of The Cochrane Library, MedLine, and CINAHL resulted in a screening of 212 abstracts of which 54 articles were assessed for quality. The 54 articles assessed covered areas on general health effects (neurobehavioral effects, immunology) and, in particular, genotoxic effects. In the scientific literature reviewed, there is evidence of exposure to anesthetics, especially nitrous oxide and halogenated gases, being associated with general health and genotoxic risks, but conflicting results have been obtained. The result of this review further stresses the need for scientific knowledge in this area and enhances the studies, above all, on people exposed for long periods.


Predicting pharmacy students' intention to apply for a residency: A systematic theory of planned behavior approach.
The current literature has identified many motivating factors and barriers influencing pharmacy students' decision to apply for residency training. Despite a growing need for residency trained pharmacists to advance the profession, it is not clear why only about one in four pharmacy students decide to pursue a residency, and which of these factors have the most influence on student decision-making. The study examines the factors associated with pharmacy students' intention to apply for a postgraduate residency using the theory of planned behavior (TPB) framework. Second and third-year students from four Texas pharmacy schools were surveyed using an online questionnaire based on the TPB. Descriptive statistics and multiple linear regression analyses were utilized to assess the study objectives. A total of 251 completed responses were received. Attitude, subjective norms (SN), and perceived behavioral control (PBC) were significant predictors of intention to apply for a pharmacy residency (β = 0.32, 0.58, and 0.36, respectively, p < 0.001). Attending ASHP's midyear meeting or other residency showcase was a significant predictor of intention (β = 0.71, p = 0.006). Additional significant predictors of intention include believing a residency would increase confidence in practicing pharmacy (β = 0.36, p < 0.001) and help achieve career goals (β = 0.16, p < 0.02); the social influence of faculty members (β = 0.10, p = 0.003) and family (β = 0.08, p = 0.02); believing financial obligations (β = 0.20, p = 0.006), feeling afraid of the competition and/or not matching (β = 0.24, p < 0.001), needing to relocate (β = 0.09, p = 0.04), and the lengthy application and/or interview process (β = 0.12, p = 0.04) would make it more difficult to apply for a residency. The TPB model was useful in predicting pharmacy students' intention to apply for a residency, and all TPB constructs were significant predictors. Therefore, interventions that target students' attitude, SN, and PBC may be valuable to increase their intention, especially the specific beliefs identified to significantly predict intention. Future research into methods in which these motivating factors can be encouraged and perceived barriers can be addressed by pharmacy stakeholders will increase interest and participation in residency training.


Actions of the Japanese Pancreas and Islet Transplantation Association regarding transplanted human islets isolated using Liberase HI.
The potential for introducing transmissible spongiform encephalopathy (TSE) into islet cells was indicated by recognizing that Liberase HI is isolated from Clostridium histolyticum grown in media containing brain-heart infusion broth. A national team within the Japanese Pancreas and Islet Transplantation Association implemented an islet transplantation program in Japan using Liberase HI. The program comprised 65 islet isolations from non-heart-beating donors and 34 transplants into 18 patients. Herein, we have summarized how the Association followed these recipients over the long term. We established an ad hoc committee to follow recipients transplanted with islets isolated using Liberase HI after becoming informed of the associated dangers of using this enzyme. We also stopped islet transplantations using Liberase. The committee addressed the major concerns of the risk of the collagenase being contaminated with TSE and of the recipient follow-up. All recipients were examined by diffusion MRI and EEG and then scheduled for evaluation and follow-up by specialists in Creutzfeldt-Jakob disease (CJD). Bioassays of bovine spongiform encephalopathy prions in the enzyme proceeded using knock-in mice expressing bovine prion protein. These assays could detect contaminating prions at a dilution of 1 × 10(4). After inactivating its collagenase activity, Liberase HI was injected into the abdominal cavities of knock-in mice. Four months later, prion infectivity in Liberase HI was evaluated by immunohistochemical staining and Western blotting of spleen homogenates using anti-prion protein antibodies. Western blotting and immunohistochemical staining did not detect prions in Liberase HI. Diffusion MRI and EEG evaluations performed by CJD specialists confirmed that none of the transplanted recipients had CJD. Three years of follow-up revealed that none of the Japanese recipients of islet transplants developed CJD. Prion bioassays showed that the Liberase HI used to isolate islets for transplantation was free of infectious TSE prions.


Improvement in myofascial pain and headaches following TMJ surgery.
Fifty patients diagnosed with TMJ internal derangement, myalgia, and headaches, who had not responded well to nonsurgical management and subsequently underwent TMJ surgery, were retrospectively evaluated. The patients were mailed a survey asking them to evaluate the following symptoms: joint pain, joint noise, facial muscle pain, cervical and shoulder muscle pain, headache frequency and intensity, and overall head and neck pain. The majority of patients reported their symptoms as moderate to severe prior to treatment. In addition to reporting decreases in TMJ pain and noise after surgery, the majority of patients responding also reported decreases in myalgia and headaches. Twenty-two patients managed nonsurgically at the same center were also surveyed. The proportion of patients reporting their symptoms as moderate to severe prior to treatment was lower in this group. Patients reporting decreases in myalgia and headaches were in the minority. The study demonstrates that myalgia and headache symptoms associated with TMJ dysfunction that are poorly responsive to nonsurgical management may improve following TMJ surgery.


Preparation of veterinary gross anatomy specimens: a method that allows storage at room temperature for four years.
On the basis of methods used to prepare human anatomic specimens, 2 Yucatan miniature pigs were embalmed over 4 years ago. Results obtained suggest that specimens commonly used in the teaching of veterinary gross anatomy may be fixed in this manner. Advantages include no requirement for refrigeration, superior long-term preservation, less offensive odor, and better tissue texture qualities, including less evidence of dehydration.


Balance performance on the postural stress test: comparison of young adults, healthy elderly, and fallers.
The purpose of this study was to compare the postural responses of three groups of individuals--healthy young adults (n = 42; age, 20-40 years); healthy, community-dwelling, elderly individuals (n = 66; age, 60-102 years), and elderly individuals with a history of frequent falls (n = 10; age, 66-95 years)--using the postural stress test (PST). The PST is a simple, clinically applicable, quantitative measure of an individual's ability to withstand a series of graded destabilizing forces applied at the level of the subject's waist. Elderly fallers tend to score lower on the PST than elderly nonfallers, but age-related differences in postural responses during the PST have not been established. Each subject underwent the PST using a method and scoring procedure described previously. Results of this study confirm previous findings that elderly fallers score significantly lower on the PST than either young adult or nonfalling elderly individuals. This study also showed that there was no difference in balance strategy scores between the young adults and the healthy elderly subjects. Therefore, it appears that poor performance on the PST cannot be attributed to age alone, but may be predictive of pathological processes that predispose an individual to frequent falls.


