In-patient withdrawal from long-term benzodiazepine use.
Twenty-one patients completed an intensive in-patient and out-patient group-based programme, to achieve withdrawal from long-term benzodiazepine dependence. By 6-month follow-up (post-withdrawal), eight patients (38%) had achieved a 'good' outcome. Generally, patients demonstrated moderate levels of psychiatric morbidity and depression in the pre-withdrawal phase; a diagnosis of a depressive disorder being associated with either an 'intermediate' or 'poor' outcome in comparison to patients receiving a diagnosis of anxiety disorder, who showed a predominantly 'good' outcome. Two patients committed suicide some time after withdrawal. Additionally, older patients fared less well than their younger counterparts. We conclude that maintenance benzodiazepine prescription, rather than withdrawal, may be the preferred treatment for some dependent patients. Furthermore, more data are required regarding the association, and causality, between depression and benzodiazepine withdrawal in long-term users.


Addressing disruptive behaviors within naturalistic developmental behavioral interventions: Clinical decision-making, intervention outcomes, and implications for practice.
Naturalistic developmental behavioral interventions are a common and well-researched type of intervention for young autistic children that focus on supporting social communication. These interventions often do not include formal guidelines on how to address disruptive behaviors, even though they are common among autistic children. This study measured how often clinicians delivering a specific naturalistic developmental behavioral intervention, Project ImPACT, adapted how they delivered the program to address disruptive behavior, and how these adaptations related to children's social communication outcomes at the end of their participation in the intervention. We also spoke with clinicians about how they address disruptive behavior and emotion regulation during their sessions. In this study, clinicians adapted Project ImPACT to address disruptive behaviors in about one-third of all sessions. These adaptations did not affect children's social communication outcomes. Clinicians discussed how they felt social communication, disruptive behavior, and emotion regulation are linked to one another and that they often try to integrate intervention strategies to address each of these areas. However, they note that a clinicians' approach to addressing disruptive behavior might vary depending on their level of training and experience. These results indicate several future directions for supporting clinicians in addressing behavior and regulation effectively within these types of interventions.


Electronic structure and linear optical properties of ZnSe and ZnSe:Mn.
As an important wide band-gap II-VI semiconductor, ZnSe has attracted much attention for its various applications in photo-electronic devices such as blue light-emitting diodes and blue-green diode lasers. Mn-doped ZnSe is an excellent quantum dot material. The electronic structures of the sphalerite ZnSe and ZnSe:Mn were calculated using the Vienna ab initio Simulation Package with ultra-soft pseudo potentials and Material Studio. The calculated equilibrium lattice constants agree well with the experimental values. Using the optimized equilibrium lattice constants, the densities of states and energy band structures were further calculated. By analyzing the partial densities of states, the contributions of different electron states in different atoms were estimated. The p states of Zn mostly contribute to the top of the valence band, and the s states of Zn and the s states of Se have major effects on the bottom of the conduction band. The calculated results of ZnSe:Mn show the band gap was changed from 2.48 to 1.1 eV. The calculated linear optical properties, such as refractive index and absorption spectrum, are in good agreement with experimental values.


Supercritical temperature synthesis of fluorine-doped VO2(M) nanoparticle with improved thermochromic property.
Fluorine-doped VO2(M) nanoparticles have been successfully synthesized using the hydrothermal method at a supercritical temperature of 490 °C. The pristine VO2(M) has the critical phase transformation temperature of 64 °C. The morphology and homogeneity of the monoclinic structure VO2(M) were adopted by the fluorine-doped system. The obtained particle size of the samples is smaller at the higher concentration of anion doping. The best reduction of critical temperature was achieved by fluorine doping of 0.13% up to 48 °C. The thin films of the fluorine-doped VO2(M) showed pronounced thermochromic property and therefore are suitable for smart window applications.


Neoadjuvant concurrent chemoradiation for curative treatment of penile squamous cell carcinoma.
Introduction. Penile cancer is a rare malignancy often treated with neoadjuvant chemotherapy followed by surgery. However, the utility of neoadjuvant chemoradiation, particularly when the tumor is resistant to chemotherapy alone, has not been established. In this study, we report a case of pT3cN3M0 penile squamous cell carcinoma with progression of nodal disease on chemotherapy, which was cured with use of neoadjuvant concurrent chemoradiation. Case Report. A 65-year-old male presented with a fixed left inguinal lymph node with associated firmness of the penile glans. Biopsies of both sites revealed evidence of squamous cell carcinoma. The patient underwent partial penectomy for the primary lesion and began neoadjuvant chemotherapy to reduce the size of the unresectable left inguinal node. However, he displayed disease progression in the left inguinal node. As such, we attempted concurrent chemoradiation therapy with regression of his nodal disease. The patient was able to undergo left inguinal node dissection and has no evidence of disease 18 months since his initial surgery. Conclusion. The use of neoadjuvant chemoradiation for bulky cN2-3 disease seems appropriate in the setting of progressive disease. Further studies are necessary to assess the utility of concurrent chemoradiation both in the neoadjuvant and salvage setting.


Mutations in olfactory signal transduction genes are not a major cause of human congenital general anosmia.
Anosmia affects the western world population, mostly the elderly, reaching to 5% in subjects over the age of 45 years and strongly lowering their quality of life. A smaller minority (about 0.01%) is born without a sense of smell, afflicted with congenital general anosmia (CGA). No causative genes for human CGA have been identified yet, except for some syndromic cases such as Kallman syndrome. In mice, however, deletion of any of the 3 main olfactory transduction components (guanidine triphosphate binding protein, adenylyl cyclase, and the cyclic adenosine monophosphate-gated channel) causes profound reduction of physiological responses to odorants. In an attempt to identify human CGA-related mutations, we performed whole-genome linkage analysis in affected families, but no significant linkage signals were observed, probably due to the small size of families analyzed. We further carried out direct mutation screening in the 3 main olfactory transduction genes in 64 unrelated anosmic individuals. No potentially causative mutations were identified, indicating that transduction gene variations underlie human CGA rarely and that mutations in other genes have to be identified. The screened genes were found to be under purifying selection, suggesting that they play a crucial functional role not only in olfaction but also potentially in additional pathways.


Diet, activity, habitat use, and ranging of two neighboring groups of food-enhanced long-tailed macaques (Macaca fascicularis).
We conducted observations of two neighboring groups of food-enhanced long-tailed macaques (Macaca fascicularis) over a period of one year. We examined their diet, behavior, habitat use, and ranging and how within-population variability reflected differential utilization of anthropogenic food resources. The group that consumed more anthropogenic food spent less time feeding on wild fruits and flowers, less time resting, and more time locomoting. They used forest habitats less often, and had a larger total home range and mean monthly home range. Some of these results contrasted with previous studies of food-enhanced primates which reported that food-enhancement resulted in smaller home ranges, shorter daily ranges, less time traveling and feeding, and more time resting. These contrasting patterns may relate to the nature of anthropogenic foods. In most studies of food-enhanced primates, anthropogenic food resources were abundant and concentrated but the macaques in this study used anthropogenic foods mainly from a few refuse sites where they had limited access, and from dispersed and irregular human provisioning. The group consuming more anthropogenic food therefore showed more spatially dispersed feeding activity and home range use, an effect that was likely further enhanced by lower natural food resource availability within their home range. The Singapore macaque population shows small-scale variability in feeding and ranging behavior, contributing to the complexity of their adaptive variability in a human-altered habitat. Our findings could have important implications for mitigating human-macaque conflict as measures applied at a higher spatial or population level may achieve highly inconsistent results, intensifying the challenges for wildlife managers.


