Saturn's Magnetosphere, Rings, and Inner Satellites.
Our 31 August to 5 September 1979 observations together with those of the other Pioneer 11 investigators provide the first credible discovery of the magnetosphere of Saturn and many detailed characteristics thereof. In physical dimensions and energetic charged particle population, Saturn's magnetosphere is intermediate between those of Earth and Jupiter. In terms of planetary radii, the scale of Saturn's magnetosphere more nearly resembles that of Earth and there is much less inflation by entrapped plasma than in the case at Jupiter. The orbit of Titan lies in the outer fringes of the magnetosphere. Particle angular distributions on the inbound leg of the trajectory (sunward side) have a complex pattern but are everywhere consistent with a dipolar magnetic field approximately perpendicular to the planet's equator. On the outbound leg (dawnside) there are marked departures from this situation outside of 7 Saturn radii (Rs), suggesting an equatorial current sheet having both longitudinal and radial components. The particulate rings and inner satellites have a profound effect on the distribution of energetic particles. We find (i) clear absorption signatures of Dione and Mimas; (ii) a broad absorption region encompassing the orbital radii of Tethys and Enceladus but probably attributable, at least in part, to plasma physical effects; (iii) no evidence for Janus (1966 S 1) (S 10) at or near 2.66 Rs; (iv) a satellite of diameter greater, similar 170 kilometers at 2.534 R(s) (1979 S 2), probably the same object as that detected optically by Pioneer 11 (1979 S 1) and previously by groundbased telescopes (1966 S 2) (S 11); (v) a satellite of comparable diameter at 2.343 Rs (1979 S 5); (vi) confirmation of the F ring between 2.336 and 2.371 Rs; (vii) confirmation of the Pioneer division between 2.292 and 2.336 Rs; (viii) a suspected satellite at 2.82 Rs (1979 S 3); (ix) no clear evidence for the E ring though its influence may be obscured by stronger effects; and (x) the outer radius of the A ring at 2.292 Rs. Inside of 2.292 Rs there is a virtually total absence of magnetospheric particles and a marked reduction in cosmic-ray intensity. All distances are in units of the adopted equatorial radius of Saturn, 60,000 kilometers.


Right hepatic artery false aneurysm secondary to acalculous cholecystitis.
The present report describes a case of an extrahepatic right hepatic artery pseudoaneurysm caused by acalculous cholecystitis. An 85-year-old man was admitted with abdominal pain, cachexia and jaundice. A CT scan showed a saccular false right hepatic artery aneurysm within a soft tissue and fluid mass that was causing biliary obstruction. The soft tissue mass raised the possibility of malignant disease, but this resolved slowly after a period of time and on reviewing the patient's history the only upper gastrointestinal problem noted was an episode of acalculous cholecystitis 3 months previously, which was believed to be the cause of the pseudoaneurysm. The false aneurysm was treated successfully with coil embolisation and the patient recovered fully from this illness.


Depressed platelet status in an elderly patient with hemorrhagic stroke after thrombolysis for acute myocardial infarction. GUSTO-III Investigators.
Impaired platelet function has been reported in acute myocardial infarction (AMI) and stroke. However, prospective data on the changes of platelet status in patients before the occurrence of hemorrhagic stroke after thrombolytic therapy are unavailable. An 86-year-old male patient was among the 23 AMI patients enrolled in the platelet study for the GUSTO-III trial. He received 325 mg of aspirin daily for at least 6 years, suffered an AMI, and was successfully reperfused with alteplase, but after 44 hours developed a large hemorrhagic stroke resulting in paraplegia. Platelet aggregation and receptor expression were measured by flow cytometry and ELISA before thrombolysis and at 3, 6, 12, and 24 hours thereafter. The percentage of platelet aggregation was lower in the stroke patient at every time point when induced by 5 micromol/L of ADP, by 10 micromol/L of ADP, and by thrombin than in the rest of the AMI group. Ristocetin and collagen-induced aggregability were within the group range. Decreased platelet glycoprotein Ib, IIb, IIIa, and IIb/IIIa and vitronectin receptor expression were observed in the stroke patient. No other differences in p24 (CD9), very late antigen-2, P-selectin, and platelet/endothelial cell adhesion molecule-1 expression were determined. Profound depression of platelet status preceded the occurrence of hemorrhagic stroke in an elderly long-term aspirin user treated with thrombolytic therapy. Initial "exhausted" platelets may be responsible for the increased risk for hemorrhagic stroke after coronary thrombolysis.


Heterodyne holographic microscopy of gold particles.
We report experimental results on heterodyne holographic microscopy of subwavelength-size gold particles. The apparatus uses continuous green-laser illumination of the metal beads in a total internal reflection configuration for dark-field operation. Detection of the scattered light at the illumination wavelength on a charge-coupled-device array detector enables 3D localization of brownian particles in water.


[Conventional and cine-MRT in patients with aneurysms of the abdominal aorta].
We studied 40 patients with aneurysms of the abdominal aorta by MRI. These results were compared with those obtained by real-time sonography (n = 40), angiography (n = 32) and CT (n = 16). In 30 patients the imaging results were compared--as far as possible--with the operative findings. MRI proved more reliable, especially if compared with sonography, in evaluating renal or iliac artery involvement. Mural thrombi were detected more often (93%) by MRI than by CT (85%) or sonography (83%). Cine-MRI showed strong turbulences in 33%. Turbulences did not correlate with the size of the aneurysm.


Activity-dependent plasticity in spinal cord injury.
The adult mammalian central nervous system (CNS) is capable of considerable plasticity, both in health and disease. After spinal neurotrauma, the degrees and extent of neuroplasticity and recovery depend on multiple factors, including the level and extent of injury, postinjury medical and surgical care, and rehabilitative interventions. Rehabilitation strategies focus less on repairing lost connections and more on influencing CNS plasticity for regaining function. Current evidence indicates that strategies for rehabilitation, including passive exercise, active exercise with some voluntary control, and use of neuroprostheses, can enhance sensorimotor recovery after spinal cord injury (SCI) by promoting adaptive structural and functional plasticity while mitigating maladaptive changes at multiple levels of the neuraxis. In this review, we will discuss CNS plasticity that occurs both spontaneously after SCI and in response to rehabilitative therapies.


Differential regulation of MAP kinase by contraction and insulin in skeletal muscle: metabolic implications.
We have investigated the activation of the extracellular signal-regulated kinases (ERK1 and ERK2) by muscle contraction and insulin in perfused rat skeletal muscle. Both stimuli activated ERK1 and ERK2 by an upstream kinase MAP/ERK kinase (MEK)-dependent mechanism, as the MEK inhibitor PD-98059 inhibited ERK phosphorylation. The presence of the phosphatidylinositol (PI) 3-kinase inhibitors LY-294002 and wortmannin totally eradicated ERK1 and ERK2 phosphorylation in response to insulin but not contraction. Insulin and muscle contraction activated muscle glucose transport, glycogen synthase, and amino acid transport independently of ERK signaling, whereas the PI 3-kinase inhibitors abolished the stimulatory effects of insulin but not those of contraction on these three cellular processes. We conclude that 1) insulin and contraction activate ERK signaling in skeletal muscle; 2) ERK signaling is not necessary for activation of glucose and amino acid transport or glycogen synthase activity by contraction and insulin in skeletal muscle; and 3) insulin-induced activation of MEK, the upstream activator of ERK, is dependent on PI 3-kinase, whereas contraction utilizes a different mechanism.


Fas determines differential fates of resident and recruited macrophages during resolution of acute lung injury.
During acute lung injury (ALI) the macrophage pool expands markedly as inflammatory monocytes migrate from the circulation to the airspaces. As inflammation resolves, macrophage numbers return to preinjury levels and normal tissue structure and function are restored. To determine the fate of resident and recruited macrophages during the resolution of ALI in mice and to elucidate the mechanisms responsible for macrophage removal. ALI was induced in mice using influenza A (H1N1; PR8) infection and LPS instillation. Dye labeling techniques, bone marrow transplantation, and surface immunophenotyping were used to distinguish resident and recruited macrophages during inflammation and to study the role of Fas in determining macrophage fate during resolving ALI. During acute and resolving lung injury from influenza A and LPS, a high proportion of the original resident alveolar macrophages persisted. In contrast, recruited macrophages exhibited robust accumulation in early inflammation, followed by a progressive decline in their number. This decline was mediated by apoptosis with local phagocytic clearance. Recruited macrophages expressed high levels of the death receptor Fas and were rapidly depleted from the airspaces by Fas-activating antibodies. In contrast, macrophage depletion was inhibited in mice treated with Fas-blocking antibodies and in chimeras with Fas-deficient bone marrow. Caspase-8 inhibition prevented macrophage apoptosis and delayed the resolution of ALI. These findings indicate that Fas-induced apoptosis of recruited macrophages is essential for complete resolution of ALI.


[The medical social aspects of ambulatory medical care to victims of road traffic accidents].
The article discusses the issues of the organization of medical care to victims of road traffic accidents. The analysis of primary appealability of patients to the first-aid center of Stavropol and Novorossiysk during 2008-2010 is presented. The sampling consisted of 904 cases of this kind of trauma. It is established that among victims of road traffic accident appealed to first-aid centers the pedestrians consist the major part. The traumas of limbs are among the most frequently occurred cases. The victims with cranio-cerebral injuries are among those who appealed most frequently for medical aid. Besides that in most cases (63.4%) the victims with cranio-cerebral injuries were transported not to the neurologic surgery clinic but to the first-aid center This action increased the number of transport stages and duration of time gap before specialized medical care was applied. The conclusion is made concerning the need of further development of out-patient urgent medical care to victims of road traffic accidents.


Identification of signature of tumor-infiltrating CD8 T lymphocytes in prognosis and immunotherapy of colon cancer by machine learning.
To explore the specific marker of CD8+ T cell subsets which are closely related to the prognosis and immunotherapy of patients with colon cancer. 18 kinds of immune cell expression profile data sets were obtained from GEO database. Compared with other immune cell types, the specific markers of CD8 (+) T cells (TI-CD8) in colorectal cancer were screened. Regression analyses were used to further screen prognostic related genes and construct a prognostic evaluation model. The patients were stratified and analyzed according to the risk scores, KRAS mutation status, stage, lymphatic infiltration and other indicators. The landscape of infiltration level, mutation and copy number variation of immune subsets in high and low TI-CD8Sig score groups were compared and analyzed. The difference of drug response between high and low TI-CD8Sig score groups was analyzed. Differential expression of the model genes was verified by the HPA database. Six prognostic-related CD8T cell-specific gene targets were further screened, and the prognostic evaluation model was constructed. The AUC value of the model is >0.75. FAT3 and UNC13C showed a high mutation state in the low-risk group, while USH2A, MUC5B et al. specifically showed a high mutation state in the high-risk group. Compared with the low-risk group, the high-risk group had lower effective rate of drug response. The expression of PD-1 gene was positively correlated with the level of TI-CD8Sig score. The risk assessment model based on CD8T cell-specific marker genes can effectively predict the prognosis and the drug response of patients with CRC.