Pial vessel caliber and cerebral blood flow during hemorrhage and hypercapnia in the rabbit.
We examined the relationship between cerebral blood flow (CBF) and pial vessel caliber responses to graded hemorrhagic hypotension at both normocapnia and hypercapnia in 31 anesthetized rabbits. Changes in CBF (hydrogen clearance) and pial arteriolar diameter (image splitting) were predictably related at all perfusion pressures (PP). Three autoregulatory regions were identified. 1) At PP greater than 65 mmHg, autoregulation was complete as CBF and the CBF response to hypercapnia remained at control levels. The pial vessels dilated progressively, and their response to hypercapnia increased. 2) At PP between 65 and 35 mmHg autoregulation continued but was incomplete. CBF decreased proportionately less than the corresponding reductions in PP due to continued pial vascular dilatation. Both the CBF and pial vessel responses to hypercapnia diminished. 3) At PP less than 35 mmHg, autoregulation was abolished. Pial arteriolar caliber and CBF decreased pressure passively, and there were no responses to hypercapnia. A comparison of changes in pial vascular resistance and total precapillary resistance indicated that the responses of pial vessels (particularly those less than 50 micron) paralleled the responses of the intraparenchymal arterioles.


The aetiology of atherosclerosis and coronary heart disease.
There are a number of important risk factors in the development atherosclerosis and coronary heart disease. This article considers the pathophysiology, the individual risk factors and the possible mechanism by which they exact an effect.


The effect of alkyl chain length on the structure and thermodynamics of protic-aprotic ionic liquid mixtures: a molecular dynamics study.
Mixtures of alkylammonium based protic ionic liquids and alkylmethylimidazolium based aprotic ionic liquids were studied by means of molecular dynamics simulations. Close to ideal mixing is observed in most studied magnitudes; however, the effect of increasing alkyl chain length in each of the cations is markedly different, with longer protic cations showing larger deviations, especially with regards to mixing enthalpy, which exhibits a strong compound forming tendency. The compound forming nature of these protic ionic liquids is shown to induce sharp changes in their local environment upon mixing.


Malignant melanoma in patients treated for psoriasis with methoxsalen (psoralen) and ultraviolet A radiation (PUVA). The PUVA Follow-Up Study.
Photochemotherapy with oral methoxsalen (psoralen) and ultraviolet A radiation (PUVA) is an effective treatment for psoriasis. However, PUVA is mutagenic, increases the risk of squamous-cell skin cancer, and can cause irregular, pigmented skin lesions. We studied the occurrence of melanoma among patients treated with PUVA. We prospectively identified cases of melanoma and documented the extent of exposure to PUVA among 1380 patients with psoriasis who were first treated with PUVA in 1975 or 1976. Using incidence data, we calculated the expected incidence of melanoma in this cohort and compared it with the observed incidence. Using regression models, we assessed the risks of melanoma associated with a long time (> or = 15 years) since the first treatment and with a large number of PUVA treatments (> or = 250). From 1975 through 1990, we detected four malignant melanomas, about the number expected in the overall population (relative risk, 1.1). From 1991 through 1996, we detected seven malignant melanomas (relative risk, 5.4; 95 percent confidence interval, 2.2 to 11.1). The risk of melanoma was higher in the later period than in the earlier one (incidence-rate ratio, 3.8) and higher among patients who received at least 250 PUVA treatments than among those who received fewer treatments (incidence-rate ratio, 3.1). About 15 years after the first treatment with PUVA, the risk of malignant melanoma increases, especially among patients who receive 250 treatments or more.


Effect of different substrata on rhizome growth, leaf biometry and shoot density of Posidonia oceanica.
The effects of different substratum typologies on Posidonia oceanica growth and morphology were estimated in four Sicilian meadows using Generalized and Linear Mixed Models combined with retrodating and biometric analyses. Substratum exerted a multiple effect, resulting in different biometric features for P. oceanica shoots settled on rock from those growing on sand and matte. On rock, values for growth rate, leaf length and shoot surface were lower than those on other substrata, with 42%, 23% and 32% the highest degree of difference respectively. The present study may have interesting methodological consequences for the comprehensive understanding of the causative variables potentially affecting meadows features and their health status. The importance of substratum in the prediction of likely biometry changes in P. oceanica meadows, means that knowledge of substratum type should receive due attention in the future to derive reliable estimates of meadow status.


Unwrapping Cochlear implants by spiral CT.
Multielectrode, intracochlear implants were designed for individuals with profound sensorineural hearing loss who derive little or no benefit form acoustic hearing aids. Determination of each electrode's position in a patient's inner ear may improve speech processor programming to maximize speech recognition. In this paper, an approach is described to use as input a volumetric spiral computed tomography (CT) image of the Nucleus electrode array (Cochlear Pty. Ltd, Lane Cove, NSW, Australia) to unwrap it, and to measure its implanted length given starting and end points. Representative curvilinear structures were digitally synthesized in image volumes of isotropic 0.1-mm voxels. The electrode array was spirally CT-scanned in vitro and in vivo, and reconstructed on an isotropic grid in 0.1-mm steps. Two algorithms were constructed to track and measure these curvilinear structures. The first algorithm is Karhunen-Loeve (K-L)-transform based, in which the K-L transform is locally applied at a current main axis position to determine the eigenvectors of the main axis voxels, the next main axis position is estimated from the current position along the principal eigendirection, adjusted to the mass center of the orthogonal cross section passing through the estimated position, and then scaled to have a prespecified step. The second algorithm is similar to the first one but avoids use of the K-L transform. In the second algorithm, the next position is directly estimated along the local direction and then processed with the same correction and scaling operations. With user-specified starting and end points as well as a local direction at the starting point, a curvilinear structure can be automatically tracked using either of the algorithms. The first algorithm is more robust, while the second one is more efficient. In the numerical and in vitro studies, the lengths of the curvilinear structures were accurately measured. Given local directions determined in the tracking process, an electrode array image can be unwrapped into a linear array with the central electrode axis as the abscissa. The unwrapping approach allows longitudinally and cross-sectionally accurate measurement and better visualization of cochlear implant images. With preimplantation knowledge of length, width, and center electrode distance, the position of individual electrodes can be estimated after unwrapping.


