Cadmium-binding proteins in Pseudomonas putida: pseudothioneins.
Pseudomonas putida adapted to growth in 3 mM cadmium. The resistance mechanism involved complexation of cadmium in polyphosphate granules, changes in the structure of the cell membrane and induction of three cysteine-rich, low molecular weight proteins (3500-7000) containing 4 to 7 g-atoms per mole of cadmium, zinc, and copper. Each protein was produced during a different phase of growth, and the smallest protein (3500) was released into the environment when the cells lysed at the end of the exponential phase. The metal binding sites of the major protein were further characterized using a range of physical methods, including 113Cd NMR. The properties of the bacterial pseudothioneins are compared to those of metallothioneins.


Clonal, in vivo behavior of the totipotent hematopoietic stem cell.
Classical and more recent studies have provided a description of the in vivo behavior of the totipotent hematopoietic stem cell and its clonal progeny. These reconstitution experiments, employing clonotypic markers have shown that single or few engrafted lymphoid-myeloid stem cells are both necessary and sufficient for long-term, stable hematopoiesis in a reconstituted mouse. This underscores the remarkable developmental capacity of individual stem cell clones. Furthermore, the long-term and retransplantation studies have provided an indication of stem cell self-renewal ability. Taken together, the long-term analyses have also shed light on the dynamic behavior of engrafted stem cell clones and of the entire reconstituted hematopoietic system. A model is presented where the developmental and proliferative behavior of totipotent stem cells is a function of time. In this model commitment versus self-renewal decisions may be governed by stochastic mechanisms. However, the actual contribution by stem cells to particular mature cell populations may be more a function of lineage specific demands as they change over post-engraftment time.


Postradiation imaging changes in the CNS: how can we differentiate between treatment effect and disease progression?
A familiar challenge for neuroradiologists and neuro-oncologists is differentiating between radiation treatment effect and disease progression in the CNS. Both entities are characterized by an increase in contrast enhancement on MRI and present with similar clinical signs and symptoms that may occur either in close temporal proximity to the treatment or later in the disease course. When radiation-related imaging changes or clinical deterioration are mistaken for disease progression, patients may be subject to unnecessary surgery and/or a change from otherwise effective therapy. Similarly, when disease progression is mistaken for treatment effect, a potentially ineffective therapy may be continued in the face of progressive disease. Here we describe the three types of radiation injury to the brain based on the time to development of signs and symptoms--acute, subacute and late--and then review specific imaging changes after intensity-modulated radiation therapy, stereotactic radiosurgery and brachytherapy. We provide an overview of these phenomena in the treatment of a wide range of malignant and benign CNS illnesses. Finally, we review the published data regarding imaging techniques under investigation to address this well-known problem.


Environmental mobility of (110m)Ag: lessons learnt from Fukushima accident (Japan) and potential use for tracking the dispersion of contamination within coastal catchments.
Silver-110 metastable ((110m)Ag) has been far less investigated than other anthropogenic radionuclides, although it has the potential to accumulate in plants and animal tissues. It is continuously produced by nuclear power plants in normal conditions, but emitted in much larger quantities in accidental conditions facilitating its detection, which allows the investigation of its behaviour in the environment. We analysed (110m)Ag in soil and river drape sediment (i.e., mud drapes deposited on channel-bed sand) collected within coastal catchments contaminated in Fukushima Prefecture (Japan) after the Fukushima Dai-ichi Nuclear Power Plant accident that occurred on 11 March 2011. Several field experiments were conducted to document radiosilver behaviour in the terrestrial environment, with a systematic comparison to the more documented radiocesium behaviour. Results show a similar and low mobility for both elements in soils and a strong affinity with the clay fraction. Measurements conducted on sediment sequences accumulated in reservoirs tend to confirm a comparable deposition of those radionuclides even after their redistribution due to erosion and deposition processes. Therefore, as the (110m)Ag:(137)Cs initial activity ratio varied in soils across the area, we justified the relevance of using this tool to track the dispersion of contaminated sediment from the main inland radioactive pollution plume generated by FDNPP accident.


Exogenous Melatonin for Delirium Prevention: a Meta-analysis of Randomized Controlled Trials.
Recently, two high-quality clinical randomized controlled trials (RCTs) regarding the preventive effect of exogenous melatonin on delirium drew inconsistent conclusions. We therefore performed a systemic review to explore whether melatonin had a benefit on delirium prevention. MEDLINE, EMBASE, and Cochrane Library were searched from January 1980 to April 2015 for English language studies. After strict selection and evaluation, the data were extracted from the included four RCTs. The primary outcome of this meta-analysis was the incidence of delirium. The secondary outcome was the improvement of sleep-wake rhythm. A total of four RCTs with 669 elderly patients were included in the present study. Melatonin group showed a tendency to decrease the incidence of delirium (relative risk [RR] 0.41, 95 % confidence interval [CI] 0.15 to 1.13; P = 0.08) compared with control group. In subgroup analysis of the elderly patients in medical wards, melatonin supplementation decreased the incidence of delirium by 75 % (RR 0.25, 95 % CI 0.07 to 0.88; P = 0.03), but not in sleep-wake disturbance (RR 1.24, 95 % CI 0.51 to 3.00; P = 0.64). No differences were found in the incidence of delirium between the two groups in the elderly patients that were presented to surgical wards. In conclusion, melatonin supplementation had a significant preventive effect in decreasing the incidence of delirium in elderly patients that were presented to medical wards. Further studies should provide sufficient evidence about the effect of melatonin on delirium in a large sample size.


[Levitra-test in diagnosis of vasculogenic erectile dysfunction].
Dopplerography in artificial erection induced by intracavernous injection of drugs is now the most common method of diagnosis in examination of patients with erectile dysfunction (ED). We studied possibility of inducing erection by the novel potent and selective oral drug levitra (vordenafil) from the group of inhibitors of phosphodiesterase of the 5th type. The comparison of the dopplerographic results of two methods (erection induced by intracavernous injection of prostaglandin E and levitra) showed no statistical differences between the two methods. Thus, levitra-test is a highly informative technique in diagnostic examination of patients with erectile dysfunction with the same pharmacodopplerographic efficacy as intracavernous injection of vasoactive drugs.


Racial/Ethnic Differences in the Longitudinal Effects of Fear of Falling on Falls.
Recent evidence suggests that the effects of fear of falling on falls may differ by race/ethnicity. This study investigated whether race/ethnicity (white, black, and Hispanic) moderated the longitudinal effects of fear of falling on the incidence of falling and having a repeated fall among community-dwelling older adults. We used data from 2011 to 2018 of the National Health and Aging Trends Study (NHATS). These included a total of 19,516 person-intervals from 5,113 respondents. Any self-reported fall in the past year was the outcome variable with baseline fear of falling as the predictor and race/ethnicity as the moderator. Covariates included self-reported sociodemographic information, probable depression, chronic conditions, functional impairment, pain, insomnia symptoms, the Clock Drawing Test, the Short Physical Performance Battery, and grip strength. Among respondents who had no experience of falling at baseline, baseline fear of falling increased the odds of having a new onset of fall at 1-year follow-up significantly among blacks, compared to whites (odds ratio [OR] = 1.85, 95% confidence interval [CI] = 1.44-2.38). No significant difference was found for Hispanics. Among respondents who already fell at baseline, baseline fear of falling increased the odds of having a repeated fall at 1-year follow-up significantly among Hispanics, compared to whites (OR = 1.91, 95% CI = 1.06-3.44). No significant difference was found for blacks. Clear evidence of racial/ethnic differences was found in the relationship between fear of falling and falls among community-dwelling older adults in the USA. Special attention should be paid to black older adults with a fear of falling but have not fallen down recently and Hispanics with fear of falling and have fallen in the past year. Readily available educational programs should be actively advertised to older adults to reduce the fear of falling, and at the same time, culturally tailored educational programs should be developed for older adults from racial/ethnic minority backgrounds.


Transneuronal labeling of neurons in rabbit brain after injection of herpes simplex virus type 1 into the aortic depressor nerve.
Herpes simplex virus type 1 (HSV1) was injected into either the aortic depressor nerve or the vagus nerve in the rabbit. Four or 5 days after injection of virus, the rabbit brain was processed immunohistochemically to demonstrate viral antigen. After injection into the aortic nerve HSV1 positive cells were found principally ipsilaterally within the nucleus tractus solitarius, area postrema, caudal and rostral ventrolateral medulla oblongata, the spinal trigeminal complex, raphe nuclei, A5 area, locus coeruleus, parabrachial nucleus, periaqueductal gray, ventrolateral hypothalamic area, paraventricular nucleus, amygdala, bed nucleus of the stria terminalis and insular cortex. Double labeling studies indicated that approximately 85% of the virus-containing neurons in the ventrolateral medulla, and virtually all the HSV-positive neurons in the A5 area and locus coeruleus also contained tyrosine hydroxylase. In the raphe nuclei and parapyramidal region approximately 33% of virus-containing cells reacted positively with PH8 antibody, a marker for serotonin synthesis. After injection of HSV1 into the vagus nerve labeled cells were found in similar brain areas, with a more bilateral distribution. The HSV-positive neurons may be involved in the processing of baroreceptor-derived information.


