What in the world is consciousness?
The concept of consciousness is multifaceted, and steeped in cultural and intellectual history. This paper explores its complexities by way of a series of contrasts: (i) states of consciousness, such as wakefulness and sleep, are contrasted with awareness, a term that picks out the contents of consciousness, which range across all our psychological capacities; (ii) consciousness is contrasted to self-consciousness, which is itself a complex term embracing self-detection, self-monitoring, self-recognition theory of mind and self-knowledge; (iii) "narrow" and "broad" senses of consciousness are contrasted, the former requiring mature human awareness capable of guiding action and self-report, the latter involving the much broader capacity to acquire and exploit knowledge; (iv) an "inner" conception of consciousness, by which awareness is essentially private and beyond the reach of scientific scrutiny, is contrasted with an "outer" conception which allows that consciousness is intrinsically linked with capacities for intelligent behavior; and finally (v) "easy" and "hard" questions of consciousness are distinguished, the former involving the underlying neurobiology of wakefulness and awareness, and the latter the allegedly more mysterious process by which biological processes generate experience - the question of whether this final distinction is valid is a focus of current debate. Varied interests converge on the study of consciousness, from the sciences and the humanities, creating scope for interdisciplinary misunderstandings, but also for a fruitful dialog.


Effects of sensation seeking, instruction set, and alcohol/placebo administration on aggressive behavior.
Sixty-three male college students were assessed on the number of aversive sound blasts they administered in response to their fictitious task partner's blasts in a variation of the Taylor aggression paradigm. Subjects were randomly assigned to one of three alcohol dosing conditions (placebo, placebo/expect alcohol, and alcohol) and one of three instruction conditions (aggression-told the noise blasts were meant to disrupt task performance; altruism-told the noise blasts were meant to improve concentration; ambiguous-either aggression or altruism). A significant three-way interaction of dosing condition by instruction by subjects' sensation seeking was found, such that high sensation seekers in the alcohol condition, compared to low sensation seekers, delivered more noise blasts in the aggression instruction condition, whereas they administered fewer blasts in the altruism condition. High sensation seekers in the placebo condition yielded an opposite pattern of results. The results were interpreted in terms of the effects of "alcohol myopia" on the disinhibition of socially disapproved behaviors and in terms of the moderating effects of personality and situational factors.


A magnetic probe to retrieve broken metallic parts of instruments during laparoscopic procedures.
To facilitate retrieval of metallic fragments out of the abdominal cavity during laparoscopic procedures, a semiflexible magnetic probe was devised. Efficacy and safety was demonstrated in two clinical cases without need for additional trocar placement or conversion to laparotomy.


Correction to: Aortic valve and coronary 18F-sodium fluoride activity: a common cause?
The article "Aortic valve and coronary 18F-sodium fluoride activity: a common cause?", written by Rong Bing and Marc R. Dweck, was originally published electronically on the publisher's internet portal (currently SpringerLink) on 27 September 2019 with open access. With the author(s)' decision to step back from Open Choice, the copyright of the article changed on 18 November 2019 to © American Society of Nuclear Cardiology 2019 and the article is forthwith distributed under the terms of copyright.


New Zealand cricket injury analysis based on 12 years of Accident Compensation Corporation data.
To provide epidemiological data for cricket injuries in New Zealand. A retrospective analytical review using epidemiological cricket data obtained from the national Accident Compensation Corporation (ACC) for 2005-2016. Injury incidence was calculated per 1000 participants. There were 86 562 injuries (77 212 males and 9350 females) during the 12 years with higher injury incidence for males (64.1) than females (36.1). While cricket-related injury claims increased by 42.6%, the injury incidence decreased from 59.0 in 2006 to 42.8 in 2016. The pooled injury rate per 1000 participants was highest for hand/fingers (9.2) and lumbar (8.1) body regions, and for contact (44.7) activities. Players aged 10-20 years were more likely to experience injury. Analysis of 12 years of ACC cricket-related injury claims showed only minimal reductions in injury incidence over the years. Therefore, cricket-related contact injuries to the hand/fingers and head need to be the focus of injury prevention programmes (eg, via promoting use of protective gear and correct technique), particularly in players aged 10-20 years.


A case of frosted branch angiitis with yellowish-white placoid lesions: fluorescein and indocyanine green angiography findings.
Severe, white sheathing of the retinal vessels and yellowish-white placoid lesions, suggesting frosted-branch angiitis, were found in both fundi of a 24-year-old woman. Fluorescein angiography showed hypofluorescence of the placoid lesions in the early phase and hyperfluorescence in the late phase. Indocyanine green angiography showed hypofluorescence during all phases. These findings imply an occlusion of the choriocapillaris. Fluorescein angiography also showed occlusion of the peripheral retinal vessels. With systemic corticosteroids and prostaglandin I2 derivative, the fundi recovered almost completely to normal 3 months later.


Deletion of 11 amino acids in p90(rsk-mo-1) abolishes kinase activity.
p90(rsk) is a distal member of the mitogen-activated protein kinase signaling pathway. It has been cloned from a variety of species including Xenopus laevis, mouse, chicken, rat, and human. The clone p90(rsk-mo-1), isolated by others from a mouse library, contains a unique 33-nucleotide deletion not found in the p90(rsk) clones from any other species that have been examined. When p90(rsk-mo-1) was expressed in Cos-7 cells that were subsequently stimulated with epidermal growth factor, the immunoprecipitated p90(rsk-mo-1) protein showed no measurable kinase activity toward the ribosomal protein S6 peptide. By comparison, expression of rat p90(rsk-1) resulted in significant kinase activity. Deletion of the 33-nucleotide region missing in the p90(rsk-mo-1) clone from the p90(rsk-rat-1) cDNA abolished kinase activity in the resulting protein. When these 33 nucleotides were introduced into the p90(rsk-mo-1) cDNA, the expressed protein showed significant kinase activity. Reverse transcription-PCR and direct sequencing of mRNA isolated from several mouse tissues indicated the presence of the full-length form of p90(rsk-1) in the mouse and showed no conclusive evidence for a deletion-containing form. This study indicates the presence of a full-length p90(rsk-1) mRNA in mouse tissues that is homologous to that identified in other species and suggests that the deletion in p90(rsk-mo-1) may be a cloning artifact. The findings provide additional support for the conclusion that the first catalytic domain of p90(rsk) is responsible for its enzymatic activity toward ribosomal protein S6.


Coastal macrophytes as bioindicators of trace metals in the Asia's largest lagoon ecosystem.
Coastal trace metal contamination is of serious concern and the role of new bioindicator species in monitoring of trace metals is essential. The present study quantified the concentration of trace metals (Co, Cr, Cu, Mn, Ni, Pb and Zn) in the sediment and the macrophytes of Chilika lagoon, India, and investigated the bioindicator potential of the seagrasses, saltmarshes and macroalgae. The Igeo values for sediment indicated significant contamination of Cu and Zn in seagrass, Cu, Ni and Zn in saltmarsh and moderate contamination of Cr, Cu and Pb in macroalgal ecosystems. In general, the Bio-Sediment Accumulation Factor (BSAF) indicated that the macrophytes accumulated higher concentration of Mn and Ni from the sediments. The high concentration of trace metals in the sediment of the three macrophytes ecosystems did not result in higher accumulation of the same metals in the tissues of the respective macrophytes suggesting metal specific and species-specific behaviour.


Microscopic insights on clathrate hydrate growth from non-equilibrium molecular dynamics simulations.
Clathrate hydrates form and grow at interfaces. Understanding the relevant molecular processes is crucial for developing hydrate-based technologies. Many computational studies focus on hydrate growth within the aqueous phase using the 'direct coexistence method', which is limited in its ability to investigate hydrate film growth at hydrocarbon-water interfaces. To overcome this shortcoming, a new simulation setup is presented here, which allows us to study the growth of a methane hydrate nucleus in a system where oil-water, hydrate-water, and hydrate-oil interfaces are all simultaneously present, thereby mimicking experimental setups. Using this setup, hydrate growth is studied here under the influence of two additives, a polyvinylcaprolactam oligomer and sodium dodecyl sulfate, at varying concentrations. Our results confirm that hydrate films grow along the oil-water interface, in general agreement with visual experimental observations; growth, albeit slower, also occurs at the hydrate-water interface, the interface most often interrogated via simulations. The results obtained demonstrate that the additives present within curved interfaces control the solubility of methane in the aqueous phase, which correlates with hydrate growth rate. Building on our simulation insights, we suggest that by combining data for the potential of mean force profile for methane transport across the oil-water interface and for the average free energy required to perturb a flat interface, it is possible to predict the performance of additives used to control hydrate growth. These insights could be helpful to achieve optimal methane storage in hydrates, one of many applications which are attracting significant fundamental and applied interests.


Comparison of the pharmacokinetic profiles of 13 phenolic acids and 6 triterpenes in normal and leukopenia rats after oral administration of Sanguisorba officinalis L. extract by LC-MS/MS.
A selective, accurate, and efficient liquid chromatography-tandem mass spectrometry method was developed for the simultaneous determination of 13 phenolic acids. Additionally, for more comprehensively determining the chemical constituents in Sanguisorba officinalis L. extract, a previously developed method was employed for the simultaneous determination of six triterpenes. Thus, two methods were used to ensure the comprehensiveness and reliability of this study. Based on these methods, the pharmacokinetic profiles of the 13 phenolic acids and 6 triterpenes in normal and leukopenia rats after oral administration of S. officinalis L. extract were compared for the first time in the present study. Quantitative detection of the 13 phenolic acids and 6 triterpenes was performed using the multiple reaction monitoring mode with the electrospray ion source in negative and positive electrospray ionization, respectively. Chromatographic separation was performed on an Agilent Eclipse Plus C18 RRHD column (50 × 2.1 mm, 1.8 µm) using gradient elution with a mobile phase composed of methanol-0.1% aqueous formic acid. The pharmacokinetic results demonstrated that the pharmacokinetic characteristics of the 19 analytes in leukopenia rats differed significantly from those determined in normal rats, which could provide a helpful reference for the clinical application of S. officinalis L. in the prevention and treatment of leucopenia.