Quality assurance and data collection: current status, problems, and pitfalls.
1. It is important to measure and improve quality of care, particularly in this era of cost consciousness. 2. It is difficult to measure quality of care. 3. Current data collection systems have many inconsistencies and errors. 4. Statistical analysis cannot correct bad data. 5. Data based solely on DRG analysis are highly suspect. 6. Measurement of acuity of illness on admission is important for valid comparisons of outcomes. 7. We have a moral and ethical obligation to strive for better systems of measuring quality and to inform the public of the results of such measurements when they become sufficiently accurate.


Drug-induced Stevens-Johnson syndrome in Indian population: A multicentric retrospective analysis.
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening hypersensitivity reactions mainly caused by drugs. Data on incubation period, hospital stay, and outcome for HIV-positive patients are sparse. Role of corticosteroids in their management is still controversial. Indoor cases of SJS, SJS-TEN overlap, and TEN were analyzed for causative drugs, incubation period, a severity-of-illness score for toxic epidermal necrolysis (SCORTEN) score, HIV status, treatment, and outcome. Comparison of parameters between HIV and non-HIV cases was done. Utilization pattern of corticosteroids and their role in outcome were evaluated. Four SJS, 15 SJS-TEN overlap, and 21 TEN cases were evaluated. Antimicrobials (27.1%), antiviral (23%), antiseizure drugs (8.4%), and analgesics (8.4%) were commonly associated drugs. Among 12 (30%) HIV-reactive cases, nevirapine (97.6%) and cotrimoxazole (41.6%) were common causative drugs. Males (75%) were affected more than females (25%) among HIV-positive individuals. Incubation period was significantly higher in HIV-reactive patients. Total 30 (75%) patients were treated with corticosteroids. Dexamethasone (90%) and prednisolone (26.6%) were most commonly used. No significant difference was found among cases treated with or without corticosteroids. Antimicrobial drugs are common to cause SJS/TEN. Among HIV-reactive patients, male have more risk, incubation period is more and severity of reaction is less. Effectiveness of corticosteroids for treatment of SJS/TEN is inconclusive.


Is physiotherapy a luxury? What can the perplexing absence of the physical therapies tell us about the profession's future?
Physiotherapists interested in the profession's future have turned in recent years to historical evidence to understand how the physical therapies were practiced before the advent of modern healthcare. However, studies to date suggest that their practice was largely confined to social elites, and those from working-class or poor populations rarely, if ever, experienced them. To test this theory further, this study focuses on British sailors during the Napoleonic wars (1803-1815). Utilizing historical and semi-fictional accounts, this study shows that healthcare on board naval fighting ships concentrated almost entirely on the prevention of disease, and the medical and surgical management of acute trauma. Even though sailors experienced shocking levels of traumatic injury, none appear to have experienced any form of physical therapy. This study supports the argument that prior to the 20th century, the physical therapies were luxuries available primarily to those with surplus time and money, and that widespread access to physiotherapy has relied on state-sponsored universal health coverage. It follows, then, that the decline of universalized healthcare may have profound implications for many marginal groups in society, as well as the physiotherapy profession itself.


Structural and biochemical analysis of the sheath of Phormidium uncinatum.
The sheath of the filamentous, gliding cyanobacterium Phormidium uncinatum was studied by using light and electron microscopy. In thin sections and freeze fractures the sheath was found to be composed of helically arranged carbohydrate fibrils, 4 to 7 nm in diameter, which showed a substantial degree of crystallinity. As in all other examined motile cyanobacteria, the arrangement of the sheath fibrils correlates with the motion of the filaments during gliding motility; i.e., the fibrils formed a right-handed helix in clockwise-rotating species and a left-handed helix in counterclockwise-rotating species and were radially arranged in nonrotating cyanobacteria. Since sheaths could only be found in old immotile cultures, the arrangement seems to depend on the process of formation and attachment of sheath fibrils to the cell surface rather than on shear forces created by the locomotion of the filaments. As the sheath in P. uncinatum directly contacts the cell surface via the previously identified surface fibril forming glycoprotein oscillin (E. Hoiczyk and W. Baumeister, Mol. Microbiol. 26:699-708, 1997), it seems reasonable that similar surface glycoproteins act as platforms for the assembly and attachment of the sheaths in cyanobacteria. In P. uncinatum the sheath makes up approximately 21% of the total dry weight of old cultures and consists only of neutral sugars. Staining reactions and X-ray diffraction analysis suggested that the fibrillar component is a homoglucan that is very similar but not identical to cellulose which is cross-linked by the other detected monosaccharides. Both the chemical composition and the rigid highly ordered structure clearly distinguish the sheaths from the slime secreted by the filaments during gliding motility.


The impact of surgical intraocular pressure reduction on visual function using various criteria to define visual field progression.
To examine the impact of surgical intraocular pressure (IOP) reduction on visual function using various methods to define visual field (VF) progression. A retrospective chart review was conducted on consecutive glaucoma patients who underwent surgical IOP reduction between January 1, 2002 and December 31, 2007. All subjects had glaucomatous optic neuropathy, a minimum of 5 preoperative and 5 postoperative VFs, and were followed for a minimum of 2 years both before and after surgery. VF progression was determined using guided progression analysis, linear regression analysis of the visual field index, and individual sensitivity values using Progressor software. Seventeen eyes of 17 patients (mean age 77.9±9.9 y) were enrolled. Subjects were followed for a mean 5.8±2.4 years before surgery and 4.5±1.5 years after surgery. The mean postoperative IOP (11.3±4.2 mm Hg) and medications (1.3±1.3) were significantly (P<0.001 and P=0.01) reduced compared with before surgery (18.0±3.9 mm Hg, 2.4±0.9, respectively). The number of eyes judged to have VF progression using any method during the postoperative period (3 of 17, 17.6%) was significantly (P=0.03) reduced compared with the preoperative period (9 of 17 eyes, 52.9%). Using visual field index criteria, 8 eyes were judged to have preoperative VF progression and 1 eye had persistent VF progression during the postoperative period. None of the eyes judged to have preoperative VF progression using Early Manifest Glaucoma Trial (n=4) and Progressor criteria (n=1) demonstrated persistent VF progression during the postoperative period. Among eyes with preoperative VF progression, the postoperative slope of mean deviation (-0.21±0.23 dB/y) was significantly (P=0.03) reduced compared with before surgery (-1.01±0.23 dB/y). Despite differences in the criteria used to define VF progression, glaucoma surgical IOP reduction significantly reduces the incidence and rate of VF progression.