Biomarkers extracted by fully automated body composition analysis from chest CT correlate with SARS-CoV-2 outcome severity.
The complex process of manual biomarker extraction from body composition analysis (BCA) has far restricted the analysis of SARS-CoV-2 outcomes to small patient cohorts and a limited number of tissue types. We investigate the association of two BCA-based biomarkers with the development of severe SARS-CoV-2 infections for 918 patients (354 female, 564 male) regarding disease severity and mortality (186 deceased). Multiple tissues, such as muscle, bone, or adipose tissue are used and acquired with a deep-learning-based, fully-automated BCA from computed tomography images of the chest. The BCA features and markers were univariately analyzed with a Shapiro-Wilk and two-sided Mann-Whitney-U test. In a multivariate approach, obtained markers were adjusted by a defined set of laboratory parameters promoted by other studies. Subsequently, the relationship between the markers and two endpoints, namely severity and mortality, was investigated with regard to statistical significance. The univariate approach showed that the muscle volume was significant for female (pseverity ≤ 0.001, pmortality ≤ 0.0001) and male patients (pseverity = 0.018, pmortality ≤ 0.0001) regarding the severity and mortality endpoints. For male patients, the intra- and intermuscular adipose tissue (IMAT) (p ≤ 0.0001), epicardial adipose tissue (EAT) (p ≤ 0.001) and pericardial adipose tissue (PAT) (p ≤ 0.0001) were significant regarding the severity outcome. With the mortality outcome, muscle (p ≤ 0.0001), IMAT (p ≤ 0.001), EAT (p = 0.011) and PAT (p = 0.003) remained significant. For female patients, bone (p ≤ 0.001), IMAT (p = 0.032) and PAT (p = 0.047) were significant in univariate analyses regarding the severity and bone (p = 0.005) regarding the mortality. Furthermore, the defined sarcopenia marker (p ≤ 0.0001, for female and male) was significant for both endpoints. The cardiac marker was significant for severity (pfemale = 0.014, pmale ≤ 0.0001) and for mortality (pfemale ≤ 0.0001, pmale ≤ 0.0001) endpoint for both genders. The multivariate logistic regression showed that the sarcopenia marker was significant (pseverity = 0.006, pmortality = 0.002) for both endpoints (ORseverity = 0.42, 95% CIseverity: 0.23-0.78, ORmortality = 0.34, 95% CImortality: 0.17-0.67). The cardiac marker showed significance (p = 0.018) only for the severity endpoint (OR = 1.42, 95% CI 1.06-1.90). The association between BCA-based sarcopenia and cardiac biomarkers and disease severity and mortality suggests that these biomarkers can contribute to the risk stratification of SARS-CoV-2 patients. Patients with a higher cardiac marker and a lower sarcopenia marker are at risk for a severe course or death. Whether those biomarkers hold similar importance for other pneumonia-related diseases requires further investigation.


A carboxy-terminally truncated form of the Vpr protein of human immunodeficiency virus type 1 retards cell proliferation independently of G(2) arrest of the cell cycle.
Vpr, one of the accessory gene products of HIV-1, is a 96-residue protein with several functions. It is involved in import of the HIV-1 preintegration complex into the nucleus of nondividing cells, in cellular differentiation, inducing cell cycle arrest at the G(2)/M phase, in immune suppression, and in enhancement of replication of the virus. We found recently that Vpr interferes with the proliferation of mouse NIH3T3 fibroblasts but fails to arrest these cells in the G(2) phase. Thus, it seems possible that Vpr might retard cell proliferation via a novel pathway that is distinct from G(2) arrest. To elucidate the mechanism by which Vpr induces the retardation of cell growth, we developed a panel of expression vectors that encoded Vpr molecules with deletions of specific putative domains, namely, the first alpha-helical domain, the second alpha-helical domain, a leucine zipper-like domain, and an arginine-rich carboxy-terminal domain. These vectors were introduced into HeLa cells since expression of Vpr can induce G(2) arrest in such cells. A carboxy-terminally truncated form of Vpr, C81, which failed to induce G(2) arrest, led to the G(1) arrest and retained the ability to prevent cell proliferation. All the other mutant proteins had completely lost the capacity to induce G(2) arrest and to suppress growth. Substitutions of Ile/Leu for Pro at positions 60, 67, 74, and 81 within the leucine zipper-like domain of Vpr or of C81 revealed that Ile60, Leu67, and Ile74 play an important role in the C81-induced suppression of growth, while Ile74 and Ile81 were found to be indispensable for Vpr-induced G(2) arrest. Collectively, our results strongly suggest that Vpr can retard cell proliferation independently of G(2) arrest of the cell cycle.


[Effect of TMV-infection on protein and carbohydrate content in hypersensitive tobacco plants and their antiviral and hemagglutinating activity].
Changes in content of proteins and carbohydrates of sensitive and supersensitive tobacco and datura plants and their antiviral and hemagglutinating activity under tobacco mosaic virus infection were investigated. It was shown that the content of these substances was increased on early stages of virus infection in hypersensitive plants. Antiviral and hemagglutinating activity of the obtained substances was shown.


A stochastic model for infectious salmon anemia (ISA) in Atlantic salmon farming.
Infectious salmon anemia (ISA) is one of the main infectious diseases in Atlantic salmon farming with major economical implications. Despite the strong regulatory interventions, the ISA epidemic is not under control, worldwide. We study the data covering salmon farming in Norway from 2002 to 2005 and propose a stochastic space-time model for the transmission of the virus. We model seaway transmission between farm sites, transmission through shared management and infrastructure, biomass effects and other potential pathways within the farming industry. We find that biomass has an effect on infectiousness, the local contact network and seaway distance of 5 km represent similar risks, but a large component of risk originates from other sources, among which are possibly infected salmon smolt and boat traffic.


Factors related to utilization of dental services during pregnancy.
The purposes of this study were to investigate factors related to utilization of dental services during pregnancy and to assess the extent of mothers' knowledge regarding oral health during pregnancy and its effect on pregnancy outcomes. Cross-sectional data were collected from 625 women using a structured questionnaire mailed to mothers who had given birth in Johnson County, Iowa from August 2001 to March 2002. The survey assessed knowledge, behaviours, attitudes toward dental care during pregnancy, and personal, demographic and pregnancy-related factors. Variables which showed associations in bivariate analysis (p< or =0.1) were considered as candidates for building logistic regression models separately by domain (demographics, dental health care behaviours, lifestyle, financial variables, pregnancy-related variables, and knowledge of the possible association between oral health and pregnancy). Significant domain-specific regression results (p< or =0.05) were used to develop a final model using forward stepwise logistic regression analyses. The overall response rate was 69%. Dental visits during pregnancy were reported by 49% of respondents. Forty-three percent were aware of the possible connection between oral health and pregnancy outcomes. In the final logistic regression analysis, factors significantly associated with reporting dental visits during pregnancy were: (1) personal factors (being married, greater frequency of visiting the dentist when not pregnant and use of inter-proximal cleaning aids); (2) financial factors (dental insurance); and (3) knowledge of the possible connection between oral health and pregnancy outcomes. There was limited knowledge of the possible relationships between oral health and pregnancy outcomes in a fairly homogeneous population of women who were of relatively high socioeconomic standing. This study suggests that better education of the importance of dental care before and during pregnancy is needed.


Changes in the expression of alpha-fodrin during embryonic development of Xenopus laevis.
Fodrin (nonerythroid spectrin) and its associated proteins have been previously implicated in the establishment of specialized membrane-cytoskeletal domains in differentiating cells. Using antiserum which is monospecific for the alpha-subunit of fodrin, we demonstrate that alpha-fodrin is present in oocytes and adult tissues of Xenopus laevis. Analyses of the de novo synthesis of alpha-fodrin during embryonic development reveal that alpha-fodrin is synthesized in oocytes, but not during early development. To investigate the level of control of alpha-fodrin expression, we isolated two cDNA clones for oocyte alpha-fodrin. The oocyte cDNA clones were identified as encoding portions of alpha-fodrin based on DNA sequence analysis and on the comparison of the predicted amino acid sequence of the cDNAs with the known sequence of human erythrocyte alpha-spectrin. The Xenopus alpha-fodrin cDNAs hybridize to a transcript of approximately 9 kb on RNA blots, and probably to a single gene type on genomic DNA blots. Both RNA blot analyses and S1 nuclease protection assays with the Xenopus alpha-fodrin cDNAs demonstrate that the observed decline in the de novo synthesis of alpha-fodrin polypeptides is controlled by a dramatic decrease in the abundance of alpha-fodrin transcripts after fertilization. In contrast, levels of actin transcripts do not decrease during this period. Inasmuch as steady-state levels of alpha-fodrin transcripts rise by the neurula stage of development, these results suggest that the synthesis of alpha-fodrin polypeptides during embryonic development of Xenopus is regulated, rather than constitutive, and that the primary level of control is the steady-state abundance of mRNA.


Cocaine use as a predictor of outcome in aneurysmal subarachnoid hemorrhage.
The goal of this study was to analyze the relationship between cocaine use and outcomes of aneurysmal subarachnoid hemorrhage (SAH). A retrospective review was performed of the medical records of patients with intracranial aneurysms treated at a single institution between January 1996 and December 2001. Only patients who presented with SAH were included in the study. The covariates chosen for the statistical analysis included the following: patient age, sex, and race; systolic and mean arterial blood pressure measurements on hospital admission; Hunt and Hess and Fisher grades; pre-existent major systemic disease; and history of alcohol, tobacco, or cocaine use. The Glasgow Outcome Scale (GOS) was used to standardize outcome and was dichotomized such that a score between 1 and 3 was considered a poor outcome and a score of 4 or 5 was considered a favorable outcome. The records of 151 patients were reviewed and 108 of these presented with aneurysmal SAH. Of these 108 patients, 36 (33.3%) had used cocaine within 24 hours before presentation. A Hunt and Hess grade of IV or V was assigned to 20 (55.6%) of 36 patients who used cocaine, compared with eight (11.1%) of 72 patients who did not; this difference was found to be statistically significant (p < 0.0001). Twenty-eight patients (77.8%) in the cocaine user group and 20 patients (27.8%) in the non-cocaine user group experienced clinically significant, angiographically confirmed vasospasm during their hospital course (p < 0.0001). Cocaine use was associated with a 2.8-fold greater risk of developing vasospasm (95% confidence interval [CI] 1.86-4.22). A GOS score of 1, 2, or 3 was assigned to 33 patients (91.7%) in the cocaine user group and to 20 patients (27.8%) in the non-cocaine user group (p < 0.0001). Cocaine use was associated with a 3.3-fold greater risk of poor outcome (95% CI 2.24-4.85). This association was found to be independent of Hunt and Hess grade as well as of vasospasm. Cocaine adversely affects both the presentation of and outcome in patients with aneurysmal SAH who are undergoing treatment for this disease. The vasoactive properties of the drug appear to aggravate the already tenuous situation of SAH and increase both the occurrence and influence of cerebral vasospasm. Statistical analysis demonstrates that cocaine directly affects both presentation and outcome in a significant manner. It is the authors' interpretation of the results of this retrospective review that cocaine use negatively affects outcome to such an extent that it should be considered equal to the presence of a major systemic illness when determining Hunt and Hess grade.