Rapid confirmation/quantitation of ecgonine methyl ester, benzoylecgonine, and cocaine in urine using on-line extraction coupled with fast HPLC and tandem mass spectrometry.
A rapid, rugged, and highly specific assay for the quantitation of cocaine (COC) and especially its primary metabolites benzoylecgonine (BZE) and ecgonine methyl ester (EME) in human urine has been established. Here, we investigated the use of on-line sample extraction coupled to rapid chromatography systems for tandem mass analysis of COC, EME, and BZE in human urine. Using this method, sample preparation consisted of a sole centrifugation step. Combined extraction and chromatographic run times were < 3.5 min. The lower limits of detection were 0.5 ng/mL, 2.0 ng/mL, and 0.5 ng/mL for EME, BZE, and COC, respectively. Linear calibration curves ranging from 7.5 ng/mL to 1000 ng/mL were produced for the test analytes. Within-day and between-day precision and accuracy of the assay were determined using human urine quality-control specimens at 5, 10, or 15; 150; and 1000 ng/mL. The analyses were performed over the course of five days, rendering %CVs < 10% for EME, BZE, and COC. Percent mean accuracy for the three analytes of 97 to 113% were obtained. Our data suggest that on-line sample extraction coupled with rapid high-performance liquid chromatography-tandem mass spectrometry may be a viable alternative for EME, BZE, and COC analyses in human urine.


Transfection of a rat cell line with the v-Ki-ras oncogene is associated with enhanced susceptibility to natural killer cell lysis.
Transfection of the v-Ki-ras oncogene into rat-1 fibroblasts resulted in the establishment of cell lines that were transformed, tumorigenic, and sensitive to lysis by natural killer (NK) cells. Characterization of effectors indicated that the killing was not related to Lyt-1+ or Lyt-2+ cells (T cells) but was associated with cells bearing NK markers (asialo GM1, NK-1.2+, and NK-2.1+). Transfected targets were also killed by cloned NK lines. The transformation determinants on rat-1 transfectants cross-competed with YAC 1.2 lymphoma cells, suggesting a common target structure on these two diverse cell types. The results indicate that the NK surveillance system can recognize and kill cells newly transformed by a member of the ras oncogene family.


Diagnostic Delay Is Associated With Complicated Disease and Growth Impairment in Paediatric Crohn's Disease.
Paediatric data on the association between diagnostic delay and inflammatory bowel disease [IBD] complications are lacking. We aimed to determine the effect of diagnostic delay on stricturing/fistulising complications, surgery, and growth impairment in a large paediatric cohort, and to identify predictors of diagnostic delay. We conducted a national, prospective, multicentre IBD inception cohort study including 1399 children. Diagnostic delay was defined as time from symptom onset to diagnosis >75th percentile. Multivariable proportional hazards [PH] regression was used to examine the association between diagnostic delay and stricturing/fistulising complications and surgery, and multivariable linear regression to examine the association between diagnostic delay and growth. Predictors of diagnostic delay were identified using Cox PH regression. Overall (64% Crohn's disease [CD]; 36% ulcerative colitis/IBD unclassified [UC/IBD-U]; 57% male]), median time to diagnosis was 4.2 (interquartile range [IQR] 2.0-9.2) months. For the overall cohort, diagnostic delay was >9.2 months; in CD, >10.8 months and in UC/IBD-U, >6.6 months. In CD, diagnostic delay was associated with a 2.5-fold higher rate of strictures/internal fistulae (hazard ratio [HR] 2.53, 95% confidence interval [CI] 1.41-4.56). Every additional month of diagnostic delay was associated with a decrease in height-for-age z-score of 0.013 standard deviations [95% CI 0.005-0.021]. Associations persisted after adjusting for disease location and therapy. No independent association was observed between diagnostic delay and surgery in CD or UC/IBD-U. Diagnostic delay was more common in CD, particularly small bowel CD. Abdominal pain, including isolated abdominal pain in CD, was associated with diagnostic delay. Diagnostic delay represents a risk factor for stricturing/internal fistulising complications and growth impairment in paediatric CD. This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast.


Crystallization and phasing of alanine dehydrogenase from Archaeoglobus fulgidus.
Alanine dehydrogenase (AlaDH) from the hyperthermophilic archaeon Archaeoglobus fulgidus is a dimer of 35 kDa chains. The archaeal enzyme appears to represent a new class of AlaDH that is not homologous to bacterial AlaDH enzymes, but has close evolutionary links to the broad ornithine cyclodeaminase/micro-crystallin family, which includes human thyroid hormone binding protein, which has 30% sequence identity to the A. fulgidus gene. The enzyme has been cloned, shown to catalyze the NAD-dependent interconversion of alanine and pyruvate and crystallized in several forms. Although the purified protein crystallized readily under many conditions, most of the crystals diffracted weakly or not at all. One polymorph growing in space group P2(1)2(1)2(1) has non-crystallographic symmetry that becomes crystallographic, changing the space group to P2(1)2(1)2, upon binding iridium or samarium. Before and after derivatization, these crystals diffracted to 2.5 A using synchrotron radiation. Multiwavelength diffraction data were collected from the non-isomorphous iridium derivative, enabling structure determination.


Rapid recovery of life at ground zero of the end-Cretaceous mass extinction.
The Cretaceous/Palaeogene mass extinction eradicated 76% of species on Earth1,2. It was caused by the impact of an asteroid3,4 on the Yucatán carbonate platform in the southern Gulf of Mexico 66 million years ago 5 , forming the Chicxulub impact crater6,7. After the mass extinction, the recovery of the global marine ecosystem-measured as primary productivity-was geographically heterogeneous 8 ; export production in the Gulf of Mexico and North Atlantic-western Tethys was slower than in most other regions8-11, taking 300 thousand years (kyr) to return to levels similar to those of the Late Cretaceous period. Delayed recovery of marine productivity closer to the crater implies an impact-related environmental control, such as toxic metal poisoning 12 , on recovery times. If no such geographic pattern exists, the best explanation for the observed heterogeneity is a combination of ecological factors-trophic interactions 13 , species incumbency and competitive exclusion by opportunists 14 -and 'chance'8,15,16. The question of whether the post-impact recovery of marine productivity was delayed closer to the crater has a bearing on the predictability of future patterns of recovery in anthropogenically perturbed ecosystems. If there is a relationship between the distance from the impact and the recovery of marine productivity, we would expect recovery rates to be slowest in the crater itself. Here we present a record of foraminifera, calcareous nannoplankton, trace fossils and elemental abundance data from within the Chicxulub crater, dated to approximately the first 200 kyr of the Palaeocene. We show that life reappeared in the basin just years after the impact and a high-productivity ecosystem was established within 30 kyr, which indicates that proximity to the impact did not delay recovery and that there was therefore no impact-related environmental control on recovery. Ecological processes probably controlled the recovery of productivity after the Cretaceous/Palaeogene mass extinction and are therefore likely to be important for the response of the ocean ecosystem to other rapid extinction events.


The use of self-management strategies for problem gambling: a scoping review.
Problem gambling (PG) is a serious public health concern that disproportionately affects people experiencing poverty, homelessness, and multimorbidity including mental health and substance use concerns. Little research has focused on self-help and self-management in gambling recovery, despite evidence that a substantial number of people do not seek formal treatment. This study explored the literature on PG self-management strategies. Self-management was defined as the capacity to manage symptoms, the intervention, health consequences and altered lifestyle that accompanies a chronic health concern. We searched 10 databases to identity interdisciplinary articles from the social sciences, allied health professions, nursing and psychology, between 2000 and June 28, 2017. We reviewed records for eligibility and extracted data from relevant articles. Studies were included in the review if they examined PG self-management strategies used by adults (18+) in at least a subset of the sample, and in which PG was confirmed using a validated diagnostic or screening tool. We conducted a scoping review of studies from 2000 to 2017, identifying 31 articles that met the criteria for full text review from a search strategy that yielded 2662 potential articles. The majority of studies examined self-exclusion (39%), followed by use of workbooks (35%), and money or time limiting strategies (17%). The remaining 8% focused on cognitive, behavioural and coping strategies, stress management, and mindfulness. Given that a minority of people with gambling concerns seek treatment, that stigma is an enormous barrier to care, and that PG services are scarce and most do not address multimorbidity, it is important to examine the personal self-management of gambling as an alternative to formalized treatment.


[Considering about the timing of cataract surgery with high myopia].
With the rapid increase in the myopic population, cataract surgery in individuals with high myopia has become increasingly prevalent. For patients, the benefits of cataract surgery in highly myopic individuals are more pronounced compared to conventional cataract surgery. However, For cataract surgeons, performing cataract surgery in highly myopic individuals presents a more complex surgical procedure with elevated surgical risks and less favorable postoperative outcomes. As a result, the decision regarding the timing of cataract surgery in highly myopic individuals exhibits a clear polarization. some patients with mild cataracts strongly advocate for early surgery, while others with severe cataracts hesitate due to concerns about surgical risks. When making surgical decisions, both medical professionals and patients should thoroughly consider the benefits and risks of the surgery, allowing for an objective selection of the most appropriate timing for the procedure.


Correlated digital back propagation based on perturbation theory.
We studied a simplified digital back propagation (DBP) scheme by including the correlation between neighboring signal samples. An analytical expression for calculating the correlation coefficients is derived based on a perturbation theory. In each propagation step, nonlinear distortion due to phase-dependent terms in the perturbative expansion are ignored which enhances the computational efficiency. The performance of the correlated DBP is evaluated by simulating a single-channel single-polarization fiber-optic system operating at 28 Gbaud, 32-quadrature amplitude modulation (32-QAM), and 40 × 80 km transmission distance. As compared to standard DBP, correlated DBP reduces the total number of propagation steps by a factor of 10 without performance penalty. Correlated DBP with only 2 steps per link provides about one dB improvement in Q-factor over linear compensation.