Effect of somatic cells count in cow milk on the formation of biogenic amines in cheese.
Comparative studies on physicochemical characteristics of milk with different somatic cells count (SCC) (L-low < 400,000 cells/ml, M-medium between 500,000 and 600,000 cells/ml and H-high > 1,000,000 cells/ml) and obtained cheeses, were conducted. No significant differences between samples were found. The H SCC milk was characterized by the highest total viable count. Higher levels of proteolysis were established in cheeses made from milk with SCC exceeding 500,000 cells/ml. After 10 months of ripening and cold storage the water-soluble nitrogen in total nitrogen (WSN/TN), noncasein nitrogen in total nitrogen (NCN/TN), nonprotein nitrogen in total nitrogen (NPN/TN) and free amino groups values of the sample with the highest SCC reached 28.4 ± 0.8%, 24.8 ± 0.9%, 18.3 ± 0.9% and 83.6 ± 0.3 mg/kg respectively. The biogenic amine concentration in the cheese samples from the L and M batches remained below 10 mg/kg throughout the ripening and cold storage period. The present study established an increase in the biogenic amine content during the ripening period and the cold storage of the cheeses made from milks with high SCC (batch H). The main amines accumulated at the end of the storage period (10th month) were tyramine (31.7 ± 0.3 mg/kg), putrescine (20.5 ± 0.2 mg/kg) and cadaverine (14.6 ± 0.2 mg/kg). Histamine was not found in any of the studied cheese samples.


Diverse susceptibility of Galleria mellonella humoral immune response factors to the exoproteinase activity of entomopathogenic and clinical strains of Pseudomonas aeruginosa.
We investigated the effects of extracellular proteinases of two Pseudomonas aeruginosa clinical isolates on the essential humoral immune response parameters in hemolymph of the insect model organism Galleria mellonella in vitro. Two culture media, rich LB and minimal M9, known to induce synthesis of different sets of proteinases secreted by P. aeruginosa were used. Changes in lysozyme, antibacterial and antifungal activities, as well as protein and peptide patterns in hemolymph treated with proteolytic fractions were evaluated. The effect of the proteolytic fractions on the apoLp-III level in hemolymph was determined by immunoblotting with antibodies against G. mellonella apolipophorin III (apoLp-III). We found that apoLp-III is hardly degraded by the proteinases of the proteolytic fractions of both clinical P. aeruginosa strains, in contrast to the high susceptibility of the protein to the proteinases of the entomopathogenic strain. The detected differences, together with the changes in the hemolymph protein and peptide patterns caused by the studied fractions, reflected the distinct composition of secreted proteinases of the entomopathogenic P. aeruginosa strain and the clinical strains tested. Our results also suggest the involvement of alkaline protease, the main proteinase of proteolytic fractions of P. aeruginosa grown in minimal medium, in the degradation of G. mellonella antimicrobial factors, such as lysozyme, antibacterial polypeptides, and proteins with antifungal activity. The diverse effects of the P. aeruginosa proteolytic fractions studied on the parameters of G. mellonella immune response indicate that this model insect may be useful in the analysis of the virulence factors of different P. aeruginosa strains.


Proton MR spectroscopy features of normal appearing white matter in neurofibromatosis type 1.
To determine whether differences exist between neurofibromatosis type 1 (NF1) patients with or without focal lesions and healthy normal volunteers in the metabolite ratios of normal appearing white matter, 27 patients with NF1 (with parenchymal lesion, MR positive, n: 17; without parenchymal lesions, MR negative, n: 10) and 20 healthy volunteers underwent MRI and short TE (31 ms) proton MR spectroscopy (MRS). In 17 patients with parenchymal lesions, 61 focal lesions were detected by MRI. MRS was performed from normal appearing frontal and posterior parietal white matter (FWM and PWM) in NF1 and from control groups. NAA/Cr, Cho/Cr and MI/Cr ratios were calculated. Significant increase in Cho/Cr and MI/Cr ratios were found in FWM and PWM in MR negative and positive groups when compared to control group. NAA/Cr ratio in MR positive group was significantly decreased in FWM compared to control group. There were no significant differences between FWM and PWM in all metabolite ratios of MR negative group. MI/Cr ratio in MR positive group was significantly elevated in PWM compared to FWM. Metabolite changes detected by MRS could indicate demyelination and gliosis in normal appearing white matter in all NF1 patients, and additionally neuroaxonal damage in the FWM of NF1 patients with focal lesions. For that reason, in the clinical evaluation and follow-up of these patients MRS features of normal appearing white matter should be considered in addition to focal lesions.


Autologous and homologous transplantation of bovine spermatogonial stem cells.
The aim of this study was to develop a method for spermatogonial stem cell transplantation into the bovine testis. Five-month-old Holstein-Friesian calves were used and half of the calves were hemicastrated to allow autologous transplantation and the other half were used for homologous transplantation. Approximately 20 g of each testis was used for cell isolation. On average 106 cells per gram of testis containing about 70% type A spermatogonia were isolated. The cells were frozen in liquid nitrogen until transplantation. Testes were irradiated locally with 10-14 Gy of X-rays to deplete endogenous spermatogenesis. At 2 months after irradiation, cells (approximately 10 x 10(6) were injected into the rete testis through a long injection needle (18 gauge), using ultrasonography and an ultrasound contrast solution. At 2.5 months after transplantation, calves were castrated and samples of testes were taken for histological examination. After 2.5 months in the irradiated non-transplanted control testes, only 45% of the tubules contained type A spermatogonia. However, after autologous spermatogonial transplantation, >80% of the tubule cross-sections contained type A spermatogonia. In addition, only 20% of the tubules of the control testes contained spermatocytes and, except for a few tubules (5%) with round spermatids, no more advanced germ cells were found. After autologous spermatogonial transplantation, about 60% of the tubules contained spermatocytes; 30% contained spermatids and in about 15% of tubules spermatozoa were found. No improvement in spermatogonial repopulation was found after homologous transplantation. The results of this study demonstrate, for the first time, successful autologous transplantation of bovine spermatogonial stem cells resulting in a complete regeneration of spermatogenesis.