Calcium antagonists, a new class of antihypertensive agents.
The mechanism of action of Ca++ antagonists remains debatable. Not all voltage-sensitive calcium channels have the same sensitivity to organic calcium blockers. Those in smooth muscle are clearly more sensitive than those in heart, and at least some of those in brain are not blocked at all. It is possible that in vascular smooth muscle, calcium antagonists act essentially on receptor-operated channels. In any case, calcium antagonists are potent antihypertensive agents, but in clinical practice they have limitations. A second generation of dihydropyridines may provide a higher degree of therapeutic selectivity.


Role of Ca2+ in sorbitol release from rat inner medullary collecting duct (IMCD) cells under hypoosmotic stress.
The role of Ca2+ was studied in the release of the organic osmolyte sorbitol from rat IMCD cells in response to hypoosmotic stress. When cells were exposed to hypoosmotic media, sorbitol release was greatly reduced in Ca-free media which, on readmission of Ca2+, returned to control values. Under isoosmotic conditions, the ionophore A23187 stimulated sorbitol release without any effect on cell volume. Addition of trifluoperazine, a calmodulin inhibitor, but not the protein kinase C inhibitor H-7, inhibited the osmotically-activated sorbitol release. These results suggest that sorbitol release is a calmodulin-dependent event, possibly activated by a rise in intracellular calcium as a result of cell swelling.


Relationships between mandibular cortical indexes, bone mineral density, and osteoporotic fractures in Brazilian men over 60 years old.
The aim of this study was to assess relationships between panoramic indexes, bone mineral density (BMD), and osteoporotic fractures in men >60 years old. Body height and weight, body mass index, lumbar spine and hip BMD, and the presence of osteoporotic fractures were determined in the 127 studied men. Dental panoramic radiographs (DPRs) were used for measuring mandibular cortical indexes. BMDs were lower in patients with thinning and resorption of mandibular cortex. No association was found between mandibular indexes and the presence of osteoporotic fractures. In a forward stepwise logistic regression model, the odds of having a T score ≤-2.5 was increased by 1.97 times for every 1-mm reduction in average mandibular cortical width. DPRs could show pronounced thinning of the inferior mandibular cortices in men >60 years old. However, there was no apparent association between vertebral fragility fractures and the appearance of mandibular cortex in elderly men.


Novel IBA57 mutations in two chinese patients and literature review of multiple mitochondrial dysfunction syndrome.
Multiple mitochondrial dysfunction syndrome (MMDS) refers to a class of mitochondrial diseases caused by nuclear gene mutations, which usually begins in early infancy and is classically characterized by markedly impaired neurological development, generalized muscle weakness, lactic acidosis, and hyperglycinemia, cavitating leukoencephalopathy, respiratory failure, as well as early fatality resulted from dysfunction of energy metabolism in multiple systems. So far, six types of MMDS have been identified based on different genotypes, which are caused by mutations in NFU1, BOLA3, IBA57, ISCA2, ISCA1 and PMPCB, respectively. IBA57 encodes a protein involved in the mitochondrial Fe/S cluster assembly process, which plays a vital role in the activity of multiple mitochondrial enzymes. Herein, detailed clinical investigation of 2 Chinese patients from two unrelated families were described, both of them showed mildly delay in developmental milestone before disease onset, the initial symptoms were all presented with acute motor and mental retrogression, and brain MRI showed diffused leukoencephalopathy with cavities, dysplasia of corpus callosum and cerebral atrophy. Exome sequencing revealed three IBA57 variants, one shared variant (c.286T>C) has been previously reported, the remaining two (c.189delC and c.580 A>G) are novel. To enhance the understanding of this rare disease, we further made a literature review about the current progress in clinical, genetic and treatment of the disorder. Due to the rapid progress of MMDS, early awareness is crucial to prompt and proper administration, as well as genetic counseling.


Pfizer and Palbociclib in China: Analyzing an Oncology Pay-for-Performance Plan.
China is poised to become the world's second-largest oncology drug market. Its ability to continue broadening health coverage is in question. Institutional innovations such as performance-based risk-sharing agreements (PBRSAs) have been developed to promote access to novel therapeutics beyond that provided by public health insurance and central procurement systems. We examine in depth the financial implications of a PBRSA developed in China for the breast cancer drug palbociclib. We generated a 2-state Markov model from PBRSA information made publicly available. Model inputs included breast cancer outcomes data from the published literature. The primary analysis estimates the percentage reduction in overall drug expenditures due to the PBRSA. Sensitivity analyses explored the financial impact of varied computed tomography scan utilization, rebate rate, and rebate duration. Estimated palbociclib expenditures for the PBRSA cohort totaled $36 278 000. Based on the publicly available information for the PBRSA, an effective discount of 1.3% was estimated. The effective discount was insensitive to changes in computed tomography scan utilization. The palbociclib PBRSA likely had negligible impact on patient access to therapy and limited downstream financial impact to patients and payers. The short duration of the rebate window, small rebate, and disease indolence contributed to the low expected rebate percentage.


Synthesis and antimalarial and antitumor effects of 2-amino-4-(hydrazino and hydroxyamino)-6-[(aryl)thio]quinazolines.
A variety of analogues of 2,4-diamino-6-[(aryl)thio]quinazolines with known antimalarial properties were prepared wherein the 4-amino group was replaced by hydrazino and hydroxyamino moieties. Such changes were found to reduce markedly the antimalarial and antitumor properties of this series.


25-Hydroxyvitamin D3 attenuates experimental periodontitis through downregulation of TLR4 and JAK1/STAT3 signaling in diabetic mice.
Vitamin D has been known to be closely associated with diabetes and periodontitis while the underlying mechanism has yet to be clarified. The present study aimed to discover the effect of 25-hydroxyvitamin D3 (25-OHD3) on glycemic control and periodontal health in mice with periodontitis superimposed on experimental diabetes (known as diabetic periodontitis). We showed that 25-OHD3 intraperitoneal injection attenuated diabetic periodontitis by reducing serum fasting blood glucose, glycosylated hemoglobin and TNF-α levels, which led to decreased alveolar bone loss. Immunohistochemical staining and western blot analysis of gingival epithelia revealed that vitamin D receptor (VDR) expression was enhanced upon 25-OHD3 treatment, while toll-like receptor 4 (TLR4) expression was reduced. The expressions of Janus family kinase (JAK) 1 and signal transducer and activator of transcription (STAT) 3 as well as their phosphorylation were inhibited in gingival epithelia of diabetic periodontitis mice, whereas the expression and phosphorylation of STAT1 remained unchanged. These results suggest that 25-OHD3 could improve diabetic periodontitis through downregulation of TLR4 and JAK1/STAT3 signaling in the gingival epithelium. Our study extends the previous findings on the regulation of diabetes with periodontitis, and may also provide a potential therapy for the patients with this disease.


Risk factors and management of primary choledocholithiasis: a systematic review.
Primary choledocholithiasis (PC) is a common disease in biliary surgery. The treatment is always challenging due to its high recurrence. A systemic review is undertaken to determine the risk factors for recurrence and provide with the individualized management strategy. Electronic databases PubMed (Medline), Embase and Cochrane Central Register of Controlled Studies were searched for relevant articles on risk factors for PC recurrence. Its therapeutic intervention was also collected and analysed. A total of 36 articles were eligible for inclusion. The recurrent risk factors include abnormalities of biliary anatomy (peripapillary diverticulum), dynamics (choledochal dilation, sharp angulation and stone number), metabolism (advanced age and hypothyroidism) and bacterial infection (Enterobacter and Helicobacter pylori). These factors eventually induce cholestasis and stone formation. At present, there is no guideline and expertise consensus for PC management. The treatment mainly consists of stone retrieval approaches and internal drainage surgeries. The former are minimally invasive methods: endoscopic sphincterotomy (EST), papillary balloon dilation (EPBD) and laparoscopic common bile duct exploration (LCBDE). The latter include choledochoduodenostomy (CDS) and choledochojejunostomy (CJS) with Roux-en-Y reconstruction. By far, the internal drainage surgeries have significantly lower recurrence than stone retrieval approaches. Abnormal biliary anatomy, dynamics, metabolism and bacterial infection are the risk factors for PC. Both EST/EPBD and LCBDE can be performed as initial treatment. For recurrent PC, CDS is more suitable to the elderly, while Roux-en-Y CJS reserves for young patients or those in good conditions.


Occupational stress in healthcare workers at a university hospital, Jeddah, Saudi Arabia.
Occupational stress can be caused by a heavy workload, insecurity, or poor relationships with coworkers or supervisors. Previous research has showed a significant prevalence of stress in healthcare personnel. This study's aim was to identify health-care professionals at risk of occupational stress and determine the factors that may cause it. A cross-sectional study was conducted among healthcare workers at a university hospital, in Jeddah, Saudi Arabia. A questionnaire solicited information on participants' demographic data including the Workplace Stress Scale, questions on their relationships with colleagues, lack of equipment, job insecurity at the workplace, changing shift patterns, job satisfaction, availability of time to rest and relax, social and family problems, responsibilities, social support, rational/cognitive coping, doctor-patient relationship, and role overload. SPSS was used for data analysis; initial analysis included descriptive statistics, and t-test chi-square test. Multiple linear regression analysis used to identify factors associated with workplace stress. About 78% of the participants were 25-35 years old, 54% were males, and 60% were physicians. Working a shift reduced the job stress index by a statistically significant amount. However, longer working hours, higher education, and having many children contributed to higher job stress; in terms of severity, a good educational level and having many children marginally increased the risk whereas having shifts decreased the job stress. In terms of the absence of organizational support, it was discovered that having many children, a high educational level, and long working hours per day boosted it, although working a shift had a negative correlation. There is a need for continued administrative assistance and appropriate training programs to deal with potentially stressful situations at health facilities.