Free beta-subunit of human chorionic gonadotropin in serum is a diagnostically sensitive marker of seminomatous testicular cancer.
We studied whether measurement of the free beta subunit of human chorionic gonadotropin (hCGbeta) in serum offers additional diagnostic information compared to determination of intact hCG alone in testicular cancer. We determined hCG and hCGbeta with ultrasensitive assays in 94 serum samples obtained preoperatively, 22 samples obtained during relapse, and 3687 samples obtained during routine follow-up of 351 patients with testicular tumors. In preoperative samples, isolated increases of hCGbeta were seen in 40% of the samples from seminoma patients (n = 42) and in 8% of those from patients with nonseminomatous testicular cancer (NSGCT) (n = 51). Both markers were increased in 12% of the seminoma and 71% of the NSGCT patients and were within reference intervals in 43% of the seminoma and 20% of the NSGCT patients. Specific determination of hCGbeta increased the frequency of marker-positive seminomas from 17% to 57% and of marker-positive relapses from 32% to 59% (n = 22). Theoretically, about 40% of marker-positive seminomas and relapses would have been missed with an assay measuring hCG and hCGbeta together. Preoperative hCG and hCGbeta concentrations correlated with stage, tumor histology, and disease-related mortality. Additionally, hCGbeta correlated with tumor size. hCGbeta is a diagnostically sensitive marker for testicular cancer. In patients with seminomatous testicular cancer, hCGbeta is superior to hCG, and in some NSGCT patients it provides additional information.


The adrenal mass: correlation of histopathology with imaging.
Computed tomography (CT) and magnetic resonance (MR) imaging can help diagnose benign adrenal adenomas, but prior studies rely on nonoperative follow-up as proof of a lesion's benign nature. We examined adrenalectomy tissues to determine if imaging characteristics correlate with histopathologic findings. We retrieved data for 196 consecutive adrenalectomies in 192 patients from 2000 to 2008. Imaging results were considered to signify benign adrenal adenoma if one or more of the following was present: Hounsfield units <10 on unenhanced CT, contrast-enhanced CT quantifying absolute contrast washout of >60% or relative contrast washout of >40%, or MR with chemical-shift imaging demonstrating loss of signal intensity on out-of-phase images. The sensitivity and specificity of preoperative imaging in predicting benign adrenal adenoma were 57 and 94%, respectively. Histopathology confirmed that all 66 adrenal masses with imaging characteristics suggesting benign adenoma were indeed benign lesions and included 61 benign adrenal adenomas and 5 benign nonadenomatous lesions (3 myelolipomas, 1 composite myelolipoma/adenoma, and 1 ganglioliponeuroma). The specificity of imaging in predicting benignity was 100%. Malignant adrenal lesions were diagnosed in 17/130 (13%) masses: 8 metastases, 7 adrenal cortical carcinomas, 1 epithelioid angiosarcoma, and 1 ganglioneuroblastoma. The sensitivity of imaging in identifying malignancy was 100%. No malignancies were diagnosed during postoperative follow-up (mean 6 months, range 0.2-67 months). CT or MR characteristics predicted the presence of benign lesions with 100% specificity. Every adrenal malignancy had CT or MR results that were inconsistent with benign adenoma (100% sensitivity). To exclude malignancy, adrenal masses with non-benign imaging characteristics should be resected.


[Death by illegal drugs in Bavaria 1990 up to 2002].
In our paper we report about drug mortality in Bavaria in the years 1990 up to 2002, using statistical trend tests (Spearman rho, Kendall tau). We observed an increase of deaths by illegal drugs in Bavaria as whole, on the other hand also decreases in different parts of the country.


Stabilization of BMIz Score is Associated with a Decrease in Visceral Fat in Children with Obesity.
BMIz-score (BMIz) is commonly used to assess childhood obesity. Whether change in BMIz score predicts change in visceral fat remains unclear. The objective of the work was to study changes in visceral fat, cardiovascular fitness (CVF), and metabolic health over 6 months in children with stable/decreased-BMIz vs. increased-BMIz. Ninety children with obesity, referred for lifestyle intervention were studied (mean age 11±3.1 years, 50% girls, 22% Hispanic). Assessment included abdominal and total fat by dual X-ray absorptiometry (DXA), sub-maximal VO2 for CVF, anthropometrics, and fasting insulin, glucose, HDL-C, triglycerides, AST and ALT at 0 and 6 months. Sixty-three children (70%) showed a stable/decrease in BMIz over 6 months. There was no significant change in total body fat between groups (-1.3±2.9% in BMIz-stable/down vs. - 0.6 ± 2.6% BMIz-up, p=0.459); however, BMIz-stable/down group showed a decrease in visceral fat compared to the BMIz-up group (-258±650 g vs.+137±528 g, p=0.009). BMIz-stable/down group also demonstrated increased CVF (+1.2 ml/kg/min, p<0.001), not seen in the BMIz-up group. Neither group had significant changes in metabolic markers. Preventing BMIz increase in obese children predicts a significant decrease in visceral fat even if total body fat is unchanged. This is often associated with increased fitness. Thus, increasing fitness level and keeping BMI stable are strategic initial goals for obese children.


Elevated serum alpha-hydroxybutyrate dehydrogenase in patients with ovarian carcinoma.
To differentiate between ovarian carcinoma and benign ovarian tumor, we compared alpha-hydroxybutyrate dehydrogenase (HBD), lactate dehydrogenase (LDH) and its isoenzyme activities in serum in 115 patients with ovarian carcinoma and benign ovarian tumor. Both serum HBD activity and total LDH activity in ovarian cancer patients were significantly (p less than 0.001) higher than that in patients with benign ovarian tumor. From analysis of serum LDH isoenzymes, a significant decrease in LDH-1, and significant increases in LDH-4 and LDH-5 in ovarian cancer patients were observed, when compared with those in patients with benign ovarian tumor. When the ovarian cancer mass could be removed surgically, a significant decrease in the HBD was observed, suggesting that the HBD might fairly reflect the tumor burden. Serum HBD activities in a half of ovarian cancer patients were higher than the mean +2 SD of those in benign control subjects.


Genome Sequence of the Mycotoxigenic Crop Pathogen Fusarium proliferatum Strain ITEM 2341 from Date Palm.
Fusarium proliferatum is a widely distributed fungal pathogen associated with more than 26 crop species important in global food security. Its strong mycotoxigenic capability with potential impacts on human and animal health is well recognized. In this work, we report the draft genome sequence of F. proliferatum strain ITEM 2341, originally isolated from date palm, providing a platform for further comparative and functional genomic investigations.


Effective Connectivity Between the Orbitofrontal Cortex and the Precuneus Differentiates Major Psychiatric Disorders: Results from a Transdiagnostic Spectral DCM Study.
We have previously identified aberrant connectivity of the left precuneus, ventrolateral prefrontal cortex, anterior cingulate cortex, and anterior insula in patients with either a paranoid (schizophrenia), or a depressive syndrome (both unipolar and bipolar). In the current study, we attempted to replicate and expand these findings by including a healthy control sample and separating the patients in a depressive episode into two groups: unipolar and bipolar depression. We hypothesized that the connections between those major nodes of the resting state networks would demonstrate different patterns in the three patient groups compared to the healthy subjects. Resting-state functional MRI was performed on a sample of 101 participants, of which 26 patients with schizophrenia (current psychotic episodes), 24 subjects with Bipolar Disorder (BD), 33 with Major Depressive Disorder (MDD) (both BD and MDD patients were in a current depressive episode), and 21 healthy controls. Spectral Dynamic Causal Modeling was used to calculate the coupling values between eight regions of interest, including the anterior precuneus (PRC), anterior hippocampus, anterior insula, angular gyrus, lateral Orbitofrontal Cortex (OFC), middle frontal gyrus, planum temporale, and anterior thalamus. We identified disturbed effective connectivity from the left lateral orbitofrontal cortex to the left anterior precuneus that differed significantly between unipolar depression, where the influence was inhibitory, and bipolar depression, where the effect was excitatory. A logistic regression analysis correctly classified 75% of patients with unipolar and bipolar depression based solely on the coupling values of this connection. In addition, patients with schizophrenia demonstrated negative effective connectivity from the anterior PRC to the lateral OFC, which distinguished them from healthy controls and patients with major depression. Future studies with unmedicated patients will be needed to establish the replicability of our findings.


Human colostral phagocytes eliminate enterotoxigenic Escherichia coli opsonized by colostrum supernatant.
Several elements in colostrum and human milk, including antibodies and nonspecific factors with bactericidal and antiviral activity, may play an important anti-infectious and protective role. In developing countries, enterotoxigenic Escherichia coli (ETEC) is the main etiological agent of diarrhea in low-socioeconomic level children. In the present work, we studied the functional activity of mononuclear (MN) and polymorphonuclear (PMN) phagocytes of human colostrum against ETEC, as well as the interactions between these cells and colostral or serum opsonins. Colostrum samples were collected from 33 clinically healthy women between 48 and 72 hours postpartum. We verified superoxide release in colostral MN and PMN using cytochrome C reduction methods, phagocytosis, and bactericidal activity using acridine orange methods and superoxide dismutase (SOD) in the colostrum supernatants. Colostral MN and PMN phagocytes exposed to ETEC opsonized with colostrum supernatants caused a significant increase (p<0.05) in superoxide release. Phagocytosis by colostral PMN cells increased significantly (p<0.5) when the phagocytes were incubated with both sources of opsonins (sera and colostrum). Increases in superoxide release in the presence of opsonized bacteria triggered the bactericidal activity of the phagocytes. Phagocyte treatment with SOD decreased their ability to eliminate ETEC. Colostrum supernatant had higher SOD concentrations (p<0.05) compared with normal human sera. These results suggest that the ability of phagocytes to eliminate ETEC depends on the activation of cellular oxidative metabolism; moreover, activation of colostral phagocytes is likely an additional breast-feeding protection mechanism against intestinal infections in infants.


A THOROUGH STUDY AND META-ANALYSIS OF THE PROGNOSTIC RELEVANCE OF THE C-REACTIVE-ALBUMIN RATIO IN ACUTE PANCREATITIS.
Although most cases of acute pancreatitis (AP) are minor, severe cases are associated with a substantial risk of death. Acute pancreatitis (AP) is a common illness. Therefore, it is critical to assess AP severity as soon as possible. This review aimed to ascertain the predictive significance of the CRP to albumin ratio in individuals with AP. We searched PubMed, Science Direct, and Cochrane Library electronic databases Until January 2023. Studies that reported the CRP/alb ratio at admission and its relationship to the severity or death of patients with AP were included. Using a random-effects model, we computed the pooled mean difference (MD) and 95% confidence interval (CI). The quality of the included studies was evaluated using the Newcastle-Ottawa scale. This meta-analysis combined data from six trials with a total of 2244 patients. Upon admission, the CRP/alb ratio was higher in patients with severe AP than in those with mild to moderate AP (pooled MD:3.59; 95% CI:2.51-4.68; p<0.00001). Additionally, non-survivor AP patients had a substantially higher CRP/alb ratio than survivor AP patients (pooled MD:2.12; 95% CI:0.43-3.8; p<0.01). Individuals with AP may benefit from a high CRP/ALB ratio as a preliminary indicator of poor prognosis.