Conditions for combining gene therapy with bone marrow transplantation in murine Krabbe disease.
Introduction: Krabbe disease (KD) is an autosomal recessive lysosomal disorder caused by mutations in the galactocerebrosidase (GALC) gene. This results in defective myelination in the peripheral and central nervous systems due to low GALC activity. Treatment at this time is limited to hematopoietic stem cell transplantation (HSCT) in pre-symptomatic individuals. While this treatment extends the lives of treated individuals, most have difficulty walking by the end of the first decade due to peripheral neuropathy. Studies in the murine model of KD, twitcher (twi) combining bone marrow transplantation (BMT) with AAVrh10-mGALC showed a great extension of life from 40 days to about 400 days, with some living a full life time. Methods: In order to find the optimum conditions for dosing and timing of this combined treatment, twi mice were injected with five doses of AAVrh10-mGALC at different times after BMT. Survival, as well as GALC expression were monitored along with studies of sciatic nerve myelination and possible liver pathology. Results: Dosing had a pronounced effect on survival and measured GALC activity. There was window of time after BMT to inject the viral vector and see similar results, however delaying both the BMT and the viral injection shortened the lifespans of the treated mice. Lowering the viral dose too much decreased the correction of the sciatic nerve myelination. There was no evidence for hepatic neoplasia. Conclusion: These studies provide the conditions optimum for successfully treating the murine model of KD. There is some flexibility in dosing and timing to obtain a satisfactory outcome. These studies are critical to the planning of a human trial combining the "standard of care", HSCT, with a single iv injection of AAVrh10-GALC.


Personality and depression: explanatory models and review of the evidence.
Understanding the association between personality and depression has implications for elucidating etiology and comorbidity, identifying at-risk individuals, and tailoring treatment. We discuss seven major models that have been proposed to explain the relation between personality and depression, and we review key methodological issues, including study design, the heterogeneity of mood disorders, and the assessment of personality. We then selectively review the extensive empirical literature on the role of personality traits in depression in adults and children. Current evidence suggests that depression is linked to traits such as neuroticism/negative emotionality, extraversion/positive emotionality, and conscientiousness. Moreover, personality characteristics appear to contribute to the onset and course of depression through a variety of pathways. Implications for prevention and prediction of treatment response are discussed, as well as specific considerations to guide future research on the relation between personality and depression.


The novel human beta-defensin-3 is widely expressed in oral tissues.
The purpose of this study was to investigate the expression of human beta-defensins (hBD), especially of the recently discovered hBD-3, in oral tissues by reverse-transcription polymerase chain reaction (RT-PCR). Primary oral keratinocytes (n = 3) and fibroblasts (n = 3), 64 non-inflamed and 40 inflamed oral tissue samples, and 10 samples of salivary glands, were examined. The transcripts for hBD-3 (61/64), as well as for hBD-1 (64/64) and hBD-2 (54/64), were found to be widely expressed in non-inflamed oral tissues. In contrast, only 23, 22 and 24 of the 40 inflamed tissues showed detectable hBD-1, -2 and -3 transcripts, respectively. In salivary glands, mRNA expression was constitutive for hBD-1, frequent for hBD-2 (9/10), and infrequent for hBD-3 (4/10). Oral keratinocytes, but not fibroblasts, contained transcripts for all beta-defensins, suggesting that the novel hBD-3 is also produced in the epithelial compartment of oral tissues. The results indicate an important role for the novel hBD-3, as well as for hBD-1 and hBD-2, in the innate oral epithelial host defense.


Glycyrrhetinic acid-decorated and reduction-sensitive micelles to enhance the bioavailability and anti-hepatocellular carcinoma efficacy of tanshinone IIA.
It remains a challenge to increase drug tumor-specific accumulation as well as to achieve intracellular-controlled drug release for hepatocellular carcinoma (HCC) chemotherapy. Herein, we developed a dual-functional biodegradable micellar system constituted by glycyrrhetinic acid coupling poly(ethylene glycol)-disulfide linkage-poly(lactic-co-glycolic acid) (GA-PEG-SS-PLGA) to achieve both hepatoma-targeting and redox-responsive intracellular drug release. Tanshinone IIA (TAN IIA), an effective anti-HCC drug, was encapsulated. Notably, it exhibited rapid aggregation and faster drug release in 10 mM dithiothreitol compared with the redox-insensitive control. Furthermore, GA-decorated micelles revealed HCC-specific cellular uptake in human liver cancer HepG2 cells with an energy-dependent manner, in which micropinocytosis and caveolae-mediated endocytosis were demonstrated as the major cellular pathways. The enhanced cytotoxicity and pro-apoptotic effects against HepG2 cells in vitro were observed, mediated by up-regulation of the intracellular ROS level, the increased cell cycle arrest at S phase, enhanced necrocytosis and up-regulation of caspase 3/7, P38 protein expression. In addition, TAN IIA-loaded micelles had a significantly prolonged circulation time, improved bioavailability, and resulted in an increased accumulation of TAN IIA in the liver. With the synergistic effects of HCC-targeting and controlled drug release, TAN IIA-loaded GA-PEG-SS-PLGA micelles significantly inhibited tumor growth and increased survival time in a mouse HCC-xenograft model. Collectively, the GA-PEG-SS-PLGA micelles with HCC-targeting and redox-sensitive characters would provide a novel strategy to deliver TAN IIA effectively for HCC therapy.


Traumatic brainstem deafness with normal brainstem auditory evoked potentials.
A 48-year-old woman became totally deaf after a head injury. Magnetic resonance imaging showed bilateral contusions around the inferior colliculi and the brainstem auditory evoked potentials (BAEP) failed to show any abnormality. This case demonstrates that small, symmetrical, bilateral lesions around the inferior colliculi may cause deafness and may still be associated with a normal BAEP.


Influence of Gratitude and Sense of Meaning in Life on Caregiving Self-Efficacy of Family Caregivers of Persons With Mental Illness.
Caregiving self-efficacy is a major factor in mitigating mental health issues and improving care satisfaction and care behavior in caregivers. This study investigated gratitude and sense of meaning in life's influence on caregiving self-efficacy of family caregivers of persons with mental illness. We collected data from 142 family caregivers using the Korean self-reporting scale of gratitude, meaning in life, and caregiving self-efficacy. Data analysis was performed using hierarchical regression analysis. Gratitude and the presence of meaning were significant factors in boosting caregiving self-efficacy. Therefore, these factors must be promoted to enhance the caregiving self-efficacy of family caregivers of persons with mental illness.


[Life-threatening appendicitis caused by Fusobacterium necrophorum].
Fusobacterium necrophorum is a well-known cause of Lemierre's syndrome. Recent studies suggest a causative association between F. necrophorum and acute appendicitis. We present a case of a 15-year-old previously healthy girl who presented with acute non-perforated appendicitis, intra-abdominal abscesses and thrombosis that led to omental necrosis. This resulted in a life-threatening septic shock with the need for prolonged intensive care. We suggest that F. necrophorum identified in pus from the abdomen caused this fulminant variation of appendicitis with findings similar to those seen with Lemierre's syndrome.


