Poly(vinyl chloride) ion-selective electrodes for piribedil determination.
Piribedil (PD) ion-selective electrodes have been constructed from poly(vinyl chloride) matrix membrane containing piribedil-tetraphenylborate (PD-TPB) as the electroactive component with dibutylphthalate or dioctylphthalate as the plasticizing solvent mediator. The electrodes displayed a linear response over the concentration range 2.0 x 10(-5) to 10(-2) M PD. The working pH ranges of the electrodes were 3.5-6.4 and 3.0-6.0, and the isothermal coefficients of the cells were 0.00129 and 0.00096 V/degrees C respectively. The electrodes were used for the determination of the diprotonated PD species, the most successful being that based on dioctylphthalate solvent mediator. The electrodes show a linear response over the concentration range of 8.0 x 10(-6) to 10(-2) M PD, with Nernstain slope 30 mV/PD concentration decade when preconditioned by soaking in distilled water for 30 min. The electrodes exhibit good selectivity for the PD with respect to a large number of inorganic cations and organic substances of biological fluids. Piribedil is determined successfully in pure solutions and in tablets or in biological fluids using the standard additions and potentiometric titration methods. The membrane withstood soaking in distilled water for more than 5 months.


[A definition of work-related asthma and its social and occupational consequences in adults and teenagers].
Work-related asthma (WRA) accounts for 10-25% of all adult asthma. It therefore seems important to raise questions regarding an asthmatic's approach to occupational or job training activities. WRA takes on two forms: work-exacerbated asthma (WEA) and occupational asthma (OA), which encompasses different subtypes of heterogeneous mechanisms. It currently represents a major challenge for occupational medicine in terms of detailed diagnosis, social care, the economic repercussions for workers and employers and, last but not least, social insurance. This review aims to sensitize health care practitioners to the peculiarities of WRA management in routine practice. More specifically, prognosis depends on early diagnosis, medical care and work adjustment measures. WEA and OA are explained in detail in view of identifying causative agents and at-risk occupations and defining adapted medical strategy. Relevant lines of questioning and complementary exams are presented. In addition, the key role of the occupational physician, especially as regards recognition and identification of occupational disease, is underlined, the objective being to facilitate optimal professional and social management. In future studies, the key role of counseling and orientation mechanisms should be highlighted as means of preventing WRA occurrence.


Plasticity of a critical antigenic determinant in the West Nile virus NY99 envelope protein domain III.
West Nile virus (WNV) is a mosquito-borne flavivirus that causes febrile illness, encephalitis, and occasionally death in humans. The envelope protein is the main component of the WNV virion surface, and domain III of the envelope protein (EIII) is both a putative receptor binding domain and a target of highly specific, potently neutralizing antibodies. Envelope E-332 (E-332) is known to have naturally occurring variation and to be a key determinant of neutralization for anti-EIII antibodies. A panel of viruses containing all possible amino acid substitutions at E-332 was constructed. E-332 was found to be highly tolerant of mutation, and almost all of these changes had large impacts on antigenicity of EIII but only limited effects on growth or virulence phenotypes.


Self-Immobilized Putrescine Oxidase Biocatalyst System Engineered with a Metal Binding Peptide.
Flavin oxidases are valuable biocatalysts for the oxidative synthesis of a wide range of compounds, while at the same time reduce oxygen to hydrogen peroxide. Compared to other redox enzymes, their ability to use molecular oxygen as an electron acceptor offers a relatively simple system that does not require a dissociable coenzyme. As such, they are attractive targets for adaptation as cost-effective biosensor elements. Their functional immobilization on surfaces offers unique opportunities to expand their utilization for a wide range of applications. Genetically engineered peptides have been demonstrated as enablers of the functional assembly of biomolecules at solid material interfaces. Once identified as having a high affinity for the material of interest, these peptides can provide a single step bioassembly process with orientation control, a critical parameter for functional immobilization of the enzymes. In this study, for the first time, we explored the bioassembly of a putrescine oxidase enzyme using a gold binding peptide tag. The enzyme was genetically engineered to incorporate a gold binding peptide with an expectation of an effective display of the peptide tag to interact with the gold surface. In this work, the functional activity and expression were investigated, along with the selectivity of the binding of the peptide-tagged enzyme. The fusion enzyme was characterized using multiple techniques, including protein electrophoresis, enzyme activity, and microscopy and spectroscopic methods, to verify the functional expression of the tagged protein with near-native activity. Binding studies using quartz crystal microbalance (QCM), nanoparticle binding studies, and atomic force microscopy studies were used to address the selectivity of the binding through the peptide tag. Surface binding AFM studies show that the binding was selective for gold. Quartz crystal microbalance studies show a strong increase in the affinity of the peptide-tagged protein over the native enzyme, while activity assays of protein bound to nanoparticles provide evidence that the enzyme retained catalytic activity when immobilized. In addition to showing selectivity, AFM images show significant differences in the height of the molecules when immobilized through the peptide tag compared to immobilization of the native enzyme, indicating differences in orientation of the bound enzyme when attached via the affinity tag. Controlling the orientation of surface-immobilized enzymes would further improve their enzymatic activity and impact diverse applications, including oxidative biocatalysis, biosensors, biochips, and biofuel production.


Dynamic contrast-enhanced MR imaging of ovarian neoplasms: current status and future perspectives.
MR imaging is useful for characterizing ovarian tumors. Dynamic contrast-enhanced MR imaging is a promising new technique useful for characterizing perfusion and angiogenesis of ovarian masses. This article describes the dynamic contrast-enhanced MR imaging technique examines the current and future applications of this technique in patients with ovarian tumors.


Bacterial secretion system skews the fate of Legionella-containing vacuoles towards LC3-associated phagocytosis.
The evolutionarily conserved processes of endosome-lysosome maturation and macroautophagy are established mechanisms that limit survival of intracellular bacteria. Similarly, another emerging mechanism is LC3-associated phagocytosis (LAP). Here we report that an intracellular vacuolar pathogen, Legionella dumoffii, is specifically targeted by LAP over classical endocytic maturation and macroautophagy pathways. Upon infection, the majority of L. dumoffii resides in ER-like vacuoles and replicate within this niche, which involves inhibition of classical endosomal maturation. The establishment of the replicative niche requires the bacterial Dot/Icm type IV secretion system (T4SS). Intriguingly, the remaining subset of L. dumoffii transiently acquires LC3 to L. dumoffii-containing vacuoles in a Dot/Icm T4SS-dependent manner. The LC3-decorated vacuoles are bound by an apparently undamaged single membrane, and fail to associate with the molecules implicated in selective autophagy, such as ubiquitin or adaptors. The process requires toll-like receptor 2, Rubicon, diacylglycerol signaling and downstream NADPH oxidases, whereas ULK1 kinase is dispensable. Together, we have discovered an intracellular pathogen, the survival of which in infected cells is limited predominantly by LAP. The results suggest that L. dumoffii is a valuable model organism for examining the mechanistic details of LAP, particularly induced by bacterial infection.


Inhibition of dopamine receptors by endogenous amines: binding to striatal receptors and pharmacological effects on locomotor activity.
Endogenous amine 1-benzyl-1,2,3,4-tetrahydroisoquinoline (1BnTIQ) derivatives are synthesized. and their activity for dopaminergic systems are evaluated in vitro and in vivo by receptor binding assay and pharmacological tests. It is proposed that 1BnTIQ derivatives can act as endogenous dopaminergic antagonists.


Dimensionality estimation for optimal detection of functional networks in BOLD fMRI data.
Estimation of the intrinsic dimensionality of fMRI data is an important part of data analysis that helps to separate the signal of interest from noise. We have studied multiple methods of dimensionality estimation proposed in the literature and used these estimates to select a subset of principal components that was subsequently processed by linear discriminant analysis (LDA). Using simulated multivariate Gaussian data, we show that the dimensionality that optimizes signal detection (in terms of the receiver operating characteristic (ROC) metric) goes through a transition from many dimensions to a single dimension as a function of the signal-to-noise ratio. This transition happens when the loci of activation are organized into a spatial network and the variance of the networked, task-related signals is high enough for the signal to be easily detected in the data. We show that reproducibility of activation maps is a metric that captures this switch in intrinsic dimensionality. Except for reproducibility, all of the methods of dimensionality estimation we considered failed to capture this transition: optimization of Bayesian evidence, minimum description length, supervised and unsupervised LDA prediction, and Stein's unbiased risk estimator. This failure results in sub-optimal ROC performance of LDA in the presence of a spatially distributed network, and may have caused LDA to underperform in many of the reported comparisons in the literature. Using real fMRI data sets, including multi-subject group and within-subject longitudinal analysis we demonstrate the existence of these dimensionality transitions in real data.


Supporting Latino communities' natural helpers: a case study of promotoras in a research capacity building course.
Promotores have unique access to underserved and hard-to-reach Latino communities facing health disparities. Although promotores are involved in community change, they rarely receive training that gives them the skills to be partners in research. We present a case study of promotoras who participated in a research capacity building course focused on assessing community health needs. Data comes from course application surveys, follow-up notes, and narratives from qualitative phone interviews of eight promotoras. Content analysis drawing from grounded theory was conducted to identify and describe emerging themes. Four themes emerged as promotoras discussed their experience learning basic research skills and teaching others: (1) challenges, (2) support, (3) building capacity, and (4) using research. Promotores play an important role in the health of Latino communities and are increasingly asked to participate in research processes; however they have few opportunities for training and professional development in this area. Capacity building opportunities for promotores need to be tailored to their needs and provide them with support. Fostering collaboration between promotores and partnering with local community-based organizations can help facilitate needed research skill-building among promotores.


Auditory lateralization of conspecific and heterospecific vocalizations in cats.
Auditory lateralization in response to both conspecific and heterospecific vocalizations (dog vocalizations) was observed in 16 tabby cats (Felis catus). Six different vocalizations were used: cat "purring," "meowing" and "growling" and dog typical vocalizations of "disturbance," "isolation" and "play." The head-orienting paradigm showed that cats turned their head with the right ear leading (left hemisphere activation) in response to their typical-species vocalization ("meow" and "purring"); on the other hand, a clear bias in the use of the left ear (right hemisphere activation) was observed in response to vocalizations eliciting intense emotion (dogs' vocalizations of "disturbance" and "isolation"). Overall these findings suggest that auditory sensory domain seems to be lateralized also in cat species, stressing the role of the left hemisphere for intraspecific communication and of the right hemisphere in processing threatening and alarming stimuli.