Effect of the neuronal nitric oxide synthase inhibitor 7-nitroindazole on methylphenidate-induced hyperlocomotion in mice.
The psychostimulant methylphenidate (MPD) is used for the treatment of attention-deficit/hyperactivity disorders (ADHD) in adolescents. In the present study we investigated the effect of repeated administration of a low (10 mg/kg) and a high (40 mg/kg) dose of MPD on the locomotor activity of Swiss Webster mice, and the influence of inhibition of the neuronal nitric oxide synthase (nNOS) on MPD-induced hyperlocomotion. In the first experiment, mice were administered either vehicle or the nNOS inhibitor 7-nitroindazole (7-NI; 25 mg/kg), prior to the administration of MPD (10 or 40 mg/kg), for five consecutive days; injections were paired with the test cage ('novel environment') on days 1 and 5. A challenge injection of MPD (10 or 40 mg/kg), given after a 10-day drug-free period, resulted in sensitization to the motor stimulating effect of the low dose of MPD but tolerance to the high dose of MPD. 7-NI blocked the induction of sensitization but had no effect on the development of tolerance. The place-dependent-hyperlocomotion (e.g. conditioning) that developed after the administration of either the low or high dose of MPD was blocked by pretreatment with the nNOS inhibitor. In the second experiment, mice were administered MPD (10 or 40 mg/kg; 5 days) in their home cage and after a 10-day drug-free period were challenged with either vehicle/MPD or 7-NI/MPD. The low dose of MPD elicited a sensitized response that was blocked by the co-administration of 7-NI. The high dose of MPD produced neither sensitization nor tolerance; 7-NI did not affect the response to the high dose of MPD. These findings suggest: (a) MPD-induced sensitization and tolerance are dependent on the dose of the drug and the environment where the drug is delivered (home cage versus test cage); (b) context-dependent hyperlocomotion developed in the absence of a sensitized response to the drug; (c) nNOS is involved in the induction and expression of sensitization to MPD as well as in the conditioned locomotion produced by the drug; (d) no involvement of nNOS in the effects of a high dose of MPD was detected.


Numerical analysis of the impact of cytoskeletal actin filament density alterations onto the diffusive vesicle-mediated cell transport.
The interior of a eukaryotic cell is a highly complex composite material which consists of water, structural scaffoldings, organelles, and various biomolecular solutes. All these components serve as obstacles that impede the motion of vesicles. Hence, it is hypothesized that any alteration of the cytoskeletal network may directly impact or even disrupt the vesicle transport. A disruption of the vesicle-mediated cell transport is thought to contribute to several severe diseases and disorders, such as diabetes, Parkinson's and Alzheimer's disease, emphasizing the clinical relevance. To address the outlined objective, a multiscale finite element model of the diffusive vesicle transport is proposed on the basis of the concept of homogenization, owed to the complexity of the cytoskeletal network. In order to study the microscopic effects of specific nanoscopic actin filament network alterations onto the vesicle transport, a parametrized three-dimensional geometrical model of the actin filament network was generated on the basis of experimentally observed filament densities and network geometries in an adenocarcinomic human alveolar basal epithelial cell. Numerical analyzes of the obtained effective diffusion properties within two-dimensional sampling domains of the whole cell model revealed that the computed homogenized diffusion coefficients can be predicted statistically accurate by a simple two-parameter power law as soon as the inaccessible area fraction, due to the obstacle geometries and the finite size of the vesicles, is known. This relationship, in turn, leads to a massive reduction in computation time and allows to study the impact of a variety of different cytoskeletal alterations onto the vesicle transport. Hence, the numerical simulations predicted a 35% increase in transport time due to a uniformly distributed four-fold increase of the total filament amount. On the other hand, a hypothetically reduced expression of filament cross-linking proteins led to sparser filament networks and, thus, a speed up of the vesicle transport.


Efficient hearing screening in noise-exposed listeners using the digit triplet test.
Hearing screening in occupational medicine is generally based on pure-tone threshold audiometry. However, reliable and valid thresholds can only be obtained in a sound-proof room, using a high-quality, well-calibrated audiometer, and by a well-trained administrator. Thresholds also need to be determined for several audiometric frequencies. This makes the test time-consuming and expensive, which is not ideal for the screening of large populations. A Speech-In-Noise test (SPIN), by contrast, does not have the abovementioned requirements. Because it can be implemented as a quick automated self-test, possibly over the Internet, a SPIN test is highly advantageous for screening purposes. However, its sensitivity for (isolated) high-frequency hearing loss, as typically seen in noise-exposed listeners, was unclear up to present. In this study, the authors investigated the sensitivity and specificity of the Digit Triplet SPIN test for detecting and monitoring (early-stage) high-frequency hearing loss, and its similarity across two different language versions. One-hundred eighteen noise-exposed workers, representing a wide range from no to severe high-frequency hearing loss, completed the French or Dutch version of the broadband Digit Triplet self-test in an office-like room. Pure-tone thresholds, collected by a professional audiologist in favorable settings, served as the reference. The 84 Dutch-speaking participants showed a very strong linear relation between the reference and the Digit Triplet test, with the pure-tone average at 2, 3, 4, and 6 kHz as a strong predictor (R = 0.86) for the speech-reception threshold. The sensitivity and specificity to detect mild high-frequency hearing loss were 92% (61 of 66) and 89% (16 of 18), respectively. The area under the receiver operating characteristic (ROC) curve was very high (≥0.91) for several degrees of high-frequency hearing loss. With a within-subject standard deviation of only 0.8 dB, the Digit Triplet test also had a low measurement error. The results of the 34 French-speaking subjects showed a highly similar trend. The Digit Triplet test proves to have a high sensitivity and specificity for detecting different degrees of high-frequency hearing loss. Given its ease of use, this test is very suitable for screening purposes in occupational medicine, and potentially for the screening of adolescents at risk of recreational noise-induced hearing loss.


Bifunctional Peptide Nanofibrils for Targeted Protein Degradation.
Proteolysis targeting chimera (PROTAC) is a state-of-the-art technology for ablating undruggable targets. A PROTAC degrader achieves targeted protein degradation (TPD) through the simultaneous binding of a protein of interest (POI) and an E3 ligase to form a ternary complex. A nanofibril-based PROTAC strategy to form a polynary (E3)m : PROTAC : (POI)n complex has not been reported in the TPD field up to this point. A recent innovation shows that a POI ligand and E3 ligase ligand don't have to be within a fused degrader molecule. Instead, they can be recruited to cellular proximity by a self-assembly-driving peptide and click chemistry. The resulting nanofibrils can recruit multiple POI and E3 ligase molecules to form a polynary complex as a degradation center. The so-called Nano-PROTAC provides a novel approach for TPD in cancer therapy.


Transcriptional organization and expression of noIXWBTUV, a locus that regulates cultivar-specific nodulation of soybean by Rhizobium fredii USDA257.
Rhizobium fredii is a nitrogen-fixing bacterial symbiont of soybean and a number of other legume species. We have studied the transcriptional organization of a Sym plasmid locus that restricts the host range of R. fredii USDA257 at both the host species and cultivar level. The genes of this host-specificity locus, noIXWBTUV, are transcribed from three promoters. Two of these, which are upstream of noIW and noIBTUV, are oriented face to face and initiate transcription at sites that are 14 bp apart. The third lies upstream from noIX. The noIW promoter is constitutive, whereas the noIB and noIX promoters are inducible by flavonoid signals. We have attempted to express genes from this locus in Escherichia coli systems, both in vivo and in vitro. We detected the insert- and orientation-specific expression of two genes, noIX and noIW, but we were unable to obtain expression of noIBTUV. Antiserum raised against NoIT nevertheless detected an abundantly expressed polypeptide of the predicted size in protein extracts of USDA257. This observation, as well as RNA dot blot data from a series of mutants, indicates that noIBTUV is expressed as a single transcriptional unit in R. fredii. Immunological detection of NoIT, and of a second protein, NoIX, was strictly dependent on flavonoid induction. The NoIX protein was larger than the size predicted from the previously published nucleotide sequence, and this led to resequencing and revision of the open reading frame.


Cationic Lipid Content in Liposome-Encapsulated Nisin Improves Sustainable Bactericidal Activity against Streptococcus mutans.
An oral infectious disease, dental caries, is caused by the cariogenic streptococci Streptococcus mutans. The expected preventive efficiency for prophylactics against dental caries is not yet completely observed. Nisin, a bacteriocin, has been demonstrated to be microbicidal against S. mutans, and liposome-encapsulated nisin improves preventive features that may be exploited for human oral health. Here we examined the bactericidal effect of charged lipids on nisin-loaded liposomes against S. mutans and inhibitory efficiency for insoluble glucan synthesis by the streptococci for prevention of dental caries. Cationic liposome, nisin-loaded dipalmitoylphosphatidylcholine/phytosphingosine, exhibited higher bactericidal activities than those of electroneutral liposome and anionic liposome. Bactericidal efficiency of the cationic liposome revealed that the vesicles exhibited sustained inhibition of glucan synthesis and the lowest rate of release of nisin from the vesicles. The optimizing ability of cationic liposome-encapsulated nisin that exploit the sustained preventive features of an anti-streptococcal strategy may improve prevention of dental caries.


Additive type moire with computer image processing.
Due to its poor visibility additive type moire is seldom used in spite of its simplicity. By means of computer image processing, the visibility of additive moire can be improved in real time to that of subtractive type moire. Experimental results for moire topography show that the additive type moire is no longer an inadequate method.