Manage the difficult patient to reduce malpractice risk.
Managed care is becoming the predominant model of health care delivery in the United States, and cost containment pressures are being felt by physicians and patients alike. As a result, the doctor-patient relationship is being subjected to greater pressures and conflicts. These conflicts can result in patients being viewed as "difficult." Difficult patients represent a clinical challenge which many providers feel unprepared to address. When difficult patients become dissatisfied and angry with care, a professional liability claim can result. This article presents difficult patient cases and management recommendations, along with evaluation results of three seminars based on the difficult patient concept.


Prolonged survival of musculoskeletal xenografts with combined cyclosporine and 15-deoxyspergualin.
This study was undertaken to evaluate the feasibility of performing vascularized musculoskeletal xenografts between mice and rats using immunosuppression. Vascularized musculoskeletal grafts were harvested from the hind limb of C57BL/6J (B6) mice, transplanted heterotopically into Lewis rats, and revascularized by microanastomoses of the graft artery and the recipient femoral artery and the graft vein to the recipient femoral vein. Recipient rats were divided into four groups. Group 1 received no immunosuppression (n = 10), group 2 was treated with cyclosporine (10 mg/kg/day; n = 10), group 3 was treated with 15-deoxyspergualin (5 mg/kg/day; n = 10), and group 4 received both cyclosporine and 15-deoxyspergualin (n = 10). Graft survival was directly examined on postoperative days 4, 7, and 14. In vitro assays were performed using mixed lymphocyte reactions and anti-donor cytotoxic antibody assays to assess the recipient's immune response. Grafts were examined by histology and immunohistochemistry. All grafts in group 1 were rejected by day 4. In groups 2 and 3, all grafts were rejected by day 7. In group 4, however, 8 of 10 recipients had viable grafts on day 14. Data from mixed lymphocyte reactions showed that cell-mediated immune responses were uniformly suppressed in groups 2, 3, and 4 compared with group 1. However, anti-donor antibody production was only partly suppressed in groups 2 and 3, suggesting that graft rejection was primarily caused by circulating cytotoxic anti-donor antibodies in groups 1, 2, and 3. Histologic observations in groups 1, 2, and 3 confirmed the important role of the humoral mechanism in xenograft rejection. Furthermore, immunohistochemical results demonstrated that the small vessels in the rejected grafts showed anti-rat immunoglobulin and complement depositions. Only a combination therapy of cyclosporine and 15-deoxyspergualin attenuated the rejection of xenografts.


Analysis of the capsular bend in posterior capsular opacification using anterior segment optical coherence tomography.
To investigate the link between the capsular bend and the morphological types and characteristics of posterior capsular opacification (PCO) using anterior segment optical coherence tomography. Thirty eyes with PCO were examined, and three types of PCO were identified: pearl, fibrosis, and mixed. We assessed anterior capsular overlap, intraocular lens-capsule adhesion, and capsular bending. In addition to measuring the intraocular lens-posterior capsule distance and capsule bending angle (CBA), the PCO parameters (area, density, and score at 6-, 5-, and 3-mm intraocular lens optic regions) were recorded. The associations between capsular bend and PCO type and characteristics were investigated. A control group of 12 eyes without PCO was used to compare the study variables. With p values greater than 0.001, there was a statistically significant difference in the mean PCO area and score at the 6-, 5-, and 3-mm optic zones in different PCO types, with the pearl type having the highest value, followed by the mixed type, and finally the fibrosis type. The PCO group had a significantly higher mean CBA than the control group (P = 0.001). CBA was positively related to intraocular lens-posterior capsule distance, PCO area, and PCO score at the 6-, 5-, and 3-mm zones (P = 0.001). The receiver operating characteristic curve's cut-off point for CBA was 96.85° when comparing PCO cases to controls. Partial overlap and incomplete adhesion were statistically more common in the PCO eyes than in the control (P = 0.001, 0.003, respectively). PCO types and CBA have a strong relationship with PCO score and intraocular lens-posterior capsule space. In PCO's eyes, CBA has a cut-off value of 96.85°.


Reversal of opiate-induced apoptosis by human recombinant growth hormone in murine foetus primary hippocampal neuronal cell cultures.
Previous studies have shown that chronic opiates may inhibit cell growth and trigger apoptosis leading to impaired cognitive capabilities in both humans and other mammals. In contrast, growth hormone (GH) has been demonstrated to stimulate cell growth and counteract apoptosis. GH has also been shown to improve learning and memory in both human and rodents. In this work, we demonstrate that GH may reverse opiate-induced apoptosis in cells derived from prenatal mouse hippocampus. Primary hippocampal cell cultures derived from 16-day-old fetal mouse neurons were treated with morphine for 7 days during growth in the absence or presence of recombinant human GH (rhGH). The release of lactate dehydrogenase (LDH) into the culture media and the level of cleaved caspase-3 were measured. Results indicate that morphine (15 microM) decreased the cell content in a concentration-dependent manner and increased LDH release and caspase-3 activity. Thus, fetal mouse neurons treated with morphine showed less viability compared with controls. Interestingly, the addition of rhGH (1 microM) counteracted the morphine-induced effect on the cell density. Furthermore, the hormone attenuated the effects on LHD release and caspase-3 activity elicited by morphine. These results suggest that the hormone is capable of preventing or even repairing morphine-induced damage to hippocampal cells.


Self-specific CD8+ T cells maintain a semi-naive state following lymphopenia-induced proliferation.
Upon transfer into T cell-deficient hosts, naive CD8(+) T cells typically undergo lymphopenia-induced proliferation (LIP, also called homeostatic proliferation) and develop the phenotypic and functional characteristics of memory CD8(+) T cells. However, the capacity of T cells with self-peptide/MHC specificity to respond in this way has not been intensively studied. We examined pmel-1 TCR transgenic CD8(+) T cells that are specific for an epitope from gp100, a protein expressed by melanoma cells and normal melanocytes. Despite their self-specificity, naive pmel-1 cells were inefficient at LIP in typical lymphopenic hosts. In CD132 (common gamma-chain)-deficient hosts, pmel-1 CD8(+) T cells underwent extensive proliferation, but, surprisingly, the majority of these cells retained certain naive phenotypic traits (CD44(low), CD122(low)) rather than acquiring the expected central-memory phenotype. Following LIP, pmel-1 T cells acquired the capacity to control B16F10 tumor growth, but only in common gamma-chain-deficient host mice. Together, these data suggest that LIP does not always favor expansion of self-specific CD8 T cells and that sustained extensive lymphopenia is required for such cells to exhibit tumor control.


Conditionally transposition-defective derivative of Mu d1(Amp Lac).
A Mu d1 derivative is described which is useful for genetic manipulation of Mu-lac fusion insertions. A double mutant of the specialized transducing phage Mu d1(Amp Lac c62ts) was isolated which is conditionally defective in transposition ability. The Mu d1 derivative, designated Mu d1-8(Tpn[Am] Amp Lac c62ts), carries mutations which virtually eliminate transposition in strains lacking an amber suppressor. In such strains, the Mu d1-8 prophage behaves like a standard transposon. It can be moved from one strain of Salmonella typhimurium to another by the general transducing phage P22 with almost 100% inheritance of the donor insertion mutation. When introduced into a recipient carrying supD, supE, or supF, 89 to 94% of the Ampr transductants were transpositions of the donor Mu d1-8, from the transduced fragment into new sites. The stability of Mu d1-8 in a wild-type, suppressor-free background was sufficient to permit use of the fusion to select constitutive mutations without prior isolation of deletions to stabilize the fusion. Fusion strains could be grown at elevated temperature without induction of the Mu d prophage. The transposition defect of Mu d1-8 was corrected by a plasmid carrying the Mu A and B genes.


A national action plan for sharable and comparable nursing data to support practice and translational research for transforming health care.
There is wide recognition that, with the rapid implementation of electronic health records (EHRs), large data sets are available for research. However, essential standardized nursing data are seldom integrated into EHRs and clinical data repositories. There are many diverse activities that exist to implement standardized nursing languages in EHRs; however, these activities are not coordinated, resulting in duplicate efforts rather than building a shared learning environment and resources. The purpose of this paper is to describe the historical context of nursing terminologies, challenges to the use of nursing data for purposes other than documentation of care, and a national action plan for implementing and using sharable and comparable nursing data for quality reporting and translational research. In 2013 and 2014, the University of Minnesota School of Nursing hosted a diverse group of nurses to participate in the Nursing Knowledge: Big Data and Science to Transform Health Care consensus conferences. This consensus conference was held to develop a national action plan and harmonize existing and new efforts of multiple individuals and organizations to expedite integration of standardized nursing data within EHRs and ensure their availability in clinical data repositories for secondary use. This harmonization will address the implementation of standardized nursing terminologies and subsequent access to and use of clinical nursing data. Foundational to integrating nursing data into clinical data repositories for big data and science, is the implementation of standardized nursing terminologies, common data models, and information structures within EHRs. The 2014 National Action Plan for Sharable and Comparable Nursing Data for Transforming Health and Healthcare builds on and leverages existing, but separate long standing efforts of many individuals and organizations. The plan is action focused, with accountability for coordinating and tracking progress designated.


Emerging technologies in health care and the patient encounter of the future.
In the last five years, the Web has changed the way information is disseminated, knowledge is gained, and health care is provided. Even though the health care industry has yet to fully realize the potential of the Internet, the Web is only the beginning. Several emerging technologies will be changing the rules again. With new forms of network connectivity and faster, new wireless technologies, the adoption rate of mobile, handheld computers in health care will grow feverishly. Intelligent, autonomous software agents that guide the patient through the continuum of care will extend the reach of health care providers to all places at all times. The author discusses these new concepts, how they might be applied in health care, and the doctor-patient health care transaction.