Decreased spontaneous activity and altered evoked nociceptive response of rat thalamic submedius neurons to lumbar vertebra thrust.
The thalamus is a central structure important to modulating and processing all mechanoreceptor input destined for the cortex. A large number of diverse mechanoreceptor endings are stimulated when a high velocity low amplitude thrust is delivered to the lumbar spine during spinal manipulation. The objective of this study was to determine if a lumbar thrust alters spontaneous and/or evoked nociceptive activity in medial thalamic submedius (Sm) neurons. Extracellular recordings were obtained from 94 thalamic Sm neurons in 54 urethane-anesthetized adult Wistar rats. Spontaneous activity was recorded 5 min before and after an L5 control (no thrust) and thrust (85% rat body weight; 100 ms) procedure. In a subset of responsive nociceptive-specific neurons, mean changes in noxious-evoked response (10-s pinch with clip; 795 g) at three sites (tail, contra- and ipsilateral hindpaw) were determined following an L5 thrust. Mean changes in Sm spontaneous activity (60 s bins) and evoked noxious response were compared using a mixed model repeated measures ANOVA with Bonferroni post hoc t tests and paired t tests, respectively. Compared to control, spontaneous Sm activity decreased 180-240 s following the lumbar thrust (p < 0.005). Inhibitory evoked responses were attenuated in the contralateral hindpaw following an L5 thrust compared to control (p < 0.05). No other changes in spontaneous or noxious-evoked Sm activity were found. A delayed, but prolonged suppression of spontaneous Sm activity along with changes in noxious-evoked inhibitory responses in the contralateral hindpaw following lumbar vertebra thrust suggest that thalamic submedius neurons may play a role in central pain modulation related to manual therapy intervention.


Children's Depression Inventory (CDI) and the Children's Depression Rating Scale-Revised (CDRS-R): reliability of the Hebrew version.
The Children's Depression Inventory (CDI) and Children's Depression Rating Scale-Revised (CDRS-R) are two widely used instruments, which measure depression in children and adolescents. This pilot study assessed the reliability of the Hebrew versions of these two instruments. Both CDRS-R and CDI were translated from English into Hebrew and then back translated. Seventeen healthy Israeli bilingual children volunteers were interviewed with both scales with a one day intermission between the interviews. Non-parametric correlations were used to compare scores in the two versions for each item. Results showed high agreement between the two versions for almost all items of the CDI and moderate to high for the CDRS-R. When CDRS-R summary scores for each item were compared, the agreement was high for this instrument as well. It is concluded that both CDI and CDRS-R Hebrew versions are reliable and can be used for studies of depression in the Israeli pediatric population.


[Microsurgery of peripheral nerves--new technologies and new requirements to surgical instruments].
The article presents new surgical instruments used in microsurgery of peripheral nerves. This ensured that effective well-known microsurgery methods have been improved and new techniques were introduced into practice. Main ways of solving of the problem of microsurgical instrument supply were defined in the article.


Copeptin Associates with Cause-Specific Mortality in Patients with Impaired Renal Function: Results from the LURIC and the 4D Study.
In chronic kidney disease (CKD) arginine vasopressin (AVP) cannot efficiently act via renal V2-receptors. AVP is upregulated leading to augmented activation of V1a- and V1b-receptors, which might contribute to the increase in cardiovascular and infectious complications in CKD. Here, we evaluate copeptin, a surrogate of AVP, and its association with cause specific mortality among patients within the whole spectrum of renal function. Copeptin was measured in baseline samples from the LURIC (n = 3131 patients with coronary angiograms) and the 4D-Study (n = 1241 type 2 diabetic hemodialysis patients). Patients were stratified into 4 groups: estimated glomerular filtration rate (eGFR) ≥90 mL/min/1.73 m2, 60-89 mL/min/1.73 m2, <60 mL/min/1.73 m2, and hemodialysis. The association of copeptin with mortality was assessed by Cox proportional hazards regression during 9.9 years of median follow-up in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study and 4 years of median follow-up in the German Diabetes Dialysis Study (4D-Study). Median copeptin increased with decreasing eGFR: 5.6 [interquartile range (IQR), 3.1-8.1] pmol/L (eGFR ≥90 mL/min/1.73 m2), 6.7 (2.9-10.5) pmol/L (eGFR 60-89 mL/min/1.73 m2), 15.3 (6.7-23.9) pmol/L (eGFR <60 mL/min/1.73 m2), and 80.8 (51.2-122) pmol/L (hemodialysis), respectively. Per SD increase in copeptin, the risk of coronary, infectious, and all-cause mortality increased by 25, 30, and 15% [hazard ratios (HR), 1.25; 95% CI, 1.13-1.39; HR, 1.30; 95% CI, 0.98-1.71; and HR, 1.15; 95% CI, 1.05-1.25], respectively, in patients with eGFR 60-89 mL/min/1.73 m2. Except for coronary death, results were similar among patients with more advanced renal disease. No significant association was found in patients with normal renal function. Copeptin concentrations were independently associated with coronary, infectious, and all-cause mortality in patients with renal impairment. In patients with normal renal function no significant association was found.


Exploring the association between grandparental care and child development: Evidence from China.
Grandparental care has become an involuntary choice in life for many families, mainly due to parents' unavailability to provide care and the lack of public or affordable private childcare. This phenomenon has raised concerns regarding the effects of grandparental care along the dimensions of child development. This study aims to test the association between grandparental care and child development in three dimensions: subjective wellbeing, behavioural traits and study performance. It used data from the 2018 China Family Panel Studies survey. First, the study outlines the data and the applied method with defined variables, on the basis of which an overview on the current stage of grandparental care is presented. It then examines the association of the impact of grandparental care in different dimensions using the general linear model, along with the other influencing factors. Finally, a cross-age group comparison is employed. The results of the study illustrate the difficulty of examining an overall picture of grandparental childcare, with its negative or positive associations. However, when evaluated using the features of different age groups of children's development, significant associations between grandparental care and child development are mainly found in the 6-11 age group, but the significant associations weaken or disappear in the 12-16 age group. Attachment theory and peer group theory are used to explain the difference between the two age groups.


Autotrophic growth of bacterial and archaeal ammonia oxidizers in freshwater sediment microcosms incubated at different temperatures.
Both bacteria and archaea potentially contribute to ammonia oxidation, but their roles in freshwater sediments are still poorly understood. Seasonal differences in the relative activities of these groups might exist, since cultivated archaeal ammonia oxidizers have higher temperature optima than their bacterial counterparts. In this study, sediment collected from eutrophic freshwater Lake Taihu (China) was incubated at different temperatures (4°C, 15°C, 25°C, and 37°C) for up to 8 weeks. We examined the active bacterial and archaeal ammonia oxidizers in these sediment microcosms by using combined stable isotope probing (SIP) and molecular community analysis. The results showed that accumulation of nitrate in microcosms correlated negatively with temperature, although ammonium depletion was the same, which might have been related to enhanced activity of other nitrogen transformation processes. Incubation at different temperatures significantly changed the microbial community composition, as revealed by 454 pyrosequencing targeting bacterial 16S rRNA genes. After 8 weeks of incubation, [(13)C]bicarbonate labeling of bacterial amoA genes, which encode the ammonia monooxygenase subunit A, and an observed increase in copy numbers indicated the activity of ammonia-oxidizing bacteria in all microcosms. Nitrosomonas sp. strain Is79A3 and Nitrosomonas communis lineages dominated the heavy fraction of CsCl gradients at low and high temperatures, respectively, indicating a niche differentiation of active bacterial ammonia oxidizers along the temperature gradient. The (13)C labeling of ammonia-oxidizing archaea in microcosms incubated at 4 to 25°C was minor. In contrast, significant (13)C labeling of Nitrososphaera-like archaea and changes in the abundance and composition of archaeal amoA genes were observed at 37°C, implicating autotrophic growth of ammonia-oxidizing archaea under warmer conditions.