Assessing the quantity of neuropeptide Y in the serum of patients referred to Baqiyatallah Hospital with covid-19 concerning inflammatory factors following steroid therapy.
With the extensive presence of Covid-19, it is imperative to find compounds that can obstruct the virus's inflammatory activity and perhaps even stop the inflammatory phase from occurring. Several neuropeptides act as immune system regulators, which nerve terminals release as co-transmitters. It has been suggested that Neuropeptide Y (NPY) may be involved in inflammatory diseases through its ability to regulate the function of inflammatory cells. Consequently, the present study was designed to examine the changes in this neuropeptide in the serum of patients with Covid-19 disease, particularly following anti-inflammatory treatment, and its relationship with other inflammatory factors such as TNF-α. The demographic information, vital and clinical signs (blood oxygen saturation level, blood pressure, heart rate, and body temperature), laboratory factors such as blood factors, inflammation, and blood electrolytes, as well as the use of steroids, were collected before and after steroid treatment the patient files. As part of the study, serum samples from patients were used to measure levels of NPY and TNF-α inflammatory factors using an ELISA kit. Additionally, the correlation between NPY values, other inflammatory factors, and other variables was examined before and after treatment. NPY, TNF-α, c-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) levels were significantly reduced after steroid treatment. But the blood urea nitrogen (BUN) factor level increased after treatment compared to the initial evaluation. Lymphocytes and neutrophils also changed after drug treatment. Results indicated a high correlation between NPY and TNF-α. In addition to TNF-α, NPY, creatinine, and BUN presented a direct and significant relationship. ESR and BUN factors showed a positive and significant correlation regarding the length of hospitalization. However, the correlation between NPY and TNF-α with hospitalization length was insignificant. Since the current study had a significant association between NPY and TNF-α, the regulating function of this peptide in Covid-19 inflammatory processes may be validated. Enough that it is crucial to consider NPY as a marker and its antagonist as a potential Covid-19 therapy. Also, the considerable reduction in NPY levels after steroid therapy to lower inflammatory variables supports the regulatory function of this peptide in inflammatory processes.


[Use of radiomodifiers during radiotherapy of patients with malignant tumors].
The utilization of various radiomodifiers (hyperbaric oxygenation, metronidazole and their combination, tourniquet and total body gas hypoxia, unconventional dose fractionation) in radiation therapy of over 2000 cancer patients with tumors of the main sites made it possible to raise therapeutic efficacy using a differentiated approach to a choice of therapeutic tactics with relation to radiobiological specificities. The results obtained made it possible to determine the prospects of a further study of the efficacy of the utilization of HBO and MZ and their combination. Tourniquet hypoxia in view of a narrow range of indications and danger of a tumor protection effect should be abandoned. As to the hypoxic gas breathing mixture containing 10% O2 the absence of such an effect must be proved. Unconventional fractionation is no less promising, and as distinct from radiomodifiers it does not require extra resources or special equipment. The use of large fractions to enhance an antitumor effect, their combination in different succession with small fractions to lessen normal tissue damage as well as superfractionation with relation to tumor oxygen supply, possible reoxygenation, a capacity for repopulation and reparation can ensure at present a true therapeutic advantage.


Constant Magnetic Field as a Tool for Modification of the Properties of Polymer Composites with Silicone Rubber Matrix.
The aim of this research was to obtain new polymer composites with a silicone rubber matrix, having favorable mechanical and functional properties. They contained admixtures in the amount of 10% by weight of expanded graphite (EG) or birch bark (BB). Additionally, some composites contained magnetic particles in the form of carbonyl iron in the amount of 20% by weight. The tensile strength, water absorption, frost resistance, surface contact angle, and free surface energy were examined. Microscopic images were taken using the SEM method and the content of some elements in selected microareas was determined using the EDXS method. In the study, a constant magnetic field with magnetic induction B was used, by means of which the properties and structure of polymer composites were modified. Scientific research in the field of polymers is the driving force behind the progress of civilization. Smart materials are able to respond to external stimuli, such as magnetic fields, with significant changes in their properties. The magnetic field affects not only chemical reactions, but also the crystallographic structure and physicochemical properties of the final products. Owing to their unique properties, such materials can be used in the space industry, automotive industry, or electrical engineering.


The savant syndrome: an extraordinary condition. A synopsis: past, present, future.
Savant syndrome is a rare, but extraordinary, condition in which persons with serious mental disabilities, including autistic disorder, have some 'island of genius' which stands in marked, incongruous contrast to overall handicap. As many as one in 10 persons with autistic disorder have such remarkable abilities in varying degrees, although savant syndrome occurs in other developmental disabilities or in other types of central nervous system injury or disease as well. Whatever the particular savant skill, it is always linked to massive memory. This paper presents a brief review of the phenomenology of savant skills, the history of the concept and implications for education and future research.


Evaluation of food quality in geriatric institutions.
The aim was to develop a strategy for evaluating food sensory quality in an institutional setting, the Parameter Specific Sensory Quality (PSSQ) approach, and to compare the inter-evaluator judgement concordance (IEC) using the PSSQ tool versus a traditional tool (TT). Inter-evaluator judgement concordance was assessed before and after participants underwent 12 (Study 1) or eight hours of training (Study 2). In Study 1, the IEC was determined before training using the traditional tool only (29 food items) and after training using both the traditional tool and the PSSQ (28 food items). In Study 2, the IEC was determined before and after training using the PSSQ (19 food items). Intraclass correlation coefficients (ICCs) were used to measure the IEC, and data were compared using Fisher's transformation. Study 1 highlighted the poor IEC for the traditional tool in general (ICC(pre)=0.41 vs. ICC(post)=0.43; p>0.1), especially in comparison with that for the PSSQ (ICC(PSSQ)=0.88 vs. ICC(TT)=0.43; p<0.01). Study 2 corroborated the excellent performance of the PSSQ, even when participants had as few as eight hours of training (ICC(post)=0.93). The inter-evaluator judgement concordance in the evaluation of food sensory quality is fundamental to the generation of valid and useful information. Study results suggest that the food sensory IEC could be improved in hospital settings through the use of a parameter-specific approach, and that this improvement could help ensure the provision of foods of consistent quality.


Moving forward on facilitation research: response to changing environments and effects on the diversity, functioning and evolution of plant communities.
Once seen as anomalous, facilitative interactions among plants and their importance for community structure and functioning are now widely recognized. The growing body of modelling, descriptive and experimental studies on facilitation covers a wide variety of terrestrial and aquatic systems throughout the globe. However, the lack of a general body of theory linking facilitation among different types of organisms and biomes and their responses to environmental changes prevents further advances in our knowledge regarding the evolutionary and ecological implications of facilitation in plant communities. Moreover, insights gathered from alternative lines of inquiry may substantially improve our understanding of facilitation, but these have been largely neglected thus far. Despite over 15 years of research and debate on this topic, there is no consensus on the degree to which plant-plant interactions change predictably along environmental gradients (i.e. the stress-gradient hypothesis), and this hinders our ability to predict how plant-plant interactions may affect the response of plant communities to ongoing global environmental change. The existing controversies regarding the response of plant-plant interactions across environmental gradients can be reconciled when clearly considering and determining the species-specificity of the response, the functional or individual stress type, and the scale of interest (pairwise interactions or community-level response). Here, we introduce a theoretical framework to do this, supported by multiple lines of empirical evidence. We also discuss current gaps in our knowledge regarding how plant-plant interactions change along environmental gradients. These include the existence of thresholds in the amount of species-specific stress that a benefactor can alleviate, the linearity or non-linearity of the response of pairwise interactions across distance from the ecological optimum of the beneficiary, and the need to explore further how frequent interactions among multiple species are and how they change across different environments. We review the latest advances in these topics and provide new approaches to fill current gaps in our knowledge. We also apply our theoretical framework to advance our knowledge on the evolutionary aspects of plant facilitation, and the relative importance of facilitation, in comparison with other ecological processes, for maintaining ecosystem structure, functioning and dynamics. We build links between these topics and related fields, such as ecological restoration, woody encroachment, invasion ecology, ecological modelling and biodiversity-ecosystem-functioning relationships. By identifying commonalities and insights from alternative lines of research, we further advance our understanding of facilitation and provide testable hypotheses regarding the role of (positive) biotic interactions in the maintenance of biodiversity and the response of ecological communities to ongoing environmental changes.


Genetic covariance between central corneal thickness and anterior chamber volume: a Hungarian twin study.
Few, and inconsistent, studies have showed high heritability of some parameters of the anterior segment of the eye; however, no heritability of anterior chamber volume (ACV) has been reported, and no study has been performed to investigate the correlation between the ACV and central corneal thickness (CCT). Anterior segment measurements (Pentacam, Oculus) were obtained from 220 eyes of 110 adult Hungarian twins (41 monozygotic and 14 same-sex dizygotic pairs; 80% women; age 48.6 ± 15.5 years) obtained from the Hungarian Twin Registry. Age- and sex-adjusted heritability of ACV was 85% (bootstrapped 95% confidence interval; CI: 69% to 93%), and 88% for CCT (CI: 79% to 95%). Common environmental effects had no influence, and unshared environmental factors were responsible for 12% and 15% of the variance, respectively. The correlation between ACV and CCT was negative and significant (r ph = -0.35, p < .05), and genetic factors accounted for the covariance significantly (0.934; CI: 0.418, 1.061) based on the bivariate Cholesky decomposition model. These findings support the high heritability of ACV and central corneal thickness, and a strong genetic covariance between them, which underscores the importance of identification of the specific genetic factors and the family risk-based screening of disorders related to these variables, such as open-angle and also angle closure glaucoma and corneal endothelial alterations.


HERG1 functions as an oncogene in pancreatic cancer and is downregulated by miR-96.
Pancreatic cancer is an aggressive malignancy with an extremely poor prognosis. The human ether-a-go-go-related potassium channel (HERG1) is a human rapid delayed rectifier, which is involved in many crucial cellular events. In this article, we find that HERG1 expression is dramatically increased both in pancreatic cancer tissues and cell lines, and that increased HERG1 expression is significantly related to the development of pancreatic cancer. HERG1 silencing in pancreatic cancer-derived cell lines PANC-1 and CFPAC-1 strongly inhibits their malignant capacity in vitro as well as tumorigenicity and metastasis in nude mice. In addition, HERG1 is identified as a direct target of miR-96, which is downregulated in pancreatic cancer tissues and cell lines. Ectopic expression of miR-96 represses the HERG1 expression in pancreatic cancer and significantly inhibits malignant behavior of pancreatic cancer cells in vitro and in vivo. Collectively, our findings suggest that miR-96 acts as a tumor suppressor in pancreatic cancer and may therefore serve as a useful therapeutic target for the development of new anticancer therapy.