Pubertal delay: the challenge of a timely differential diagnosis between congenital hypogonadotropic hypogonadism and constitutional delay of growth and puberty.
Distinguishing between constitutional delay of growth and puberty (CDGP) and congenital hypogonadotropic hypogonadism (CHH) may be challenging. CDGP and CHH appear to belong to the same clinical spectrum (with low sex hormones and low LH and FSH), although one is classically transient and known as a self-limited form of delayed puberty (CDGP) while the other is permanent (CHH). Thus, the clinical history and the outcomes of these two conditions require different approaches, and an adequate and timely management for the patients is mandatory. Since the initial presentation of CDGP and CHH is almost identical and given the similarities of CDGP and partial forms of CHH (i.e. patients with partial and early interrupted pubertal development) the scientific community has been struggling to find some diagnostic tests able to allow an accurate differential diagnosis between these two conditions in delayed puberty. In this review we provide an up to date insight on the tests available, their meanings and accuracy, as well as some clues to effectively differentiate between constitutional pubertal delay and pathologic CHH.


[Experiences with continuous fetal measurements during pregnancy].
Experiences by continuous ultrasonic measurements during pregnancy. The authors have published earlier a diagram for use to evaluate the fetal development. The aptitude in practice has been proved.--To evaluate normal fetal growth the percentiles curves of Lubchenco are less suitable than of the GDR. But also the last show the normal weight 100 to 150 g to small during the 30th to 36th gestation week in comparison to the calculated fetal weight of normal pregnancies. The intrauterine retardation and hypertrophy can well be diagnosed if the beginning of the measures occurs at the end of the first trimenon of the pregnancy. But it is necessary to know the possibilities of apparent "abnormalities" in normal pregnancy, as ceccation of the fetal growth for 3 or 4 weeks, the late flattening of the biparietal diameter in breech presentation etc.--Our effort to simulatae the fetal growth in intrauterine retardation by using beta-stimulating sympathicomimetics, was without of success.


Neutrophil extracellular traps contain calprotectin, a cytosolic protein complex involved in host defense against Candida albicans.
Neutrophils are the first line of defense at the site of an infection. They encounter and kill microbes intracellularly upon phagocytosis or extracellularly by degranulation of antimicrobial proteins and the release of Neutrophil Extracellular Traps (NETs). NETs were shown to ensnare and kill microbes. However, their complete protein composition and the antimicrobial mechanism are not well understood. Using a proteomic approach, we identified 24 NET-associated proteins. Quantitative analysis of these proteins and high resolution electron microscopy showed that NETs consist of modified nucleosomes and a stringent selection of other proteins. In contrast to previous results, we found several NET proteins that are cytoplasmic in unstimulated neutrophils. We demonstrated that of those proteins, the antimicrobial heterodimer calprotectin is released in NETs as the major antifungal component. Absence of calprotectin in NETs resulted in complete loss of antifungal activity in vitro. Analysis of three different Candida albicans in vivo infection models indicated that NET formation is a hitherto unrecognized route of calprotectin release. By comparing wild-type and calprotectin-deficient animals we found that calprotectin is crucial for the clearance of infection. Taken together, the present investigations confirmed the antifungal activity of calprotectin in vitro and, moreover, demonstrated that it contributes to effective host defense against C. albicans in vivo. We showed for the first time that a proportion of calprotectin is bound to NETs in vitro and in vivo.


Protein glycosylation pathways in filamentous fungi.
Glycosylation of proteins is important for protein stability, secretion, and localization. In this study, we have investigated the glycan synthesis pathways of 12 filamentous fungi including those of medical/agricultural/industrial importance for which genomes have been recently sequenced. We have adopted a systems biology approach to combine the results from comparative genomics techniques with high confidence information on the enzymes and fungal glycan structures, reported in the literature. From this, we have developed a composite representation of the glycan synthesis pathways in filamentous fungi (both N- and O-linked). The N-glycosylation pathway in the cytoplasm and endoplasmic reticulum was found to be highly conserved evolutionarily across all the filamentous fungi considered in the study. In the final stages of N-glycan synthesis in the Golgi, filamentous fungi follow the high mannose pathway as in Saccharomyces cerevisiae, but the level of glycan mannosylation is reduced. Highly specialized N-glycan structures with galactofuranose residues, phosphodiesters, and other insufficiently trimmed structures have also been identified in the filamentous fungi. O-Linked glycosylation in filamentous fungi was seen to be highly conserved with many mannosyltransferases that are similar to those in S. cerevisiae. However, highly variable and diverse O-linked glycans also exist. We have developed a web resource for presenting the compiled data with user-friendly query options, which can be accessed at www.fungalglycans.org. This resource can assist attempts to remodel glycosylation of recombinant proteins expressed in filamentous fungal hosts.


Targeted therapy and personalized medicine in gastrointestinal stromal tumors: drug resistance, mechanisms, and treatment strategies.
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. Since the discovery that the KIT and PDGFRA receptor tyrosine kinases are the primary oncogenic drivers in the vast majority of GISTs, targeted therapy with tyrosine kinase inhibitors has been the mainstay of treatment for this disease. Using molecular profiling of tumor specimens, researchers also discovered that KIT and PDGFRA mutations are non-random and occur in specific regions of the receptors, and furthermore, that particular genotypes predicted response or resistance to targeted therapy. Imatinib, the first tyrosine kinase inhibitor used to treat GIST, remains the first-line therapy in advanced GIST and the only therapy confirmed through clinical trials in the adjuvant or neoadjuvant setting for resectable disease. Resistance to imatinib is well described and is either primary or secondary. Primary resistance is associated with specific tumor genotypes, so genotyping of individual patient tumors helps guide decision-making into whether to offer imatinib and at what dose. Secondary resistance occurs due to the acquisition of secondary mutations during therapy. Currently, the main strategy to combat imatinib resistance is to switch to another tyrosine kinase inhibitor, because imatinib-resistant GIST is usually still oncogenically addicted to KIT/PDGFRA signaling. Surgery can also be used to combat resistant disease in select settings. Unfortunately, progression-free and overall survival remains dismal for patients who develop imatinib-resistant disease, and further research into alternative strategies is still needed.