MRI-based radiomics of rectal cancer: preoperative assessment of the pathological features.
This study aimed to evaluate the significance of MRI-based radiomics model derived from high-resolution T2-weighted images (T2WIs) in predicting tumor pathological features of rectal cancer. A total of 152 patients with rectal cancer who underwent surgery without any neoadjuvant therapy between March 2017 and September 2018 were included retrospectively. The patients were scanned using a 3-T magnetic resonance imaging, and high-resolution T2WIs were obtained. Lesions were delineated, and 1029 radiomics features were extracted. Least absolute shrinkage and selection operator was used to select features, and multilayer perceptron (MLP), logistic regression (LR), support vector machine (SVM), decision tree (DT), random forest (RF), and K-nearest neighbor (KNN) were trained using fivefold cross-validation to build a prediction model. The diagnostic performance of the prediction models was assessed using the receiver operating characteristic curves. A total of 1029 features were extracted, and 15, 11, and 11 features were selected to predict the degree of differentiation, T stage, and N stage, respectively. The best performance of the radiomics model for the degree of differentiation, T stage, and N stage was obtained by SVM [area under the curve (AUC), 0.862; 95% confidence interval (CI), 0.750-0.967; sensitivity, 83.3%; specificity, 85.0%], MLP (AUC, 0.809; 95% CI, 0.690-0.905; sensitivity, 76.2%; specificity, 74.1%), and RF (AUC, 0.746; 95% CI, 0.622-0.872; sensitivity, 79.3%; specificity, 72.2%). This study demonstrated that the high-resolution T2WI-based radiomics model could serve as pretreatment biomarkers in predicting pathological features of rectal cancer.


c-Jun N-terminal kinase activation has a prognostic implication and is negatively associated with FOXO1 activation in gastric cancer.
Since the biological function of c-Jun N-terminal kinase (JNK) in gastric cancer remains unclear, we investigated the clinical significance of JNK activation and its association with FOXO1 activation. Immunohistochemical tissue array analysis of 483 human gastric cancer specimens was performed, and the results of the immunostaining were quantified. The correlation between JNK activation (nuclear staining for pJNK) and clinicopathological features, the proliferation index, prognosis or FOXO1 inactivation (cytoplasmic staining for pFOXO1) was analyzed. The SNU-638 gastric cancer cell line was used for in vitro analysis. Nuclear staining of pJNK was found in 38 % of the gastric carcinomas and was higher in the early stages of pTNM (P < 0.001). pJNK staining negatively correlated with lymphatic invasion (P = 0.034) and positively correlated with intestinal type by Lauren's classification (P = 0.037), Ki-67-labeling index (P < 0.001), cyclin D1 (P = 0.045), cyclin E (P < 0.001) and pFOXO1 (P < 0.001). JNK activation correlated with a longer patients survival (P =0.008) and patients with a JNK-active and FOXO1-inactive tumor had a higher survival rate than the remainder of the population (P = 0.004). In vitro analysis showed that JNK inhibition by SP600125 in SNU-638 cells decreased cyclin D1 protein expression and increased FOXO1 activation. Further, JNK inhibition markedly suppressed colony formation, which was partially restored by FOXO1 shRNA expression. Our results indicate that JNK activation may serve as a valuable prognostic factor in gastric cancer, and that it is implicated in gastric tumorigenesis, at least in part, through FOXO1 inhibition.


Efficient Expression and Processing of Ebola Virus Glycoprotein Induces Morphological Changes in BmN Cells but Cannot Rescue Deficiency of Bombyx Mori Nucleopolyhedrovirus GP64.
Ebola virus (EBOV) disease outbreaks have resulted in many fatalities, yet no licensed vaccines are available to prevent infection. Recombinant glycoprotein (GP) production may contribute to finding a cure for Ebola virus disease, which is the key candidate protein for vaccine preparation. To explore GP1,2 expression in BmN cells, EBOV-GP1,2 with its native signal peptide or the GP64 signal peptide was cloned and transferred into a normal or gp64 null Bombyx mori nucleopolyhedrovirus (BmNPV) bacmid via transposition. The infectivity of the recombinant bacmids was investigated after transfection, expression and localization of EBOV-GP were investigated, and cell morphological changes were analyzed by TEM. The GP64 signal peptide, but not the GP1,2 native signal peptide, caused GP1,2 localization to the cell membrane, and the differentially localized GP1,2 proteins were cleaved into GP1 and GP2 fragments in BmN cells. GP1,2 expression resulted in dramatic morphological changes in BmN cells in the early stage of infection. However, GP1,2 expression did not rescue GP64 deficiency in BmNPV infection. This study provides a better understanding of GP expression and processing in BmN cells, which may lay a foundation for EBOV-GP expression using the BmNPV baculovirus expression system.


The reliability of continuous brain responses during naturalistic listening to music.
Low-level (timbral) and high-level (tonal and rhythmical) musical features during continuous listening to music, studied by functional magnetic resonance imaging (fMRI), have been shown to elicit large-scale responses in cognitive, motor, and limbic brain networks. Using a similar methodological approach and a similar group of participants, we aimed to study the replicability of previous findings. Participants' fMRI responses during continuous listening of a tango Nuevo piece were correlated voxelwise against the time series of a set of perceptually validated musical features computationally extracted from the music. The replicability of previous results and the present study was assessed by two approaches: (a) correlating the respective activation maps, and (b) computing the overlap of active voxels between datasets at variable levels of ranked significance. Activity elicited by timbral features was better replicable than activity elicited by tonal and rhythmical ones. These results indicate more reliable processing mechanisms for low-level musical features as compared to more high-level features. The processing of such high-level features is probably more sensitive to the state and traits of the listeners, as well as of their background in music.


Association Between Timed Up-and-Go Test and Future Changes in the Frailty Status in a Longitudinal Study of Japanese Community-Dwelling Older Adults.
This study aimed to evaluate the relationship between timed up-and-go (TUG) test time and changes in frailty status in a longitudinal cohort study of rural Japanese older adults. This prospective cohort study included 545 community-dwelling older adults. Initial and 2-year follow-up surveys were conducted. We compared the number of the Japanese version of the Cardiovascular Health Study components during the follow-up period and classified the participants into three groups: the favorable change, unchanged as prefrail, and unfavorable change groups. Associations between changes in frailty status and TUG time in the first survey were examined. The predictive ability of the TUG test was determined using the receiver operating characteristic (ROC) curve. The favorable change group comprised 315 individuals (57.8%), the unchanged as prefrail group 105 (19.2%), and the unfavorable change group 125 (22.9%). TUG time was associated with the favorable and unfavorable changes after adjustment for covariates (OR 0.79, 95% CI 0.68-0.92, P=0.001 and OR 1.27, 95% CI 1.09-1.49, P=0.002). The ROC curve of TUG time as a predictor of unfavorable changes showed an area under the curve of 0.59. A cut-off point of TUG was calculated as 6.3 s with 49.6% sensitivity and 66.0% specificity. TUG time in the first survey was significantly associated with changes in frailty status 2 years later. However, its predictive value as a stand-alone test is limited and has the potential to predict future changes in the frailty status in older adults in combination with other tests.


The management and outcome of patients with germ-cell tumours treated in the Edinburgh Cancer Centre between 1988 and 2002.
The aim of this retrospective analysis was to review the outcome of patients with germ-cell tumours treated in the Edinburgh Cancer Centre over the past 15 years, and to see whether there had been any changes over three 5-year cohorts. Patients referred with gonadal and extra-gonadal primary germ-cell tumours, between 1988 and 2002, were identified from the departmental database, and survival by stage and prognostic group was analysed. The proportion of patients with stage I seminoma has significantly increased. The good prognosis of patients with early stage disease is confirmed, with the outcome for some groups of patients being better than expected. There is a non-significant trend to improved results over the three 5-year cohorts. The outcome for patients with stage IV seminoma is worse than would be expected, but numbers are small. The poor prognosis of patients with non-seminomatous germ-cell tumours who fall into the International Germ Cell Consensus Classification (IGCCC) poor-prognostic group is confirmed. Failure of patients with metastatic non-seminomatous germ-cell tumours to achieve a complete response to initial therapy is shown to be a poor prognostic indicator.


Indoor radon distribution in Switzerland: lognormality and Extreme Value Theory.
Analysis and modeling of statistical distributions of indoor radon concentration from data valorization to mapping and simulations are critical issues for real decision-making processes. The usual way to model indoor radon concentrations is to assume lognormal distributions of concentrations on a given territory. While these distributions usually model correctly the main body of the data density, they cannot model the extreme values, which are more important for risk assessment. In this paper, global and local indoor radon distributions are modeled using Extreme Value Theory (EVT). Emphasis is put on the tails of the distributions and their deviations from lognormality. The best fits of distributions to real data set density have been computed and goodness of fit with Root Mean Squared Error (RMSE) is evaluated. The results show that EVT performs better than lognormal pdf for real data sets characterized by high indoor radon concentrations.


MHAM-NPI: Predicting ncRNA-protein interactions based on multi-head attention mechanism.
Non-coding RNA (ncRNA) is a functional RNA molecule that plays a key role in various fundamental biological processes, such as gene regulation. Therefore, studying the connection between ncRNA and proteins holds significant importance in exploring the function of ncRNA. Although many efficient and accurate methods have been developed by modern biological scientists, accurate predictions still pose a major challenge for various issues. In our approach, we utilize a multi-head attention mechanism to merge residual connections, allowing for the automatic learning of ncRNA and protein sequence features. Specifically, the proposed method projects node features into multiple spaces based on multi-head attention mechanism, thereby obtaining different feature interaction patterns in these spaces. By stacking interaction layers, higher-order interaction modes can be derived, while still preserving the initial feature information through the residual connection. This strategy effectively leverages the sequence information of ncRNA and protein, enabling the capture of hidden high-order features. The final experimental results demonstrate the effectiveness of our method, with AUC values of 97.4%, 98.5%, and 94.8% achieved on the NPInter v2.0, RPI807, and RPI488 datasets, respectively. These impressive results solidify our method as a powerful tool for exploring the connection between ncRNAs and proteins. We have uploaded the implementation code on GitHub: https://github.com/ZZCrazy00/MHAM-NPI.


Quantification of particle deposition in asymmetrical tracheobronchial model geometry.
The primary objective of this study was to quantify the local inspiratory and expiratory aerosol deposition in a highly asymmetric five-generation tracheobronchial tree. User-enhanced commercial codes and self-developed software was used to compute the air velocity field as well as particle deposition distributions for a large size range of inhalable particles. The numerical model was validated by comparison of our results with experimental flow measurements and particle deposition data available in the open literature. Our simulations show highly localised deposition patterns for all particle sizes, but mainly for the larger particles. As expected, deposition efficiencies and deposition fractions proved to be very sensitive to the particle size. The deposition density in the hot spots can be hundreds and even thousand times higher than the mean deposition density. Present results can be of interest to researchers involved in the assessment of adverse health effects of inhaled aerosols or optimising the drug aerosol delivery into the lung.