Efficacy of an oral nutraceutical for the treatment of canine osteoarthritis. A double-blind, randomized, placebo-controlled prospective clinical trial.
To assess the safety and efficacy of an orally administered nutraceutical (Glu/CS+; + for additional ingredient) for the treatment of clinical osteoarthritis (OA) in dogs. In this double-blind, randomized, placebo-controlled clinical trial, client-owned dogs with clinical signs of OA in one or more joints were assigned to a Glu/CS+ (n = 30) or placebo (n = 30) group. Dogs were administered Glu/CS+ or placebo orally and wore an activity monitor (AM) continuously throughout a 97 day study period. Prior to the initiation of the treatment, seven days of baseline activity was collected. On days -7, 30, 60 and 90 of the study, owners completed a patient assessment form (Canine Brief Pain Inventory). Data between groups were compared. No serious adverse events were reported. No difference was found between groups when evaluating daily activity counts during the seven-day pre-treatment period and the 90-day treatment period. Owner assessment (pain interference and pain severity scores) improved over the 90-day treatment period for both groups, however no difference was found between treatment groups. Treatment with oral Glu/CS+ for a 90 day treatment period when compared to placebo treatment did not result in a significant increase in activity counts in dogs with clinical OA. However, owner assessment scores similarly improved throughout the study period for dogs in both groups, suggesting a caregiver placebo effect in this outcome measure.


Human "live cadaver" neurovascular model for proximal and distal mechanical thrombectomy in stroke.
Preclinical testing platforms that accurately replicate complex human cerebral vasculature are critical to advance neurointerventional knowledge, tools, and techniques. Here, we introduced and validated a human "live cadaveric" head-and-neck neurovascular model optimized for proximal and distal vascular occlusion and recanalization techniques. Human cadaveric head-and-neck specimens were cannulated bilaterally in the jugular veins, carotid, and vertebral arteries. Specimens were then coupled with modular glass models of the aorta and extracranial carotid arteries, as well as radial and femoral access ports. Intracranial physiological flow was simulated using a flow-delivery system and blood-mimicking fluid. Baseline anatomy, histological, and mechanical properties of cerebral arteries were compared with those of fresh specimens. Radiopaque clot analogs were embolized to replicate proximal and distal arterial occlusions, followed by thrombectomy. Experienced interventionalists scored the model on different aspects. Compared with counterpart fresh human arteries, formalin-fixed arteries showed similar mechanical properties, including maximum stretch, increased tensile strength/stiffness, and friction coefficients were also not significantly different. On histology, minimal endothelial damage was noted in arteries after 3 months of light fixation, otherwise the arterial wall maintained the structural integrity. Contrast angiographies showed no micro- or macro-vasculature obstruction. Proximal and distal occlusions created within the middle cerebral arteries were consistently obtained and successfully recanalized. Additionally, interventionists scored the model highly realistic, indicating great similarity to patients' vasculature. The human "live cadaveric" neurovascular model accurately replicates the anatomy, mechanics, and hemodynamics of cerebral vasculature and allows the performance of neurointerventional procedures equivalent to those done in patients.


Topical vancomycin for treatment of methicillin-resistant Staphylococcus epidermidis infection in a rat spinal implant model.
Basic science. Investigate the ability of local applicaiton of vancomycin, either in powder form or suspended within poly(lactic-co-glycolic acid) microspheres (MS), to treat infection using a rat spinal model. Surgical site infections (SSIs) are a serious complication after spine surgery and are associated with high morbidity and mortality and often caused my coagulase negative staphylococci. A comprehensive approach to reduce SSIs has been recommended including the use of topical vancomycin. Animal and human studies have shown improved control of infection with local compared to systemic antibiotics. K-wires seeded with methicillin-resistant Staphylococcus epidermidis RP62A (MRSE) were treated with vancomycin powder, carboxymethylcellulose sodium salt (CMC) (microsphere carrier), vancomycin powder, blank MS or vancomycin-loaded MS for 24 or 48 h in vitro after which bacteria were enumerated. In addition, a spinal instrumentation model was developed in rats with a bacterial seeded K-wire implanted into the right side of L4 and L5. Rats underwent no treatment or were treated locally with either vancomycin powder, blank MS or vancomycin-loaded MS. After 8 weeks, the K-wire, bone, soft tissue and wire fastener were cultured and results analyzed. Vancomycin powder and vancomycin-loaded MS resulted in significantly fewer bacteria remaining in vitro than did CMC. Vancomycin powder- treated animals' cultures were significantly lower than all other groups (P < 0.0001) with negative culture results, except for one animal. The vancomycin-loaded MS-treated animals had lower bone bacterial counts than the controls (P < 0.0279); blank MS-treated animals had no differences in bacterial densities when compared to non-treated animals. Vancomycin powder and vancomycin-loaded MS were active against MRSE in vitro, in a rat MRSE implant model; however, vancomycin MS were inferior to the topical vancomycin powder. Vancomycin powder prevented MRSE infection in a rat spinal implant infection model.


Diverse origins of waxy foxtail millet crops in East and Southeast Asia mediated by multiple transposable element insertions.
The naturally occurring waxy and low-amylose variants of foxtail millet and other cereals, like rice and barley, originated in East and Southeast Asia under human selection for sticky foods. Mutations in the GBSS1 gene for granule-bound starch synthase 1 are known to be associated with these traits. We have analyzed the gene in foxtail millet, and found that, in this species, these traits were originated by multiple independent insertions of transposable elements and by subsequent secondary insertions into these elements or deletion of parts of the elements. The structural analysis of transposable elements inserted in the GBSS1 gene revealed that the non-waxy was converted to the low-amylose phenotype once, while shifts from non-waxy to waxy occurred three times, from low amylose to waxy once and from waxy to low amylose once. The present results, and the geographical distribution of different waxy molecular types, strongly suggest that these types originated independently and were dispersed into their current distribution areas. The patterns of GBSS1 variation revealed here suggest that foxtail millet may serve as a key to solving the mystery of the origin of waxy-type cereals in Asia. The GBSS1 gene in foxtail millet provides a new example of the evolution of a gene involved in the processes of domestication and its post-domestication fate under the influence of human selection.


Osmotic water permeabilities of cultured, well-differentiated normal and cystic fibrosis airway epithelia.
Current hypotheses describing the function of normal airway surface liquid (ASL) in lung defense are divergent. One theory predicts that normal airways regulate ASL volume by modulating the flow of isosmotic fluid across the epithelium, whereas an alternative theory predicts that ASL is normally hyposmotic. These hypotheses predict different values for the osmotic water permeability (P(f)) of airway epithelia. We measured P(f) of cultures of normal and cystic fibrosis (CF) airway epithelia that, like the native tissue, contain columnar cells facing the lumen and basal cells that face a basement membrane. Xz laser scanning confocal microscopy recorded changes in epithelial height and transepithelial volume flow in response to anisosmotic challenges. With luminal hyperosmotic challenges, transepithelial and apical membrane P(f) are relatively high for both normal and CF airway epithelia, consistent with an isosmotic ASL. Simultaneous measurements of epithelial cell volume and transepithelial water flow revealed that airway columnar epithelial cells behave as osmometers whose volume is controlled by luminal osmolality. Basal cell volume did not change in these experiments. When the serosal side of the epithelium was challenged with hyperosmotic solutions, the basal cells shrank, whereas the lumen-facing columnar cells did not. We conclude that (a) normal and CF airway epithelia have relatively high water permeabilities, consistent with the isosmotic ASL theory, and the capacity to restore water on airway surfaces lost by evaporation, and (b) the columnar cell basolateral membrane and tight junctions limit transepithelial water flow in this tissue.


Recurrent nephrotic syndrome after living-related renal transplantation resistant to plasma exchange: report of two cases.
We encountered two patients of recurrent nephrotic syndrome (NS) after renal transplantation that was resistant to plasma exchange (PEX). Case 1 was a 34-year-old man with a living-related renal transplant for type-I membranoproliferative glomerulonephritis (MPGN) related end-stage renal disease (ESRD). He developed overt proteinuria 7 months post-transplant and presented with NS 5 months later. Biopsy of the transplant kidney revealed recurrent type I MPGN, but no features of acute rejection (AR) or chronic allograft nephropathy (CAN). He was treated with cyclophosphamide (CP), oral prednisolone (40 mg/d), an anti-platelet agent, heparin sulfate, and PEX, but the nephrotic state persisted and renal function was deteriorated. He recommenced hemodialysis 3 yr and 9 months after renal transplant. Case 2 was a 47-year-old male who underwent living-related renal transplant for ESRD due to focal segmental glomerulosclerosis (FSGS). He presented with proteinuria shortly after renal transplantation. He also had frequent episodes of AR. Graft biopsy revealed recurrent FSGS. Treatment of pulse methylprednisolone and PEX was transiently effective, but NS relapsed shortly after PEX. Graft biopsy at our hospital showed features of CAN with moderate interstitial fibrosis and tubular atrophy, presence of intraglomerular foam cells but no segmental sclerosis. Treatment with 12 courses of low-density lipoprotein apheresis (LDL-A) reduced proteinuria from 9.6 to 2.0 g/d, and incomplete remission has been maintained for more than 1 yr after LDL-A with slowly progressive renal dysfunction. Despite recent therapeutic advances, including the use of immunosuppressants and PEX, treatment of recurrent disease remains difficult. The LDL-A might be useful in cases with recurrent FSGS resistant to PEX.


An Integrated Analysis of Network Pharmacology and Experimental Validation to Reveal the Mechanism of Chinese Medicine Formula Naotaifang in Treating Cerebral Ischemia-Reperfusion Injury.
Cerebral ischemia-reperfusion injury (CIRI) is a crucial factor leading to a poor prognosis for ischemic stroke patients. As a novel Chinese medicine formula, Naotaifang (NTF) was proven to exhibit a neuroprotective effect against ischemic stroke, clinically, and to alleviate CIRI in animals. However, the mechanisms underlying the beneficial effect have not been fully elucidated. In this study, we combined a network pharmacology approach and an in vivo experiment to explore the specific effects and underlying mechanisms of NTF in the treatment of ischemia-reperfusion injury. A research strategy based on network pharmacology, combining target prediction, network construction, gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and molecular docking was used to predict the targets of NTF in treating the ischemic stroke and CIRI. On the other hand, we used HPLC and HRMS to identify biologically active components of NTF. Middle cerebral artery occlusion models in rats were utilized to evaluate the effect and the underlying mechanisms of NTF against CIRI after ischemic stroke. Network pharmacology analysis revealed 43 potential targets and 14 signaling pathways for the treatment of NTF against CIRI after ischemic stroke. Functional enrichment analysis showed that a STAT3/PI3K/AKT signaling pathway serves as the target for in vivo experimental study validation. The results of animal experiments showed that NTF significantly alleviated CIRI by decreasing neurological score, infarct volume, numbers of apoptotic neuronal cells, increasing density of dendritic spines and survival of neurons. Furthermore, NTF could increase the expression of p-STAT3, PI3K, p-AKT. In addition, the detection of apoptosis-related factors showed that the NTF could raise the expression of Bcl-2 and reduce the expression of Bax. This network pharmacological and experimental study indicated that NTF, as a therapeutic candidate for the management of CIRI following ischemic stroke, may exert a protective effect through the STAT3/PI3K/AKT signaling pathway.