Simulating the structural phase transitions of metal-organic frameworks with control over the volume of nanocrystallites.
Flexible metal-organic frameworks (MOFs) can undergo structural transitions with significant pore volume changes upon guest adsorption or other external triggers while maintaining their porosity. In computational studies of this breathing behavior, molecular dynamics (MD) simulations within periodic boundary conditions (PBCs) are commonly performed. However, to account for the finite size and surface effects affecting the phase transition mechanism, the simulation of non-periodic nanocrystallite (NC) models without the constraint of PBCs is an important alternative. In this study, we present an approach allowing the analysis and control of the volume of finite-size structures during MD simulations by a tetrahedral tessellation of the (deformed) NC's volume. The method allows for defining the current NC's volume during the simulation and manipulating it regarding a particular reference volume to compute free energies for the phase transformation via umbrella sampling. The application on differently sized DMOF-1 and DUT-128 NCs reveals flexible pore closing mechanisms without significant biasing of the transition pathway. The concept provides the theoretical foundation for further research on flexible materials regarding targeted initialization of the structural phase behavior to elucidate the underlying mechanism, which can be used to improve the applications of flexible materials by targeted controlling of the phase transition.


Are People Willing to Take Regular COVID-19 Vaccines? Prevalence and Determinants of Hesitancy for Regular COVID-19 Vaccination: A Random Population-Based Survey in Hong Kong.
The emergence of new coronavirus variants and evidence of waning immunity offered by COVID-19 vaccines draw attention to the need for regular vaccination. Vaccine hesitancy is one of the top ten threats to global health. There is a dearth of knowledge on people's hesitancy to take regular COVID-19 vaccines. This study aimed to investigate the prevalence and determinants of hesitancy for regular COVID-19 vaccination. A population-based, random telephone survey was performed in Hong Kong in April 2022 (n = 1213). The age-standardized hesitancy rate for regular COVID-19 vaccines among Hong Kong adults was 39.4% (95% CI = 35.3-44.1%), exhibiting a sloping S-shape with age. Regression analyses revealed that females, young adults, self-perceived fair/bad health, low COVID-19 vaccine uptake, and believing there are better ways for prevention of infection were positive determinants of hesitancy for regular vaccination. Vaccine confidence, perceived severity and availability, trust in manufacturers and government, and civic duty inclination were negative determinants. Tailored vaccine promotions are needed for females, young adults, and people perceiving poor health and receiving fewer doses. Information on infection severity, vaccine availability, and trust in suppliers, products, and governments are key attitude-change facilitators to decrease hesitancy for regular COVID-19 vaccination and cope with future pandemics.


Species of Botryosphaeriaceae associated with citrus branch diseases in China.
Citrus is an important and widely cultivated fruit crop in South China. Although the species of fungal diseases of leaves and fruits have been extensively studied, the causal organisms of branch diseases remain poorly known in China. Species of Botryosphaeriaceae are known as important fungal pathogens causing branch diseases on citrus in the USA and Europe. To determine the diversity of Botryosphaeriaceae species associated with citrus branch diseases in China, surveys were conducted in the major citrus-producing areas from 2017 to 2020. Diseased tissues were collected from twigs, branches and trunks with a range of symptoms including cankers, cracking, dieback and gummosis. Based on morphological characteristics and phylogenetic comparison of the DNA sequences of the internal transcribed spacer region (ITS), the translation elongation factor 1-alpha gene (tef1), the β-tubulin gene (tub2) and the DNA-directed RNA polymerase II second largest subunit (rpb2), 111 isolates from nine provinces were identified as 18 species of Botryosphaeriaceae, including Botryosphaeria dothidea, B. fabicerciana, Diplodia seriata, Dothiorella alpina, Do. plurivora, Lasiodiplodia citricola, L. iraniensis, L. microconidia, L. pseudotheobromae, L. theobromae, Neodeightonia subglobosa, Neofusicoccum parvum, and six previously undescribed species, namely Do. citrimurcotticola, L. guilinensis, L. huangyanensis, L. linhaiensis, L. ponkanicola and Sphaeropsis linhaiensis spp. nov. Botryosphaeria dothidea (28.8 %) was the most abundant species, followed by L. pseudotheobromae (23.4 %), which was the most widely distributed species on citrus, occurring in six of the nine provinces sampled. Pathogenicity tests indicated that all 18 species of Botryosphaeriaceae obtained from diseased citrus tissues in this study were pathogenic to the tested Citrus reticulata shoots in vitro, while not all species are pathogenic to the tested Cocktail grapefruit (C. paradisi × C. reticulata) shoots in vivo. In addition, Lasiodiplodia was the most aggressive genus both in vitro and in vivo. This is the first study to identify Botryosphaeriaceae species related to citrus branch diseases in China and the results provide a theoretical basis for the implementation of prevention and control measures. Citation: Xiao XE, Wang W, Crous PW, et al. 2021. Species of Botryosphaeriaceae associated with citrus branch diseases in China. Persoonia 47: 106-135. https://doi.org/10.3767/persoonia.2021.47.03.


Insight into the potential mechanism of bicarbonate assimilation promoted by mixotrophic in CO2 absorption and microalgae conversion system.
CO2 absorption-microalgae conversion (CAMC) system is a promising carbon capture and utilization technology. However, the use of HCO3- as a carbon source often led to a slower growth rate of microalgae, which also limited the application of CAMC system. In this study, the assimilation efficiency of HCO3- in CAMC system was improved through mixotrophic, and the potential mechanism was investigated. The HCO3- assimilation efficiency and biomass under mixotrophic were 34.79% and 31.76% higher than that of control. Mixotrophic increased chlorophyll and phycocyanin content, which were beneficial to capture more light energy. The content of ATP and NADPH reached 566.86 μmol/gprot and 672.86 nmol/mgprot, which increased by 31.83% and 27.67% compared to autotrophic. The activity of carbonic anhydrase and Rubisco increased by 18.52% and 22.08%, respectively. Transcriptome showed that genes related to photosynthetic and respiratory electron transport were up-regulated. The synergy of photophosphorylation and oxidative phosphorylation greatly improved energy metabolism efficiency, thus accelerating the assimilation of HCO3-. These results revealed a potential mechanism of promoting the HCO3- assimilation under mixotrophic, it also provided a guidance for using CAMC system to serve carbon neutrality.


Endocannabinoid tone versus constitutive activity of cannabinoid receptors.
This review evaluates the cellular mechanisms of constitutive activity of the cannabinoid (CB) receptors, its reversal by inverse agonists, and discusses the pitfalls and problems in the interpretation of the research data. The notion is presented that endogenously produced anandamide (AEA) and 2-arachidonoylglycerol (2-AG) serve as autocrine or paracrine stimulators of the CB receptors, giving the appearance of constitutive activity. It is proposed that one cannot interpret inverse agonist studies without inference to the receptors' environment vis-à-vis the endocannabinoid agonists which themselves are highly lipophilic compounds with a preference for membranes. The endocannabinoid tone is governed by a combination of synthetic pathways and inactivation involving transport and degradation. The synthesis and degradation of 2-AG is well characterized, and 2-AG has been strongly implicated in retrograde signalling in neurons. Data implicating endocannabinoids in paracrine regulation have been described. Endocannabinoid ligands can traverse the cell's interior and potentially be stored on fatty acid-binding proteins (FABPs). Molecular modelling predicts that the endocannabinoids derived from membrane phospholipids can laterally diffuse to enter the CB receptor from the lipid bilayer. Considering that endocannabinoid signalling to CB receptors is a much more likely scenario than is receptor activation in the absence of agonist ligands, researchers are advised to refrain from assuming constitutive activity except for experimental models known to be devoid of endocannabinoid ligands.


Hepatic artery thrombosis in infants. A comparison of whole livers, reduced-size grafts, and grafts from living-related donors.
Hepatic artery thrombosis (HAT) is a major cause of patient morbidity and graft loss in pediatric liver transplantation (OLT). Although some grafts may be salvaged by arterial thrombectomy and reconstruction, many patients require retransplantation. Patient survival is reduced by HAT. It has been suggested that the incidence of HAT may be altered by the use of reduced-size grafts (RSG). We analyzed our series of infants receiving OLT to determine the frequency of HAT in full-size OLT, cadaveric RSG, and living-related RSG. The role of arterial anastomotic technique in the development of HAT was also examined. Between 10/1/84 and 12/7/90 433 liver transplants were performed. During this period 100 patients between 3 months and 2 years of age (mean 13 months) received 134 liver grafts. The mean weight at the time of transplant was 7.9 kg. (range: 1.9-15 kg). Of the 134 grafts, 60 were whole livers, 61 were cadaveric RSGs, and 13 were living-related RSGs. The cadaveric RSGs were 9 right lobe grafts, 21 left lobe grafts, and 31 left lateral segment grafts. Twenty-seven of the cadaveric RSGs were from split livers, while the other 34 were simple reductions. All 13 living-related RSGs were left lateral segments. HAT occurred in 15 of 60 (25%) whole livers, 9 of 61 (15%) cadaveric RSGs, and 3 of 13 (23%) of the living-related-donor RSGs (P = NS). Subdividing the cadaveric RSGs revealed that HAT occurred in 3 of 9 (33%) right lobe grafts, 3 of 21 (14%) left lobe grafts, and 3 of 31 (10%) left lateral segment grafts (P = NS). The site of the arterial anastomosis in the recipient correlated with the incidence of HAT (hepatic artery 21/86 [24%], celiac axis 1/9 [11%], aorta 2/32 [6%], P = 0.06). In conclusion, it appears that use of a cadaveric left lobe or left lateral segment graft and an aortic arterial anastomosis reduces the risk of hepatic artery thrombosis in liver transplant recipients less than 2 years of age.


Chemical surface alteration of biodegradable magnesium exposed to corrosion media.
The understanding of corrosion processes of metal implants in the human body is a key problem in modern biomaterial science. Because of the complicated and adjustable in vivo environment, in vitro experiments require the analysis of various physiological corrosion media to elucidate the underlying mechanism of "biological" metal surface modification. In this paper magnesium samples were incubated under cell culture conditions (i.e. including CO(2)) in electrolyte solutions and cell growth media, with and without proteins. Chemical mapping by high-resolution electron-induced X-ray emission spectroscopy and infrared reflection microspectroscopy revealed a complex structure of the formed corrosion layer. The presence of CO(2) in concentrations close to that in blood is significant for the chemistry of the oxidised layer. The presence of proteins leads to a less dense but thicker passivation layer which is still ion and water permeable, as osmolality and weight measurements indicate.