Structure of the Cpf1 endonuclease R-loop complex after target DNA cleavage.
Cpf1 is an RNA-guided endonuclease that is emerging as a powerful genome-editing tool. Here we provide insight into its DNA-targeting mechanism by determining the structure of Francisella novicida Cpf1 with the triple-stranded R-loop generated after DNA cleavage. The structure reveals the machinery involved in DNA unwinding to form a CRISPR RNA (crRNA)-DNA hybrid and a displaced DNA strand. The protospacer adjacent motif (PAM) is recognized by the PAM-interacting domain. The loop-lysine helix-loop motif in this domain contains three conserved lysine residues that are inserted in a dentate manner into the double-stranded DNA. Unzipping of the double-stranded DNA occurs in a cleft arranged by acidic and hydrophobic residues facilitating the crRNA-DNA hybrid formation. The PAM single-stranded DNA is funnelled towards the nuclease site through a mixed hydrophobic and basic cavity. In this catalytic conformation, the PAM-interacting domain and the helix-loop-helix motif in the REC1 domain adopt a 'rail' shape and 'flap-on' conformations, respectively, channelling the PAM strand into the cavity. A steric barrier between the RuvC-II and REC1 domains forms the 'septum', separating the displaced PAM strand and the crRNA-DNA hybrid, avoiding DNA re-annealing. Mutations in key residues reveal a mechanism linking the PAM and DNA nuclease sites. Analysis of the Cpf1 structures proposes a singular working model of RNA-guided DNA cleavage, suggesting new avenues for redesign of Cpf1.


The migration of bronchoalveolar macrophages into hilar lymph nodes.
The migration of bronchoalveolar macrophages ( BAMs ) into hilar lymph nodes ( HLNs ) was investigated in order to assess their potential importance in pulmonary immune responses. 51Chromium- or 111Indium-labeled broncholaveolar cells ( BACs ) or purified BAMs were inoculated into the tracheas of syngeneic guinea pigs, and the number of cells that reached HLN at 24-72 hours was estimated by 1) measuring the cell-associated radioactivity in HLN and 2) counting the radiolabeled cells in autoradiographic preparations. It was determined that 400-2900 BAM/10(7) inoculated BACs or BAMs reached the HLNs within a 3-day period. From this data, it was calculated that in a normal animal as many as 8700 BAMs might reach HLNs daily. These migratory phagocytes are potentially important in facilitating the systemic spread of macrophage-resistant intracellular organisms from the lung. Furthermore, following phagocytosis and killing of microorganisms in the alveolus, BAMs might migrate to HLNs and present antigen to stimulate a primary immune response.


Combined targeting of EGFR-dependent and VEGF-dependent pathways: rationale, preclinical studies and clinical applications.
Cellular heterogeneity, redundancy of molecular pathways and effects of the microenvironment contribute to the survival, motility and metastasis of cells in solid tumors. It is unlikely that tumors are entirely dependent on only one abnormally activated signaling pathway; consequently, treatment with an agent that interferes with a single target may be insufficient. Combined blockade of functionally linked and relevant multiple targets has become an attractive therapeutic strategy. The EGFR and ERBB2 (HER2) pathways and VEGF-dependent angiogenesis have a pivotal role in cancer pathogenesis and progression. Robust experimental evidence has shown that these pathways are functionally linked and has demonstrated a suggested role for VEGF in the acquired resistance to anti-ERBB drugs when these receptors are pharmacologically blocked. Combined inhibition of ERBB and VEGF signaling interferes with a molecular feedback loop responsible for acquired resistance to anti-ERBB agents and promotes apoptosis while ablating tumor-induced angiogenesis. To this aim, either two agents highly selective against VEGF and ERBB respectively, or, alternatively, a single multitargeted agent, can be used. Preclinical studies have proven the efficacy of both these approaches and early clinical studies have provided encouraging results. This Review discusses the experimental rationale for, preclinical studies of and clinical trials on combined blockade of ERBB and VEGF signaling.


Comparison of CampyPak II with standard 5% oxygen and candle jars for growth of Campylobacter jejuni from human feces.
To determine optimal temperature and atmospheric conditions for isolating Campylobacter jejuni from fecal specimens of humans, we studied six laboratory isolates and 19 fecal specimens that were known to contain C. jejuni. We compared incubations in 5% oxygen, the CampyPak II (BBL Microbiology Systems, Cockeysville, Md.) with 6 plates per jar (CP-6) and 12 plates per jar (CP-12), and candle jars at 37 and 42 degrees C. At both temperatures, the colony sizes for the laboratory strains were larger in the 5% O2 and the CP-6 than under the other two conditions. For the primary isolations, CP-12 failed to detect one and two campylobacters at 42 and 37 degrees C, respectively, whereas the candle jar failed to detect one at 42 degrees C and four at 37 degrees C. Colony size was again larger in the 5% O2 and the CP-6. For all four atmospheric conditions tested, colonies were significantly larger at 42 degrees C than at 37 degrees C. These studies showed that incubation at 42 degrees C in either 5% O2 or the CampyPak II with six plates per jar was optimal for primary isolation of C. jejuni from fecal specimens of humans. The candle jars incubated at 42 degrees C appeared to be satisfactory for primary isolation of C. jejuni from human feces, but incubation at 37 degrees C was not acceptable.


Updated Concepts on Treatment Outcomes for Obstructive Sleep Apnea.
Obstructive sleep apnea is a highly prevalent and poorly understood condition that not only leads to significant individual patient health damage, but carries a large societal cost secondary to excessive healthcare utilization, motor-vehicle accidents, and work absenteeism. While a significant fund of knowledge about its damaging effects on the cardiovascular system and neural pathways has been gathered over the past few decades, the translation to direct patient care still presents numerous challenges. With the exception of clear issues such as socially unacceptable snoring and breathing irregularities, the exact cause and effect relationship between airway narrowing, hypoxemia, and sleep fragmentation with subjective sleep-related complaints and neurocognitive symptoms is less clear. Besides better-defined clinical diagnostic criteria, the need for clear serum, saliva, or urine biomarkers to assess the physiologic burden of disease remains a work in progress, as are well-defined long-term clinically relevant outcomes of interest. Here, readers will be guided to a critical evaluation on the current main metrics of sleep study, suggested steps on diagnostic and treatment goals, and introduced to the concept of a continuum of disease.


Review of two genera of Nirvanini leafhoppers (Hemiptera: Cicadellidae: Evacanthinae) from Africa.
Two Nirvanini genera, Afronirvana Evans and Afrokana Heller, including two new species, Afronirvana leptoclada sp. nov. and Afrokana transmaculata, sp. nov. from Africa are described. One new combination, Afronirvana africana (Heller) n. comb., is proposed. The female genitalia of these two genera are described and illustrated for the first time. Afronirvana and Afrokana are similar to the Oriental Kana Distant (= Yaoundea Linnavuori, syn. nov. with K. semela (Linnavuori), n. comb.) in having the aedeagus straight through most of its length but with a posteroventrally curved distal section that is strongly appressed to the shaft. Descriptions, illustrations and a key to species of Afronirvana and Afrokana are provided.