Unexpected Positive Prospective Crossmatches in Organ Transplant.
Preformed donor-specific antibodies against human leukocyte antigen can induce antibody-mediated rejection after organ transplant. Hence, future transplant recipients undergo pretransplant screening for preformed antibodies (ie, virtual crossmatch). Subsequently, prospective (analytic) crossmatching is performed using conventional, complement-dependent cytotoxicity assays and/or flow cytometry-based methods. The present article reviews factors that must be considered when unexpected, positive, prospective crossmatches are observed. First, the prozone effect caused by the interference of complement or immunoglobulin M must be abrogated by treating the serum with moderate heat, dilution, hypotonic dialysis, EDTA, or dithiothreitol. Second, the physician must check for the presence of potentially interfering autoantibodies (in a context of autoimmune disease or human immunodeficiency virus infection) or therapeutic antibodies (such as rituximab and antithymocyte globulin). In conclusion, knowledge of each assay's technical characteristics will enable the physician to reliably interpret any discrepancies. The reasons for an unexpected, positive, prospective crossmatch must be elucidated before transplant to ensure efficient organ allocation and optimize patient outcomes.


Fusion of synaptic vesicles and plasma membrane in the presence of synaptosomal soluble proteins.
Fusion between synaptic vesicles and plasma membranes isolated from rat brain synaptosomes is regarded as a model of neurosecretion. The main aim of current study is to investigate whether the synaptosomal soluble proteins are essential members of Ca(2+)-triggered fusion examined in this system. Fusion experiments were performed using fluorescent dye octadecylrhodamine B, which was incorporated into synaptic vesicle membranes at self-quenching concentration. The fusion of synaptic vesicles, containing marker octadecylrhodamine B, with plasma membranes was detected by dequenching of the probe fluorescence. Membrane fusion was not found in Ca(2+)-supplemented buffer solution, but was initiated by the addition of the synaptosomal soluble proteins. When soluble proteins were treated with trypsin, they lost completely the fusion activity. These experiments confirmed that soluble proteins of synaptosomes are sensitive to Ca(2+) signal and essential for membrane fusion. The experiments, in which members of fusion process were treated with monoclonal antibodies raised against synaptotagmin and synaptobrevin, have shown that antibodies only partially inhibited fusion of synaptic vesicles and plasma membranes in vitro. These results indicate that other additional component(s), which may or may not be related to synaptobrevin or synaptotagmin, mediate this process. It can be assumed that fusion of synaptic vesicles with plasma membranes in vitro depends upon the complex interaction of a large number of protein factors.


Is there any benefit to adding intravenous ketamine to patient-controlled epidural analgesia after thoracic surgery? A randomized double-blind study.
Thoracic surgery is associated with severe acute postoperative pain, leading to pulmonary complications and hyperalgesia-induced chronic pain. Thoracic patient-controlled epidural analgesia is also considered as the gold-standard postoperative analgesia. As previously described in major digestive surgery, combination with low-dose intravenous (i.v.) ketamine could potentiate epidural analgesia and facilitate pulmonary function recovery following thoracotomy. In a randomized, double-blind trial, 60 patients scheduled to undergo thoracotomy were included. All patients received a thoracic epidural catheter placed before surgery, and standardized general anaesthesia. They were allocated to two groups to receive either an i.v. bolus of ketamine at induction, followed by a continuous infusion during surgery and the first 48 h postoperatively, or an i.v. placebo (a saline solution under the same infusion modalities). Cumulative epidural ropivacaine consumption, postoperative pain scores (patient self-rated numeric pain intensity scale), analgesic rescue consumption, residual pain, haemodynamics and respiratory recovery function were recorded from 12 h to 3 months. Data were expressed as mean ± standard deviation or median ± interquartile range (25-75%). The comparisons between ketamine and placebo groups were performed using χ(2) or Fisher's exact tests for frequencies, and Mann-Whitney tests for quantitative variables. Epidural ropivacaine consumption was similar between groups during the first 48 postoperative hours. Postoperative pain scores and spirometric parameters were not significantly different between groups. But the incidence of postoperative nausea was significantly increased in patients owning to the ketamine group. Finally, the incidence of residual pain was similar between groups at 1 and 3 months following thoracotomy. Adding i.v. ketamine did not potentiate epidural analgesia neither to reduce acute and chronic postoperative pain nor to improve pulmonary dysfunction following thoracic surgery. Pain scores were low in both groups, mainly because of an optimized analgesia provided by the patient-controlled epidural mode, and might explain this lack of benefit in adding i.v. ketamine.


Transjugular intrahepatic portosystemic shunt compared with endoscopic treatment for prevention of variceal rebleeding: A meta-analysis.
Endoscopic treatment (ET) is frequently used to prevent variceal rebleeding but this still occurs in about 50% of patients. Recently, transjugular intrahepatic portosystemic shunt (TIPS) has been compared with ET in several trials. Using a meta-analysis, we evaluated randomized trials comparing TIPS to ET assessing prevention of rebleeding, survival, and the effects on resource use and the quality of patients' lives. Medical databases were searched between January 1988 and January 1999 as well as published citations and conference proceedings. Sensitivity analyses for type of publication, methodological quality score, mean duration of follow-up, type of ET, etiology, and severity of liver disease were performed. Eleven randomized trials involving 811 patients fulfilled the selection criteria. The median follow-up ranged from 10 to 32 months. Variceal rebleeding was significantly more frequent with ET (47%) compared with TIPS (19%) (odds ratio [OR], 3.8; 95% confidence interval [CI], 2.8-5.2; P <.001), but there was no difference in mortality (OR, 0.97; 95% CI, 0.71-1.34). Post-treatment encephalopathy occurred significantly less often after ET (19%) than after TIPS (34%) (OR, 0.43; 95% CI, 0.30-0.60; P <.001). In the studies showing resource use this was more extensive for TIPS. The sensitivity analyses did not alter the main conclusion, and sole comparison with endoscopic ligation did not alter these results. In conclusion, in patients with variceal bleeding, TIPS compared with ET reduces the rebleeding rate, but does not improve survival, and increases the incidence of encephalopathy in a period of 1 to 2.5 years. Thus, TIPS cannot be recommended as the first choice treatment for prevention of variceal rebleeding.


Immunohistochemical profile of steroid cell tumor of the ovary: a study of 14 cases and a review of the literature.
Fourteen steroid cell tumors (SCTs) of the ovary were studied by immunohistochemistry including inhibin, calretinin, CD99, Melan A, androgen receptor, and AE1/3. Twelve tumors were primary and 2 were recurrent. The primary tumors included 5 stromal luteomas (SL), 5 SCTs, not otherwise specified, and 2 Leydig cell tumors, 1 of the hilar type and 1 of the nonhilar type. All tumors were classified according to the predominant cell type. Six tumors were eosinophilic cell type, 3 clear-cell type, and 5 were mixed eosinophilic-clear-cell type. Inhibin, calretinin, and CD99 were positive in all 14 tumors. Twelve of 14 tumors (86%) were positive for Melan A and 9 of 14 (64%) for androgen receptor. AE 1/3 immunopositivity was found in 5 of 14 tumors (36%). Immunohistochemistry helps in the distinction between SCTs of the ovary and other primary or metastatic ovarian neoplasms with eosinophilic and clear-cell histology. In addition, immunohistochemistry can confirm the presence of recurrent SCT, if no sufficient clinical history is provided. As some SCTs can be positive for epithelial markers and histologically similar epithelial tumors can be positive for sex cord stromal markers, the use of multiple immunohistochemical stains is recommended.


Intermittent chaos in the Bray-Liebhafsky oscillator. Temperature dependence.
Intermittent oscillations as a chaotic mixture of large amplitude relaxation oscillations, grouped in bursts and small-amplitude sinusoidal ones or even quiescent parts between them known as gaps, were found and examined in the Bray-Liebhafsky (BL) reaction performed in CSTR under controlled temperature variations. They were obtained in a narrow temperature range from 61.0 °C to 63.1 °C, where 61.0 °C is the critical temperature for burst emergence from the stable steady state and 63.1 °C is the critical temperature for gap emergence from regular oscillations. Since intermittencies appear gradually from the regular oscillatory state, and no hysteresis was obtained with decreasing/increasing temperature in the vicinity of these two bifurcations, a linear relationship between (τB/τ)(2) and (τG/τ)(2) (where τB, τG and τ denotes duration of bursts, gaps, and whole experiment, respectively), as a function of the temperature as the control parameter, was expected and obtained. Although these intermittent oscillations are chaotic with respect to the lengths of individual gaps as well as bursts, their deterministic behavior related to temperature was additionally established. Thus, the number of bursts or gaps per unit of time (NB/τ and NG/τ) has the form of a normal distribution function over the temperature range in the region where intermittencies are obtained. Temperature dependence of the Lyapunov exponents was also described by a function of the normal distribution form. Hence, we established some regularities in the chaotic behavior of intermittent oscillations that are common in life but difficult for determinations.


Hydrogen Sulfide: A Worthwhile Tool in the Design of New Multitarget Drugs.
H2S is a gaseous molecule able to trigger a plethora of central physiological and pharmacological effects as antioxidant, pro- and anti-inflammatory, pro- and anti-nociceptive, neuromodulator, and cytoprotective. The polypharmacology of H2S depends on the wide variety of targets implicated, but, despite the efforts, the mechanisms of action that should clarify its activity are still not completely unrevealed. Nevertheless, many attempts to exploit the multifaceted profile of this molecule have already been accomplished and many chemical entities containing an H2S-releasing pharmacophore have been synthetized. Here we discuss recent investigations on multitarget molecules able to release H2S, with a particular focus on the combinations of "native drug" with moieties structurally able to release H2S and their applications as therapeutic tools in bone disease, gastrointestinal system and neurodegenerative disorders.