Transmission at a 'direct' electrical connexion mediated by an interneurone in the leech.
1. Touch sensory neurones in the leech excite a rapidly conducting interneurone called the S-cell. Although the electrical synaptic connexion between the two cells is monosynaptic by physiological criteria, intracellular staining reveals that the touch cells and the S-cell do not make contact, but instead are linked by a pair of small interneurones. 2. The electrical coupling between touch cells and S-cells rectifies, in that depolarizing current but not hyperpolarizing current passes from the touch cell into the S-cell. The rectifying junction is between the touch cells and coupling interneurones, while the connexion between coupling interneurones and the S-cell passes current in both directions. 3. Selective destruction of the coupling interneurones by intracellular injection of a protease interrupts the disynaptic electrical connexion between touch and S-cells. 4. The touch cell's geometry and membrane properties account for the failure of impulses that are generated in certain portions of the receptive field in the skin to propagate beyond the first branch-points of the touch cell axon within the ganglion. Conduction block at branch-points is used to examine physiologically the spatial distribution of contacts between the touch cell and the coupling interneurones. In addition, it is shown that under natural conditions branch-point failure presynaptically reduces the effectiveness of the electrical synaptic connexions.


Heterologous expression of a thermophilic diacylglycerol acyltransferase triggers triglyceride accumulation in Escherichia coli.
Triglycerides (TAGs), the major storage molecules of metabolic energy and source of fatty acids, are produced as single cell oil by some oleogenic microorganisms. However, these microorganisms require strict culture conditions, show low carbon source flexibilities, lack efficient genetic modification tools and in some cases pose safety concerns. TAGs have essential applications such as behaving as a source for added-value fatty acids or giving rise to the production of biodiesel. Hence, new alternative methods are urgently required for obtaining these oils. In this work we describe TAG accumulation in the industrially appropriate microorganism Escherichia coli expressing the heterologous enzyme tDGAT, a wax ester synthase/triacylglycerol:acylCoA acyltranferase (WS/DGAT). With this purpose, we introduce a codon-optimized gene from the thermophilic actinomycete Thermomonospora curvata coding for a WS/DGAT into different E. coli strains, describe the metabolic effects associated to the expression of this protein and evaluate neutral lipid accumulation. We observe a direct relation between the expression of this WS/DGAT and TAG production within a wide range of culture conditions. More than 30% TAGs were detected within the bacterial neutral lipids in 90 minutes after induction. TAGs were observed to be associated with the hydrophobic enzyme while forming round intracytoplasmic bodies, which could represent a bottleneck for lipid accumulation in E. coli. We detected an increase of almost 3-fold in the monounsaturated fatty acids (MUFA) occurring in the recombinant strains. These MUFA were predominant in the accumulated TAGs achieving 46% of the TAG fatty acids. These results set the basis for further research on the achievement of a suitable method towards the sustainable production of these neutral lipids.


Transforming growth factor-β1 functional polymorphisms in myeloablative sibling hematopoietic stem cell transplantation.
Hematopoietic stem cell transplantation (HSCT) with sibling donors (s.d.) is a life-saving intervention for patients with hematological malignancies. Numerous genetic factors have a role in transplant outcome. Several functional polymorphisms have been identified in TGF-β1 gene, such as single-nucleotide polymorphism (SNP) at +29C>T within exon 1. Two hundred and forty five patient/donor pairs who underwent a s.d. HSCT in our centers were genotyped for this SNP. In the myeloablative cohort, +29CC donors were associated with an increase in severe chronic GvHD (32% vs 16%, hazard ratio (HR) 9.0, P=0.02). Regarding survival outcomes, +29CC patients developed higher non relapse mortality (NRM) (1-5 years CC 28-32% vs TC/TT 7-10%; HR 5.1, P=0.01). Recipients of +29TT donors experienced a higher relapse rate (1-5 years TT 37-51% vs TC 19-25% vs CC 13%-19%; HR 2.4, P=0.01) with a decreased overall survival (OS) (1-5 years TT 69-50% vs TC/CC 77-69%; HR 1.9, P=0.05). Similar to previous myeloablative unrelated donors HSCT results, we confirmed that +29CC patients had higher NRM. In addition we found that +29TT donors might be associated with a higher relapse rate and lower OS. These results should be confirmed in larger series. Identification of these SNPs will allow personalizing transplant conditioning and immunosuppressant regimens, as well as assisting in the choice of the most appropriate donor.


Use of nanoparticles for cerebral cancer.
Nanoparticles made of poly(butyl cyanoacrylate) (PBCA) or poly(lactic-co-glycolic acid) (PLGA) coated with polysorbate 80 or poloxamer 188 enable the transport of cytostatics such as doxorubicin across the blood-brain barrier (BBB). Following intravenous injection to rats bearing intracranially the very aggressive glioblastoma 101/8 these particles loaded with doxorubicin significantly increased the survival times and led to a complete tumor remission in 20-40% of the animals. Moreover, these particles considerably reduced the dose-limiting cardiotoxicity and also the testicular toxicity of this drug. The drug transport across the BBB by nanoparticles appears to be due to a receptor-mediated interaction with the brain capillary endothelial cells, which is facilitated by certain plasma apolipoproteins adsorbed by nanoparticles in the blood.


Distinct Mechanisms Are Responsible for Nrf2-Keap1 Pathway Activation at Different Stages of Rat Hepatocarcinogenesis.
Activation of the Nrf2-Keap1 pathway, the main intracellular defense against environmental stress, has been observed in several human cancers, including hepatocellular carcinoma (HCC). Here, we assessed whether distinct mechanisms of activation may be involved at different stages of hepatocarcinogenesis. We adopted an experimental model consisting of treatment with diethylnitrosamine (DENA) followed by a choline-devoid methionine-deficient (CMD) diet for 4 months. The CMD diet was then replaced with a basal diet, and the animals were killed at 6, 10 or 13 months after DENA injection. Nrf2 activation occurred at early steps of hepatocarcinogenesis and persisted throughout the tumorigenic process. While Nrf2 mutations were extremely frequent at early steps (90%), their incidence diminished with the progression to malignancy (25%). Conversely, while p62 was almost undetectable in early nodules, its accumulation occurred in HCCs, suggesting that Nrf2 pathway activation at late stages is mainly due to Keap1 sequestration by p62. We demonstrate that, in a model of hepatocarcinogenesis resembling human non-alcoholic fatty liver disease, Nrf2 mutations are the earliest molecular changes responsible for the activation of the Nrf2-Keap1 pathway. The progressive loss of mutations associated with a concomitant p62 accumulation implies that distinct mechanisms are responsible for Nrf2-Keap1 pathway activation at different stages of hepatocarcinogenesis.


Health outcomes of women exposed to household alcohol abuse: a Family Practice Training Site Research Network (FPTSRN) study.
There is a paucity of knowledge about the effects of exposure to alcohol abuse in the household on women who do not abuse alcohol. The purpose of this study was to determine whether women who did not abuse alcohol demonstrated any health-related adverse effects because they lived with family members who did abuse alcohol. This study was a historical prospective survey of female patients at five primary care practices. Survey instruments included the CAGE questionnaire, a five-item screening test for exposure to alcoholism, and the Medical Outcomes Study 36-item Short Form Health Survey (MOS SF-36). Patient records were examined for specific diagnoses. A total of 267 patients completed the questionnaires and had complete medical records available for analysis. Forty-two (15.7%) potential alcohol abusers were excluded from the sample leaving a working total of 225; 70 (31.1%) were potentially exposed to alcoholism in the household. Women exposed to alcohol abuse in the home did not experience an increased risk for the medical diagnoses studied, but they did demonstrate decreased health-related quality of life as measured by the MOS-SF-36 for the following scales: role physical (P = .025), role emotional (P = .038), social functioning (P = .001), bodily pain (P = .016), and mental health (P = .040). Women exposed to alcohol abuse in the household are more likely to perceive themselves as less healthy. Although they may not have received a clinical diagnosis of depression, they are more likely to feel depressed. The extent to which subjects' health-related quality of life is influenced by exposure to alcohol abuse suggests that the medical diagnosis may be insensitive as a description of health status in this population.


Human virome in nasopharynx and tracheal secretion samples.
In Brazil the implementation of the Sentinel Surveillance System of Influenza began in 2000. Central public health laboratories use reverse transcription-quantitative polymerase chain reaction (RT-qPCR) for diagnosis of respiratory viruses, but this protocol identifies only specific targets, resulted in inconclusive diagnosis for many samples. Thus, high-throughput sequencing (HTS) would be complementary method in the identification of pathogens in inconclusive samples for RT-qPCR or other specific detection protocols. This study aimed to detect unidentified viruses using HTS approach in negative samples of nasopharynx/tracheal secretions by the standard RT-qPCR collected in the Federal District, Brazil. Nucleic acids were extracted from samples collected in winter period of 2016 and subjected to HTS. The results were confirmed by the multiplex PR21 RT-qPCR, which identifies 21 respiratory pathogens. The main viruses identified by HTS were of families Herpesviridae, Coronaviridae, Parvoviridae and Picornaviridae, with the emphasis on rhinoviruses. The presence of respiratory viruses in the samples was confirmed by the PR21 multiplex RT-qPCR. Coronavirus, enterovirus, bocavirus and rhinovirus were found by multiplex RT-qPCR as well as by HTS analyses. Wide virus diversity was found by different methodologies and high frequency of rhinovirus occurrence was confirmed in population in winter, showing its relevance for public health.


Right from the start: the family practice orientation study.
Orientation to a residency program introduces residents to the essential functions of their duties, clarifies expectations, and acclimates them to a new social group. This study identified the orientation goals of family practice residency directors and compared those goals to the perceived needs of first-year family practice residents. We surveyed program directors and PGY-1 residents at 100 accredited family practice residency programs. Questionnaires obtained descriptive information about orientation programs and resident demographics and assessed directors' goals and residents' needs from orientations. The orientation goal ranked most highly by directors was development of group cohesion. The need ranked most highly by residents was introduction to call duties and inpatient problems. Ranked responses of each group were not well associated. The orientation goals of program directors and the reported orientation needs of residents were poorly associated. Most directors chose nonclinical areas as their most important goals for orientation. In contrast, most residents valued clinically related information during orientation to residency.


Mouse mammary tumour virus and polyoma virus information in mammary tumours of athymic mice inoculated with polyoma virus.
Polyoma virus inoculation of athymic mice results in the development of mammary tumours with a much higher incidence than the development of salivary gland tumours, the latter being the most common for immunocompetent normal mice. The possibility existed that polyoma virus might act as a co-carcinogen in activating the expression of mouse mammary tumour virus (MMTV). Molecular hybridization studies, however, showed that the mammary tumour development was accompanied by neither the amplification of MMTV genomic sequences nor by their more extensive transcription. In contrast, tumour tissue contained about 60 to 100 copies of polyoma virus genome equivalents per cell and some of these sequences were apparently transcribed into RNA. While these results do not rule out the transient involvement of MMTV expression in mammary tumour development, it appeared that the mammary gland cells were directly transformed by polyoma virus. Apparently, polyoma virus displayed a tropism in athymic mice that was different from that in normal mice.