Crystallization and preliminary X-ray analysis of human Brn-5 transcription factor in complex with DNA.
The Brn-5 protein plays an important role in the control of cellular development and belongs to a class of transcription factors that usually contain two domains: the POU homeodomain (POU(HD)) and the POU-specific domain (POU(S)). Since high-quality crystals suitable for crystallographic studies of the proteins of this class are difficult to obtain, all the known structural information available is for POU(HD) and/or POU(S). This paper describes several critical steps that allowed the production of high-quality crystals of the full-length Brn-5 protein complexed with its cognate DNA.


226Ra/238U disequilibrium in an upland organic soil exhibiting elevated natural radioactivity.
This paper presents the results of a study into the anomalous 226Ra/238U disequilibrium (226Ra/238U of 0.5-9) exhibited by an upland organic soil in Co. Donegal, Ireland. Radiochemical speciation of 226Ra, 238U and 225Ra indicates that in this organic soil the high 226Ra/238U ratio is due to loss of 235U relative to 226Ra via oxidation and mobilisation of 238U in the upper layers of the soil and subsequent loss in solution. At the lower, more reducing depths of the soil profile, 238U and 226Ra are essentially in equilibrium. Loss of 238U appears to occur primarily from the easily oxidised organic and iron oxide fractions of the soil, samples exhibiting high 226Ra/238U ratios displaying significantly lower 238U levels in these fractions than samples whose ratio is below the average value for the soil of the valley. Selective enrichment of 226Ra by plants or preferential leaching of 226Ra from the underlying rock is not supported by the results of this study.


Cholinergic neurons contain Calbindin-D28k in the monkey medial septal nucleus and nucleus of the diagonal band: an immunocytochemical study.
The distribution patterns of choline acetyltransferase (CAT), as a marker for cholinergic neurons, and Calbindin-D28k (CaBP) immunoreactivities in the forebrain basal ganglia of the Japanese monkey Macaca fuscata were compared. Similar distribution patterns of CAT and CaBP immunoreactivities were found in the medial septal nucleus (MS) and the nucleus of the diagonal band of Broca (DBB). Double-labeling fluorescence immunocytochemistry revealed that most, but not all, cholinergic neurons were CaBP-immunoreactive in the MS and DBB. The results suggest that CaBP may play a role in the septohippocampal cholinergic neuron system of the monkey.


Microbiological inoculation with and without biochar reduces the bioavailability of heavy metals by microbial correlation in pig manure composting.
Biochar provides a suitable microenvironment for the growth of microorganisms. It may directly or indirectly affect changes in the population of microorganisms, thus affecting heavy metal bioavailability. This study aims to explore the effects of microbiological inoculation with and without biochar on microorganisms and on the bioavailability of heavy metals during pig manure composting. Three composting experiments were conducted under various conditions including no treatment (CK), only microbiological inoculation (TA), and integration with biochar (TB). Compared with raw materials before compost, TA reduced the bioavailability of Cu by 25.1%, Zn by 25.64%, and both Pb and Cr by 1.75%. TB reduced the bioavailability of Cu by 35.38%, Zn by 19.34%, Pb by 0.81%, and Cr by 3.9%. Furthermore, correlation analysis demonstrated that Debaryomyces were the primary fungi, possibly controlling the passivation of Cr. Bacillus, Fusarium, Pseudogracilibacillus, Sinibacillus, and Botryotrichum were the primary bacteria and fungi potentially governing the passivation of Zn, Lastly, Debaryomyces and Penicillium were the primary bacteria and fungi potentially controlling the passivation of Pb and Cu, respectively. Overall, we demonstrated that pig manure added to the microbial inoculum and biochar effectively reduced the bioavailability of heavy metals, thereby offering an applicable technology for reducing heavy metal contamination during pig manure composting.


Determination of organic priority pollutants in the low nanogram-per-litre range in water by solid-phase extraction disk combined with large-volume injection/gas chromatography-mass spectrometry.
Polybrominated diphenyl ethers, polychlorinated biphenyls, polycyclic aromatic hydrocarbons and organochlorine pesticides in the low nanogram-per-litre range in water were enriched by solid-phase extraction (SPE) disks and their concentration determined by large-volume injection/gas chromatography-mass spectrometry (LVI/GC-MS). One advantage of using SPE disks in comparison with SPE cartridges is that suspended particulate matter (SPM) does not have to be separated prior to the enrichment step, which saves time and effort. To increase the sensitivity of the method, the SPE disk procedure was combined with LVI/GC-MS, which has not been reported so far for water analysis. The method was calibrated in ranges from 0.25 to 2.5 ng/L and from 2.5 to 25 ng/L. The average recovery was 76% at an analyte concentration of 2.5 ng/L. The limits of quantification, defined at a signal-to-noise ratio of 6:1, reach from 0.1 to 24.0 ng/L and are up to 400 times lower than previously reported in water analysis. By the developed SPE/LVI/GC-MS method, it is possible to investigate the whole water sample without prior separation of the SPM within 2 h including GC-MS analysis.


Gastric perforation secondary to metastasis from ovarian cancer: Case report.
Metastasis from ovarian cancer occurs frequently through the peritoneal cavity in the form of peritoneal carcinomatosis; isolated gastric metastasis is rarely reported in literature. We present a case of 43-year-old infertile lady, who developed a picture of acute abdomen four days post total abdominal hysterectomy and salpingoopherectomy for ovarian cancer. Further contrast-enhanced CT scan demonstrated massive free gas and fluid in the abdomen. She underwent antrectomy with truncal vagotomy due to 3cm×4cm prepyloric gastric ulcer. Final pathology proved the presence of metastatic serous cystadenocarcinoma of ovarian origin. Our patient had a gastric perforation secondary to ovarian metastasis. Being isolated, the absence of ascites and the transmural nature of the gastric metastasis suggest haematogenous spread .To the best of our knowledge perforated gastric metastasis secondary to ovarian cancer was not reported in literature before. Gastric metastasis should be kept in mind in patients with a well-known ovarian cancer who present with gastric lesions, ulcers, bleeding or perforation.


A Rare Case of Ossifying Fibroma with Cystic Degeneration: Diagnostic Challenge with Literature Review.
Cystic degeneration can occur with various bone lesions. These non-epithelial lined cysts vary from aneurysmal bone cyst, solitary bone cyst or non specific cystic degeneration. In jaws, this association is not well documented. In literature only three cases have been reported as ossifying fibroma (OF) with cystic degeneration. This case appears to be the fourth case to highlight non specific cystic changes in OF. We report a case of OF in 23 year old female with asymptomatic swelling over the left side of face for the past 3 years involving the maxilla, maxillary sinus as well as nasal cavity. Histopathology revealed it to be OF complicated by non-specific cystic degeneration. OF of jaws is an odontogenic neoplasm arising from tooth bearing areas. It occurs more commonly in women in posterior mandible region. Microscopically it shows variable mixture of osteoid bone and basophilic acellular spherules while bony trabeculae frequently demonstrate both woven and lamellar patterns. Various pathogenesis have also been highlighted behind the cystic degeneration's in bony lesions. A review is also tabulated of OFs with cystic degenerations in the jaws reported in the past.


Childhood maltreatment and depressive disorders in Chinese children and adolescents: A population-based case-control study.
The association between childhood maltreatment (CM) and clinically diagnosed depressive disorders (DD) in children and adolescents remains inconclusive, in large part due to a lack of high-quality epidemiological evidence. This study aimed to investigate the association between CM and DD in a large sample of Chinese children and adolescents. The study subjects were chosen from the Mental Health Survey for Children and Adolescents in Yunnan (MHSCAY), and a population-based and individually-matched case-control study design was adopted. CM was in general associated with an odds ratio (OR) of 5.38 (95% CI: 3.33, 8.71) for DD in children and adolescents, and a prominent dose-response association was detected. For the five specific types of CM, emotional abuse was independently related to the highest odds of DD (OR=3.90, 95% CI: 2.75, 5.54), followed by physical neglect (OR=2.04, 95% CI: 1.45, 2.87) and physical abuse (OR=1.51, 95% CI: 1.06, 2.13), while insignificant associations were found between DDs and sexual abuse and emotional neglect. Subsequently performed stratified analyses identified noticeable effect modification by important demographic factors. CM was significantly associated with increased risk of DD in Chinese children and adolescents. The major findings of the current study suggest that victims of CM, especially those who had been emotionally abused, were susceptible to early-onset DD. Targeted interventions should be considered.


Longevity minimalists: life table studies of two species of northern Michigan adult mayflies.
Life table studies were conducted on both sexes of newly emerged subimagoes of the mayfly species, Hexagenia limbata (n = 4472) and Ephemera simulans (n = 1254), which have two- and one-year life cycles, respectively. The expectation of life at emergence for H. limbata was approximately 2.6 days for both sexes with the last individual (a female) dying on day 8. Expectation of life for E. simulans was 1.6 and 2.0 days for males and females, respectively, with the last individuals (both sexes) dying on day 3. The results reveal that mortality does not occur in one large step in this group of rapidly senescing organisms. Rather deaths are spread over several days when the adult mayflies are maintained under laboratory conditions.


Application of the transgenic adenocarcinoma mouse prostate (TRAMP) model for pre-clinical therapeutic studies.
The suitability of (C57BL/6 TRAMP x C57BL/6)F1 transgenic (TRAMP+) mice with well- to moderately-differentiated prostate cancer (PCa) was assessed for pre-clinical therapeutic studies. TRAMP+ and TRAMP- mice were assessed for variability in genitourinary tract weight, seminal vesicle weight, prostate weight/volume and histopathology. Time-points included the reported ages of average tumour onset (approximately 25 weeks) and PCa-induced death (approximately 33 weeks). Seventy % of TRAMP+ mice aged 25-33 weeks had well- to moderately-differentiated PCa. At 25-28 weeks, the mean genitourinary tract weight was 2X greater and the mean prostate weight/volume was 1.5X more in TRAMP+ than in TRAMP- mice, respectively. Prostate weight/volume showed significant increases (p < 0.0001) by 2X and 3X, respectively by 31-33 weeks of age. The window for using the TRAMP model successfully for pre-clinical experimentation is 25-33 weeks provided that mice with poorly-differentiated PCa showing a large tumour burden are excluded.