Chemical Diversity and α-Glucosidase Inhibitory Activity in Needles Essential Oils of Four Pinus Species from Northwestern Himalaya, India.
This work describes the study of the chemical profiling and α-glucosidase inhibitory activity of essential oils (EOs) from four Pinus species (P. wallichiana, P. patula, P. roxburghii and P. gerardiana). The identification and quantification of EOs metabolites were performed by GC/MS, GC-FID and 13 C-NMR. The needles of P. wallichiana and P. gerardiana presented the highest oil yields (0.35 % and 0.36 %, respectively). Twenty-four constituents were characterized in among samples exhibiting 93.8-97.7 % of the total EOs. The components and yields of the targeted samples were varied according to the species. Major components of the oils were α-pinene (20.5-34.1 %), β-pinene (1.4-53.0 %), δ-3-carene (0.2-47.0 %), limonene (1.7-13.4 %), β-phellandrene (0.2-23.4 %), β-myrcene (1.8-7.2 %) and α-terpinolene (0.6-7.9 %). The extracted EOs showed strong α-glucosidase inhibitory activity, which was close to the positive control, acarbose. This study showed that the EOs of Pinus species may be used as natural antidiabetic.


Predicting vaccination using numerical and affective risk perceptions: the case of A/H1N1 influenza.
During the 2009 A/H1N1 flu pandemic, German health authorities recommended vaccination; however, the efficacy of such programs largely depends on individuals' risk perception. Risk perceptions are commonly determined through numerical-cognitive estimates such as the perceived likelihood and severity of the hazard. Instead, we argue that risk perceptions, which include more affect-related aspects such as worry and threat, are more powerful predictors of protective behaviors. Moreover, vaccines are often perceived as double-edged since they offer protection but also involve adverse side-effects. As such, in the context of the A/H1N1 vaccine uptake, risk perception is not only disease-related (A/H1N1 infection) but also vaccine-related (A/H1N1 vaccine). The present longitudinal study was conducted during the run-up to the German A/H1N1 vaccination campaign and measured cognitive and affective risk perceptions associated with both the A/H1N1 infection and its vaccine (T1, October 2009, N=397) in order to assess their impact on (self-reported) A/H1N1 vaccination eight weeks later (T2, December 2009; N=285). As assumed, greater perceived likelihood and severity of infection were associated with greater affective risk perception at T1. The more threatened and worried people felt, the more they intended to get vaccinated; however, the greater the perceived likelihood and severity of vaccine adverse side-effects, the greater the amount of vaccine related affective risk perception, impeding vaccination intention. Finally, vaccination intention predicted vaccination eight weeks later at T2 (OR=2.2). The results suggest that numerical-cognitive risk perceptions, which are typically the target of public vaccination campaigns, do not impact preventive intention directly; instead, they facilitate affect-related risk perceptions, which motivate protective action.


Measuring visual field progression in the central 10 degrees using additional information from central 24 degrees visual fields and 'lasso regression'.
To measure progression of the visual field (VF) mean deviation (MD) index in longitudinal 10-2 VFs more accurately, by adding information from 24-2 VFs using Lasso regression. A training dataset consisted of 138 eyes from 97 patients with glaucoma or ocular hypertension and a testing dataset consisted of 40 eyes from 34 patients with glaucoma or ocular hypertension. The Lasso method was used to predict total deviation (TD) values in training patients' 10-2 VFs based on information from their 24-2 VFs (52 TD values, foveal sensitivity and mean deviation MD). Then, the MD of each patient's 10-2 VF was estimated as the average of these Lasso-predicted TD values (10-2 VF 'Lasso MD'; LMD). Finally, linear regression was applied to each testing patient's series of longitudinal 10-2 VF MDs with and without additional Lasso-derived LMDs in order to predict future MDs not included in the regression analysis. Absolute prediction errors were compared when only actual 10-2 MDs were regressed against when a combination of actual 10-2 MDs and LMDs were regressed. THE AVERAGE ABSOLUTE PREDICTION ERROR WAS SIGNIFICANTLY SMALLER FOR THE NOVEL METHOD INCORPORATING LMDS (RANGE: 1.6 to 1.8 dB) compared with the standard approach (range: 1.7 to 3.4 dB) (p<0.05, ANOVA test). Deriving 10-2 VF MD values from 24-2 VFs improves the prediction accuracy of progression. This approach will help clinicians to predict patients' visual function in the parafoveal area.


What can the Allium cepa test say about pesticide safety? A review.
The increasing use of pesticides has caused global concerns about the toxic effects and adverse consequences of pesticides on humans and the environment. Among the ways to understand the impact of pesticides, the Allium cepa bioassay stands out. This test is suitable to evaluate different toxic, cytotoxic, genotoxic, and mutagenic outcomes. In this context, the present review aimed to summarize the history of using the A. cepa bioassay to investigate pesticide damages. Data on the experimental conditions were also discussed. The reviewed studies showed the toxicity profile of 113 active ingredients primarily tested in the laboratory, using water for exposure. The most used biomarkers were the mitotic index, chromosomal aberrations, and nuclear abnormalities. All active ingredients caused some toxicity levels in A. cepa, showing the efficiency and sensibility of this bioindicator and the adverse effect of pesticides on humans and the environment. Furthermore, it was evident that pesticides have great potential to damage the mitotic spindle and DNA because almost all active ingredients tested induced chromosomal aberrations and nuclear abnormalities. The current review showed that the A. cepa bioassay is an effective and appropriate model to evaluate pesticide toxicity, and it might indicate research gaps and recommendations for further studies.


Effect of treatment adherence training given to patients with bipolar disorder on treatment adherence, social functioning and quality of life: A pilot study.
and purpose: Treatment non-adherence is quite common among patients with bipolar disorder, negatively affects the social functioning of patients and reduces the quality of life. This pilot study aims to measure the effect of treatment adherence training given to patients with bipolar disorder on treatment adherence, social functioning and quality of life. The pilot study was conducted with 40 bipolar disorder patients, 19 in the intervention group and 21 in the control group, using a quasi-experimental research design. The data were collected using the Participant Information Form, Medication Adherence Rating Scale, Social Functioning Scale and Short Form of the World Health Organization Quality of Life Questionnaire. Treatment adherence training was given once a week individually for a total of five sessions. There was no significant difference between the demographic characteristics and pre-test scale scores of the patients in the intervention and control groups before the treatment adherence training (p > 0.05). The mean treatment adherence, social functioning and quality of life scores of the patients in the intervention group were higher in the post-test and follow-up test compared to the patients in the control group (p < 0.001). The intervention had a positive effect on treatment adherence, social functioning and quality of life of patients. Considering the promising results of this pilot study, treatment adherence training should be studied further in the patients with biplor disorder.


The effects of pentoxifylline on patients with intermittent claudication.
All patients who had intermittent claudication (IC) over an 18-month period were given prescriptions for pentoxifylline (PTFX) 400 mg, three times daily. Patients were required to purchase their medication at a cost of $28 to $35 per month. The drug was administered regardless of the severity of symptoms, and no patient was offered operation without at least a 6-week trial of PTFX. An assessment of the severity of IC was made at the initial visit based on noninvasive data and the impact of the IC on the patient's life-style. One hundred thirty patients were enrolled in the study and were followed for 9 +/- 1 months. Patients were seen every 2 months for treadmill exercise or induced hyperemic testing and interviews until the effects of the medication were determined. The duration of IC before the start of treatment had no effect on the results. IC did not improve in 88 patients (71%) followed for 7.2 +/- 1 month. Thirty-six of these patients stopped the drug themselves because there was no benefit and the expense of PTFX was a hardship. An initial but short-lived improvement in walking was noted in another 13 patients (10%) following 14 +/- 2 months, and the medication was eventually discontinued. Only 23 patients (19%) followed for 11.6 +/- 2 months felt that IC had improved to the point where they did not feel limited in any way. Gastrointestinal symptoms occurred in 13 patients and were severe in eight patients (6%) who stopped taking the medication. The results of PTFX in this group of patients with IC were disappointing at best.(ABSTRACT TRUNCATED AT 250 WORDS)


Benthic ecological status of Algerian harbours.
This work is an overview of all available benthic data collected in the Algerian harbours between 1983 and 2001. So, total of 571 stations were reported in the 10 major Algerian harbours along the Algerian coast (1200km). Two main categories of harbours were distinguished according to their hydrodynamic regime and volume of water exchange between inner harbour basins and the entrance of the harbours. Univariate, multivariate, benthic indices and Biological Traits of Life approaches were applied on stations sampled in the late 1990s and long-term observations in six out of these ten harbours. These approaches assessed the main characteristics and ecological statuses from these south Mediterranean harbours. One of the main characteristics of the Algerian harbours was the very high species diversity (847 species). Although all the fauna was dominated by pollution-tolerant species; some harbours such as Bethioua and Djendjen hosted normal benthic communities as found in the open sea, but also included some pollution indicator species typical of a slight polluted system. On the contrary, the newly constructed port of Skikda showed perturbed benthic communities in relation to hydrocarbon pollution. Biological Traits of Life analysis reinforced the separation of benthic species along a gradient reflecting their sensitivity or tolerance to pollution. This response was related to an increase in organic matter content, probably associated with a general organic and metal contamination, from the entrance of the harbour to the innermost basins in areas with weak circulation, high sedimentation rate and concentrations of pollutants. Except for Oran harbour, where the poor to moderate ecological status remained unchanged with time, the other harbours showed an improvement or a slight degradation. A strategy of long-term monitoring should be promoted, based on a restricted and selected number of stations characteristic of the different basins and water masses occupying the harbours.


Prevalence of transmitted HIV-1 drug resistance among young adults attending HIV counselling and testing clinics in Kigali, Rwanda.
Scaling-up antiretroviral therapy (ART) in resource-limited settings has raised concerns of emerging HIV drug resistance (DR) and its transmission to newly infected individuals. To assess the prevalence of transmitted drug resistance (TDR) in recently HIV-infected individuals, a WHO TDR threshold survey was conducted among young adults in Kigali, Rwanda. Between May and July 2011, HIV subtype and genotyping were performed on dried blood spots (DBS) prepared from blood specimens collected from newly HIV-diagnosed and ART-naive individuals aged 15 to 21 years in eight HIV voluntary counselling and testing (VCT) sites in Kigali. In total, 57 of the 68 DBS collected from eligible participants were successfully amplified. The median age of participants was 20 years and 86% were female. Most participants (96%) were infected with subtype A1 virus. Two participants (4%) had the K103N non-nucleoside reverse transcriptase inhibitor (NNRTI) mutation and one (2%) had the M46L protease inhibitor (PI) mutation. The TDR prevalence was 3.5% (95% CI 0.4, 12.1) for NNRTI and 1.8% (95% CI 0.0, 9.4) for PI. The prevalence of HIV TDR in VCT attendees in Kigali was characterized as low (<5%) for all drug classes according to the WHO HIV DR threshold survey methodology. Despite a decade of widespread ART in Rwanda, TDR prevalence remains low, and so the current first-line ART regimens should continue to be effective. However, as scale-up of ART continues, frequent HIV DR surveillance is needed to monitor the effectiveness of available ART regimens at the population level.