The role of artificial intelligence in the battle against antimicrobial-resistant bacteria.
Antimicrobial resistance (AMR) in bacteria is a global health crisis due to the rapid emergence of multidrug-resistant bacteria and the lengthy development of new antimicrobials. In light of this, artificial intelligence in the form of machine learning has been viewed as a potential counter to delay the spread of AMR. With the aid of AI, there are possibilities to predict and identify AMR in bacteria efficiently. Furthermore, a combination of machine learning algorithms and lab testing can help to accelerate the process of discovering new antimicrobials. To date, many machine learning algorithms for antimicrobial-resistance discovery had been created and vigorously validated. Most of these algorithms produced accurate results and outperformed the traditional methods which relied on sequence comparison within a database. This mini-review will provide an updated overview of antimicrobial design workflow using the latest machine-learning antimicrobial discovery algorithms in the last 5 years. With this review, we hope to improve upon the current AMR identification and antimicrobial development techniques by introducing the use of AI into the mix, including how the algorithms could be made more effective.


High prevalence of asymptomatic malaria infections in adults, Ashanti Region, Ghana, 2018.
Ghana is among the high-burden countries for malaria infections and recently reported a notable increase in malaria cases. While asymptomatic parasitaemia is increasingly recognized as a hurdle for malaria elimination, studies on asymptomatic malaria are scarce, and usually focus on children and on non-falciparum species. The present study aims to assess the prevalence of asymptomatic Plasmodium falciparum and non-falciparum infections in Ghanaian adults in the Ashanti region during the high transmission season. Asymptomatic adult residents from five villages in the Ashanti Region, Ghana, were screened for Plasmodium species by rapid diagnostic test (RDT) and polymerase chain reaction (PCR) during the rainy season. Samples tested positive were subtyped using species-specific real-time PCR. For all Plasmodium ovale infections additional sub-species identification was performed. Molecular prevalence of asymptomatic Plasmodium infection was 284/391 (73%); only 126 (32%) infections were detected by RDT. While 266 (68%) participants were infected with Plasmodium falciparum, 33 (8%) were infected with Plasmodium malariae and 34 (9%) with P. ovale. The sub-species P. ovale curtisi and P. ovale wallikeri were identified to similar proportions. Non-falciparum infections usually presented as mixed infections with P. falciparum. Most adult residents in the Ghanaian forest zone are asymptomatic Plasmodium carriers. The high Plasmodium prevalence not detected by RDT in adults highlights that malaria eradication efforts must target all members of the population. Beneath Plasmodium falciparum, screening and treatment must also include infections with P. malariae, P. o. curtisi and P. o. wallikeri.


Effect of aqueous extract of Astragalus membranaceus on behavioral cognition of rats living at high altitude.
To investigate the effect of aqueous extract of Astragalus membranaceus on cognitive ability of rats living at high altitude. Rats were exposed to a simulated highaltitude hypobaric hypoxia chamber. The behavior of rats was tested by eight-arm maze. The contents of malondialdehyde (MDA), glutathione (GSH), reactive oxygen species (ROS) and activity of total superoxide dismutase (T-SOD) in hippocampus were measured. The expressions of mammalian target of rapamycin (mTOR) and cleaved capase-3 in hippocampus were determined by reverse transcription-polymerase chain reaction and Western blot. The behavioral cognitive ability of the hypoxic control group was significantly lower than that of the normoxic control group. Under hypoxic environment, after the administration of aqueous extract of Astragalus membranaceus, the behavioral cognitive ability of rats was significantly improved. In hippocampal tissue, the content of MDA and ROS were significantly decreased, while the content of GSH and activity of T-SOD in hippocampus were significantly increased. The mRNA expression of mTOR and P70S6K and the protein expression of p-mTOR were significantly increased; the mRNA expression of 4E-binding protein 1 (4E-BP1) and the protein expression of phosphorylated-4E-BP1 (p-4EBP1) and cleaved capase-3 were significantly decreased. When the rats are exposed to high altitude hypoxia, the behavioral cognitive ability could be significantly reduced. Aqueous extract of Astragalus membranaceus can significantly improve cognitive function in rats under hypoxia. The potential mechanism is related to improving oxidative stress, reducing the accumulation of free radicals and metabolites, and activating mTOR signaling pathway.


Mediastinal teratomas: review of 15 pediatric cases.
One hundred fifty-three children with a teratoma presented to one hospital between 1970 and March 1992. The clinical and pathological features of 15 patients with mediastinal teratomas are reviewed; six were newborn and nine aged from infancy to 13 years. Thirteen patients including the six newborns presented with respiratory distress and all 15 patients had a mass on chest radiograph. A definite diagnosis of teratoma was not made preoperatively in any of these patients. At operation, a median sternotomy was used to approach seven anterior tumors and a lateral thoracotomy performed in the other eight patients. Histologically two were mature, 10 had immature elements, and three were malignant teratomas. The patients with malignant tumors were all over 12 years of age and died within 6 months of treatment. All six neonates had immature teratomas. Raised serum alpha-fetoprotein levels provided useful markers in two patients with recurrent tumors. Three conclusions can be drawn: (1) mediastinal teratomas are rare in children and frequently are not diagnosed before operation; (2) in newborns these tumors may be immature and present with respiratory distress; and (3) a median sternotomy gives excellent exposure for anterior mediastinal tumors.


Effect of phorbol 12,13-dibutyrate on smooth muscle tone in rat stomach fundus.
We investigated the effects of phorbol 12,13-dibutyrate (PDBu), a typical protein kinase C (PKC) activator, on smooth muscle tone in the rat stomach fundus. In 5-hydroxytriptamine (5-HT)-precontracted stomach fundus strips, PDBu induced dose-dependent relaxation, but 4alpha-phorbol 12,13-didecanoate, a phorbol ester that does not activate PKC, did not induce relaxation. A PDBu-induced dose-dependent relaxation was also observed in strips precontracted with platelet-activating factor (PAF), carbachol, or 60 mM K+. In stomach fundus strips pretreated with PDBu, the contractile responses to 5-HT and PAF were completely blocked, but those induced by carbachol and endothelin-1 (ET-1) were only partially inhibited. In stomach fundus strips preincubated with carbachol in Ca2+-free medium, the Ca2+-induced contraction was decreased by preincubation with PDBu. In strips preincubated with 5-HT, PAF, or ET-1 in Ca2+-free medium, Ca2+-induced contractions were greatly inhibited by pretreatment with PDBu. These results suggest that in rat stomach fundus strips, PDBu-induced relaxation is mediated by activation of PKC. We speculate that a major factor mediating the relaxant action of PDBu in rat stomach fundus smooth muscle is represented by a reduction in Ca2+ influx via an inhibition of Ca2+ channels.