Care maps for children with medical complexity.
Children with medical complexity require multiple providers and services to keep them well and at home. A care map is a patient/family-created diagram that pictorially maps out this complex web of services. This study explored what care maps mean for families and healthcare providers to inform potential for clinical use. Parents (n=15) created care maps (hand drawn n=10 and computer-generated n=5) and participated in semi-structured interviews about the process of developing care maps and their perceived impact. Healthcare providers (n=30) reviewed the parent-created care maps and participated in semi-structured interviews. Data were analysed for themes and emerging theory using a grounded theory analytical approach. Data analysis revealed 13 overarching themes that were further categorized into three domains: features (characteristics of care maps), functions (what care maps do), and emerging outcomes (benefits of care map use). These domains further informed a definition and a theoretical model of how care maps work. Our findings suggest that care maps may be a way of supporting patient- and family-centred care by graphically identifying and integrating experiences of the family as well as priorities for moving forward. Care maps were endorsed as a useful tool by families and providers. They help healthcare providers better understand parental priorities for care. Parents can create care maps to demonstrate the complex burden of care. They are a unique visual way to incorporate narrative medicine into practice.


Nitrate reductase is a key enzyme responsible for nitrogen-regulated auxin accumulation in Arabidopsis roots.
Nitrate reductase (NR) is one of the key enzymes for plant nitrogen assimilation and root architecture remodeling. However, crosstalk between NR-mediated signaling and auxin-mediated root development in nitrogen-status responses has not been investigated in details before. In this study, root phenotype and auxin distribution in nia1/nia2 (nitrate reductase) double mutant and chl1-5 (nitrate transporter NRT1.1) mutant under different nitrogen availabilities were compared. The nia1/nia2 mutant showed very low expression levels of auxin biosynthetic/signaling genes and was insensitive to nitrogen changes. While the chl1-5 mutant showed a high NR activity with a high level of auxin in the meristematic zone and a weaker response to nitrogen changes, when compared with the wild-type plants. We firstly found that NR activity was roughly positive-correlated with the root auxin level, and there is a crosstalk between nitrate signaling and auxin signaling. The putative signaling pathways downstream of NR have been discussed.


Proliferative effect of dextran sulfate sodium (DSS)-pulsed macrophages on T cells from mice with DSS-induced colitis and inhibition of effect by IgG.
The authors have previously reported that homologous immunoglobulin (Ig)G reduces the occurrence of dextran sulfate sodium (DSS)-induced colitis, mainly by suppressing recruitment of immunocompetent cells into colitis lesions. However, the mechanisms of cell recruitment and of its suppression by IgG remain unclear. In addressing these questions, this study focused on the activation of T cells in the presence of macrophages. The authors found that [3H]-thymidine uptake of T cells from DSS-induced colitis mice, but not from normal mice, was significantly enhanced when cultured with DSS-pulsed macrophages. From the profile of cytokine production, it was suggested that T helper 1 (Th1)-type cells become predominant during stimulation. Addition of homologous IgG significantly suppressed T cell proliferation in a dose-dependent manner, while no suppressive effect was observed with heterologous IgG. Mouse IgG F(ab')2, but not Fc, fragments partially mimicked the suppressive effect of whole IgG. These findings provide evidence that Th1-type cells may play an important role in the development of DSS-induced colitis and that homologous IgG exerts its protective action at least in part through the F(ab')2 portion.


Social participation is reduced in type 3 Von Willebrand disease patients and in patients with a severe bleeding phenotype.
The negative impact of haemophilia on social participation is well established in previous studies, however, the impact of Von Willebrand disease (VWD) on social participation has not been studied. To compare the social participation of a large cohort of VWD patients in the Netherlands with the general Dutch population. In addition, to identify factors associated with social participation in VWD. Patients participating in the "Willebrand in the Netherlands" study completed an extensive questionnaire on educational level, absenteeism from school or work, and occupational disabilities. Seven-hundred and eighty-eight VWD patients were included (mean age 38.9 years, 59.5% females), of whom 136 children < 16 years. Adult patients with type 3 VWD more often had a low educational level (52.9%) compared to type 1 (40.2%), type 2 VWD (36.8%) and the general population (36.4%) (p = .005). Moreover, in patients aged ≥16 years the days lost from school and/or work in the year prior to study inclusion differed significantly between the VWD types (p = .011). Using negative binomial regression analysis, the occurrence of bleeding episodes requiring treatment in the year preceding study inclusion was significantly associated with the number of days lost from school and/or work among patients aged ≥16 years. Multivariable logistic regression analysis showed that a higher total bleeding score, older age and presence of at least one comorbidity were significantly associated with occupational disability in patients aged ≥16 years. Our study shows that social participation was lower in type 3 VWD and VWD patients with a more severe bleeding phenotype.


Adolescent Cannabis Users Who Have Never Smoked A Combustible Cigarette: Trends and Level of Addictive Drug Use from 1976 to 2020.
Adolescents cannabis users are at a substantially elevated risk for use of highly addictive drugs such as cocaine, heroin, and nonmedical use of prescription drugs. Unknown is whether this elevated risk applies to adolescent cannabis users who have never smoked a combustible cigarette, a group that has grown considerably in size in recent years. This study documents the recent growth in the proportion of adolescent cannabis users who abstain from combustible cigarette use, and examines their probability for use of addictive drugs. Data are annual, cross-sectional, nationally-representative Monitoring the Future surveys of 607,932 U.S. 12th grade students from 1976-2020. Among ever cannabis users, the percentage who had never smoked a combustible cigarette grew from 11% in 2000 to 58% in 2020. This group had levels of addictive drug use that were 8% higher than their peers. In comparison, adolescents who had ever used cannabis - regardless of whether they had ever smoked a cigarette - had levels of addictive drug use 500% higher than their peers. Adolescent cannabis users who have not smoked a combustible cigarette have much lower levels of addictive drug use than the group of cannabis users as a whole. These results suggest policies and laws aimed at reducing adolescent prevalence of addictive drugs may do better to focus on cigarette use of adolescent cannabis users rather than cannabis use per se.


The involvement of lactate and calcium as mediators of the electrical and mechanical responses of the myocardium to conditions of simulated ischaemia.
1. Rat isolated and superfused atria were exposed to a lactate-containing solution simulating the composition of extracellular fluid during myocardial ischaemia (SI). 2. Atria subjected to SI showed a decreased adenosine 5'-triphosphate (ATP) content, a rise in diastolic tension, a diminished conduction velocity of action potentials and shortened refractory periods. All these changes were less pronounced during lactate-free SI. 3. Atria preloaded with calcium displayed exaggerated responses measured electrically and mechanically during exposure to SI, whereas atria previously depleted of calcium displayed diminished electrical and mechanical responses to SI. Neither calcium loading nor calcium depletion modified the SI-induced depletion of the atrial stores of ATP. 4. Sulphinpyrazone protected atria against all aspects of the response to SI, but failed to protect the muscle under conditions of lactate-free SI. It is concluded that during SI, sulphinpyrazone protects against a lactate-mediated inhibition of the glycolytic synthesis of ATP. 5. Flufenamate exaggerated all responses of the atria to SI. These deleterious actions were still observed during lactate-free SI. It is concluded that flufenamate inhibits the synthesis of ATP in the mitochondria.


Morbidity and mortality in children with anemia at initiation of dialysis.
Studies in adult dialysis patients have identified anemia as a risk factor for patient morbidity and mortality. Limited comparable outcome data are available from children. We used the database from the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) to identify patients <18 years of age who initiated dialysis (hemodialysis and peritoneal dialysis) between 1992 and 2001 with no prior history of dialysis or transplantation. A Cox proportional hazards model was used to evaluate the association between anemia (hematocrit <33%) at 30 days post initiation of dialysis and patient mortality. The association between anemia and prolonged hospitalization was also evaluated. Of the 1,942 patients (male 56%), 68% were anemic on day 30. One hundred and seventy-one patient deaths were reported over the 9-year observation period. The multivariate analysis demonstrated anemia to be associated with a 52% higher risk of death (adjusted relative risk 1.52, 95% confidence interval 1.03-2.26, P=0.037). Cardiopulmonary disease was the primary reported cause of death associated with anemia, accounting for 22% of cases. The presence of anemia was also associated with an increased risk for prolonged hospitalization, irrespective of dialysis modality. In conclusion, the presence of anemia 1 month after initiation of dialysis iis associated with an increased risk of prolonged hospitalization and death in pediatric patients. Further studies should ascertain whether anemia per se increases the risk of death or whether it is a marker for other conditions that shorten patient survival, such as chronic inflammation or recurrent infection.


Stem cells in breast tumours: are they ready for the clinic?
The concept of stem-like cells in cancer has been gaining currency over the last decade or so since evidence for stem cell activity in human leukaemia and solid tumours, including breast cancer, was first published. The evidence established that sub-populations of cells identified by antibodies to cell surface markers behaved like developmental stem cells in their capacity to re-grow the human tumour for several generations in experimental immune-deficient hosts. The experiments established that cells with tumourigenic capacity expressed 'cancer stem cell' (CSC) markers and that activity could also be measured by self-renewal of tumour sphere colonies in culture. In breast and other cancers, there is good evidence that CSCs are relatively resistant to radio- and chemotherapy indicating that novel CSC-targeted therapies are needed. Several pathways are promising targets in breast CSCs. There are several ways of combating CSC activity including inducing their apoptosis, inhibiting stem cell self-renewal to either stop their division or to promote their differentiation, or targeting the CSC niche that supports them. The first challenge for developing novel CSC therapies is to ascertain which of these CSC properties is being targeted. The second challenge is to determine suitable CSC biomarkers to measure the efficacy of the novel CSC therapies. We propose using biomarkers as a means to identify and assess CSC activity in clinical trials. This is likely to be demanding but feasible in the near future. Thus, we asked if CSCs are ready for the clinic, however, the emerging question becomes: is the clinic ready for cancer stem cells?


Occurrence of endocrine-disrupting compounds in reclaimed water from Tianjin, China.
Continuous disposal of endocrine-disrupting compounds (EDCs) into the environment can lead to serious human health problems and can affect plants and aquatic organisms. The determination of EDCs in water has become an increasingly important activity due to our increased knowledge about their toxicities, even at low concentration. The EDCs in water samples from the reclaimed water plant of Tianjin, northern China, were identified by gas chromatography (GC)-mass spectrometry (MS). Important and contrasting EDCs including estrone (E1), 17beta-estradiol (E2), 17alpha-ethynylestradiol (EE2), 4-tert-octylphenol (OP), 4-nonylphenol (NP), bisphenol A (BPA), di-n-butyl phthalate (DnBP), diisobutyl phthalate (DIBP), and di(2-ethylhexyl)phthalate (DEHP) were selected as the target compounds. Concentrations of steroid hormones, alkylphenolic compounds and phthalates ranged from below the limit of detection (LOD) to 8.1 ng L(-1), from <LOD to 14.2 ng L(-1), and from 1.00 microg L(-1) to 23.8 microg L(-1), respectively. The average removal efficiencies for target EDCs varied from 30% to 82%. These results indicate that environmental endocrine disrupting compounds are not completely removed during reclaimed water treatment and may be carried over into the general aquatic environment.