Virtual Interactions and the 2020-2021 Residency Application Cycle in General Surgery: A Look Ahead.
General surgery residency training programs adapted to the COVID-19 pandemic by going online instead of in-person, through virtual interviews, social media engagement, and virtual open houses. The impact of these virtual interactions is unknown. We sought to understand their effectiveness as per residency program directors and assistant program directors. An institutional review board approval was obtained to conduct this anonymous survey. A Qualtrics XM survey containing multiple-choice and short-answer questions was distributed to 590 residency program and assistant program directors through the Association of Program Directors in Surgery (APDS) listserv on July 6, July 13, and July 20. We observed a response rate of approximately 11% across the 590 surgeons contacted. Nearly all (90%) respondents offered virtual preinterview interactions, primarily virtual open houses, virtual facility tours, and virtual question and answer (Q&A) sessions with residents and faculty; 48% of respondents were unsure of the utility of virtual interactions and the majority (54%) felt that virtual interaction limits a program's ability to evaluate applicants. Virtual Q&As were ranked to be the most effective interaction (7.6/10); 80% of respondents felt that visiting rotations were "somewhat important" to "very important," the two highest options available. In addition, 74% felt that applicants missed out on fully experiencing the program by forgoing these rotations. Most respondents (78%) noted that evaluation of applicants' preinterview did not change as a result of virtual interactions. Nearly half (48%) of the respondents offered more interview days due to the virtual format. A fifth (21%) of respondents stated that virtual interactions resulted in a change in the rank position of an applicant. Respondents ranked Twitter and Instagram higher in applicant engagement than Facebook. Factors that impacted interview or rank order list the most were late/absent step two CK scores (33%) and a lack of away rotations (31%), both being limitations largely due to the pandemic. With respect to future application cycles, most (71%) raised concerns regarding disparities between applicants applying in-person and virtually if both or either are offered. Our study suggests that program directors and associate program directors have reservations about the use of virtual interactions with applicants. Interestingly, these data suggest that visiting subinternships are useful for programs in evaluating applicants. This may encourage students to pursue rotations at other institutions at the expense of already-limited resources. It remains unclear whether virtual interactions will be used in the future, but respondents largely agreed that the virtual means of interacting with and disseminating information to the applicants of the 2020-2021 general surgery Match were a success.


Multiple plasma cell granuloma of the central nervous system: a unique case with brain and spinal cord involvement. Case report and review of literature.
Single subject (male, 34 years-of-age) case report. To describe a unique case of plasma cell granuloma (PCG) with simultaneous brain and spinal cord involvement. Private hospital, capital city, Turkey. The patient presented with headache and paraplega. T2 weighted MR images showed multiple hyperintense cerebral, cerebellar, brainstem and spinal cord lesions that enhanced homogeneously with contrast medium. The patient was operated on, and the two intramedullary spinal cord lesions at T11 and T12 were totally excised. After 3 months of an intense physiotherapy programme the patient was able to walk with help. We report for the first time, the occurrence of multiple, simultaneous brain and intramedullary spinal cord plasma cell granulomas.


Comparative evaluation of nine faecal immunochemical tests for the detection of colorectal cancer.
Faecal immunochemical tests (FITs) for haemoglobin are increasingly used for non-invasive screening for colorectal cancer (CRC) but large scale comparative studies of different FITs for detection of CRC, overall and by stage, are sparse. We aimed to determine and compare performance of different FITs for the detection of CRC, and to assess their stage-specific sensitivities. We assessed sensitivity, specificity and their corresponding 95% confidence intervals for six qualitative FITs among 74 CRC cases (59% stage I or II cancers) and 1480 controls free of colorectal neoplasm. Overall and stage-specific receiver operating characteristic curves were derived for three quantitative FITs. The areas under the curves (AUCs) were calculated and compared. Pairs of overall sensitivity and specificity of the qualitative FITs ranged from 66% and 96% to 92% and 62%, respectively. For the three quantitative tests, AUCs ranged from 0.90 to 0.92, with sensitivities ranging from 80% to 87% at cut-offs yielding 90% specificity. AUCs ranged from 0.85 to 0.92, 0.94 to 0.96, and 0.86 to 0.93 for stage I, stage II and advanced stages (stage III and IV) cancers, respectively. At a specificity of 90%, the tests detected 65%-85% of stage I cancers. The diagnostic performance of FITs regarding detection of CRC is promising, even though the pre-defined cut-offs of some of the qualitative FITs need to be adjusted to limit false-positive rates in screening setting. At cut-off levels yielding 90% specificity, the quantitative tests detected the vast majority of CRCs, even at early stages.


Impact of different pacing modes on left ventricular contractility following cardiopulmonary bypass.
Acute left ventricular (LV) dysfunction after cardiopulmonary bypass (CBP) is a serious complication in cardiac surgery. The aim of this study was to investigate the effect of different epicardial pacing modes on LV contractility and changes of myocardial oxygen extraction (MVO(2)) following CPB in an animal model. The utility of conductance catheter measurement versus left ventricular outflow tract mean systolic acceleration (LVOT(Acc)) for quantification of LV function was evaluated. Fourteen piglets underwent median sternotomy and CPB for 90 minutes, myocardial ischemia for 60 minutes, and reperfusion for 30 minutes. Different pacing modes were obtained before and after CPB to investigate changes in LV function. LV Function was quantified by end-systolic-pressure-volume relationships (ESPVR) as measured by the conductance catheter method and by LVOT(Acc) obtained from transepicardial echocardiographic studies. LV contractility improved significantly by biventricular and atrial pacing compared with natural sinus rhythm (SR). MVO(2) remained stable or even decreased with biventricular pacing after surgery compared with SR. Right ventricular pacing resulted in poor LV-function with a rise of MVO(2). LVOT(Acc) showed a strong correlation to invasively measured ESPVR. Postoperative biventricular pacing was associated with an improved LV contractility without rise of MVO(2) compared with SR and atrial pacing. At termination of CPB, this appears to facilitate the management of LV failure and potentially may reduce the need for inotropic support, additionally protecting myocardial metabolism. The echocardiographic assessment of LVOT(Acc) was a simple and reliable as well as effective method to quantify LV contractility and showed a good correlation with the more invasive conductance catheter.


Epidermoid tumors. Review of the literature.
Reports of epidermoid tumors from 1965 through 1986 were reviewed with emphasis on new and unusual findings. Clinical data considered were rapid onset, rare symptoms, size and rate of growth, and complications. Uncommon locations included multiple sites in one patient and the anterior fontanelle. The radiologic data from computed tomography were the main contributors to diagnosis. An immunohistochemical test disclosed that cells of craniopharyngiomas are keratin-positive. Histologically benign epidermoids can behave as highly malignant tumors, and can become carcinomatous. Postoperative results for benign tumors were often excellent. Evidence was presented of the close relation among epidermoid and dermoid tumor, craniopharyngioma, ameloblastoma (adamantinoma), Rathke's cleft cyst, and aural cholesteatoma.


Potential of enzymatic process as an innovative technology to remove anticancer drugs in wastewater.
Anticancer drugs are a class of pharmaceutical compounds that have been found in hospital, domestic, and industrial wastewaters and also in surface waters. They have been showing recalcitrance to conventional wastewater treatment technologies and present a potential risk to environment and human health, since they exhibit cytotoxic, teratogenic, and carcinogenic among other effects in higher organisms, even at low concentrations. The presence of these compounds in the environment is a recent challenge for wastewater treatment and some alternative strategies to remove them were already studied, such as white-rot fungi (WRF) technologies. Despite promising results, processes involving fungi are complex, have high reaction times, and require nutrient addition for fungus growth and maintenance. Due to this potential, strategies to make the technology feasible were studied, such as the possibility for direct application of enzymes secreted by WRF. Enzymatic processes were studied in the removal of other pharmaceuticals such as antibiotics, anti-inflammatory, and steroid hormones; however, to the best of our knowledge, there is a gap on literature about their direct action on anticancer drugs.


Visualization of release factor 3 on the ribosome during termination of protein synthesis.
Termination of protein synthesis by the ribosome requires two release factor (RF) classes. The class II RF3 is a GTPase that removes class I RFs (RF1 or RF2) from the ribosome after release of the nascent polypeptide. RF3 in the GDP state binds to the ribosomal class I RF complex, followed by an exchange of GDP for GTP and release of the class I RF. As GTP hydrolysis triggers release of RF3 (ref. 4), we trapped RF3 on Escherichia coli ribosomes using a nonhydrolysable GTP analogue. Here we show by cryo-electron microscopy that the complex can adopt two different conformational states. In 'state 1', RF3 is pre-bound to the ribosome, whereas in 'state 2' RF3 contacts the ribosome GTPase centre. The transfer RNA molecule translocates from the peptidyl site in state 1 to the exit site in state 2. This translocation is associated with a large conformational rearrangement of the ribosome. Because state 1 seems able to accommodate simultaneously both RF3 and RF2, whose position is known from previous studies, we can infer the release mechanism of class I RFs.


Circadian rhythm of water balance and aldosterone excretion in the whitebellied sunbird Nectarinia talatala.
Nectarivorous whitebellied sunbirds, Nectarinia talatala, demonstrate distinct circadian patterns in osmoregulatory parameters. We recorded intake of a 1 mol/l sucrose solution which enabled calculation of total water gain, and collected cloacal fluid for measurements of volume, osmolality and aldosterone concentration. These variables were assessed hourly over 12 h of photophase, and averaged over the 12-h scotophase period. Overnight, when sunbirds were in negative water balance, aldosterone concentrations and outputs were significantly higher than diurnal levels, reflecting a shut-down of cloacal fluid production. Early morning was marked by a high rate of osmotic excretion, disproportionate to water gain or cloacal fluid output, followed by steady intake and cloacal fluid output during the morning and early afternoon. Reduced water flux (decreased feeding and cloacal fluid output) during mid-afternoon was accompanied by a paradoxical decline in osmotic excretion, whilst a significant increase in the discrepancy between water intake and output was recorded as the birds effectively stored water before the scotophase. These patterns of intake and excretion may be informative in explaining drinking and foraging behaviour in the field.