Deep Learning Reconstruction Plus Single-Energy Metal Artifact Reduction for Supra Hyoid Neck CT in Patients With Dental Metals.
Purpose: We investigated the effect of deep learning reconstruction (DLR) plus single-energy metal artifact reduction (SEMAR) on neck CT in patients with dental metals, comparing it with DLR and with hybrid iterative reconstruction (Hybrid IR)-SEMAR. Methods: In this retrospective study, 32 patients (25 men, 7 women; mean age: 63 ± 15 years) with dental metals underwent contrast-enhanced CT of the oral and oropharyngeal regions. Axial images were reconstructed using DLR, Hybrid IR-SEMAR, and DLR-SEMAR. In quantitative analyses, degrees of image noise and artifacts were evaluated. In one-by-one qualitative analyses, 2 radiologists evaluated metal artifacts, the depiction of structures, and noise on five-point scales. In side-by-side qualitative analyses, artifacts and overall image quality were evaluated by comparing Hybrid IR-SEMAR with DLR-SEMAR. Results: Artifacts were significantly less with DLR-SEMAR than with DLR in quantitative (P < .001) and one-by-one qualitative (P < .001) analyses, which resulted in significantly better depiction of most structures (P < .004). Artifacts in side-by-side analysis and image noise in quantitative and one-by-one qualitative analyses (P < .001) were significantly less with DLR-SEMAR than with Hybrid IR-SEMAR, resulting in significantly better overall quality of DLR-SEMAR. Conclusions: Compared with DLR and Hybrid IR-SEMAR, DLR-SEMAR provided significantly better supra hyoid neck CT images in patients with dental metals.


Influence of postharvest application of chitosan combined with ethanolic extract of liquorice on shelflife of apple fruit.
Edible coatings are useful method that applied to preserve postharvest quality of production. The coatings can extend the shelf life of products and inhibit microbial growth. Chitosan based coatings are one of the best methods to prolong fruit and vegetable shelf life. The antimicrobial and other properties of chitosan are developed when it is combined with other functional ingredients. The effectiveness of chitosan, ethanolic extract of liquorice (LE) and complex of chitosan-liquorice extract (CHLE) was evaluated for controlling blue mold and extending shelf life in apples. The fruits were coated with chitosan(1.0%), LE (62.5 mg/ml) and CHLE coating, and stored at 25 °C. Quality properties of fruit (such as weight loss, firmness, total soluble solid content(TSS), titrable acidity and pH) and decay incidence were assessed on 0,1,4,7 and 14 days of incubation, respectively. The results of experiments indicated that minimum of water loss(3.8%), TSS(14.53) and firmness(5.6 kg/cm2 ) were in CHLE coated apples. In addition, this coating significantly inhibited penicillium expansum during the storage and the lowest decay incidence was for apples coated with CHLE(29 mm). Chitosan and LE coating retarded undesirable changes during postharvest storage and inhibited decay incidence compared with uncoated samples. There was no significant difference (p ≤ 0/05) between treatments and control overtime in terms of titrable acidity and pH levels. The results reported here indicate importance and efficacy of CHLE coating in extending shelflife and reduction of postharvest losses of apple in storage time.


Prior failed ipsilateral percutaneous endovascular intervention in patients with critical limb ischemia predicts poor outcome after lower extremity bypass.
Although open surgical bypass remains the standard revascularization strategy for patients with critical limb ischemia (CLI), many centers now perform peripheral endovascular intervention (PVI) as the first-line treatment for these patients. We sought to determine the effect of a prior ipsilateral PVI (iPVI) on the outcome of subsequent lower extremity bypass (LEB) in patients with CLI. A retrospective cohort analysis of all patients undergoing infrainguinal LEB between 2003 and 2009 within hospitals comprising the Vascular Study Group of New England (VSGNE) was performed. Primary study endpoints were major amputation and graft occlusion at 1 year postoperatively. Secondary outcomes included in-hospital major adverse events (MAE), 1-year mortality, and composite 1-year major adverse limb events (MALE). Event rates were determined using life table analyses and comparisons were performed using the log-rank test. Multivariate predictors were determined using a Cox proportional hazards model with multilevel hierarchical adjustment. Of 1880 LEBs performed, 32% (n = 603) had a prior infrainguinal revascularization procedure (iPVI, 7%; ipsilateral bypass, 15%; contralateral PVI, 3%; contralateral bypass, 17%). Patients with prior iPVI, compared with those without a prior iPVI, were more likely to be women (32 vs 41%; P = .04), less likely to have tissue loss (52% vs 63%; P = .02), more likely to require arm vein conduit (16% vs 5%; P = .001), and more likely to be on statin (71% vs 54%; P = .01) and beta blocker therapy (92% vs 81%; P = .01) at the time of their bypass procedure. Other demographic factors were similar between these groups. Prior PVI or bypass did not alter 30-day MAE and 1-year mortality after the index bypass. In contrast, 1-year major amputation and 1-year graft occlusion rates were significantly higher in patients who had prior iPVI than those without (31% vs 20%; P = .046 and 28% vs 18%; P = .009), similar to patients who had a prior ipsilateral bypass (1 year major amputation, 29% vs 20%; P = .022; 1 year graft occlusion, 33% vs 18%; P = .001). Independent multivariate predictors of higher 1-year amputation and graft occlusion rates were prior iPVI, prior ipsilateral bypass, dialysis dependence, prosthetic conduit and distal (tibial and pedal) bypass target. Prior iPVI is highly predictive for poor outcome in patients undergoing LEB for CLI with higher 1-year amputation and graft occlusion rates than those without prior revascularization, similar to prior ipsilateral bypass These findings provide information, which may help with the complex decisions surrounding revascularization options in patients with CLI.


The modified D-max is a valid lactate threshold measurement in veteran cyclists.
The ageing process has the potential to impact upon the manner in which an athlete responds to training stimuli. This study investigated if power output (PO) and heart rate (HR) at the modified D-max lactate transition threshold (D-max) was comparable with the mean HR and power that could be sustained during a 30-min laboratory time trial (TT30) in veteran athletes. Nine veteran (> or = 35 years) cyclists performed an incremental exercise test to determine PO and HR at D-max, and peak physiological values. Participants then performed a TT30 during which mean HR and PO were measured for comparison with D-max values. The PO and HR at D-max were significantly correlated with the mean PO and HR during the TT30 (r=0.95, p<0.001 and r=0.88, p=0.002, respectively). Bland and Altman plots revealed a close agreement between D-max and average values sustained during the time trials for PO (95% CI=-14 to +3W) and HR (95% CI=-6 to +3bpm). This study has demonstrated that in veteran cyclists the D-max is accurate in predicting the highest average PO and HR that can be sustained during a 30-min time trial.