The initiation of antigen-induced B cell antigen receptor signaling viewed in living cells by fluorescence resonance energy transfer.
Binding of antigen to the B cell antigen receptor (BCR) triggers signaling that ultimately leads to B cell activation. Using quantitative fluorescence resonance energy transfer imaging, we provide evidence here that the BCR is a monomer on the surface of resting cells. Binding of multivalent antigen clustered the BCR, resulting in the simultaneous phosphorylation of and a conformational change in the BCR cytoplasmic domains from a closed to an open form. Notably, the open conformation required immunoreceptor tyrosine-activation motif and continuous Src family kinase activity but not binding of the kinase Syk. Thus, the initiation of BCR signaling is a very dynamic process accompanied by reversible conformational changes induced by Src family kinase activity.


Incident light microscopy of normal and transformed cultured fibroblasts stained with coomassie blue R250.
Incident light microscopy of fibroblasts stained with Coomassie blue R250 results in images of the cytoskeleton with a similar high contrast to those obtained by specific immunofluorescence microscopy. This technique is especially useful for the routine visualization of the cytoskeleton of transformed cells.


Patterns and correlates of time use and energy expenditure in older Australian workers: A descriptive study.
How people use their time has health implications, but use of time may be influenced by factors such as age, sex, education and health. This study aimed to provide detailed information on the daily activity patterns of older working people. 139 older Australian adults (aged 50-79 years) undertook comprehensive interviews on their use of time. This paper presents a cross-sectional analysis of the baseline findings from a longitudinal study. Use of time was measured using the Multimedia Activity Recall for Children and Adults (MARCA), administered via computer-assisted phone interview. Activity patterns were described, and compared on the basis of sex, education and health status. The main activities undertaken were sleep (mean 466min/day), work (mean 233min/day) and chores (mean 160min/day), with little time spent on physical activity (mean 13min/day). Women spent more time doing chores (p<0.001) while men spent more time on vigorous activities (p<0.001). Participants with "fair" health spent less time on inside chores (p=0.05) and grooming (p=0.02) than healthier participants. Healthy lifestyle interventions for older workers should aim to increase physical activity levels by targeting specific activities, depending on sex and health status.


Growth factors in progression of human esophageal and gastric carcinomas.
Human esophageal and gastric carcinomas express multi-autocrine growth factors and hormones including epidermal growth factor (EGF), transforming growth factor (TGF)-alpha and beta, platelet-derived growth factor (PDGF), insulin-like growth factor (IGF) and sex hormones. Overexpression of EGF, TGF-alpha and EGF receptor (EGFR) by tumor cells is closely correlated with the tumor invasion and patient prognosis. This is substantiated by the facts that EGF and TGF-alpha act as autocrine growth factors and then induce the expression of mRNAs for multi-growth factors and their receptors (EGF, TGF-alpha, EGFR, ERBB2, PDGF). Moreover, they stimulate the expression of metalloproteinase genes suggesting that EGF and TGF-alpha successively evoke cascade phenomena which are most convenient for tumor progression, invasion and metastasis. On the other hand, multiple oncogene alterations take place in the process of tumor progression. HST-1 and INT-2 genes which is a member of fibroblast growth factor gene family, are amplified in approximately 50% of primary tumors and all the metastatic tumors of esophageal carcinomas. The amplification of ERBB2 gene in metastatic gastric carcinomas is detected more frequently than in primary carcinomas. Overexpression of multi-growth factor-receptor systems might lead to genetical alterations. Scirrhous gastric carcinoma has vast fibrous stroma with rapid and extensive growth and exhibits high malignancy. Its fibrous stroma may account for synchronous overexpression of EGF, TGF-alpha, PDGF, IGF and TGF-beta by tumor cells. Most of well differentiated adenocarcinomas show overexpression of p 185ERBB2 and coexpression of p 185ERBB2, and EGFR evidently correlates with high malignancy. In conclusion, the accumulation and interaction of several growth factors produced by tumor cells are necessary for the progression of human esophageal and gastric carcinomas. They may be attributed to genetic changes including activation of oncogenes, inactivation and deletion of anti-oncogenes and transcriptional regulatory sequences.


Plasma lipid analysis by thin-layer chromatography with flame ionisation detection and quantitation.
A method is presented whereby cholesterol, cholesterol ester, triacylglycerol, non-esterified fatty acid and polar lipid in plasma may be simultaneously quantitated. Following the addition of umbelliferyl palmitate as internal standard, plasma (0.1 ml) is extracted with chloroform/methanol (2 : 1, v/v). A portion of the extract is chromatographed on silica gel fused to a narrow cylindrical quartz rod. After chromatography the rod is traversed through a flame ionisation detector and the responses recorded and integrated. The procedure is shown to be sensitive, linear, reproducible and to compare well with conventional methods for the determination of plasma lipid classes.


5-aza-2'-deoxycytidine therapy in patients with acute leukemia inhibits DNA methylation.
The effect of 5-aza-2'-deoxycytidine (5-AZA-dCyd) on methylation of DNA in blood leukemic cells from patients with lymphoid and myeloid leukemia was investigated. After treatment with continuous infusion of 5-AZA-dCyd (1.0 mg/kg/h) the blood leukemic cells were isolated and incubated in vitro with [6-3H]deoxycytidine and the incorporation of radioactivity into 5-methylcytosine and cytosine of DNA determined. 5-AZA-dCyd produced greater than 70% inhibition of DNA methylation in the leukemic cells. The antileukemic action of 5-AZA-dCyd may be related to the inhibition of DNA methylation.


The association between Chinese Visceral Adipose Index and coronary heart disease: A cohort study in China.
The purpose of this study is to explore the relationship between Chinese visceral adipose index (CVAI) and the risk of coronary heart disease (CHD) in Chinese through a large cohort study. This study included 42,165 adults who were without CHD at baseline and who completed at least one annual follow-up between 2009 and 2016. We used the Cox proportional hazards model to estimate Hazard Ratios (HRs) and 95% Confidence Intervals (CIs) for the association between CVAI and risk of CHD. During the median follow-up of 3.36 years (154,808 person years), 520 participants developed CHD, including 374 males and 146 females. Compared with the first quartile of CVAI, the risk of CHD was significantly increased in the fourth quartile of CVAI in multivariate model (HR [95% CI]: 9.92 [5.45, 18.04], P < 0.001). Sensitivity analysis by excluding incident CHD developed in the first two years of follow-up reinforced our results. Gender stratification analyses showed that the relationship between CVAI and CHD risk was higher in males than that in females. The restricted cubic spline showed a non-linear dose-response relationship between CVAI and CHD risk. In addition, CVAI was associated with CHD risk in the subgroups of participants without T2DM, without hypertension, and without fatty liver. CVAI was significantly associated with the risk of CHD. Individuals should keep CVAI at normal level to prevent CHD.


Large vessel vasculitis in a patient with acute Q-fever: A case report.
Q fever is a zoonosis caused by the rickettsial organism Coxiella burnetii. Infection has an acute course, usually with a self-limited febrile illness and the possibility of the evaluation to a chronic course with endocardial involvement. The presence of autoantibodies and various autoimmune disorders have also been associated with C. burnetii infection. We report a case of acute Q fever in which the patient developed large vessel vasculitis. The FDG-PET/CT scan detected inflammation of the thoracic aortic wall, suggesting an unusual immunologic host response to acute Q fever infection.


Laminated single impression technique for cast posts and cores.
A laminated single impression technique for cast post and core has been described. Its advantages are the ease and versatility with prefabricated or customized post techniques (Fig. 14) and the one-step registration of single or multiple divergent canals. Its disadvantage is the necessity for additional laboratory procedures.


Nutritional differentiation among populations of the mediterranean shrub Dittrichia viscosa (Asteraceae) in siliceous and calcareous habitats.
Dittrichia (ex Inula) viscosa is a ruderal species that has recently become an invading plant in the northwest Mediterranean basin. A previous study failed to demonstrate the occurrence of morphologically differentiated ecotypes among populations of the species but suggested the existence of nutritional ecotypes. This latter possibility is examined here by comparing the ability of plants from contrasting habitats to control cation accumulation balance. Dittrichia viscosa plants, from eight siliceous habitats and nine calcareous habitats of southern France and neighbouring Spain and Italy, were cloned and grown together hydroponically with a solution simulating an acid soil with an aluminium constraint. Two independent hydroponic units containing solution supplemented with two levels of Al were used (2 Al levels x17 populations x3 genotypes x3 replicates). The growth and cation content (K, Ca, Mg and Na) of plant shoots and the chemical composition of the soil of each habitat were analysed. At the high Al level (1.1MM), populations differed in K, Ca and Mg plant proportions. Two groups could be distinguished: one containing all but one siliceous populations and the other containing all but one calcareous populations. Plants of the siliceous group accumulated proportionally more K and less Ca, and had better growth, than plants of the calcareous group, in the same way as calcifuge and calcicole species when grown on acid soil. At the lowest Al level (0.37MM), differences between siliceous and calcareous populations were less marked. The results suggest that differences in the ability of plants to control K and Ca balance, which appear to be of adaptive significance, could have arisen through selection, and that Dittrichia viscosa has evolved calcifuge and calcicole nutritional ecotypes in siliceous and calcareous habitats respectively. Various degrees of calcifugy, and to a lesser extent of calcicoly, can thus be suggested to occur among the studied populations, some in relation to the intensity of mineral stress in the natural habitats. So far, only functional traits have provided evidence of ecotypic differentiations within Dittrichia viscosa.