Factors controlling postfire seedling establishment in southern California chaparral.
This paper discusses the interactions among prefire shrub abundance, soil moisture, and plant and animal species on postfire seedling establishment in mixed chparral in southern California. Postfire germination and survival of seedlings in a stand dominated by a facultative seeder (Adenostoma fasciculatum) and by an obligate seeder (Ceanothus greggii) were monitored for 2 years. Relative to prefire abundance, germination of C. greggii was higher than that of A. fasciculatum. Survival during the first year was also higher in C. greggii than in A. fasciculatum. During the second year, however, mortality of C. greggii was greater than that of A. fasciculatum, mostly due to a psyllid infection. Germination of A. fasciculatum was negatively related to prefire shrub abundance. C. greggii germination was not associated with prefire shrub abundance. Seedling mortality of both species was very strongly related to the depletion of soil moisture the first few months after germination. A. fasciculatum was more sensitive than C. greggii to the drying of the soil, especially in the upper levels. C. greggii seedlings had longer roots, greater root/shoot biomass ratios, higher water potentials, and a later peak in seasonal growth activity compared to A. fasciculatum. Herbs promoted greater survival of A. fasciculatum. Our results indicate that the obligate seeder species, C. greggii, is better adapted to establish seedling in chaparral by producing greater relative germination and greater seedling survival than the facultative seeder species A. fasciculatum. The greater adaptability of C. greggii to the physical environment is counteracted by interspecific interference by plant and animal interactions which tend to favor A. fasciculatum over C. greggii.


Pilot trial of "Epi-school" group psychosocial education program for patients with epilepsy and their relatives in Japan.
In epilepsy treatment, it is important for patients with epilepsy (PWE) to have accurate knowledge of epilepsy and to actively engage in treatment. In Japan, there are a few facilities for implementing learning programs for PWE, and their long-term usefulness has not been established. We conducted a pilot group psychosocial education program for PWE and their relatives in Japan. Participants were PWE and their relatives who were 18 years old or older, were able to consent to participate in the study, and who were visiting the outpatient clinic of Saitama Medical Center from September 2019 to March 2020. As an intervention, we created a psychosocial educational program called "Epi-school" for PWE and their relatives, consisting of three sessions. Outcomes included patients' quality of life (QOL) measured with the epilepsy-31-P (QOLIE-31P), Rosenberg self-esteem scale (RSES), Stigma scale for chronic neurological disease (SSCI-8), and Epilepsy knowledge scale, before and after Epi-school. In addition, in a free-form questionnaire, we collected the impressions of patients and their relatives regarding the experience of participating in a group psychosocial education program. We examined 11 patients (two males, nine females) and 12 relatives (four males, eight females) who participated in Epi-school during the target period. The analyses revealed that only the scales measuring knowledge about epilepsy in the effect index showed significant increases in both patients and relatives after the program compared with before the program (patients: F [1,5.30] = 13.65, P < .05; relatives: F [1,4] = 17.50, P < .05). Moreover, a large effect size (d = 0.85) was obtained in patients, and a large effect size (d = 1.03) was obtained in relatives. In the open-ended questionnaire after participating in Epi-school, respondents reported changes in the psychological state of patients in the "learning epilepsy knowledge and coping methods", including changes in "acquired knowledge of illness" and "acquisition of coping with psychological aspects". Furthermore, it reports of "discovery/surprise", "thanks to medical staff", "interaction with other patients/relatives", and "new anxiety". In addition, "positive thoughts on treatment", "hopes for the future", "expectations for interaction with medical staff", "expectations for interaction with colleagues with the same disease", and "coming out of epilepsy" were reported. Regarding the psychological state of relatives after participating in Epi-school, it revealed "thanks to medical staff", "interactions with other patients/relatives", and "awareness of and remarks about other patients' statements". The results also revealed responses including "positive thoughts about treatment", "expectations of medical care", and "expectations of the community". The results confirmed that Epi-school led to improved knowledge, and psychological changes, including improved QOL and positive acceptance of epilepsy. Participants' awareness about epilepsy appeared to improve through encounters with other participants' attitudes toward epilepsy, possibly changing via the ways participants interacted. It is important to promote understanding of epilepsy, enhance the effects of treatment, and reduce psychosocial restrictions. Epi-school may be useful as part of epilepsy treatment to improve the QOL of PWE by making it easier for patients and their relatives to develop acceptance of living with epilepsy. The main limitation in the current study was the small sample size and the lack of a control group. In future studies, we plan to further investigate the usefulness of psychosocial education programs in Japan, including Epi-school, by increasing the sample size, including a control comparison, and collecting more comprehensive data. We hope that the current findings will encourage the provision of appropriate medical insurance funding for patient learning programs in Japan.


Potential adverse outcome pathways with hazard identification of organophosphate esters.
Data-driven analysis and pathway-based approaches contribute to reasonable arrangements of limited resources and laboratory tests for continuously emerging commercial chemicals, which provides opportunities to save time and effort for toxicity research. With the widespread usage of organophosphate esters (OPEs) on a global scale, the concentrations generally reached up to micromolar range in environmental media and even in organisms. However, potential adverse effects and toxicity pathways of OPEs have not been systematically assessed. Therefore, it is necessary to review the current situation, formulate the future research priorities, and characterize toxicity mechanisms via data-driven analysis. Results showed that the early toxicity studies focused on neurotoxicity, cytotoxicity, and metabolic disorders. Then the main focus shifted to the mechanisms of cardiotoxicity, endocrine disruption, hepatocytes, reproductive and developmental toxicity to vulnerable sub-populations, such as infants and embryos, affected by OPEs. In addition, several novel OPEs have been emerging, such as bis(2-ethylhexyl)-phenyl phosphate (HDEHP) and oxidation derivatives (OPAsO) generated from organophosphite antioxidants (OPAs), leading to multiple potential ecological and human health risks (neurotoxicity, hepatotoxicity, developmental toxicity, etc.). Notably, in-depth statistical analysis was promising in encapsulating toxicological information to develop adverse outcome pathways (AOPs) frameworks. Subsequently, network-centric analysis and quantitative weight-of-evidence (QWOE) approaches were utilized to construct and evaluate the putative AOPs frameworks of OPEs, showing the moderate confidences of the developed AOPs. In addition, frameworks demonstrated that several events, such as nuclear receptor activation, reactive oxygen species (ROS) production, oxidative stress, and DNA damage, were involved in multiple different adverse outcome (AO), and these AOs had certain degree of connectivity. This study brought new insights into facilitating the complement of AOP efficiently, as well as establishing toxicity pathways framework to inform risk assessment of emerging OPEs.


A population-based study of drug resistance and transmission of tuberculosis in an urban community.
A low-income neighborhood of Sao Paulo, Brazil. To determine the incidence, risk factors and transmission patterns of multidrug-resistant tuberculosis (MDR-TB). Prospective longitudinal study of patients with pulmonary TB (PTB). Sputum culture-confirmed patients with PTB were recruited between March 2000 and May 2002. Bivariate and multivariate logistic regression analyses were performed to identify factors associated with MDR-TB. Mycobacterium tuberculosis isolates were tested for drug susceptibility and typed by IS6110-RFLP analysis. Of 420 patients, respectively 71% and 27% were new and previously treated; 15.5% of the patients' M. tuberculosis isolates were resistant to at least one drug; of these, 11% and 27% were found among new and previously treated cases, respectively. Respectively 1% and 16.7% of the new and previously treated cases were MDR-TB. RFLP analysis showed that new transmission of MDR strains was uncommon. By multivariate logistic regression analysis, previous TB and hospitalization in the 24 months before TB diagnosis were identified as independent predictors of MDR-TB. The results showed an intermediate level of MDR-TB incidence in a neighborhood of Sao Paulo and identified predictors that can be targeted for intervention by national and local TB control programs.


Distal radial artery (snuffbox) access for carotid artery stenting - Technical pearls and procedural set-up.
To report use of distal radial artery (dRA) access for carotid artery stenting (CAS) and to discuss procedural setup and technical considerations for a successful intervention. A retrospective review of our prospective neurointerventional database of CAS was conducted between May 2019 and March 2020. All CAS cases via dRA in the anatomical snuffbox were identified. Patient demographics, clinical information, procedural and radiographic data was collected. 22 CAS procedures in 20 patients via dRA were identified. Patients' mean age was 69.4 years (range 53-87 years). 3 patients were female. Mean radial artery diameter was 2.1 mm (range 1.6-2.8 mm). dRA access was achieved in all cases. Conversion to femoral access was required in 2 cases (9.1%) due to persistent radial artery vasospasm resulting in patient discomfort despite multiple additional doses of intraarterial vasodilators and added intravenous sedation as well as tortuous vessel anatomy and limited support of the catheters in a type 3 aortic arch for left CAS. Our preliminary experience with dRA access for CAS suggests this approach to be feasible and safe for patients. Technical considerations are important and preprocedural planning is necessary for a successful intervention. Catheter systems and devices specifically designed for radial access are needed to enable more interventionalists to safely perform neurointerventional procedures via wrist access.


Diagnosis of symptomatic alkaline reflux gastritis and prediction of response to bile diversion operation by intragastric alkali provocation.
Because accurate diagnosis of the alkaline reflux gastritis syndrome has been elusive, surgical treatment has had a high failure rate, particularly with respect to relief of pain. We have used intragastric infusion of alkali as a provocative test in 147 patients with symptoms and endoscopic findings suggestive of bile gastritis and in 19 asymptomatic control subjects. Subjects received saline solution, 0.1 normal hydrochloric acid, and 0.1 normal sodium hydroxide solutions, as well as their own gastric aspirates in random blinded fashion by a nasogastric tube. There were no complications. A positive test result was defined as pain with sodium hydroxide but not with saline solution or hydrochloric acid infusion. All of the control subjects had negative test results. A total of 87 percent of the symptomatic patients have been followed (mean 4.3 years, minimum 1 year); 47 of those 128 had a Roux-Y gastrojejunal reconstruction to divert duodenal contents from the stomach. Correlation of the test results and the subsequent clinical status showed 87 percent of those with negative test results improved spontaneously or with other treatment versus 15 percent if the test results were positive (p less than 0.001), and 78 percent of those with positive test results had lasting relief of pain after surgical diversion versus a 30 percent success rate if the test results were negative (p less than 0.01). We conclude that positive alkali infusion test results predict that symptoms will likely respond best to surgical diversion of duodenal contents, and that negative test results should be a strong deterrent to surgical diversion. The test is safe, simple, and deserves further trial.