Design of a randomized, non-inferiority trial to evaluate the reliability of videoconferencing for remote consultation of diabetes.
An estimated 366 million people are living with diabetes worldwide and it is predicted that its prevalence will increase to 552 million by 2030. Management of this disease and its complications is a challenge for many countries. Optimal glycaemic control is necessary to minimize complications, but less than 70% of diabetic patients achieve target levels of blood glucose, partly due to poor access to qualified health care providers. Telemedicine has the potential to improve access to health care, especially for rural and remote residents. Video teleconsultation, a real-time (or synchronous) mode of telemedicine, is gaining more popularity around the world through recent improvements in digital telecommunications. If video consultation is to be offered as an alternative to face-to-face consultation in diabetes assessment and management, then it is important to demonstrate that this can be achieved without loss of clinical fidelity. This paper describes the protocol of a randomised controlled trail for assessing the reliability of remote video consultation for people with diabetes. A total of 160 people with diabetes will be randomised into either a Telemedicine or a Reference group. Participants in the Reference group will receive two sequential face-to-face consultations whereas in the Telemedicine group one consultation will be conducted face-to-face and the other via videoconference. The primary outcome measure will be a change in the patient's medication. Secondary outcome measures will be findings in physical examination, detecting complications, and patient satisfaction. A difference of less than 20% in the aggregated level of agreement between the two study groups will be used to identify if videoconference is non-inferior to traditional mode of clinical care (face-to-face). Despite rapid growth in application of telemedicine in a variety of medical specialties, little is known about the reliability of videoconferencing for remote consultation of people with diabetes. Results of this proposed study will provide evidence of the reliability of specialist consultation offered by videoconference for people with diabetes. Australian New Zealand Clinical Trials Registry ACTRN12612000315819.


[Development of the arthroplasty method in coxarthrosis].
On the basis of analysis of surgical treatment of 753 patients with coxarthrosis during 1970-1987, the authors set forth the stages of arthroplasty development in the USSR, using the experience of the Kharkov research institute of orthopaedics and traumatology named after M. I. Sitenko on the problems of arthrodesis operations, endoprosthetics and biological arthroplasty. In the article are presented the peculiar features of diagnostic and surgical tactics in case of patients with idiopathic and dysplastic coxarthrosis; operation technique for each form is presented in details. The authors have developed a new perosseous access to the hip joint, which made a good showing and permits to preserve the integrity of periarticular muscles and neurovascular formations. Application of the given access made possible the extension of indications for arthroplasty in case of grave forms of coxarthrosis, met earlier in a reserved manner.


Ex vivo multiplex profiling of protein tyrosine kinase activities in early stages of human lung adenocarcinoma.
Despite constant improvement in existing therapeutic efforts, the overall survival rate of lung cancer patients remains low. Enzyme activities may identify new therapeutically targetable biomarkers and overcome the marked lack of correlation between cellular abundance of translated proteins and corresponding mRNA expression levels. We analysed tyrosine kinase activities to classify lung adenocarcinoma (LuAdCa) resection specimens based on their underlying changes in cellular processes and pathways that are agents of or result from malignant transformation. We characterised 71 same-patient pairs of early-stage LuAdCa and non-neoplastic LuAdCa resection specimen lysates in the presence or absence of a tyrosine kinase inhibitor. We performed ex vivo multiplex tyrosine phosphorylation assays using 144 selected microarrayed kinase substrates. The obtained 76 selected phosphotyrosine signature peptides were subsequently analysed in terms of follow-up treatments and outcomes recorded in the patient files. For tumour, node, metastasis (TNM) stage 1 LuAdCa patients, we noticed a larger tyrosine kinase inhibitor-induced decrease in tyrosine phosphorylation for long-term as opposed to short-term disease survivors, for which 26 of 76 selected peptides were significantly (p < 0.01, FDR < 3%) more inhibited in the long-term survivors. Using statistical class prediction analysis, we obtained a 'prognostic-signature' for long- versus short-term disease survivors and correctly predicted the survival status of 73% of our patients. Our translational approach may assist clinical disease management after surgical resection and may help to direct patients for an optimal treatment strategy.


Occupational health nursing practice, education, and research in Taiwan.
This article describes occupational health nursing practice, education, research, and future perspectives in Taiwan. It also provides a brief overview of major occupational health and safety problems, laws and regulations, and organizations in Taiwan.


Half or more of the somatic mutations in cancers of self-renewing tissues originate prior to tumor initiation.
Although it has been hypothesized that some of the somatic mutations found in tumors may occur before tumor initiation, there is little experimental or conceptual data on this topic. To gain insights into this fundamental issue, we formulated a mathematical model for the evolution of somatic mutations in which all relevant phases of a tissue's history are considered. The model makes the prediction, validated by our empirical findings, that the number of somatic mutations in tumors of self-renewing tissues is positively correlated with the age of the patient at diagnosis. Importantly, our analysis indicates that half or more of the somatic mutations in certain tumors of self-renewing tissues occur before the onset of neoplasia. The model also provides a unique way to estimate the in vivo tissue-specific somatic mutation rates in normal tissues directly from the sequencing data of tumors. Our results have substantial implications for the interpretation of the large number of genome-wide cancer studies now being undertaken.


Galectin-3 levels are elevated following nintedanib treatment.
Idiopathic pulmonary fibrosis (IPF) is a common and severe form of pulmonary fibrosis. Nintedanib, a triple angiokinase inhibitor, is approved for treating IPF. Galectin 3 (Gal-3) activates a variety of profibrotic processes. Currently, the Gal-3 inhibitor TD139 is being tested in phase II clinical trials. Since this treatment is given 'on top' of nintedanib, it is important to estimate its effect on Gal-3 levels. Therefore, we evaluated the impact of nintedanib on Gal-3 expression using both in vitro and in vivo models, in addition to serum samples from patients with IPF. Gal-3 levels were evaluated in IPF and control tissue samples, primary human lung fibroblasts (HLFs) following nintedanib treatment (10-100 nM, quantitative polymerase chain reaction), and in a silica-induced fibrosis mouse model with/without nintedanib (0.021-0.21 mg/kg) by immunohistochemistry. In addition, Gal-3 levels were analyzed in serum samples from 41 patients with interstitial lung disease patients with/without nintedanib treatment by ELISA. Nintedanib addition to HLFs resulted in significant elevations in Gal-3, phospho-signal transducer and activator of transcription 3 (pSTAT3), as well as IL-8 mRNA levels (p < 0.05). Gal-3 expression was higher in samples from IPF patients compared with non-IPF controls at the protein and mRNA levels (p < 0.05). In the in vivo mouse model, Gal-3 levels were increased following fibrosis induction and even further increased with the addition of nintedanib, mostly in macrophages (p < 0.05). Patients receiving nintedanib presented with higher Gal-3 serum levels compared with those who did not receive nintedanib (p < 0.05). Nintedanib elevates Gal-3 levels in both experimental models, along with patient samples. These findings highlight the possibility of using combined inhibition therapy for patients with IPF.


Types of family practice teachers and residents: a comparative study.
A study of personality types using the Myers-Briggs Type Indicator was performed on family practice teachers and residents. The combined group was found to be different from the general medical population. There was a larger percentage of persons who tended to be practical, realistic, present-oriented, organized, and able to deal effectively with factual information. The majority were persons who enjoy seeing immediate results of actions and can made decisions quickly and effectively using whatever information is available. These personality types are similar to those found in the older field of general practice. The residents and faculty were similar in the above respects but a higher percentage of the residents tended to make judgments using impersonal logic and a factual basis for reaching decisions. The faculty, however, had a significantly higher percentage of types who make judgments by considering human values and understanding of people.


Proteomics analysis of carotid body tumor revealed potential mechanisms and molecular differences among Shamblin classifications.
Carotid body tumors (CBTs) are a rare type of paraganglioma, and surgical resection is the only effective treatment. Because of the proximity of CBTs to the carotid artery, jugular vein, and cranial nerve, surgery is extremely difficult, with high risks of hemorrhage and neurovascular injury. The Shamblin classification is used for CBT clinical evaluation; however, molecular mechanisms underlying classification differences remain unclear. This study aimed to investigate pathogenic mechanisms and molecular differences between CBT types. In Shamblin I, II, and III tumors, differentially expressed proteins (DEPs) were identified using direct data-independent acquisition (DIA). DEPs were validated using immunohistochemistry. Proteomics profiling of three Shamblin subtypes differed significantly. Bioinformatics analysis showed that adrenomedullin signaling, protein kinase A signaling, vascular endothelial growth factor (VEGF) signaling, ephrin receptor signaling, gap junction signaling, interleukin (IL)-1 signaling, actin cytoskeleton signaling, endothelin-1 signaling, angiopoietin signaling, peroxisome proliferator-activated receptor (PPAR) signaling, bone morphogenetic protein (BMP) signaling, hypoxia-inducible factor 1-alpha (HIF-1α) signaling, and IL-6 signaling pathways were significantly enriched. Furthermore, 60 DEPs changed significantly with tumor progression. Immunohistochemistry validated several important DEPs, including aldehyde oxidase 1 (AOX1), mediator complex subunit 22 (MED22), carnitine palmitoyltransferase 1A (CPT1A), and heat shock transcription factor 1 (HSF1). To our knowledge, this is the first application of proteomics quantification in CBT. Our results will deepen the understanding of CBT-related pathogenesis and aid in identifying therapeutic targets for CBT treatment.


A novel mutation of the claudin 16 gene in familial hypomagnesemia with hypercalciuria and nephrocalcinosis mimicking rickets.
Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is caused by a mutation in the gene CLDN16, which encodes paracellin 1 (claudin-16), atight junction protein mediating paracellular transport which is expressed in the thick ascending loop of Henle and in the distal convoluted tubule, where reabsorption of magnesium occurs. We present a 4 years old Turkish female child with a chief complaint of hypocalcemic tetany. A diagnosis of FHHNC was confirmed by genetic testing for a mutation in claudin 16 gene. Claudin 16 gene revealed homozygosity for the p.K183E(AAA>GAA) C. 547A>G indicating the diagnosis of hypomagnesemia with hypercalciuria and nephrocalcinosis. To our knowledge, this is the first case of FHHNC reported in Turkish population diagnosed at molecular level.