The effect of cryopreservation on ciliary beat frequency of human respiratory epithelium.
The effect of cryopreservation on ciliary activity of human nasal respiratory epithelium was evaluated. Samples were cryopreserved in a solution containing nutrient medium, 10% fetal calf serum, and two different concentrations (10 or 20%) of dimethyl sulfoxide and stored in liquid nitrogen at -196 degrees C for 2 weeks. Ciliary beat frequencies (CBF) of the samples before and after cryopreservation were compared. Mean CBF values did not differ significantly with both concentrations of dimethyl sulfoxide. The mean intrasample coefficient of variation of the CBF decreased significantly after cryopreservation. After thawing, CBF remained unchanged for at least 4 hr. It is concluded that normal ciliated epithelial cells can be frozen and stored in liquid nitrogen at 196 degrees C while maintaining their CBF.


Protein dynamics detected by magic-angle spinning relaxation dispersion NMR.
Magic-angle spinning (MAS) nuclear magnetic resonance (NMR) is establishing itself as a powerful method for the characterization of protein dynamics at the atomic scale. We discuss here how R1ρ MAS relaxation dispersion NMR can explore microsecond-to-millisecond motions. Progress in instrumentation, isotope labeling, and pulse sequence design has paved the way for quantitative analyses of even rare structural fluctuations. In addition to isotropic chemical-shift fluctuations exploited in solution-state NMR relaxation dispersion experiments, MAS NMR has a wider arsenal of observables, allowing to see motions even if the exchanging states do not differ in their chemical shifts. We demonstrate the potential of the technique for probing motions in challenging large enzymes, membrane proteins, and protein assemblies.


Post-procedural hypertension following transcatheter aortic valve implantation: incidence and clinical significance.
This study sought to investigate the blood pressure (BP) response after transcatheter aortic valve implantation (TAVI) and its correlation with short- and mid-term clinical outcomes. TAVI is an emerging therapy for aortic stenosis patients at high surgical risk. The acute hemodynamic sequelae of this procedure and their clinical relevance are yet unclear. Consecutive patients who underwent TAVI in a single center were prospectively monitored for BP response during 5 post-procedural days. Clinical parameters, adverse events, and medical treatment were recorded during hospitalization, at 30 days, and at 12 months after the procedure. Patients were divided according to their post-procedural BP response into 2 groups: increased BP and stable BP. One hundred and five patients were analyzed. Overall, systolic BP increased immediately after TAVI in the entire cohort by an average of 15 ± 31 mm Hg. This rise was sustained and led to intensification of antihypertensive treatment in 53 patients (51%); these patients were designated as the increased BP group. The increase in systolic BP after TAVI was associated with an increase in stroke volume and cardiac output and was not related to age, baseline cardiac function, or procedural outcomes. Patients with increased BP after TAVI had a significantly better prognosis with fewer adverse events in the hospital (21% vs. 62%, p < 0.01), after 30 days (30% vs. 71%, p < 0.01), and after 12 months (53% vs. 83%, p < 0.01) as compared with patients with stable BP. After TAVI, a substantial number of patients have a significant rise in systolic BP necessitating long-term treatment. This increase in BP is associated with an increase in cardiac output and predicts a better clinical outcome.


The Best Evidence for the Prevention and Management of Lower Extremity Deep Venous Thrombosis After Gynecological Malignant Tumor Surgery: A Systematic Review and Network Meta-Analysis.
To search and obtain the relevant evidence of prevention and management of lower extremity deep venous thrombosis (DVT) after gynecological malignant tumor operation and to summarize the relevant evidence. We searched the JBI evidence summary, up to date, the national comprehensive cancer network of the United States, the guide library of the National Institute of clinical medicine of the United Kingdom, PubMed, the Chinese biomedical literature database, CNKI, Wanfang, and other relevant evidence on the prevention and management of DVT in patients with gynecological malignant tumors. It includes clinical practice guidelines, best practice information book, expert consensus, evidence summary, original research, etc. The retrieval time limit is from database establishment till August 20, 2021. Two researchers independently evaluated the literature quality, combined with professional judgment, and extracted the literature that met the standards. Finally, 18 literatures were included, including eight guidelines, three evidence summaries, four systematic evaluations, two expert consensuses, and one best practice information volume. A total of 26 pieces of the best evidence on the prevention and management of postoperative venous thrombosis in gynecological malignant tumors were summarized. It includes risk assessment, drug prevention, mechanical prevention, management strategy, and health education. This study summarized the best evidence of risk, prevention, and health management of DVT in postoperative patients with gynecological malignant tumors to provide evidence-based basis for clinical nurses and to improve the nursing level.


Hydatid disease of bone. A case report.
A patient presented with a pathological fracture of the femur; on biopsy of the lesion the characteristic grapeskin cysts of hydatid disease poured out of the bone. The patient was treated conservatively.


Injury to dopaminergic neurons development via the Lmx1a/Wnt1 autoregulatory loop induced by simazine.
Simazine is a kind of persistent organic pollutant that is detected in both ground and water and has several routes of exposure. Here, we explored the mechanisms underlying simazine-related effects on dopaminergic neurons via development-related factors using mouse embryos and embryonic mesencephalic hybrid cell line (MN9D cells). We treated pregnant mice with 50 μg/kg bw, 200 μg/kg bw simazine from the 0.5 day to the 10.5 day of embryonic phase and MN9D cells with 600 μM simazine for 24 h to research the mechanism of dopaminergic neurons acute respond to simazine through preliminary experiments. Protein expressions of LIM homeobox transcription factor 1-alpha (Lmx1a) and LIM homeobox transcription factor 1-beta (Lmx1b) displayed a dose- and time-dependent increase after the exposure to simazine. In the 200 μg/kg bw of embryos and the 24h-600 μM of MN9D cells, protein levels of dopaminergic developmental factors were significantly upregulated, and dopaminergic function was significantly damaged for the abnormal expression of Dyt5b. We demonstrated simazine induced the injury to dopaminergic neurons via the Lmx1a/wingless-related integration site 1 (Wnt1) and Lmx1b pathways. In the transfection experiments, we knocked down Lmx1a and Lmx1b of cells to verify the potential target of simazine-induced injury to dopaminergic neurons, respectively. We detected the protein and mRNA levels of development-related genes of dopaminergic neurons and intracellular dopamine levels in different treatment groups. Based on our experiments' results, we demonstrated an acute response to 24 h-600 μM simazine treatment, the simazine-induced injury to dopaminergic neuronal which leads to abnormal dopamine levels and dopaminergic impairment is via the activation of the Lmx1a/Wnt1 autoregulatory loop. Lmx1a is a promising target in the search for the mechanisms underlying simazine-induced dopaminergic injury.


Superior analytical sensitivity of electromagnetic excitation compared to contact electrode instigation of transverse acoustic waves.
Quartz disks incorporated into an electrolyte flow-through configuration have been excited by both direct electrode contact and electromagnetic fields to generate propagating transverse acoustic waves in to the fluid. The conventional thickness-mode device was operated at the first harmonic (9 MHz) whereas the EM excited structure functioned successfully at 453 MHz (nominal 49th harmonic). The nature of signals produced by the two devices and potential contributions to noise are evaluated. A comparison of the response of the higher frequency sensor to the introduction of the protein neutravidin to the system reveals at least a seven times higher signal-to-noise ratio than is the result for the conventional bulk-acoustic wave structure. This increase in sensitivity coupled with the possibilities for tuning the frequency of the electromagnetic device and its potential for non-contact excitation offer significant advantages in terms of analytical sensor technology.


Theoretical study on the adsorption and oxidation of glucose on Au(111) surface.
While Au-based catalysts recently have shown tremendous potential in glucose oxidation to gluconic acid, the detailed reaction mechanism is still unclear, which impedes the development of direct glucose fuel cell (DGFC). Using density functional theory (DFT), we exhibit some new adsorption configurations and oxidation mechanisms by considering both the open chain form and the ring form of glucose on Au(111) surface in the presence of OH. The strong interactions between glucose and the OH adsorbed surface are obtained. Moreover, form the calculated energy pathways, the oxidation of glucose in the open chain involves the dissociation of the formyl C - H bond by the adsorbed OH, while the ring form glucose oxidation is initiated by O - H bond rupture rather than C - H bond scission and preferentially undergoes the ring-open process to generate the open chain form glucose. Meanwhile, the results demonstrate that the adsorbed OH assists in reducing the activation energy of reaction process.


Mapping visual working memory models to a theoretical framework.
The body of research on visual working memory (VWM)-the system often described as a limited memory store of visual information in service of ongoing tasks-is growing rapidly. The discovery of numerous related phenomena, and the many subtly different definitions of working memory, signify a challenge to maintain a coherent theoretical framework to discuss concepts, compare models and design studies. A lack of robust theory development has been a noteworthy concern in the psychological sciences, thought to be a precursor to the reproducibility crisis (Oberauer & Lewandowsky, Psychonomic Bulletin & Review, 26, 1596-1618, 2019). I review the theoretical landscape of the VWM field by examining two prominent debates-whether VWM is object-based or feature-based, and whether discrete-slots or variable-precision best describe VWM limits. I share my concerns about the dualistic nature of these debates and the lack of clear model specification that prevents fully determined empirical tests. In hopes of promoting theory development, I provide a working theory map by using the broadly encompassing memory for latent representations model (Hedayati et al., Nature Human Behaviour, 6, 5, 2022) as a scaffold for relevant phenomena and current theories. I illustrate how opposing viewpoints can be brought into accordance, situating leading models of VWM to better identify their differences and improve their comparison. The hope is that the theory map will help VWM researchers get on the same page-clarifying hidden intuitions and aligning varying definitions-and become a useful device for meaningful discussions, development of models, and definitive empirical tests of theories.


Passive--active immunization in a neonate treated with repeated doses of high-titred hepatitis B immune globulin.
A newborn infant, born to a HBsAg-positive drug addict with HBeAg and DNA-polymerase activity in serum, was treated with repeated very high doses of hepatitis B immune globulin (HBIg). The mother turned HBsAg-negative about 8 months after deliver and the HBIg prophylaxis was then discontinued. A check-up of the infant about a year later revealed normal liver function tests but significantly increased levels of antibodies against HBcAg and HBsAg indicating a post subclinical hepatitis B infection, apparently without harm to the infant.


Bladder hemangioma: ultrasonographic demonstration.
We report a child with bladder hemangioma, which is a very rare benign vascular tumor. Postvoid excretory urography and ultrasound of the bladder demonstrated the lesions. The merits and demerits of various imaging modalities and the possible role of computed tomography (CT) and magnetic resonance imaging (MRI) are also discussed.