Factors affecting independence in eating among elderly with Alzheimer's disease.
In elderly patients with dementia, disturbed eating behavior is understood to be a core symptom or a behavioral and psychological symptom of dementia (BPSD). The purpose of the present study was to investigate the factors affecting self-feeding in elderly patients with Alzheimer's disease (AD). A total of 150 AD patients who were hospitalized in dementia wards, or were residents of institutions or group homes were enrolled. The patients underwent an eating behavior examination, cognitive assessment, neurological examination and vital function tests. The eating behavior examination consisted of observation of the patients at mealtime. Items assessing eating behavior included the number of feeding cycles, stopping of eating or agitation and dysfunction. Logistic regression analysis carried out to identify factors with a significant effect on decreased independence in eating were difficulty in beginning a meal (OR = 14.498, CI = 2.067-101.690), presence of dysphagia signs (OR = 5.214, CI = 1.031-26.377) and the severity of dementia (OR = 4.538, CI = 1.154-17.843). The present study is the first to generate objective data showing that difficulty in beginning a meal is a factor that hinders independence in eating in AD, in addition to the presence of dysphagia signs and the severity of dementia. Assisting AD patients in maintaining eating independence might be effectively achieved by eliminating environmental factors that interfere with beginning a meal, and by providing assistance that will promote beginning a meal. The present results show the necessity of developing effective methods for assisting elderly patients with AD.


A sublethal dose of TNFalpha potentiates kainate-induced excitotoxicity in optic nerve oligodendrocytes.
Glutamate receptor-induced cell death, known as excitotoxicity in both neurons and oligodendrocytes, has been implicated as a common pathway of cell death in numerous central nervous system (CNS) diseases and trauma. Research in both neuronal and oligodendrocyte excitotoxicity has examined glutamate's receptor-mediated effects on CNS cells, and explored strategies to protect cells exposed to the elevated glutamate levels that occur in CNS trauma and disease. Proinflammatory cytokines are also elevated in the injured CNS, and have also been implicated in CNS cell death. Recently, several laboratories have examined cytokines' effects on neuronal and glial excitotoxicity. Here, we review literature concerning the dynamic susceptibility of both neurons and oligodendrocytes to excitotoxicity, and present new data from our laboratory showing that the susceptibility of oligodendrocytes to excitotoxicity is acutely potentiated by the proinflammatory cytokine TNFalpha.


Zirconia-Platinum Nanohybrids for Ultrasound-Activated Sonodynamic-Thermodynamic Bimodal Therapy by Inducing Intense Intracellular Oxidative Stress.
The therapeutic exploration of nano-zirconia semiconductor largely remains untouched in the field of fundamental science to date. Here, a robust nano-sonosensitizer of ZrO2- x @Pt is strategically formulated by in situ growth of Pt nanocrystal onto the surface of oxygen-deficient ZrO2- x . Compared to 3.09 eV of nano-ZrO2- x , the bandgap of ZrO2- x @Pt Schottky junction is narrowed down to 2.74 eV. The band bending and bandgap narrowing enables an enhanced e- /h+ separation in the presence of aPt electron sink, which facilitates a high yield of singlet oxygen (1 O2 ) and hydroxyl radicals (·OH) under ultrasound (US) irradiation. Moreover, nanozyme Pt with catalase-mimic activity can promote 1 O2 generation by relieving the hypoxic tumor microenvironment. Upon further modification of 2,2'-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride (AIPH), US-stimulated local thermal shock can disintegrate AIPH to create cytotoxic alkyl radicals (• R). US-triggered reactive oxygen species generation and hyperthermia-induced alkyl radical production lead to severe and irreversible tumor cell death. Such combinatorial sonodynamic-thermodynamic therapy benefits the tumor eradication and metastasis inhibition at the animal level, with the aid of immunogenetic cell death and immune checkpoint blockade. Taken together, this proof-of-concept paradigm expands the medical use of nano-zirconia and provides useful insights for its therapeutic perspectives.


A Pretreatment Method for Analysing Albendazole by HPLC in Plant Material.
Albendazole (ALB) belongs to a group of benzimidazoles-classified as antiparasitic pharmaceuticals. Its widespread application results in the presence of this pharmaceutical in natural environment (water and soil). In this paper a suitable pretreatment method was established including sampling, freeze-drying and extraction. Vicia faba was used as model organism. ALB accumulation by plant tissues was observed in hydroponic culture as well as in soil. The range of pharmaceutical concentrations was 1.7 × 10-5 mol/L (in hydroponic culture) and 1.7 × 10-5 to 1.7 × 10-4 mol/kg air dry soil (in soil). Observations were conducted for 14 days. After this time biological material was freeze-dried and after homogenization, dimethyl sulfoxide (DMSO) extraction was performed. The recovery of ALB for the roots was 93 % while for the shoots 86 %. After cleaning, the samples were subjected to further analysis by HPLC system. Phosphate buffer and acetonitrile (50:50) were used as a mobile phase. Drug retention time was 6.3 min. Results obtained in this experiment indicate higher drug accumulation in roots rather than in the hypocotyl part of the plant, cultivated both in soil and in hydroponic culture.


Exploring the Ancestral Mechanisms of Regulation of Horizontally Acquired Nitrogenases.
The vast majority of Pseudomonas species are unable to fix atmospheric nitrogen. Although several studies have demonstrated that some strains belonging to the genus Pseudomonas sensu stricto do have the ability to fix nitrogen by the expression of horizontally acquired nitrogenase, little is known about the mechanisms of nitrogenase adaptation to the new bacterial host. Recently, we transferred the nitrogen fixation island from Pseudomonas stutzeri A1501 to the non-nitrogen-fixing bacterium Pseudomonas protegens Pf-5, and interestingly, the resulting recombinant strain Pf-5 X940 showed an uncommon phenotype of constitutive nitrogenase activity. Here, we integrated evolutionary and functional approaches to elucidate this unusual phenotype. Phylogenetic analysis showed that polyhydroxybutyrate (PHB) biosynthesis genes from natural nitrogen-fixing Pseudomonas strains have been acquired by horizontal transfer. Contrary to Pf-5 X940, its derived PHB-producing strain Pf-5 X940-PHB exhibited the inhibition of nitrogenase activity under nitrogen-excess conditions, and displayed the typical switch-on phenotype observed in natural nitrogen-fixing strains after nitrogen deficiency. This indicates a competition between PHB production and nitrogen fixation. Therefore, we propose that horizontal transfer of PHB biosynthesis genes could be an ancestral mechanism of regulation of horizontally acquired nitrogenases in the genus Pseudomonas.


Gene × environment interaction models in psychiatric genetics.
Gene-environment (G × E) interaction research is an emerging area in psychiatry, with the number of G × E studies growing rapidly in the past two decades. This article aims to give a comprehensive introduction to the field, with an emphasis on central theoretical and practical problems that are worth considering before conducting a G × E interaction study. On the theoretical side, we discuss two fundamental, but controversial questions about (1) the validity of statistical models for biological interaction and (2) the utility of G × E research for psychiatric genetics. On the practical side, we focus on study characteristics that potentially influence the outcome of G × E interaction studies and discuss strengths and pitfalls of different study designs, including recent approaches like Genome-Environment Wide Interaction Studies (GEWIS). Finally, we discuss recent developments in G × E interaction research on the most heavily investigated example in psychiatric genetics, the interaction between a serotonin transporter gene promoter variant (5-HTTLPR) and stress on depression.


Congenital pulmonary atresia with tricuspid insufficiency: morphologic study.
In an anatomic study of 21 cases of pulmonary atresia with tricuspid insufficiency (pulmonary atresia with intact ventricular septum, type II), the morphologic features of the tricuspid valve and the right ventricle were found to differ greatly from those seen in pulmonary atresia with tricuspid stenosis (pulmonary atresia with intact ventricular septum, type I). Morphologically, pulmonary atresia with tricuspid insufficiency (type II) has a greater resemblance to Ebstein's disease with pulmonary atresia than to type I pulmonary atresia. The anomaly may be more amenable to surgery than pulmonary atresia with tricuspid stenosis because the right ventricle in the former may be converted into a functional chamber by a valvotomy combined with a shunting procedure and atrial septostomy.


Effect of nuclear actin on endothelial nitric oxide synthase expression.
Previously, we showed that the 27nt repeat polymorphism in endothelial nitric oxide synthase (eNOS) intron 4 was associated with altered eNOS mRNA and protein levels, nitric oxide (NO) production and vascular disease risk; the 27-nt repeats had a cis-acting role in eNOS promoter function. In the present study, we investigated nuclear protein that binds the 27nt repeat and mediates eNOS expression. Using 5'-biotin-labeled 27nt DNA duplex and streptavidin-agarose beads pull-down assay and mass spectrometry, we identified that nuclear beta-actin was one of the major 27nt binding proteins. Using the pGL3 reporter vectors containing the 5x27nt repeats as an enhancer in an in vitro transcription assay, we found that exogenous beta-actin significantly increased reporter gene transcription efficiency. The beta-actin's upregulating effect was compromised when exogenous 27nt RNA duplex was added. Furthermore, the eNOS expression was reduced when beta-actin gene was silenced by specific siRNA, and actin overexpression upregulated eNOS expression >3-fold. Our data demonstrate that beta-actin as a transcription factor stimulates eNOS expression; and the transcriptional effect appears to be 27nt-dependent. Our findings represent a novel molecular mechanism regulating eNOS expression, which could potentially lead to discoveries of eNOS specific pharmaceutical agents, eg, active peptides, with clinical applications.