A Study on the Jejungwon Hospital Building in Jaedong and Gurigae, and Uses of the Hospital after its Relocation.
Jejungwon hospital, the first modern healthcare facility to be built in Korea, was built at Jaedong in 1885 and moved to Gurigae in 1887. Finally, it was moved to Dodong, outside the Namdaemun Gate, and its name was changed to Severance Hospital. The Jaedong Jejungwon hospital was located at a former house of HONG Youngsik, and it was expanded by renovating existing buildings and constructing new buildings in 2 years. The Gurigae Jejungwon hospital, which was located near Myeongdong Cathedral, was bigger than the Jaedong Jejungwon one and even provided residence to doctors. Jejungwon hospital was a good example of the healthcare facilities that were available in early modern Korea; however, due to a lack of historical materials, it is not easy to analyze the buildings of Jejungwon hospital. Recently, several architectural drawings made by Japanese and photographs taken by foreigners in the early 20th century were discovered, which help us to understand the buildings of the Jejungwon hospitals in Jaedong and Gurigae. This study analyzes the locations and layouts of the buildings of Jejungwon hospital and, furthermore, traces the history of Jejungwon hospital following its relocation. The Jaedong Jejungwon hospital was located at 35 Jaedong, as already known. By analyzing the architectural drawing of Kyeongseong Women's High-School Dormitory, the exact size of the existing building of Jaedong Jejungwon was calculated as 12m × 3.9m. Since the relocation of Jejungwon hospital to Gurigae in 1887, the remnants of Jejungwon buildings were used as Gwangjewon (1900-1907); a vaccine-manufacturing plant (1907-1910); and, finally, the dormitory of Kyeongseong Women's High School(1910s-1950s). The Gurigae Jejungwon hospital was assumed to be located at 193, 2nd street of Koganecho () and 4, 1st street of Meijicho (). In particular, the residence of Avison, which was built after 1894, was located at 4, 1st Street of Meijicho, the place with the highest elevation compared to surrounding areas. After 1905, Stevens, a foreign affairs adviser, lived there for one year, following which the Korean government office for agriculture and industry took over the place. The buildings that were used as the hospital at 193, 2nd street of Koganecho were transformed into the Daedong Japanese Club. By analyzing the newly found research materials, it is possible to examine and revise the previous research on the Jaedong Jejungwon and Gurigae Jejungwon hospital buildings. Furthermore, it is noteworthy that the buildings of Jejungwon hospital in Jaedong and Gurigae have been reused as healthcare facilities over the years.


The effects of alerting signals in masked priming.
Alerting signals often serve to reduce temporal uncertainty by predicting the time of stimulus onset. The resulting response time benefits have often been explained by facilitated translation of stimulus codes into response codes on the basis of established stimulus-response (S-R) links. In paradigms of masked S-R priming alerting signals also modulate response activation processes triggered by subliminally presented prime stimuli. In the present study we tested whether facilitation of visuo-motor translation processes due to alerting signals critically depends on established S-R links. Alerting signals resulted in significantly enhanced masked priming effects for masked prime stimuli that included and that did not include established S-R links (i.e., target vs. novel primes). Yet, the alerting-priming interaction was more pronounced for target than for novel primes. These results suggest that effects of alerting signals on masked priming are especially evident when S-R links between prime and target exist. At the same time, an alerting-priming interaction also for novel primes suggests that alerting signals also facilitate stimulus-response translation processes when masked prime stimuli provide action-trigger conditions in terms of programmed S-R links.


[Neonatal hyperthyroidism in non-diagnosed Basedow's disease of the mother. Problems of diagnosis and therapy illustrated by a case history].
A male preterm infant (born at 34 weeks, birth weight 2130 g) developed jaundice (total bilirubin 7.4 mg/dl), hepatosplenomegaly, thrombocytopenia (82,000/microliters) and a raised C-reactive protein (1.2 mg/dl). Although sepsis was suspected, no organism was demonstrated. When the mother visited the child for the first time after 2 weeks, she had florid hyperthyroidism. This explained many of the child's clinical features (poor weight gain, tachycardia, exophthalmos). Both mother and child had raised TSH receptor antibodies (mother: 684.6 U/l; 54.1 U/l, normal < 15 U/l), an increased free T4 and a suppressed TSH. Because of the tachycardia, the child was treated with propranolol (1 mg/kg.d for 5 weeks). He was also initially given Lugol's solution (25 mg iodide/kg.d for 1 week) and then propylthiouracil (7 mg/kg.d) because of the increasing total T3. L-Thyroxine replacement was subsequently required for a period of 2.5 weeks because of treatment-related hypothyroidism. Since stopping treatment (at 12 weeks of age), the child has developed normally.--Neonatal hyperthyroidism due to transplacental transfer of TSH receptor antibodies associated with maternal Graves' disease is a rare self-limiting condition. However, it may pose considerable danger to the child both in utero and postnatally (with a mortality if untreated of up to 20%). Interdisciplinary cooperation is essential.


The neural basis of ego- and allocentric reference frames in spatial navigation: evidence from spatio-temporal coupled current density reconstruction.
Different strategies in spatial navigation during passages through computer-simulated tunnels were investigated by means of EEG source reconstruction. The tunnels consisted of straight and curved segments and provided only visual flow, but no landmark, information. At the end of each tunnel passage, subjects had to indicate their end position relative to the starting point of the tunnel. Even though the visual information was identical for all subjects, two different strategy groups were identified: one group using an egocentric and the other group an allocentric reference frame. The current density reconstruction revealed the use of one or the other reference frame to be associated with distinct cortical activation patterns during critical stages of the task. For both strategy groups, an occipito-temporal network was dominantly active during the initial, straight tunnel segment. With turns in the tunnel, however, the activation patterns started to diverge, reflecting translational and/or rotational changes in the underlying coordinate systems. Computation of an egocentric reference frame was associated with prevailing activity within a posterior parietal-premotor network, with additional activity in frontal areas. In contrast, computation of an allocentric reference frame was associated with dominant activity within an occipito-temporal network, confirming right-temporal structures to play a crucial role for an allocentric representation of space.


Hypophonia as a sign of thalamus lesion: a case report.
Hypophonia is a neurological sign usually seen after brainstem or peripheral damage, either at the recurrent laryngeal nerve or vocal cord level. However, it has been described as a sign of supratentorial strokes in a few studies, specifically when anterior and ventral thalamic involvement is reported. In addition, it is a prominent sign of other neurological disorders such as Parkinson disease and other extrapyramidal conditions. We describe a case of hypophonia secondary to a left thalamic hemorrhage, after a careful search of other potential causes of this deficit, and we discuss the underlying neuroanatomical circuits.


Repeated neurovascular imaging in subarachnoid hemorrhage when initial studies are negative.
Approximately 15% of patients with non-traumatic subarachnoid hemorrhage have no causative lesion identified on their initial angiogram. We present two patients with non-traumatic subarachnoid hemorrhage with negative initial angiograms who were subsequently found to have small basilar perforator aneurysms on delayed neurovascular imaging. We discuss the possible mechanisms for false negative diagnostic cerebral angiograms. These patients support the current standard of care with repeat angiography in cases of subarachnoid hemorrhage when no causative lesion can be identified on initial neurovascular imaging.


Color Doppler indices of orbital arterial flow in end-stage renal disease patients; are the changes related to chronic hemodialysis or chronic renal failure?
Endothelial injury is a well-known complication in chronic kidney disease (CKD) and hemodialysis. One of the sites in which early vascular changes may be detected is the retina. Of course, these flow changes may not be detected in ophthalmologic exams, but it seems that color Doppler sonography of retinal arteries may be helpful in these cases. In previous studies on CKD patients who underwent chronic hemodialysis,hemodynamic changes were noted in retinal arteries, but no study has been performed to determine which of the two processes (CKD or chronic hemodialysis) can produce these changes. In this study, we tried to answer this question. Doppler ultrasonography of the orbital vasculature including the ophthalmic artery and the central retinal artery was carried out in 17 patients (34 eyes) with chronic renal failure (CRF) who underwent hemodialysis, 17 patients (34 eyes)with CRF without a history of hemodialysis and 17 normal patients (34 eyes). The peak systolic velocity (PSV), end diastolic velocity (EDV) and resistance index were measured excluding hypertensive, diabetic patients and patients with cardiovascular disease. The mean PSV and EDV were lower only in the ophthalmic artery of CRF patients irrespective of the history of hemodialysis (PSV was 35.2 in hemodialysis, 38.8 in CRF and 51.6 in normal patients, P value = 0.001 and EDV was 7.4, 9.4, 11.8, respectively, P value =0.001) with no significant difference in the resistance index of the ophthalmic artery and other parameters [EDV, PSV, Resistance Index (RI)] in the central retinal artery. The mean PSV and DSV in the ophthalmic artery were lower only in the ophthalmic artery of CRF patients regardless of the history of hemodialysis. No significant difference in the resistance index of the ophthalmic artery and other parameters (EDV, PSV) of the central retinal artery were noted between different groups. These findings suggest that microvascular disease and endothelial cell dysfunction of the orbital vasculature are related to CRF and not to chronic hemodialysis.