Vedolizumab is effective and safe in elderly inflammatory bowel disease patients: a binational, multicenter, retrospective cohort study.
Immune modulating therapies are associated with an increased risk of infections and malignancies. This is of particular concern in elderly inflammatory bowel disease patients. This study aims to compare the safety and efficacy of vedolizumab between young and elderly inflammatory bowel disease patients. A binational, multicentre, retrospective, cohort study was performed from 2015 to 2019. Patients who underwent treatment with vedolizumab and were followed for at least 14 weeks were studied. They were divided according to age into groups: 40 years or less or 60 years or older. Clinical and endoscopic responses at weeks 14 and 52 and infection development were compared between young and elderly inflammatory bowel disease patient groups. There were 144 patients (82 Crohn's disease and 62 ulcerative colitis) in the elderly cohort and 140 patients (83 Crohn's disease and 57 ulcerative colitis) in the young cohort. The average age was 70.2 ± 7.3 years and 29.6 ± 5.7 years, respectively. Clinical and endoscopic responses were comparable between the groups (week 52 remission of Crohn's disease: 40% vs. 35%, P = 0.7; week 52 remission of ulcerative colitis: 48% vs. 51%, P = 0.84). Previous anti-tumour necrosis factor biological therapy was independently associated with poor clinical remission rates at week 52 (Crohn's disease: odds ratio 0.23, 95% confidence interval 0.06-0.79; P = 0.02 and ulcerative colitis: odds ratio 0.10 95% confidence interval 0.01-0.74; P = 0.024). There were significantly more infections in the elderly cohort (2% vs. 12%, P = 0.002), none of which were fatal. Vedolizumab is equally effective in elderly and young inflammatory bowel disease patients. The findings of this study demonstrate an increased risk of infections among the elderly treated with vedolizumab, which may be related to their age and underlying diseases.


Congenital penile curvature (chordee without hypospadias).
We treated 30 patients aged six months to nine years with congenital penile curvature from 1988 to 1993. Twenty-four patients appeared to have a primary curvature with normal corpus spongiosum. In 12 of these 24 patients dissecting skin and dartos fascia were adequate to straighten the penis. In the other 12 patients, artificial erection demonstrated a varied degree of convexity of the penis after the skin and dartos fascia release, implying a disproportion of the corpora cavernosa bodies. We corrected this deformity using dorsal tumica albuginea plications (TAP). The remaining 6 patients presented with a primary curvature and hypoplastic urethra. In 5 of these patients we divided the hypoplastic midportion of the urethra leaving the meatus naturally on the glans and replaced the midurethral segment using a tubularized island flap. Of these 5 patients 2 required TAP for penile straightening. The final patient with a hypoplastic urethra was managed by preserving the urethral plate and applying an only island flap urethroplasty. Complications were one fistula and two mild ventral penile curvatures, presently not severe enough for reoperation (mean follow-up 2.6 years). We present a systematic approach for the repair of congenital penile curvature using intraoperative artificial erection, TAP, and the island flap urethroplasty when needed.


Incidence of Frailty in Community-Dwelling United States Older Veterans.
Determine the incidence rates of frailty among community-dwelling older veterans. Population-based retrospective cohort study. Veterans Health Administration Medical Center study included community-dwelling veterans 60 years and older with determinations of frailty from 2013 to 2014 and followed until September 2019. A 31-item frailty index was generated at baseline and during each subsequent primary care encounters as a proportion of potential variables from electronic health record data. Period prevalence was calculated by dividing total number of cases of frailty during the baseline period. After adjusting for covariates, the association of frailty with mortality was determined using a multivariate Cox regression model. Using baseline and follow-up data, incidence rates of frailty per 1000 person/years based on event rates and mean duration of follow-up were calculated, including survivor and entire cohorts. Patients in this cohort were 16,761 veterans, mean age 72.18 (9.32) years, 74.00% Caucasian, 90.75% non-Hispanic, and 97.78% male. The period prevalence of frailty in this cohort was 20.84%. Over a median follow-up of 3.96 (interquartile range = 3.73) years, 25.86% of the baseline population died during follow up. Veterans with frailty had a higher all-cause mortality during follow up, adjusted hazard ratio = 3.12 (95% confidence interval 2.87-3.38), P value of < .0005. Among 10,513 veterans who survived a median follow-up of 4.81 (interquartile range = 3.12) years, 29.84% became frail. The incidence rate of frailty was 75.05 cases per 1000 person-years. Among the entire cohort of 13,268 nonfrail veterans, 29.93% became frail. The incidence rate of frailty was 84.03 cases per 1000 person-years. This study shows high incidence of frailty in community dwelling older US veterans. Future studies should be done for identification, implementation of adequate interventions aimed at preventing frailty or reducing frailty-related complications in community dwelling older individuals.


EGFL9 promotes breast cancer metastasis by inducing cMET activation and metabolic reprogramming.
The molecular mechanisms driving metastatic progression in triple-negative breast cancer (TNBC) patients are poorly understood. In this study, we demonstrate that epidermal growth factor-like 9 (EGFL9) is significantly upregulated in basal-like breast cancer cells and associated with metastatic progression in breast tumor samples. Functionally, EGFL9 is both necessary and sufficient to enhance cancer cell migration and invasion, as well as distant metastasis. Mechanistically, we demonstrate that EGFL9 binds cMET, activating cMET-mediated downstream signaling. EGFL9 and cMET co-localize at both the cell membrane and within the mitochondria. We further identify an interaction between EGFL9 and the cytochrome c oxidase (COX) assembly factor COA3. Consequently, EGFL9 regulates COX activity and modulates cell metabolism, promoting a Warburg-like metabolic phenotype. Finally, we show that combined pharmacological inhibition of cMET and glycolysis reverses EGFL9-driven stemness. Our results identify EGFL9 as a therapeutic target for combating metastatic progression in TNBC.


Clinical Significance of Splenic Hilar Dissection with Splenectomy in Advanced Proximal Gastric Cancer: An Analysis at a Single Institution in Japan.
Significance of splenic hilar node dissection with splenectomy is now denied for advanced gastric cancer of upper one-third of the stomach without invasion to the greater curvature by the Japan Clinical Oncology Group 0110, a pivotal randomized study from Japan. However, a question remains for tumors which involve the greater curvature, as this study excluded such tumors. We retrospectively analyzed 421 consecutive patients with gastric cancer who underwent curative total gastrectomy with splenectomy from 1992 to 2009. The survival curves, state of lymph node (LN) metastasis, and index of the estimated benefit from LN dissection of each station were evaluated according to the tumor location. The incidence of No. 10 metastasis was 9.3 % (39/421), with 15.9 % in patients with tumors involving the greater curvature (Gre group, n = 132) and 6.2 % in those without (non-Gre group, n = 289) (P = 0.032). The 5-year overall survival (OS) of patients with and without No. 10 metastasis was 35.4 and 43.1 % (P = 0.135) in the Gre group and 32.8 and 66.5 % (P = 0.0006) in the non-Gre group, respectively. The index of No. 10 LN dissection was 5.6 and 2.0 in the Gre and non-Gre groups, respectively. In the Gre group, the index was relatively higher in patients aged < 65 years, within pT3, and with Borrmann type 4 tumors. Splenectomy may have a survival benefit when a tumor shows involvement with the greater curvature, especially in relatively young patients and those without serosal exposure.


Degradation of carbamazepine in environmentally relevant concentrations in water by Hydrodynamic-Acoustic-Cavitation (HAC).
The antiepileptic drug carbamazepine is one of the most abundant pharmaceuticals in the German aquatic environment. The effect of low carbamazepine concentrations (1-50 μg L(-1)) is discussed controversially, but ecotoxicological studies revealed reproduction toxicity, decreased enzymatic activity and bioaccumulation in different test organisms. Therefore, as a preventive step, an efficient and cost-effective technique for wastewater treatment plants is needed to stop the entry of pharmaceuticals into the aquatic environment. Cavitation, the formation, growth, and subsequent collapse of gas- or vapor-filled bubbles in fluids, was applied to solve this problem. The technique of Hydrodynamic-Acoustic-Cavitation was used showing high synergistic effect. Under optimized conditions carbamazepine (5 μg L(-1)) was transformed by pseudo-first order kinetics to an extent of >96% within 15 min (27% by hydrodynamic cavitation, 33% by acoustic cavitation). A synergistic effect of 63% based on the sum of the single methods was calculated. Carbamazepine concentrations were monitored by a sensitive and selective immunoassay and after 60 min no known metabolites were detectable by LC-MS/MS.


Effect of CYP3A Inhibition and Induction on the Pharmacokinetics of Suvorexant: Two Phase I, Open-Label, Fixed-Sequence Trials in Healthy Subjects.
Suvorexant is an orexin receptor antagonist indicated for the treatment of insomnia, characterized by difficulties with sleep onset and/or sleep maintenance. As suvorexant is metabolized primarily by Cytochrome P450 3A (CYP3A), and its pharmacokinetics may be affected by CYP3A modulators, the effects of CYP3A inhibitors (ketoconazole or diltiazem) or an inducer (rifampin [rifampicin]) on the pharmacokinetics, safety, and tolerability of suvorexant were investigated. In two Phase I, open-label, fixed-sequence trials (Studies P008 and P038), healthy subjects received a single oral dose of suvorexant followed by co-administration with multiple once-daily doses of strong/moderate CYP3A inhibitors (ketoconazole/diltiazem) or a strong CYP3A inducer (rifampin). Treatments were administered in the morning: suvorexant 4 mg with ketoconazole 400 mg (Study P008; N = 10), suvorexant 20 mg with diltiazem 240 mg (Study P038; N = 20), and suvorexant 40 mg with rifampin 600 mg (Study P038; N = 10). Area under the plasma concentration-time curve from time zero to infinity (AUC0-∞), maximum plasma concentration (Cmax), half-life (t½), and time to Cmax (tmax) were derived from plasma concentrations of suvorexant collected at prespecified time points up to 10 days following CYP3A inhibitor/inducer co-administration. Adverse events (AEs) were recorded. Co-administration with ketoconazole resulted in increased exposure to suvorexant [AUC0-∞: geometric mean ratio (GMR); 90% confidence interval (CI) 2.79 (2.35, 3.31)] while co-administration with diltiazem resulted in a lesser effect [GMR (90% CI): 2.05 (1.82, 2.30)]. Co-administration with rifampin led to a marked decrease (88%) in suvorexant exposure. Consistent with morning administration and known suvorexant pharmacology, somnolence was the most frequently reported AE. These results are consistent with expectations that strong CYP3A inhibitors and inducers exert marked effects on suvorexant pharmacokinetics. In the context of a limited sample size, single suvorexant doses were generally well tolerated in healthy subjects when co-administered with/without a CYP3A inhibitor/inducer.