In vitro-in vivo relationship for amorphous solid dispersions using a double membrane dissolution-permeation setup.
The use of amorphous solid dispersions (ASDs) is one commonly applied formulation strategy to improve the oral bioavailability of poorly water-soluble drugs by overcoming dissolution rate and/or solubility limitations. While bioavailability enhancement of ASDs is well documented, it has often been a challenge to establish a predictive model describing in vitro-in vivo relationship (IVIVR). In this study, it is hypothesized that drug absorption might be overestimated by in vitro dissolution-permeation (D/P)-setups, when drug in suspension has the possibility of directly interacting with the permeation barrier. This is supported by the overprediction of drug absorption from neat crystalline efavirenz compared to four ASDs in a D/P-setup based on the parallel artificial membrane permeability assay (PAMPA). However, linear IVIVR (R2 = 0.97) is established in a modified D/P-setup in which the addition of a hydrophilic PVDF-filter acts as a physical boundary between the donor compartment and the PAMPA-membrane. Based on microscopic visualization, the improved predictability of the modified D/P-setup is due to the avoidance of direct dissolution of drug particles in the lipid components of the PAMPA-membrane. In general, this principle might aid in providing a more reliable evaluation of formulations of poorly water-soluble drugs before initiating animal models.


Plasma content of extracellular nucleic acids in donors and patients with mammary tumors.
The concentrations of extracellular DNA and RNA were measured in the plasma of donors and patients with fibroadenoma and breast cancer. The content of extracellular DNA surpassed the normal in 80% plasma samples from patients with mammary tumors. Extracellular RNA was detected in 30% plasma samples from donors and patients with breast tumors. No correlations were found between plasma concentration of extracellular DNA and size and stage of tumor growth. Hence, measurement of extracellular DNA in the plasma of patients can be used only as an accessory test for tumor diagnosis.


Knowledge and beliefs about dementia among the general public: A preliminary report on the Cuban population.
The number of people diagnosed with dementia globally has dramatically increased in recent years. The objective of this study was to explore beliefs and knowledge among the Cuban population with regard to the risk factors that may lead to dementia and the actions that may be taken to prevent it. In an exploratory cross-sectional study, we surveyed a total of 391 people aged between 18 and 96 years. The results were stratified by sex, age range, level of education, and contact with dementia. Dementia was the fourth most worrying disease. A total of 64.5% of participants believed that the risk of dementia could be reduced, and 60% that the appropriate time to begin prevention measures is after the age of 40. Cognitive stimulation and healthy diet were more frequently cited as useful activities to reduce risk. Survey respondents reported little presence in their lifestyle of behaviours that are beneficial for reducing the risk of dementia. Although dementia is an important health issue for respondents, their knowledge about disease prevention is still insufficient. The results obtained constitute a starting point for the design of policies aimed at increasing knowledge about the disease and improving prevention.


A high percentage of hospital-acquired neonatal bacteraemia but rare resistance to standard antibiotic regimens.
We examined community and hospital-acquired bacteraemia, namely bloodstream infections or meningitis, and looked at the clinical features and outcomes of cases. The study comprised infants under 3 months of age, who were admitted to a tertiary referral centre in northern Israel with bacteraemia from 2010-2019. Causative pathogens, antibiotic susceptibility and mortality were retrospectively recorded. We identified 314 infants, 325 episodes of bacteraemia and 344 pathogens. Meningitis was identified in 22 (7.0%) infants. Hospital-acquired bacteraemia accounted for 84.8% of the 325 episodes. Coagulase-negative staphylococci (33.9%) was the most prevalent pathogen in the hospital-acquired cases, while Escherichia coli (37.2%) dominated the community-acquired cases. The susceptibility of Gram-negative early-onset sepsis cases to ampicillin-gentamicin or ampicillin-cefotaxime was 96% and 94.7% for hospital-acquired cases and 91.7% and 88% for community-acquired cases, respectively. Susceptibility to piperacillin-tazobactam or amikacin in late-onset sepsis were 92.8% and 98%, respectively, in hospital-acquired cases. The 30-day mortality was 5.7% in infants with hospital-acquired cases. Risk factors were Arab ethnicity (p < 0.028), haemodynamic instability (<0.001) and Gram-negative sepsis (0.043). Most cases of bacteraemia were acquired during hospitalisation and these accounted for the majority of the deaths. Resistance to standard antibiotic regimens was rare.


A complementary approach to identifying and assessing the remediation potential of hydrocarbonoclastic bacteria.
The isolation and assessment of hydrocarbonoclastic bacteria often represents a key strategy in the bioremediation of hydrocarbon-contaminated sites. However the isolation and assessment of such bacteria is often a lengthy and expensive procedure. The aim of this study was to identify potential isolates for use in the remediation of hydrocarbon contaminated sites using a combination of selective isolation plating, the Biolog system and subsequent multivariate analyses. The use of weathered oil as the main C source restricted the number of isolates growing to 5×10(2)CFUg soil(-1). Isolates (n=96) were then assessed individually using Biolog MT2 plates with seven different hydrocarbons (dodecane, tridecane, hexadecane, octadecane, eicosane, naphthalene and phenanthrene). The results indicated that all isolates were able to grow on at least one hydrocarbon from the seven chosen. This confirmed that the isolation media developed was selective in isolating hydrocarbonoclastic bacteria only. Cluster analysis of Biolog data separated the isolates into two discrete clusters with cluster 2 identifying hydrocarbonoclastic bacteria that are effective in degrading a variety of contaminants. Further study on the isolates from cluster 2 was carried out based on their phylogenetic analysis. Phylogenetic analysis of 28 bacterial isolates from cluster 2 based on the 1500bp sequences from 16S rDNA genes using MRBAYES confirmed all isolates as being hydrocarbonoclastic, providing supportive evidence that isolates from cluster 2 have a potential use in bioremediation. This approach could improve both the speed and efficiency of the commercial bioremediation process.


[Multiple exostoses disease (observations in 21 reported cases)].
With reference to 21 cases the authors describe the clinical, radiological and anatomo-pathological findings of multiple exostoses disease. The indications for the surgical treatment are discussed; they are, however, the same to the solitary osteochondroma.


Sustained impairment of α2A-adrenergic autoreceptor signaling mediates neurochemical and behavioral sensitization to amphetamine.
In rodents, drugs of abuse induce locomotor hyperactivity, and repeating injections enhance this response. This effect, called behavioral sensitization, persists months after the last administration. It has been shown that behavioral sensitization to amphetamine develops parallel to an increased release of norepinephrine (NE) in the prefrontal cortex (PFC). Rats and mice were repeatedly treated with amphetamine (1 or 2 mg/kg intraperitoneally, respectively) to obtain sensitized animals. The NE release in the PFC was measured by microdialysis in freely moving mice (n = 55). Activity of locus coeruleus (LC) noradrenergic neurons was determined in anaesthetized rats (n = 15) by in vivo extracellular electrophysiology. The α2A-adrenergic autoreceptor (α2A-AR) expression was assessed by autoradiography on brain slices, and Gαi proteins expression was measured by western blot analysis of LC punches. In sensitized rats LC neurons had a higher spontaneous firing rate, and clonidine-an α2A-adrenergic agonist-inhibited LC neuronal firing less efficiently than in control animals. Clonidine also induced lower levels of NE release in the PFC of sensitized mice. This desensitization was maintained by a lower density of Gαi1 and Gαi2 proteins in the LC of sensitized mice rather than weaker α2A-AR expression. Behavioral sensitization was facilitated by α2A-AR antagonist, efaroxan, during amphetamine injections and abolished by clonidine treatment. Our data indicate that noradrenergic inhibitory feedback is impaired for at least 1 month in rats and mice repeatedly treated with amphetamine. This work highlights the key role of noradrenergic autoreceptor signaling in the persistent modifications induced by repeated amphetamine administration.


Low anthropometric indices in elderly females with fractured neck of femur.
Anthropometric measurements were made in 3 groups of elderly females (1) with fractured neck of femur, (2) those admitted to acute medical and geriatric wards, and (3) healthy women in the community. Mid-arm circumference was different in the three groups with mean values of 22.8 +/- 0.21 cm, 25.9 +/- 0.41 cm and 28.6 +/- 0.27 cm respectively; (p < 0.001 for all comparisons). Triceps skinfold thickness was 24.7 +/- 0.70 mm in the healthy elderly but only 13.0 +/- 0.59 mm in the fracture group (p < 0.001). Fractured femur patients are therefore thinner than both healthy controls and unselected elderly female medical in-patients. These differences are most apparent in anthropometric indices dependent on body fat and this may be significant in terms of the aetiology of fractured femur.


Enhancement by stem cell factor of interleukin-2 (IL-2)-induced DNA synthesis in human decidual CD16- CD56bright natural killer cells mediated by increased expression of the IL-2 receptor alpha chain.
Extracts of chorionic villous and decidual tissue specimens from women in the early stages of pregnancy contained stem cell factor (SCF), the amount in the latter tissue (246.6+/-119.7 pg/mg protein) being approximately three times that in the former. Immunohistochemical analysis revealed the presence of SCF in the mesenchymal cells of the chorion, the trophoblast, and decidual stromal cells, whereas the SCF receptor, c-kit, was detected in the trophoblast and decidual mononuclear leukocytes but not in decidual stromal cells. Reverse transcription and polymerase chain reaction analysis detected transcripts corresponding to both secretory and membrane-bound types of SCF in chorionic tissue, but only those encoding the secretory type in decidual tissue. Flow cytometric analysis showed that c-kit was expressed on decidual CD16- CD56bright natural killer (NK) cells, CD14+ macrophages, and CD34+ hematopoietic progenitor cells, but not on CD3+ T cells or CD16+ NK cells. Although SCF alone had no effect on DNA synthesis in decidual CD16- CD56bright NK cells, it enhanced the proliferative effect of interleukin-2 (IL-2) at IL-2 concentrations that selectively saturate the high-affinity IL-2 receptor (IL-2R). Flow cytometry of decidual mononuclear leukocytes cultured in the presence of SCF demonstrated that this factor increased the expression of the IL-2Ralpha chain, but not IL-2Rbeta and gamma chain expression on CD16- CD56bright NK cells. Results suggest that SCF produced in the decidua increases the expression of the IL-2Ralpha which is usually present in smaller amounts than other two IL-2R chains on decidual CD16- CD56bright NK cells, and thereby promotes the proliferation of these cells in response to low concentrations of IL-2, resulting in an increase of the high affinity IL-2Rs.