Preliminary 6 month results from the Argus II epiretinal prosthesis feasibility study.
The Argus II 60 channel epiretinal prosthesis has been developed in order to provide partial restoration of vision to subjects blinded from outer retinal degenerative disease. To date the device has been implanted in 21 subjects as part of a feasibility study. In 6 month post-implantation door finding and line tracking orientation and mobility testing, subjects have shown improvements of 86% and 73%, respectively, for system on vs. system off. In high-contrast Square Localization tests using a touch screen monitor 87% of tested subjects performed significantly better with the system on compared with off. These preliminary results show that the Argus II system provides some functional vision to blind subjects.


[Correlation between C-reactive protein to albumin ratio and restenosis after femoral popliteal stenting in patients with lower extremity arteriosclerotic obliterans].
Objective: To investigate the study of the correlation between C-reactive protein to albumin ratio (CAR) and restenosis after stenting in patients with lower extremity atherosclerotic occlusive disease(LEASO). Methods: The clinical data of 95 patients with LEASO admitted to the Department of Vascular Surgery of Nanjing Drum Tower Hospital from June 2020 to December 2022 were retrospectively analyzed. There were 67 males and 28 females,aged (73.1±9.4) years (range:51 to 92 years). The patients were classified into the restenosis group (n=61) and the patency group (n=34) according to the CT angiography results. Independent sample t test,Mann-Whitney U test and χ2 test were used to compare the data between two groups. Risk factors for restenosis after femoropopliteal artery stenting in patients with LEASO were analyzed using multivariate Cox regression. The relationship between preoperative CAR level and restenosis after stent placement was analyzed. Subject operating characteristic(ROC) curves of CAR were plotted to assess the predictive value of CAR for restenosis after stenting,and the results were expressed as area under the curve (AUC). Results: The aortoiliac calcification grade,number of stents,length of stents,C-reactive protein and CAR levels in restenosis group were higher than those in the patency group,and the serum albumin level was lower than that in the patency group(all P<0.05). And the results of multifactorial Cox regression analysis showed that higher pre-procedure CAR level and lower ABI value was an independent risk factor for in-stent restenosis. The AUC of the ROC curve for restenosis was 0.737,95%CI (0.617 to 0.856),the AUC of the ROC curve for 12-month restenosis was 0.709,95%CI (0.602 to 0.815),and the AUC of the ROC curve for 24-month restenosis was 0.702,95%CI (0.594 to 0.811). Conclusion: Higher pre-procedural CAR levels in patients with LEASO is risk factor for in-stent restenosis,and CAR has a predictive value for restenosis after lower extremity arterial stent dilatation and angioplasty.


Production of ethylene and other volatiles and changes in cellulase and laccase activities during the life cycle of the cultivated mushroom, Agaricus bisporus.
Nine volatile hydrocarbons, as well as methyl chloride, carbonyl sulphide and carbon disulphide, have been identified by mass spectrometry as products of Agaricus bisporus in the compost used in comerical mushroom beds. Of these, only ethylene showed a pattern of production that could be correlated with developmental phases of the crop, high levels being produced whenever fruit bodies were rapidly enlarging. In laboratory flask cultures, under controlled conditions, high levels of ethylene occurred whenever young fruit bodies entered the expansion phase. The enhanced rate of ethylene production continued over several days, irrespective of whether fruit bodies were removed. Production occurred within the colonized compost; no ethylene was evolved by the fruit body itself. When the first fruit bodies expanded, either in beds or culture flasks, laccase levels in the compost fell and those of a beta-1,4-glucanase (cellulase) rose. The enzyme switch occurred once only, during maturation of the first fruit bodies, whereas an elevated ethylene production was associated with each occasion when fruit body maturation took place. The low level of laccase and high of cellulase characterized the whole of the reproductive stage of A. bisporus, whereas the phasic periods of high ethylene production distinguished between periods of fruit body maturation and intervening resting periods.


Exploring the Health Informatics Occupational Group in the 2018 Australian Health Information Workforce Census.
There has been no empirical evidence about the health informatics workforce in Australia produced in the last ten years. This study reports the findings from an analysis of a subset of the 2018 Australian Health Informatics Workforce Census data. Analysing 420 responses that were identified as the occupational group Health Informatics, the results indicate that whilst most of the workforce is classified as aged (>45 years), many respondents are still relatively early in their health informatics careers. Furthermore, most do not possess any formal education in health informatics and almost a quarter undertake their health informatics role alongside another health-related role. The broad range of position titles and functions demonstrates the breadth within this workforce. Ongoing monitoring of this occupational group is required to inform workforce reform and renewal.


Exploring the Potential of Bee-Derived Antioxidants for Maintaining Oral Hygiene and Dental Health: A Comprehensive Review.
Honey bee products comprise various compounds, including honey, propolis, royal jelly, bee pollen, bee wax and bee venom, which have long been recognized for their pharmacological and health-promoting benefits. Scientists have discovered that periodontal disorders stem from dental biofilm, an inflammatory response to bacterial overgrowth produced by dysbiosis in the oral microbiome. The bee products have been investigated for their role in prevention of oral diseases, which are attributed to a myriad of biologically active compounds including flavonoids (pinocembrin, catechin, caffeic acid phenethyl ester (CAPE) and galangin), phenolic acids (hydroxybenzoic acid, hydroxycinnamic acid, p-coumaric, ellagic, caffeic and ferulic acids) and terpenoids. This review aims to update the current understanding of role of selected bee products, namely, honey, propolis and royal jelly, in preventing oral diseases as well as their potential biological activities and mechanism of action in relation to oral health have been discussed. Furthermore, the safety of incorporation of bee products is also critically discussed. To summarize, bee products could potentially serve as a therapy option for people suffering from a variety of oral disorders.


Impact of meteorological parameters on extracted landfill gas composition and flow.
The objective of this study was to investigate the impact of four pre-selected meteorological parameters (barometric pressure, wind speed, ambient temperature and solar radiation) on recovered landfill gas (LFG) flow, methane (CH4) content of the LFG and the recovered CH4 flow by performing statistical correlation tests and a visual check on correlations in scatterplots. Meteorological parameters were recorded at an on-site weather station, while LFG data were recorded when entering the gas engine. LFG CH4 concentration, LFG flow and CH4 flow correlated highly with both barometric pressure and changes in barometric pressure, and the correlations were statistically significant. A higher correlation was observed when studying changes in barometric pressure in comparison to the absolute value of barometric pressure. LFG recovery data correlated highly and significantly with wind speed during winter, but not during summer. Ambient temperature and solar radiation were not major meteorological parameters affecting LFG recovery, as low correlation coefficients were observed between these two parameters and the LFG recovery data.


Acupuncture in the management of chronic low back pain: a blinded randomized controlled trial.
To assess the efficacy of acupuncture in the treatment of chronic low back pain. Patients (n = 60) with chronic low back pain were recruited and randomly allocated to either Acupuncture therapy or Placebo transcutaneous electrical nerve stimulation (TENS) groups. Patients were treated weekly for 6 weeks, and blinded assessments were carried out pre- and post-treatment using the McGill Pain Questionnaire (MPQ) and visual analog scales (VAS) for pain, the Short-form 36 quality-of-life questionnaire, and a simple range of motion measurement. A total of 46 patients completed the trial and were followed up at 6 months. Analysis of results using t tests showed that in both groups there were significant pre-post improvements for all scores, except for MPQ scores in the Placebo-TENS group. There was no significant difference between the 2 groups for any of the outcome measures at the end of treatment. Results from the 6-month follow-up would suggest that the response was better in the acupuncture group. Further research is necessary to fully assess the efficacy of this treatment in combating chronic low back pain using larger sample sizes or alternative control groups.


Scientific Contributions of Population-Based Studies to Cardiovascular Epidemiology in the GWAS Era.
Longitudinal, well phenotyped, population-based cohort studies offer unique research opportunities in the context of genome-wide association studies (GWAS), including GWAS for new-onset (incident) cardiovascular disease (CVD) events, the assessment of gene x lifestyle interactions, and evaluating the incremental predictive utility of genetic information in apparently healthy individuals. Furthermore, comprehensively phenotyped community-dwelling samples have contributed to GWAS of numerous traits that reflect normal organ function (e.g., cardiac structure and systolic and diastolic function) and for many traits along the CVD continuum (e.g., risk factors, circulating biomarkers, and subclinical disease traits). These GWAS have heretofore identified many genetic loci implicated in normal organ function and different stages of the CVD continuum. Finally, population-based cohort studies have made important contributions to Mendelian Randomization analyses, a statistical approach that uses genetic information to assess observed associations between cardiovascular traits and clinical CVD outcomes for potential causality.


The use of computed tomography of the spine to identify patients at high risk for epidural metastases.
The usefulness of spinal computed tomography (CT) in predicting the presence of epidural tumor was evaluated in cancer patients undergoing CT myelography for suspected epidural tumor. Two hundred ninety two vertebral levels were evaluated in 30 patients. Spinal CT demonstrated cortical disruption surrounding the epidural space from metastatic cancer in 109 vertebrae. Eighty-five (78%) of these vertebral levels had tumor extension into the adjacent epidural space. The incidence of epidural tumor adjacent to vertebrae which had normal spinal CT or metastatic tumor without cortical disruption was 11%. Eighty-six percent of the epidural tumor adjacent to these vertebrae were a result of craniocaudal tumor extension in the epidural space from adjacent vertebral levels with cortical disruption. Twenty-one of 23 patients (91%) with cortical disruption at more than one vertebral level on spinal CT had epidural tumor. Synchronous noncontiguous epidural lesions were observed in 38% of patients with epidural tumor. Spinal CT is an important diagnostic test in determining which patients are at high risk for epidural tumor. Myelography should be performed in all patients with suspected epidural tumor to accurately define the full extent of tumor.