Perceiving and acting upon spaces in a VR rugby task: expertise effects in affordance detection and task achievement.
This study used a virtual, simulated 3 vs. 3 rugby task to investigate whether gaps opening in particular running channels promote different actions by the ball carrier player and whether an effect of rugby expertise is verified. We manipulated emergent gaps in three different locations: Gap 1 in the participant's own running channel, Gap 2 in the first receiver's running channel, and Gap 3 in the second receiver's running channel. Recreational, intermediate, professional, and nonrugby players performed the task. They could (i) run with the ball, (ii) make a short pass, or (iii) make a long pass. All actions were digitally recorded. Results revealed that the emergence of gaps in the defensive line with respect to the participant's own position significantly influenced action selection. Namely, "run" was most often the action performed in Gap 1, "short pass" in Gap 2, and "long pass" in Gap 3 trials. Furthermore, a strong positive relationship between expertise and task achievement was found.


Setting research priorities to reduce malaria burden in a post graduate training programme: lessons learnt from the Nigeria field epidemiology and laboratory training programme scientific workshop.
Although several research groups within institutions in Nigeria have been involved in extensive malaria research, the link between the research community and policy formulation has not been optimal. The workshop aimed to assist post graduate students to identify knowledge gaps and to develop relevant Malaria-related research proposals in line with identified research priorities. A training needs assessment questionnaire was completed by 22 students two week prior to the workshop. Also, a one page concept letter was received from 40 residents. Thirty students were selected based the following six criteria: - answerability and ethics; efficacy and impact; deliverability, affordability; scalability, sustainability; health systems, partnership and community involvement; and equity in achieved disease burden reduction. The workshop was over a three day period. The participants at the workshop were 30 Nigeria Field Epidemiology and Laboratory Training Programme (NFELTP) residents from cohorts 4 and 5. Ten technical papers were presented by the experts from the academia, National Malaria Elimination (NMEP) Programme, NFELTP Faculty and Implementing partners including CDC/PMI. Draft proposals were developed and presented by the residents. The "strongest need" for training was on malaria prevention, followed by malaria diagnosis. Forty seven new research questions were generated, while the 19 developed by the NMEP were shared. Evaluation revealed that all (100%) students either "agreed" that the workshop objectives were met. Full proposals were developed by some of the residents. A debriefing meeting was held with the NMEP coordinator to discuss funding of the projects. Future collaborative partnership has developed as the residents have supported NMEP to develop a research protocol for a national evaluation. Research prioritization workshops are required in most training programmes to ensure that students embark on studies that address the research needs of their country and foster collaborative linkages.


Relationship between brain perfusion computed tomography variables and cerebral perfusion pressure in severe head trauma patients.
To compare brain perfusion-computed tomography (CT) results with invasive cerebral perfusion pressure (CPP) monitoring in severe head trauma patients. Prospective cohort study. Emergency room and surgical intensive care unit of our hospital. Sixty-one severe head trauma patients. We prospectively collected 103 perfusion-CT examinations with simultaneous measurement of mean arterial pressure and intracranial pressure, affording calculation of CPP. The statistical relationship between perfusion-CT results and the corresponding CPP values was evaluated using Wilcoxon (Mann-Whitney) and generalized F-tests. The functional outcome of the 61 patients was evaluated 3 months after trauma on the basis of the Glasgow Outcome Scale score and compared between groups using Fisher's exact tests. Perfusion-CT enabled us to distinguish between two groups of patients. Within each group, a significant correlation (p <.001) between the CPP values and the corresponding perfusion-CT results was demonstrated. There was also a significant correlation (p <.001) between the CPP values and the extent of the abnormal perfusion-CT areas (R up to.817). The first group was characterized by a weak dependence of perfusion-CT results on the corresponding CPP values (low slope) and the second group by a strong dependence (steep slope). These groups were interpreted as having preserved (or pseudo) and impaired cerebral vascular autoregulation, respectively. The functional outcome was better in the second group of patients. Intermittent perfusion-CT measurements plus continuous CPP measurement provide more information than continuous CPP alone. Perfusion-CT gives unique information regarding regional heterogeneity of brain perfusion. It might allow clinicians to distinguish between patients with preserved auto-regulation (or pseudoautoregulation) and those with impaired autoregulation and could therefore guide interpretation of CPP measurements and therapy.


Unravelling the Role of Habenula Subnuclei on Avoidance Response: Focus on Activation and Neuroinflammation.
Understanding the mechanisms responsible for anxiety disorders is a major challenge. Avoidance behavior is an essential feature of anxiety disorders. The two-way avoidance test is a preclinical model with two distinct subpopulations-the good and poor performers-based on the number of avoidance responses presented during testing. It is believed that the habenula subnuclei could be important for the elaboration of avoidance response with a distinct pattern of activation and neuroinflammation. The present study aimed to shed light on the habenula subnuclei signature in avoidance behavior, evaluating the pattern of neuronal activation using FOS expression and astrocyte density using GFAP immunoreactivity, and comparing control, good and poor performers. Our results showed that good performers had a decrease in FOS immunoreactivity (IR) in the superior part of the medial division of habenula (MHbS) and an increase in the marginal part of the lateral subdivision of lateral habenula (LHbLMg). Poor performers showed an increase in FOS in the basal part of the lateral subdivision of lateral habenula (LHbLB). Considering the astroglial immunoreactivity, the poor performers showed an increase in GFAP-IR in the inferior portion of the medial complex (MHbl), while the good performers showed a decrease in the oval part of the lateral part of the lateral complex (LHbLO) in comparison with the other groups. Taken together, our data suggest that specific subdivisions of the MHb and LHb have different activation patterns and astroglial immunoreactivity in good and poor performers. This study could contribute to understanding the neurobiological mechanisms responsible for anxiety disorders.


Performance evaluation of common effluent treatment plant for tanneries at Pallavaram CETP.
The Pallavaram Tanners Industrial Effluent Treatment Company Limited has been a forerunner in ensuring cleaner and safe environment. The project was implemented by a company formed by the tanners of the Pallavaram area. Tamil Nadu Pollution Control Board (TNPCB) was the counterpart of UNIDO and took the overall responsibility for implementation of the project. The present study has been undertaken to evaluate performance efficiency of the treatment plant. Water samples were collected at different stages of treatment units and analysed for the major water quality parameters, such as pH, biological oxygen demand (BOD), chemical oxygen demand (COD), total suspended solids (TSS) and total dissolved solids (TDS). The performance efficiency of each unit in treating the pollutants was calculated. The generated data presented evidence to that the common effluent treatment plant has been working with the norms of TNPCB and meeting the discharge standard limits.