Mild Stroke, Serious Problems: Limitations in Balance and Gait Capacity and the Impact on Fall Rate, and Physical Activity.
After mild stroke persistent balance limitations may occur, creating a risk factor for fear of falling, falls, and reduced activity levels. Objective. To investigate whether individuals in the chronic phase after mild stroke show balance and gait limitations, elevated fall risk, reduced balance confidence, and physical activity levels compared to healthy controls. An observational case-control study was performed. Main outcomes included the Mini-Balance Evaluation Systems Test (mini-BEST), Timed Up and Go (TUG), 10-m Walking Test (10-MWT), and 6-item version Activity-specific Balance Confidence (6-ABC) scale which were measured in 1 session. Objectively measured daily physical activity was measured for 7 consecutive days. Fall rate in daily life was recorded for 12 months. Individuals after a mild stroke were considered eligible when they: (1) sustained a transient ischemic attack or stroke longer than 6 months ago, resulting in motor and/or sensory loss in the contralesional leg at the time of stroke, (2) showed (near-) complete motor function, that is, ≥24 points on the Fugl-Meyer Assessment-Lower Extremity (range: 0-28). Forty-seven healthy controls and 70 participants after mild stroke were included. Participants with stroke fell more than twice as often as healthy controls, had a 2 point lower median score on the mini-BEST, were 1.7 second slower on TUG, 0.6 km/h slower on the 10-MWT, and had a 12% lower 6-ABC score. Intensity for both total activity (8%) as well as walking activity (6%) was lower in the participants with stroke, while no differences were found in terms of duration. Individuals in the chronic phase after a mild stroke demonstrate persistent balance limitations and have an increased fall risk. Our results point at an unmet clinical need in this population.


Deep sequencing is an appropriate tool for the selection of unique Hepatitis C virus (HCV) variants after single genomic amplification.
Hepatitis C virus (HCV) evolves rapidly in a single host and circulates as a quasispecies wich is a complex mixture of genetically distinct virus's but closely related namely variants. To identify intra-individual diversity and investigate their functional properties in vitro, it is necessary to define their quasispecies composition and isolate the HCV variants. This is possible using single genome amplification (SGA). This technique, based on serially diluted cDNA to amplify a single cDNA molecule (clonal amplicon), has already been used to determine individual HCV diversity. In these studies, positive PCR reactions from SGA were directly sequenced using Sanger technology. The detection of non-clonal amplicons is necessary for excluding them to facilitate further functional analysis. Here, we compared Next Generation Sequencing (NGS) with De Novo assembly and Sanger sequencing for their ability to distinguish clonal and non-clonal amplicons after SGA on one plasma specimen. All amplicons (n = 42) classified as clonal by NGS were also classified as clonal by Sanger sequencing. No double peaks were seen on electropherograms for non-clonal amplicons with position-specific nucleotide variation below 15% by NGS. Altogether, NGS circumvented many of the difficulties encountered when using Sanger sequencing after SGA and is an appropriate tool to reliability select clonal amplicons for further functional studies.


Transplantation of bone marrow-derived mesenchymal stem cells rescue photoreceptor cells in the dystrophic retina of the rhodopsin knockout mouse.
Retinitis pigmentosa belongs to a large group of degenerative diseases of the retina with a hereditary background. It involves loss of retinal photoreceptor cells and consequently peripheral vision. At present there are no satisfactory therapeutic options for this disease. Just recently the use of mesenchymal stem cells has been discussed as one therapeutical option for retinal degeneration, as they have been shown to differentiate into various cell types, including photoreceptor cells. In this article we wanted to investigate the potency of mesenchymal stem cells to induce rescue effects in an animal model for retinitis pigmentosa, the rhodopsin knockout mouse. For the experiments, three experimental groups of 10 animals each were formed. The first group consisted of untreated rhodopsin knockout (rho(-/-)) animals used as controls. The second group consisted of rho(-/-) mice that had received an injection of mouse mesenchymal stem cells, which were transduced using an adenoviral vector containing the sequence for the green fluorescent protein (GFP) prior to transplantation. In the third sham group, animals received an injection of medium only. Thirty-five days after transplantation, GFP-expressing cells were detected in whole-mount preparations of the retinas as well as in cryostat sections. For the detection of rescue effects, semi-thin sections of eyes derived from all experimental groups were produced. Furthermore, rescue effects were also analysed ultrastructurally in ultrathin sections. Histological analysis revealed that after transplantation, cells morphologically integrated not only into the retinal pigment epithelium but also into layers of the neuroretina displaying neuronal and glial morphologies. Furthermore, significant rescue effects, as demonstrated by the occurrence of preserved photoreceptor cells, were detected. Our data indicate that mesenchymal stem cells can prolong photoreceptor survival in the rhodopsin knockout mouse, also providing evidence of a therapeutical benefit in retinitis pigmentosa.


[Organizational and economic aspects of psychiatry].
The main trends in the organization and economic transformations in psychiatric services of Russia in 1989-1996 are analyzed: financial support of the institutions of psychiatric care, changes in the organizational structure of services, new forms and types of care. The opinion of the authorities of regional services concerning the organization and economic changes in institutions of psychiatric care are presented.


NT-proBNP concentrations in mountain marathoners.
The 76 amino acid N-terminal proB-type natriuretic peptide (NT-proBNP) is proposed for evaluating and monitoring heart pathologies characterized by myocardial wall stress. Strenuous exercise might generate transitory ischemia, myocardial stress, and diastolic left ventricular dysfunction, possibly inducing an increase of some biochemical parameter concentrations. An alert has been claimed owing to biochemical and instrumental signs of heart dysfunction in recreational athletes during marathon races. We studied the behaviour of NT-proBNP in 15 mountain marathoners before and after a race. The concentrations of the parameter were lower than that observed in controls at rest and were similar to that observed in professional soccer and rugby players. The concentrations significantly increased after the race. NT-proBNP is low at rest in professional athletes, and the increase after physical exercise is physiological. The marathoners, even when performing races in a high-altitude environment, show NT-proBNP concentrations similar to those of athletes from other sports disciplines, characterized by low levels of effort and by a mix of aerobic and anaerobic metabolism. The increase of NT-proBNP is linked to strenuous physical exercise and to heavy heart effort, testified also by an increase of troponin I. However, the role of the NT-proBNP could be important to screen recreational and professional marathoners to avoid possible heart problems and sudden cardiac death in subjects with occult heart disease. The results of the present study are relevant to the design and evaluation of training programs for improving strength and function of professional marathoners.


The importance of the preactivation peptide in the two-stage mechanism of human plasminogen activation.
The two stages in the activation of human plasminogen by urokinase have been examined kinetically in order to evaluate the significance of each stage in the activation process. The cleavage of the preactivation peptide from the NH2 terminus of native plasminogen (NH2-terminal glutamic acid) is clearly catalyzed by urokinase and is the rate-limiting first step in activation (Stage 1); this reaction is 20-fold slower than the conversion of the intermediate plasminogen (NH2-terminal lysine) to plasmin (Stage 2). Both lysine and its analogoue, epsilon-aminocaproic acid, exert two effects on the activation of native plasminogen. At low concentrations of these agents, activation is greatly accelerated. Analysis of activation in the presence and absence of these agents by sodium dodecyl sulfate gel electrophoresis indicates that the activation pathway is the same in both cases with the formation of a transient intermediate plasminogen; only the kinetics of proteolysis are altered. This enhancement in the rate of activation results solely from acceleration of the Stage 1 reaction; Stage 2 is essentially unaffected at low concentrations. Stage 1 is maximally enhanced (75-fold) at either 0.0025 M epsilon-aminocaproic acid or 0.025 M lysine and occurs 4 times more rapidly than Stage 2, which becomes the rate-limiting step at these concentrations. Plasmin also cleaves the preactivation peptide from native plasminogen and this reaction rate is enhanced by the same concentrations of lysine and epsilon-aminocaproic acid. These data suggest that lysine and epsilon-aminocaproic acid, which are known to bind to plasminogen and significantly alter its conformation, may thereby enhance preactivation peptide cleavage and consequently, plasminogen activation. At high concentrations, both Stages 1 and 2 are similarly inhibited by these agents, which suggests that this effect may be exerted by the direct inhibition of urokinase. The relative rates of preactivation peptide cleavage by the enzymes urokinase, plasmin, thrombin, and ancrod were also determined. Urokinase is 10 times more effective than plasmin in catalyzing this reaction and 1.8 X 10(4) times more effective than thrombin, while ancrod does not exert an effect. No plasmin is formed by either thrombin or ancrod.


Profiling and elucidation of the phenolic compounds in the aerial parts of Gynura bicolor and G. divaricata collected from different Chinese origins.
Gynura bicolor and G. divaricata are not only known to be nutritive as cultured vegetables, but also beneficial as folk medicines in East Asia. As demonstrated by the current phytochemical knowledge, the genus Gynura is a promising source of phenolics with multiple medicinal activities. To expand this phytochemical knowledge, the phenolic secondary metabolites of G. bicolor and G. divaricata were studied. From the aerial parts of these two species, collected in five different Chinese locations, two fractions of phenolic compounds with different polarity were obtained by extraction and chromatographic separation. Using UPLC/MS/MS analysis, a total of 53 phenolics were either identified by comparison with respective reference compounds or tentatively characterized by their chromatographic behavior, UV-absorption patterns, and MS fragmentations. Some naturally existing positional isomers of O-caffeoylquinic acid, O-p-coumaroylquinic acid, O-feruloylquinic acid, and dicaffeoylquinic acid as well as their methyl esters were qualitatively characterized by their specific fragmentation patterns in targeted MS/MS. In addition, the aerial parts of the two Gynura species contained kaempferol, quercetin oligoglycosides, and a variety of derivatives of benzoic acid, hydroxycinnamic acid, and caffeic acid. Furthermore, the distribution of phenolic compounds in the two species from different Chinese origins was discussed. Finally, an investigation of the total phenolic content and in vitro antioxidant activity of the various phenolic fractions was completed, to evaluate the potential of the extracts of these species for medicinal development. The free-radical-scavenging activities of the extracts derived from plants originating from Nanjing were proven to be higher than those of the other extracts, which correlated well with their total phenolic content.


Stent graft for popliteal aneurysms. Six cases with Cragg Endo-Pro System 1 Mintec.
Six popliteal aneurysms were treated by transluminal exclusion with the Cragg Endopro System 1, a Stent-Graft manufactured by MINTEC. In one case, incomplete distal exclusion has led to a recurrent aneurysm at 6 months. In one case thrombosis occurred at 7 months, with successful reopening by fibrinolysis and an additional stent. The 4 other cases remained patent at 9, 8, 4 and 1 month. Despite these encouraging results, the stent-grafting of popliteal aneurysms seems still to be reserved for elderly or poor condition patient.