PRR14L mutations are associated with chromosome 22 acquired uniparental disomy, age-related clonal hematopoiesis and myeloid neoplasia.
Acquired uniparental disomy (aUPD, also known as copy-neutral loss of heterozygosity) is a common feature of cancer cells and characterized by extended tracts of somatically-acquired homozygosity without any concurrent loss or gain of genetic material. The presumed genetic targets of many regions of aUPD remain unknown. Here we describe the association of chromosome 22 aUPD with mutations that delete the C-terminus of PRR14L in patients with chronic myelomonocytic leukemia (CMML), related myeloid neoplasms and age-related clonal hematopoiesis (ARCH). Myeloid panel analysis identified a median of three additional mutated genes (range 1-6) in cases with a myeloid neoplasm (n = 8), but no additional mutations in cases with ARCH (n = 2) suggesting that mutated PRR14L alone may be sufficient to drive clonality. PRR14L has very limited homology to other proteins and its function is unknown. ShRNA knockdown of PRR14L in human CD34+ cells followed by in vitro growth and differentiation assays showed an increase in monocytes and decrease in neutrophils, consistent with a CMML-like phenotype. RNA-Seq and cellular localization studies suggest a role for PRR14L in cell division. PRR14L is thus a novel, biallelically mutated gene and potential founding abnormality in myeloid neoplasms.


[Study on repair of subacute spinal cord injury by transplantation of olfactory ensheathing cells combined with chondroitinase ABC in adult rats].
To investigate the synergetic effect and possibility of repairing spinal cord injury (SCI) by transplantation of olfactory ensheathing cells (OECs) and chondroitinase ABC (ChABC) in adult rats. Three adult male SD rats were used to isolated olfactory bulb and primarily cultured OECs. In the 8th or 9th day, OECs were transplanted, the concentration of cells was modulated to 1 x 10(5)/microL. Fifty-four SD rats were made the models of T8 spinal cord crush injury and divided into 4 groups. In group A (control, n = 36), injured site was not treated; in groups B, C and D (n = 6), OECs, ChABC and OECs+ChABC were injected into injured site, respectively. At 1, 2, 3, 7 and 14 days after injury, the BBB score system was used to evaluate the motion function. At 0, 1, 2, 3, 7, 14 days in group A and at 14 days in groups B, C, D after injury, the maximal transverse diameter and gross area of necrosis were evaluated on HE stained sections. The immunofluorescence double labeling staining for glial-fibrillary acidic protein (GFAP)/CS56, GFAP/growth associated protein 43 (GAP-43) and GFAP/neurofilament 160 (NF160) was carried out to evaluate the regeneration of nerve fiber. At 14 days after injury, there were significant difference in the BBB scores between group A and groups B, C, D (P < 0.05), and between groups B, C and group D (P < 0.05), HE staining showed that the formation of cavity was observed in each group at 14 days after injury. There were significant difference in the maximal transverse diameter and gross area of necrosis between groups B, C, D and group A (P < 0.01), and between groups B, C and group D (P < 0.01). The immunofluorescence staining indicated that expression of GFAP were more intense in group A than in other groups, and the cavity of the lesion site was apparent, but it was moderate in groups B and C. The expression of GAP-43 was more intense in group D than in groups B and C. The expression of NF160 was more intense in group D. Transplantation strategy of OECs combined with ChABC was effective in the repair of SCI in some extent.


CORRECTION OF ANOMALOUS VENOUS RETURN FROM THE RIGHT LUNG TO THE INFERIOR VENA CAVA (SCIMITAR DEFORMITY).
Anomalous pulmonary venous drainage to the inferior vena cava is a rare congenital cardiac defect. Oxygenated blood from the right lung enters the right atrium resulting in a left-to-right shunt. Because the radiographic shadow of the anomalous vein resembles a curved saber, this defect has been called the "scimitar" deformity. From 1958 through June 30, 1975, 11 patients underwent surgical correction of this anomaly at our institution with 10 survivors. Diagnosis was made by routine roentgenography of the chest in all but one patient. Eight patients had total correction which consisted of implanting the anomalous vein into the right atrium, opening the interatrial septum and applying a patch graft as a baffle to direct pulmonary venous blood into the left atrium. Five patients had associated cardiac defects which were also repaired. Three patients underwent pneumonectomy and all survived. The only operative death occurred in a 5-year-old female with an atrial septal defect and endocardial cushion defect. We believe the existence of a large left-to-right shunt justifies surgical intervention. The prognosis appears to depend upon the presence of other cardiac or pulmonary anomalies.


Associations between Staphylococcus aureus Genotype, Infection, and In-Hospital Mortality: A Nested Case-Control Study.
We screened 14,008 adult nonsurgical patients for Staphylococcus aureus nasal carriage at hospital admission and assessed them for invasive S. aureus disease and in-hospital mortality. Multilocus sequence typing was performed on endogenous invasive strains and nasal strains of matched asymptomatic carriers to investigate whether virulent clones could be identified in nasal carriers. Clonal complex (CC) 45 was significantly underrepresented (odds ratio [OR], 0.16 [95% confidence interval {CI}, 0.04-0.59]) and CC30 was overrepresented (not statistically significant) among invasive strains (OR, 1.91 [95% CI, 0.91-4.0]). The distribution of CCs of invasive S. aureus strains in noncarriers did not differ from that in carriers. Those infected with S. aureus strains belonging to a CC had higher mortality than those infected with strains not belonging to a CC (P<.05), which indicates the coevolution of S. aureus virulence and spread in humans.


The Language of End-of-Life Decision Making: A Simulation Study.
Framing is known to influence decision making. The study objective was to describe language used by physicians when discussing treatment options with a critically and terminally ill elder. High-fidelity simulation was used, involving an elder with end-stage cancer and life-threatening hypoxia, followed by a debriefing interview. Subjects were hospitalist, emergency medicine, and critical care physicians from three academic medical centers. Measures were observation of encounters in real time followed by content analysis of simulation and debriefing interview transcripts. During the simulation we identified the first mention ("broaching") of principal treatment options--intubation and mechanical ventilation (life-sustaining treatment [LST]) and palliation in anticipation of death (palliation)--and used constant comparative methods to identify language used. We identified physician opinions about the use of LST in this clinical context during the debriefing interviews, and compared language used with opinions. Among 114 physician subjects, 106 discussed LST, 86 discussed palliation, and 84 discussed both. We identified five frames: will (decided), must (necessary), should (convention), could (option), and ask (elicitation of preferences). Physicians broached LST differently than palliation (p<0.01), most commonly framing LST as necessary (53%), while framing palliation as optional (49%). Among physicians who framed LST as imperative (will or must), 16 (30%) felt intubation would be inappropriate in this clinical situation. In this high-fidelity simulation experiment involving a critically and terminally ill elder, the majority of physicians framed the available options in ways implying LST was the expected or preferred choice. Framing of treatment options could influence ultimate treatment decisions.


Embryonic stem cell-related miRNAs are involved in differentiation of pluripotent cells originating from the germ line.
Cells originating from the germ cell lineage retain the remarkable property under special culture conditions to give rise to cells with embryonic stem cell (ESC) properties, such as the multipotent adult germline stem cells (maGSCs) derived from adult mouse testis. To get an insight into the mechanisms that control pluripotency and differentiation in these cells, we studied how differences observed during in vitro differentiation between ESCs and maGSCs are associated with differences at the level of microRNAs (miRNAs). In this work, we provide for a first time a connection between germ cell origin of maGSCs and their specific miRNA expression profile. We found that maGSCs express higher levels of germ cell markers characteristic for primordial germ cells (PGCs) and spermatogonia compared with ESCs. Retained expression of miR-290 cluster has been previously reported in maGSCs during differentiation and it was associated with higher Oct-4 levels. Here, we show that this property is also shared by another pluripotent cell line originating from the germ line, the embryonic germ cells. In addition, we provide proof that the specific miRNA expression profile of maGSCs has an impact on their differentiation potential. Low levels of miR-302 in maGSCs during the first 10 days of leukaemia inhibitory factor deprivation are shown to be necessary for the maintenance of high levels of early germ cell markers.


Migration patterns and changes in population biology associated with the worldwide spread of the oilseed rape pathogen Leptosphaeria maculans.
Pathogen introductions into novel areas can lead to the emergence of new fungal diseases of plants. Understanding the origin, introduction pathways, possible changes in reproductive system and population size of fungal pathogens is essential in devising an integrated strategy for the control of these diseases. We used minisatellite markers to infer the worldwide invasion history of the fungal plant pathogen Leptosphaeria maculans, which causes stem canker (blackleg) of oilseed and vegetable brassicas. Clustering analyses partitioned genotypes into distinct populations corresponding to major geographic regions, along with two differentiated populations in Western Canada. Comparison of invasion scenarios using Approximate Bayesian Computation suggested an origin of the pathogen in the USA, the region where epidemics were first recorded, and independent introductions from there over the last few decades into Eastern Canada (Ontario), Europe and Australia. The population in Western Canada appeared to be founded from a source in Ontario and the population in Chile resulted from an admixture between multiple sources. A bottleneck was inferred for the introduction into Western Canada but not into Europe, Ontario or Australia. Clonality appeared high in Western Canada, possibly because environmental conditions there were less conducive to sexual reproduction. Leptosphaeria maculans is a model invasive pathogen with contrasting features in different regions: shallow population structure, high genetic variability and regular sexual recombination in some regions, by comparison with reduced genetic variability, high rates of asexual multiplication, strong population structure or admixture in others.


Diabetes in Africa. Challenges to health care for diabetes in Africa.
The aim of this review is to summarize the contextual, clinical and health system challenges to the delivery of health care for diabetes in Africa. Planners need to allocate sufficient resources in a context where resources for health in general are insufficient. Choices need to be made between different options for health care within this context and mechanisms are required to facilitate the implementation of the selected options and ensure that quality of care is maintained.


Approaches to transfusion therapy and iron overload in patients with sickle cell disease: results of an international survey.
To gain an insight into current transfusion and chelation practice in patients with sickle cell disease (SCD), a survey of international experts has been conducted. The findings demonstrate that general utilization of transfusion therapy is low, the primary barrier to treatment being concerns over resultant iron overload and the subsequent need for iron chelation therapy. Where patients were transfused, many physicians indicated that a high proportion of patients had hemosiderosis. As evidence suggests more patients with SCD could benefit from regular transfusion therapy, it is apparent that greater awareness of the need to monitor and treat iron overload in transfused patients is required.