Prognostic Impact of N2 of the Primary Tumour in Surgical Resection for Colorectal Liver Metastases.
The status of lymph node metastasis of primary tumours remains to be completely investigated. This study investigated the prognostic impact of the degree of primary lymph node metastasis in patients with colorectal liver metastasis. We retrospectively analysed the clinical data of 106 patients with colorectal liver metastases who underwent surgical resection. Prognostic factors, including the degree of the positive primary lymph nodes, positive lymph node ratio, and log odds of positive lymph nodes, were evaluated. The T factor and N2 status were independent risk factors for overall survival in patients who underwent surgical resection. Survival was significantly lower in the N2 group than in the N0-1 group. Additionally, ≥N2 status showed better prognostic performance than ≥N1 status. N2 of primary tumours is an independent useful prognostic factor in colorectal liver metastasis and can help determine the indication of surgical resection and pre/post-operative chemotherapy.


Constructing intervals for the intracluster correlation coefficient using Bayesian modelling, and application in cluster randomized trials.
Studies in health research are commonly carried out in clustered settings, where the individual response data are correlated within clusters. Estimation and modelling of the extent of between-cluster variation contributes to understanding of the current study and to design of future studies. It is common to express between-cluster variation as an intracluster correlation coefficient (ICC), since this measure is directly comparable across outcomes. ICCs are generally reported unaccompanied by confidence intervals. In this paper, we describe a Bayesian modelling approach to interval estimation of the ICC. The flexibility of this framework allows useful extensions which are not easily available in existing methods, for example assumptions other than Normality for continuous outcome data, adjustment for individual-level covariates and simultaneous interval estimation of several ICCs. There is also the opportunity to incorporate prior beliefs on likely values of the ICC. The methods are exemplified using data from a cluster randomized trial.


Skyrmion Qubits: A New Class of Quantum Logic Elements Based on Nanoscale Magnetization.
We introduce a new class of primitive building blocks for realizing quantum logic elements based on nanoscale magnetization textures called skyrmions. In a skyrmion qubit, information is stored in the quantum degree of helicity, and the logical states can be adjusted by electric and magnetic fields, offering a rich operation regime with high anharmonicity. By exploring a large parameter space, we propose two skyrmion qubit variants depending on their quantized state. We discuss appropriate microwave pulses required to generate single-qubit gates for quantum computing, and skyrmion multiqubit schemes for a scalable architecture with tailored couplings. Scalability, controllability by microwave fields, operation time scales, and readout by nonvolatile techniques converge to make the skyrmion qubit highly attractive as a logical element of a quantum processor.


[Case report of extra-intestinal manifestation of salmonella infection].
The case history of a 75 year old man is demonstrated, who developed an abscess in the scar after B-II-resection 30 years ago. In this abscess S. typhi murium was detected. Diabetes mellitus was an additional risk factor. A review of the literature is given concerning extraintestinal manifestations of salmonellosis with emphasis to the predisposing conditions.


Oligosaccharides containing fucose linked alpha(1-3) and alpha(1-4) to N-acetylglucosamine cause decompaction of mouse morulae.
Two- to four-cell and eight-cell mouse embryos were incubated in various fucosylated and unfucosylated oligosaccharides, fucose binding protein, and fucosylated BSA. Compaction at the eight-cell stage was reversed by a mixture containing the oligosaccharides lacto-N-fucopentaose II (80-90%), in which fucose is linked alpha(1-4) to N-acetylglucosamine, and lacto-N-fucopentaose III (10-20%), in which fucose is linked alpha(1-3) to N-acetylglucosamine. Pure lacto-N-fucopentaose III (LNFP III) and 3-fucosyl lactose (containing fucose alpha(1-3)glucose) had a similar effect. All three molecules affected blastocyst formation. Various closely related fucosylated and unfucosylated oligosaccharides did not induce decompaction or inhibit blastocyst formation. The proportion of embryos incubated from the two- to four-cell stage in LNFP II/III which reached the eight-cell stage and formed blastocysts was reduced. Those which formed compact morulae subsequently decompacted. Precompact or early compacting eight-cell embryos incubated in LNFP II/III compacted normally but subsequently decompacted and failed to form blastocysts. Decompaction of eight-cell embryos in LNFP II/III occurred during a specific period of development (80-90 hr post-hCG) and was reversible up to 84-86 hr post-hCG, but not by 92 hr post-hCG. The period of sensitivity to LNFP II/III was associated with the decrease in the ability of calcium-free medium to cause decompaction. It appears that LNFP II/III interferes with a later calcium-independent phase of compaction and we propose that LNFP III and II inhibit an endogenous lectin-saccharide interaction between membranes involved in the stabilization of compaction.


Long-term effect of dual antiplatelet treatment after off-pump coronary artery bypass grafting.
Recent studies have found increased long-term cardiovascular morbidity after off-pump coronary artery bypass surgery (OPCAB). We evaluated the efficacy and safety of dual antiplatelet therapy (DAT) in the prevention of cardiovascular events at two years after OPCAB surgery. Retrospective study that included all patients that underwent OPCAB surgery in our institution between 2009 and 2010. Single or dual antiplatelet therapy was initiated at hospital discharge, and its effect in patients' prognosis was analyzed. Follow-up was conducted by telephone and using the hospital databases. The primary end-point was the composite of acute coronary syndrome (ACS), revascularization, stroke, or cardiovascular death. The study included 237 patients divided into: (A) 128 patients who received single antiplatelet therapy and (B) 109 patients who received dual antiplatelet therapy. The mean follow-up was 23.85 months (standard deviation 0.5 months). 13.9% of patients had a primary end-point event. Patients in group A had a higher event rate compared with group B (18.8% vs. 8.3%, p = 0.02), with a significant reduction in hospital readmissions for ACS (10.9% vs. 3.7%, p = 0.035). In the multivariate analysis, dual antiplatelet therapy was an independent protective factor in the occurrence of events (hazard ratio = 0.395, 95% CI, 0.176 to 0.885, p = 0.024). There were no significant differences between the two groups with respect to bleeding events. Dual antiplatelet therapy after OPCAB surgery is associated with a decrease in the appearance of new cardiovascular events, due to a reduction in the number of hospital readmissions for ACS.


Twisting until it breaks: a rare cause of ICD lead failure.
We describe a rare case of Twiddler's syndrome that resulted in a complex ICD lead fracture involving both the insulation and the conductor. The conductor fracture resulted in noise artefact that was interpreted by the device as ventricular fibrillation, but the patient had not received any shocks because the "episodes" were non-sustained. The patient did not have traditional risk factors for Twiddler's syndrome.


Gelation of fibrinogen in plasma. A kinetic study by turbidity measurement.
Studies of the turbidity profiles of diluted (1/55, v/v) normal plasma, thrombin activity free serum plus commercial fibrinogen, and 0.15 M NaCl, pH 7.4, plus commercial fibrinogen, activated by thrombin or reptilase and measured at 350 nm, have shown that the latency time (LT) hardly varies for the fibrinogen concentration within limits of 0.03-0.15 mg/ml; however, it does vary for the thrombin concentration. The rate of gelation (RG) varies linearly with the fibrinogen (FG) concentration, conforming to the equation RG = 0.027 (FG)1.8; it hardly varies for thrombin concentrations greater than 0.50 NIH U/ml. On the other hand, RG values obtained for 0.46 NIH U/ml of thrombin or 0.92 BU/ml of reptilase show no significant differences. The variation in LT for the thrombin or reptilase concentration allows the rate of activation to be estimated, giving values of 5.9 X 10(-12) and 3.2 X 10(-12) mol/U/s, respectively, for a fibrinogen concentration in plasma of 1.1 X 10(-10) mol/ml. The mean value estimated for the ratio LT/FG in normal plasma is 35.76 +/- 18.3 and 85.62 +/- 18.3 s mg-1 ml for activation by thrombin and reptilase, respectively. We have studied in normal plasma the parameters that define the gelation of fibrin as measured by turbidity curves and their variation according to the fibrinogen concentration. This permits us to establish the kinetics of fibrin gel formation and normal range values.