High-dose chemotherapy and autologous peripheral blood stem cell transplantation in adult patients with high-risk or advanced Ewing and soft tissue sarcoma.
Despite the availability of combined-modality treatment for Ewing sarcoma (ES) and soft tissue sarcomas (STS), results from independent groups still indicate a poor prognosis for high-risk and metastasized patients. The benefit of high-dose chemotherapy (HDCT) with autologous peripheral blood stem cell transplantation (ASCT) as compared to standard treatment is not defined. Here, we report of HDCT in 35 consecutive adult patients with poor-risk ES or rhabdomyosarcoma (n = 11) and STS (n = 24) undergoing ASCT between July 1992 and March 2003. At a median follow-up of 100.6 months after ASCT, 11 patients are alive, with nine in sustained complete remission (CR) and each one in partial remission (PR) and stable disease. Median overall survival (OS) from ASCT was 17.1 months. Response to pretreatment, Karnofsky index > 80%, R (0) resection and first-line ASCT were associated with long-term OS (p < 0.05). These data indicate that (1) patients achieving a CR or PR following induction, with preserved performance status and R (0) resection may benefit from ASCT and (2) that this can be an useful therapeutic modality in a subset of patients, in some achieving remarkable responses.


Relationship between antioxidant defense in Acanthamoeba spp. infected lungs and host immunological status.
The role of oxidative stress in the pathogenicity of acanthamoebiasis is an important aspect of the intricate and complex host-parasite relationship. The aim of this experimental study was to determine oxidative stress through the assessment of lipid peroxidation product (LPO) levels and antioxidant defense mechanism in Acanthamoeba spp. lung infections in immunocompetent and immunosuppressed hosts. In Acanthamoeba spp. infected immunocompetent mice we noted a significant increase in lung lipid peroxidation products (LPO) at 8 days and 16 days post infection (dpi). There was a significant upregulation in lung LPO in immunocompetent and immunosuppressed mice infected by Acanthamoeba spp. at 16 dpi. The superoxide dismutase activity decreased significantly in lungs in immunosuppressed mice at 8 dpi. The catalase activity was significantly upregulated in lungs in immunocompetent vs. immunosuppressed group and in immunocompetent vs. control mice at 16 dpi. The glutathione reductase activity was significantly lower in immunosuppressed group vs. immunosuppressed control at 24 dpi. We found significant glutathione peroxidase downregulation in immunocompetent and immunosuppressed groups vs. controls at 8 dpi, and in immunosuppressed vs. immunosuppressed control at 16 dpi. The consequence of the inflammatory response in immunocompetent and immunosuppressed hosts in the course of experimental Acanthamoeba spp. infection was the reduction of the antioxidant capacity of the lungs resulting from changes in the activity of antioxidant enzymes. Therefore, the imbalance between oxidant and antioxidant processes may play a major role in pathology associated with Acanthamoeba pneumonia.


Cell Proteins Interacting with the Human Immunodeficiency Virus in Immunoblotting can be Detected by R5- or X4- Tropic Human Immunodeficiency Virus Particles.
The present study reported a new immunoblot assay, with revelation by R5- or X4-whole free human immunodeficiency virus (HIV) particles or recombinant gp160. The assay was optimized to identify cell proteins interacting with HIV. Whole cell lysates were prepared from peripheral blood lymphocytes (PBLs), dendritic cells (DC), monocyte-derived macrophage (MDM), and Henrietta Lacks (Hela, wild-type or transfected with DC-specific intracellular adhesion molecule-3-Grabbing Non-Integrin, HeLa) and Human endometrial cells (HEC-1A) lines; HIV particles used were the R5-tropic HIV-1JRCSF and the X4-tropic HIV-1NDK. Experiments with PBL lysates and both viruses demonstrated different bands, including a unique band at 105-117 kDa in addition to nonspecific bands. The 105-117 kDa band migrated at the same level of that observed in controls using total PBL lysate and anti-CD4 mAb for detection and thus likely corresponds to the cluster difference (CD) 4 complex. Blots using lysates of DCs, MDM, HeLa cell line, and HEC-1A cell line allowed identifying several bands that positions were similar to that seen by recombinant gp160 or whole R5- or X4-HIV particles. Blot of whole lysates of various HIV target cells is recognized by free HIV particles and allows identifying a wide range of HIV-interacting cell proteins. Such optimized assay could be useful to recognize new cellular HIV attachment proteins.


Differences in pathogenic community assembly processes and their interactions with bacterial communities in river and lake ecosystems.
Pathogenic bacterial infections caused by water quality degradation are one of the most widespread environmental problems. Clarifying the structure of pathogens and their assembly mechanisms in lake ecosystems is vital to prevent the infestation of waterborne pathogens and maintain human health. However, the composition and assembly mechanisms of pathogenic bacterial communities in river and lake ecosystems are still poorly understood. In this study, we collected 17 water and 17 sediment samples from Lake Chaohu and its 11 inflow rivers. Sequencing of 16S rRNA genes was used to study bacterial pathogen communities. The results of the study showed that there was a significant difference (P < 0.05) in the composition of the pathogen community between riverine and lake habitats. Acinetobacter (36.49%) was the dominant bacterium in the river, whereas Flavobacterium (21.6%) was the most abundant bacterium in the lake. Deterministic processes (i.e., environmental filtering and species interaction) drove the assembly of pathogenic bacterial communities in the lake habitat, while stochastic processes shaped river pathogenic bacterial communities. Spearman correlation analysis showed that the α-diversity of bacterial communities was linearly and negatively linked to the relative abundance of pathogens. Having a higher bacterial community diversity had a suppressive effect on pathogen abundance. In addition, co-occurrence network analysis showed that bacterial communities were tightly linked to pathogenic bacteria. Pseudomonas aeruginosa and Salmonella enterica were identified as keystone species in an inflow water sampling network (W_FR), reducing the complexity of the network. These results provide a reference for assessments of water quality safety and pathogenic bacteria posing risks to human health in large freshwater lakes.


Native electrophoretic separation and femtomolar detection of 65Zn-containing proteins by storage phosphorimaging.
Over 300 zinc-containing proteins have been described and over 1000 genes in the human genome encode proteins with zinc finger domains. Despite the important role of zinc in mammalian physiology, understanding its cellular homeostasis remains limited. In this study, we demonstrate the utility of radioactive zinc detection using nondenaturating, native electrophoresis. We tested 65Zn-labeled enterocyte and enterocyte brush border membrane proteins and 65Zn-metallothionein. The radioactive decay of 65Zn is efficiently captured by storage phosphorimaging screen, enabling detection of 65Zn-labeled metalloproteins in subpicogram range. This powerful technique has a wide potential for studies of zinc absorption, incorporation of zinc into apoproteins and transcription factors that require zinc, zinc turnover in metallothionein, and other aspects of cellular zinc metabolism.


Homodimer formation of retinoid X receptor induced by 9-cis retinoic acid.
Retinoid response pathways are mediated by two classes of receptors, the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs). A central question is whether distinct response pathways are regulated by these two classes of receptors. The observation that the stereoisomer 9-cis-retinoic acid binds with high affinity to RXRs suggested that this retinoid has a distinct role in controlling RXR activity, but it was almost simultaneously discovered that RXRs function as auxiliary receptors for RARs and related receptors, and are essential for DNA binding and function of those receptors. Hence, although RARs seem to operate effectively only as heterodimeric RAR/RXR complexes, RXRs themselves apparently function predominantly, if not exclusively, as auxiliary receptors. Here we report that 9-cis-retinoic acid induces RXR homodimer formation. Our results demonstrate a new mechanism for retinoid action by which a ligand-induced homodimer mediates a distinct retinoid response pathway.


New potent accelerator of neurite outgrowth from Lawsonia inermis flower under non-fasting condition.
The methanolic extract of Lawsonia inermis L. (henna) showed accelerative effects on nerve growth factor-induced neurite outgrowth in PC12 cells under non-fasting conditions. To elucidate the active constituents responsible for the neuronal differentiation, we conducted a search of the constituents and examined their accelerative effects on neurite outgrowth in PC12 cells. We isolated a new acetophenone glycoside, inermioside A, which exerted a significant accelerative effect on neurite outgrowth. We also confirmed the activities of nine known compounds, including quercetin and lalioside. In addition, we found that quercetin, one of the active constituents, increased Vav3 mRNA expression.


Quantitative differentiation of breast lesions at 3T diffusion-weighted imaging (DWI) using the ratio of distributed diffusion coefficient (DDC).
To investigate the accuracy of diffusion coefficients and diffusion coefficient ratios of breast lesions and of glandular breast tissue from mono- and stretched-exponential models for quantitative diagnosis in diffusion-weighted magnetic resonance imaging (MRI). We analyzed pathologically confirmed 170 lesions (85 benign and 85 malignant) imaged using a 3.0T MR scanner. Small regions of interest (ROIs) focusing on the highest signal intensity for lesions and also for glandular tissue of contralateral breast were obtained. Apparent diffusion coefficient (ADC) and distributed diffusion coefficient (DDC) were estimated by performing nonlinear fittings using mono- and stretched-exponential models, respectively. Coefficient ratios were calculated by dividing the lesion coefficient by the glandular tissue coefficient. A stretched exponential model provides significantly better fits then the monoexponential model (P < 0.001): 65% of the better fits for glandular tissue and 71% of the better fits for lesion. High correlation was found in diffusion coefficients (0.99-0.81 and coefficient ratios (0.94) between the models. The highest diagnostic accuracy was found by the DDC ratio (area under the curve [AUC] = 0.93) when compared with lesion DDC, ADC ratio, and lesion ADC (AUC = 0.91, 0.90, 0.90) but with no statistically significant difference (P > 0.05). At optimal thresholds, the DDC ratio achieves 93% sensitivity, 80% specificity, and 87% overall diagnostic accuracy, while ADC ratio leads to 89% sensitivity, 78% specificity, and 83% overall diagnostic accuracy. The stretched exponential model fits better with signal intensity measurements from both lesion and glandular tissue ROIs. Although the DDC ratio estimated by using the model shows a higher diagnostic accuracy than the ADC ratio, lesion DDC, and ADC, it is not statistically significant. J. Magn. Reson. Imaging 2016;44:1633-1641.