Ki-67 is an independent predictor of bladder cancer outcome in patients treated with radical cystectomy for organ-confined disease.
To determine the association of the cell proliferative marker Ki-67 with pathologic features and disease prognosis in patients with transitional cell carcinoma (TCC) of the urinary bladder. Immunohistochemical staining for Ki-67 was done on serial cuts from tissue microarrays containing cystectomy specimens from 9 patients without bladder cancer and 226 consecutive patients with bladder TCC. We also assessed malignant lymph nodes from 50 of the 226 cystectomy patients. Ki-67 expression was increased in 42.5% cystectomy specimens and in 54% metastatic lymph nodes. In contrast, it was absent in all nine benign cystectomy specimens. Ki-67 overexpression was associated with advanced pathologic stage, higher grade, lymphovascular invasion, and metastases to lymph nodes (P = 0.001, 0.040, 0.031, and 0.036, respectively). In multivariate analyses, pathologic stage and lymph node metastases were independent predictors of disease recurrence and bladder cancer-specific mortality. In the subgroup of patients with organ-confined disease (<pT(3) N(0); n = 91), excluding patients who received neoadjuvant or adjuvant chemotherapy, Ki-67 status was an independent predictor of both disease recurrence (risk ratio, 7.591; P = 0.001) and bladder cancer-specific mortality (risk ratio, 4.045; P = 0.041). Ki-67 overexpression is associated with features of aggressive bladder TCC and adds independent prognostic information to standard pathologic features for prediction of clinical outcome after radical cystectomy.


Is PGL-1 also present in Leishmania donovani promastigotes?
A soluble antigen complex (SAC) derived from the ruptured promastigotes of Leishmania donovani parasites (LD-SAC) was used for complement fixation test (CFT) in leprosy Cases of tuberculoid and borderline tuberculoid leprosy, post-kala azar dermal leishmaniasis (TT, BT, PKDL) and control sera gave negative CFT. Smear-positive cases of borderline (BB, BL) and lepromatous (LL) leprosy and drug-resisting cases of pulmonary tuberculosis gave positive CFT; smear-negative cases of LL leprosy sera also gave positive CFT. Sera of smear-negative inactive LL patients contained only PGL-1 and PDIM antigens for a long time after they become inactive. Therefore, the positive CFT in inactive LL makes us suspect whether PGL-1 is present in LD promastigotes.


Inadvertent Hypothermia After Procedural Sedation and Analgesia in a Cardiac Catheterization Laboratory: A Prospective Observational Study.
To identify the prevalence of and risk factors for inadvertent hypothermia after procedures performed with procedural sedation and analgesia in a cardiac catheterization laboratory. A single-center, prospective observational study. A tertiary-care private hospital in Australia. 399 patients undergoing elective procedures with procedural sedation and analgesia were included. Propofol infusions were used when an anesthesiologist was present. Otherwise, bolus doses of either midazolam or fentanyl or a combination of these medications was used. None Hypothermia was defined as a temperature<36.0°C. Multivariate logistic regression was used to identify risk factors. Hypothermia was present after 23.3% (n = 93; 95% confidence interval [CI] 19.2%-27.4%) of 399 procedures. Sedative regimens with the highest prevalence of hypothermia were any regimen that included propofol (n = 35; 40.2%; 95% CI 29.9%-50.5%) and the use of fentanyl combined with midazolam (n = 23; 20.3%; 95% CI 12.9%-27.7%). Difference in mean temperature from pre-procedure to post-procedure was -0.27°C (standard deviation 0.45). Receiving propofol (odds ratio [OR] 4.6 95% CI 2.5-8.6), percutaneous coronary intervention (OR 3.2; 95% CI 1.7-5.9), body mass index<25 (OR 2.5; 95% CI 1.4-4.4) and being hypothermic prior to the procedure (OR 4.9; 95% CI 2.3-10.8) were independent predictors of post-procedural hypothermia. A moderate prevalence of hypothermia was observed. The small absolute change in temperature observed may not be a clinically important amount. More research is needed to increase confidence in the authors' estimates of hypothermia in sedated patients and its impact on clinical outcomes.


The Dualistic Model of Passion Applied to Recreational Marijuana Consumption.
This study was designed to evaluate the application of the dualistic model of passion (Vallerand, 2015; Vallerand et al., 2003) to recreational marijuana consumption. Using a web-based recruitment and data collection procedure, an online sample of 524 frequent marijuana consumers were administered a modified version of the Passion Scale (Marijuana-Harmonious and Obsessive Passion Scale; M-HOPS) and other questionnaires. Results from a canonical correlation analysis indicated that obsessive passion scores were significantly positively associated with past 30-day consumption, average number of sessions per day, craving, and number of consumption-related problems, while controlling for gender, ethnicity, and harmonious passion scores. Additionally, harmonious passion scores were significantly negatively associated with consumption-related problems and positively associated with life satisfaction, while controlling for ethnicity, gender, and obsessive passion scores. Future research could evaluate whether obsessive passion is associated with future problems related to consumption and the development of a cannabis use disorder. Clinicians and prevention specialists could use the M-HOPS as a means to understand and address the dualistic experience of passion for marijuana consumption, which might contribute to persistent use over time.


Prostate whole-mount histology reconstruction and registration to MRI for correlating in-vivo observations with biological findings.
Multi-parametric magnetic resonance imaging (mMRI) is the standard exam for prostate cancer diagnosis, staging and risk assessment in current clinical routine. Correlating mMRI in-vivo observations with biological findings from radical prostatectomy specimen would improve the optimal therapy selection. Thus, we proposed a method for reconstructing and registering the prostate whole-mount histology (WMH) to the MRI, considering a thin slicing of the prostatectomy specimen. The method was evaluated on 3 patients, included in a prospective study, for which hematein-eosinsafran and immunohistochemistry stainings were performed. The registration error was assessed by measuring the Euclidean distance between landmarks, previously identified by an expert on both mMRI and histological slices. The mean error was 4:90α1:34 mm. Our method demonstrated promising results for registering prostate WMH to in-vivo mMRI, thus allowing for spatial accurate correlation between radiologic observations and biological information.