The inferior olive of a prosimian primate Galago senegalensis. I. Conformation and spino-olivary projections.
Spino-olivary projections to inferior olive (IO) in a prosimian primate, Galago senegalensis, were studied by using a modification of the Fink and Heimer ('67) technique. Prior to examining the arrangement of spinal axons within IO, its conformation was determined from a series of cresyl violet acetate sections. Galago IO is composed of typical medial accessory (MAO), dorsal accessory (DAO), and principal (PO) olivary nuclei. The MAO is divisible into subgroups a, b, c, d, a ventrolateral outgrowth (VLO), and a dorso-medial cell column (DMCC). Cytoarchitectural and experimental data indicate that DAO is subdivided into lateral (DAOl) and medial (DAOm) parts. The PO of Galago consists of dorsal and ventral lamellae connected by a lateral bend. Following hemisections of the spinal cord at cervical, thoracic, and lumbar cord levels, degeneration is present in essentially identical subgroups of Galago IO. The preponderance of degeneration is found throughout the rostrocaudal extent of ipsilateral DAOl. Moderate amounts of axonal debris are located in caudal parts of subgroup a of ipsilateral MAO, and only a few degenerated fibers extend into adjacent subgroup b after cervical lesions. A distinct contralateral component is evident only following a C1 hemisection. The moderate numbers of degenerated axons found in contralateral DAOm arise exclusively from cervical levels C1 to C3. Spino-olivary fibers terminating in MAO appear to ascend in the ventral funiculus while the majority of those to DAOl course through the lateral funiculus.


Photobiology: Fish eggs go sunny side up.
The UV radiation in sunlight can damage organisms. A new study reveals that female zebrafish deposit a chemical sunscreen into their eggs to protect their developing embryos, a feat that has been lost in fish species whose embryos never experience sunlight.


Guidelines for management of intra-abdominal infections.
Intra-abdominal infections are one of the most common gastrointestinal emergencies and a leading cause of septic shock. A consensus conference on the management of community-acquired peritonitis was published in 2000. A new consensus as well as new guidelines for less common situations such as peritonitis in paediatrics and healthcare-associated infections had become necessary. The objectives of these Clinical Practice Guidelines (CPGs) were therefore to define the medical and surgical management of community-acquired intra-abdominal infections, define the specificities of intra-abdominal infections in children and describe the management of healthcare-associated infections. The literature review was divided into six main themes: diagnostic approach, infection source control, microbiological data, paediatric specificities, medical treatment of peritonitis, and management of complications. The GRADE(®) methodology was applied to determine the level of evidence and the strength of recommendations. After summarising the work of the experts and application of the GRADE(®) method, 62 recommendations were formally defined by the organisation committee. Recommendations were then submitted to and amended by a review committee. After 2 rounds of Delphi scoring and various amendments, a strong agreement was obtained for 44 (100%) recommendations. The CPGs for peritonitis are therefore based on a consensus between the various disciplines involved in the management of these patients concerning a number of themes such as: diagnostic strategy and the place of imaging; time to management; the place of microbiological specimens; targets of empirical anti-infective therapy; duration of anti-infective therapy. The CPGs also specified the value and the place of certain practices such as: the place of laparoscopy; the indications for image-guided percutaneous drainage; indications for the treatment of enterococci and fungi. The CPGs also confirmed the futility of certain practices such as: the use of diagnostic biomarkers; systematic relaparotomies; prolonged anti-infective therapy, especially in children.


Increase in middle cerebral artery velocity on breath holding: a simplified test of cerebral perfusion reserve.
Resting middle cerebral artery velocity (Vmca) as well as its rate of increase on breath holding was measured on both sides in 11 age matched controls (Group I), in six symptomatic patients with unilateral internal carotid artery occlusion (Group II) and in nine symptomatic patients with unilateral internal carotid stenosis of greater than 75% (Group III), using a transcranial doppler velocimeter. There was a significantly lower resting Vmca in Group II patients on the occluded side, but not on the stenosed side in Group III, but there was considerable overlap of results. However, during breath holding, the rate of increase of Vmca allowed better separation of the occluded side (Group II) from the contralateral normal side as well as from controls, and from the stenosed side in Group III. Also there was a lower rate of rise of Vmca on the stenosed side in Group III than controls. As a test in symptomatic patients with a relevant carotid occlusion, values of less than 2.4 mm/sec2 were found in 100% of patients and only 4.5% of controls. Reactivity to breath holding promises to be a useful test in the evaluation of symptomatic patients with extra cranial carotid artery disease.


Bedtime blues. Helping your children get a good night's sleep.
All new parents expect some broken nights but when a child's wakefulness becomes excessive it can lead to exhaustion and even marital breakdown. Sleep counsellors can help but are often in short supply.


Energetic salts from nitroformate ion.
Development of new energetic salts is the key factor in replacing low performance compounds in conventional formulations of high explosives as well as propellants. Ten salts based on the nitroformate anion and various nitrogen-rich cations were designed and their geometric optimizations carried out using the density functional method. With reasonable oxygen balance (from -36% to 0%), heats of formation (47-624 kJ mol(-1)) and high densities (1.81-1.89 g cm(-3)), the detonation velocity (D) and pressure (P) values of salts were calculated as 8.62-9.36 km s(-1) and 33.10-40.01 GPa, respectively. Lastly, the nitroformate salts studied in this work are of prospective interest as high performance explosives.


Increased serum levels of soluble vascular cell adhesion molecule-1 and E-selectin in patients with systemic sclerosis.
To determine the serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble E-selectin (sE-selectin) in patients with systemic sclerosis (SSc). Serum samples from 80 patients with SSc and 20 healthy control subjects were examined by a sensitive enzyme-linked immunosorbent assay. The serum levels of sVCAM-1 and sE-selectin were significantly higher in the patients with SSc than in the healthy controls. The serum levels of sVCAM-1 were correlated with the presence of pulmonary fibrosis, joint involvement and elevated erythrocyte sedimentation rate levels. The serum levels of sE-selectin were correlated with the presence of pulmonary fibrosis. These results suggest that endothelial activation is involved in the development of this disease.


Novel neuroprotective mechanism of action of rasagiline is associated with its propargyl moiety: interaction of Bcl-2 family members with PKC pathway.
Our studies have provided new insights into the biological mechanism of neuroprotection of the anti-Parkinson drug, rasagiline [N-propargyl-(1R)-aminoindan], involving the association of Bcl-2 family proteins with protein kinase C (PKC) pathway. In a model of serum withdrawal-induced apoptosis of rat pheochromocytoma PC12 cells, rasagiline and its propargyl moiety, N-propargylamine, decreased cell death via multiple neuroprotective pathways that include the stimulation of PKC phosphorylation; upregulation of PKCepsilon mRNA; induction of Bcl-X(L), Bcl-w, and brain-derived neurotrophic factor (BDNF) mRNAs; and downregulation of PKCgamma, Bad, and Bax mRNAs. Moreover, these drugs inhibited the cleavage and activation of pro-caspase-3 and poly(ADP-ribose) polymerase (PARP), while PKC inhibitor, GF109203X, reversed these actions. In addition, rasagiline decreased serum-free-induced levels of the important regulator of cell death, Bad, which was also blocked by GF109203X, indicating the involvement of PKC-dependent cell survival activity of rasagiline. Structure activity studies have established that N-propargylamine is essential for the novel neuroprotective and the neuronal cell survival activity of rasagiline since this moiety itself revealed similar protective effects and mechanisms of action. These results have led us to develop several multifunctional neuroprotective drugs containing the propargyl moiety and iron-chelating property for the treatment and/or prevention of neurodegenerative diseases.


Effect of social class on tumour size at diagnosis and surgical treatment in Danish women with breast cancer.
This study examines the effect of socio-economic inequalities on the tumour size at diagnosis and the choice of surgical treatment in Danish women with breast cancer. The Danish Breast Cancer Cooperative Group (DBCG) registers all women with breast cancer in Denmark and provides clinical register data on tumour size and surgical treatment for 1594 women <75 yr diagnosed with breast cancer between 1991 and 1996. A questionnaire including questions on social class was sent to the women. The tumour size at diagnosis (an indicator of access to treatment) and the surgical procedure (lumpectomy or mastectomy) for patients who were potential candidates for lumpectomy were the main outcome measures examined. Social class was not associated with tumour size at diagnosis. The tumour size was associated with age and the existence of a mammographic screening program in the county. However, treatment was strongly related to social class. Among women considered candidates for lumpectomy 77% underwent lumpectomy in the highest social class, compared to 50% in the lowest social class. Treatment was associated with age, tumour size and hospital status. It was concluded that the study showed no socio-economic inequalities related to access to health services as measured by tumour size, though significant social differences were found regarding treatment.


Subclavian artery aneurysm in association with congenital absence of ipsilateral internal carotid artery.
Aneurysms of the subclavian artery are rare. Similarly, congenital absence of the internal carotid artery is an extremely rare vascular anomaly. In this report, we discuss the case of a 54 year-old woman with an unusual aneurysm of the right subclavian artery in association with congenital absence of the right internal carotid artery. The aneurysm was successfully surgically repaired. On the basis of the appearance of the aneurysm and the absence of known atherosclerotic risk factors in this patient, it is hypothesized that the aneurysm is, in fact, congenital and related to anomalous development of the embryonic aortic arch branches.


Brain solutions for hearing problems during the COVID-19 pandemic and the misery of wearing a mask.
In COVID-19 pandemics days, wearing facial mask in public places has become obligatory to prevent the virus spread. In addition to its valuable protection, wearing facial mask can affect verbal communication in an adverse fashion and makes mutual understanding difficult. This happens because the mask eliminates the positive effect of the lip-reading phenomenon in direct communications. The mirror neuron system is responsible for automatic imitation, associative sequence learning, and motor mimicry. This system is a strong candidate justifying an unexpected action described in this article. Taking the facial mask off, to help the listener understanding better is a normal reaction. However, unexpectedly, one does the same as the listener when he/she is unable to comprehend the speaker. Herein, we suggest a hypothesis proposing the basic role of Mirror neuron system in this action. Most of the research on these cells have been conducted on monkeys, where the researchers observed that, these neuron discharge pulses both when a monkey performs an action and when it observes another monkey or a person committing the similar action. The driving mechanism of an unanticipated action of taking off mask while listening to a speaker is emphasized in this paper. Herein, we try to clarify how we came up with the idea that mirror neuron system drives a surprising action observed in COVID-19 pandemics days. As a result, we suggest possible clinical studies to verify our hypothesis.