[Iodine concentration in fluid of the follicles and ovarian cysts of cows].
Biochemical investigations on the principle of the alkali-mineralizing method were carried out with fluid of 16 follicles and 18 ovarial cysts of cows and heifers (which were not treated with potassium iodide) in order to establish the quantitative values of the total iodine in micrgram% per 100 cm3 of fluid. It was found that total iodine in follicle fluid was 5.7 microgram%, and 3.1 microgram% in ovarial cysts. The parameters of the quantitative values of iodine of follicle fluid vary from 0.3 to 11.1 microgram%, and those of the ovarial cyst fluid--from 0.6 to 7.2 microgram%.


[Are there antidepressants specially indicated in certain depressive disorders?].
Treatment for depression has improved and several well tolerated antidepressants have been developed. The diagnosis is less important for the choice of treatment than the severity of the symptoms. Antidepressants are indicated if a depression is of at least moderate severity. For many years attempt has been made to find specific criteria for the choice of the "right" antidepressant. At present the scientific results do not allow unequivocal formulation of criteria for the differential indication of antidepressants. When treating patients we have nevertheless to decide which antidepressants to prescribe. Based on scientific results and long therapeutic experience, the author indicates which antidepressants may be more successful in which depression (retarded depression, agitated depression, delusional depression, suicidal ideas, anxiety, obsessive compulsive symptoms, eating disorders and atypical depression).


Study of upper gastrointestinal tract involvement in pemphigus by esophago-gastro-duodenoscopy.
Involvement of upper gastrointestinal tract in pemphigus vulgaris is not uncommon. To study the involvement of upper gastrointestinal tract (UGIT) with the help of esophago-gastro-duodenoscopy (EGD) in patients of vesiculobullous dermatoses with emphasis on pemphigus vulgaris. Forty-two patients (M-22, F-20) with vesiculobullous dermatoses, diagnosed on the basis of clinical features and skin histopathology as pemphigus vulgaris (PV)-40 patients and pemphigus foliaceus (PF)-2 patients were included in the study. The EGD was performed and mucosa of the esophagus, stomach and first part of the duodenum were examined. Mucosal biopsies were taken from the lower esophagus in 26 patients of PV and studied after H and E staining. On EGD, esophageal involvement was seen in 67% patients of PV (27/40). Of these, Grade I esophagitis was observed in seven, Grade II in 11, Grade III in four and Grade IV involvement was seen in five patients of PV. Three PV patients had associated esophageal candidiasis. Involvement of esophageal mucosa was also observed in one out of two patients of PF. Gastric mucosa was involved in 52% and duodenal mucosa in 20% of PV patients. Acantholysis was observed in seven out of 26 (27%) esophageal biopsies of PV patients. Two patients of PV vomited a tube-like structure, indicative of 'esophagitis dissecans superficialis'. The involvement of the gastric mucosa in patients with history of oral corticosteroid intake (60%) was compared to the group without history of oral corticosteroids (30%). Among PV patients under study, significant involvement of oral (87%), esophageal (67%), gastric (52%) and duodenal mucosa (20%) was observed.


Localization of preformed, circulating immune complexes in murine skin.
The cutaneous localization of intravenously injected preformed immune complexes was examined in C57B1/6J mice and the importance of complex size and antibody charge was assessed for deposition and persistence in cutaneous structures. After a single intravenous bolus, large-latticed complexes deposited transiently in an interstitial extravasated pattern, and persisted longer in a vascular pattern. Small-latticed complexes, prepared at 50 times antigen excess, did not deposit. When large-latticed complexes were prepared with reduced and alkylated antibodies, their vascular deposition was similar, but they did not localize in the interstitium due to decreased extravasation. Large-latticed complexes prepared with cationized antibodies deposited in a vascular and interstitial pattern as well as at the dermal-epidermal junction. Complexes prepared with anionized antibodies deposited comparable to unaltered complexes. Cutaneous deposition of circulating immune complexes in mice requires a large lattice. Circulating immune complexes formed with cationic antibodies deposit at the dermal-epidermal junction.


[A case of esophageal cancer with a funnel chest].
Esophageal cancer is a disease that is difficult to manage before and after surgery and is associated with a high in-hospital mortality rate despite there being reports of improved outcomes after multidisciplinary treatment. Meanwhile, although funnel chest is generally a subclinical condition, patients with this deformity may sometimes present with cardiac failure and chest pain. We report a case of advanced esophageal cancer with a funnel chest deformity that was very difficult to reconstruct after thoracoscopy-assisted resection.


Identification of extended-spectrum-β-lactamase-positive Klebsiella pneumoniae urinary tract isolates harboring KPC and CTX-M β-lactamases in nonhospitalized patients.
Forty-seven extended-spectrum-β-lactamase-positive Klebsiella pneumoniae urinary tract isolates from nonhospitalized patients were identified, and 79% harbored KPC and/or CTX-M β-lactamases. Approximately 90% of the isolates were resistant to trimethoprim-sulfamethoxazole and levofloxacin, and 40% were resistant to a carbapenem, while 92% were susceptible to polymyxin B, 87% were susceptible to tigecycline, and 79% were susceptible to fosfomycin. Increased use of broader-spectrum antibiotics may help to prevent their dissemination and reduce the risk of progression to invasive disease.


Reoperations after valvular heart surgery: indications and late results.
The incidence of reoperations after valvular heart surgery was higher after valve-preserving procedures and after valve replacement with biological prostheses than after implantation of mechanical prostheses. The indication for reoperation was elective in the vast majority of cases; usually it was due to progressive late deterioration of repaired valves or of tissue valves. Symptoms are not a sensitive indicator in timing the reintervention. Progression of clinical signs, radiological and ECG alterations and echocardiographic criteria must be followed closely once late deterioration has been diagnosed. Criteria for reoperation are basically the same as for primary valve surgery. Hemolytic anemia and recurrent emboli were rare indications for reoperation in the presented material. Paravalvular leak was the most frequent indication for reoperation following the implantation of mechanical heart valve prostheses. A number of valve-related complications requiring emergency reoperations are presented; immediate recognition of these conditons and immediat intervention are mandatory. Bacterial endocarditis remains a severe complication after valvular heart surgery and threatens patients with mechanical prostheses in particular. The late results of reoperations depend mainly upon the state of disease reached by the time of reintervention, i.e., upon the right timing of the reoperation.


cAMP controls the balance between dormancy and activation of primordial follicles in mouse ovaries.
In mammalian ovaries, the balance between dormancy and activation of primordial follicles determines the female fecundity and endocrine homeostasis. Recently, several functional molecules and pathways have been reported to be involved in the activation of primordial follicles. However, the homeostasis regulatory mechanisms of primordial follicle activation are still scant. Our previous study has proved that a relatively higher concentration of cyclic AMP (cAMP) is required for primordial follicle formation. Here, we identified that cAMP also plays a vital role in the balance between dormancy and activation of primordial follicles. Our results showed that the concentration of cAMP remained stable in neonatal mouse ovaries, which is due to ADCY3, the synthetase of cAMP, and PDE3A, the hydrolytic enzyme of cAMP, were synchronously increased during the activation of primordial follicles in mouse ovaries. Once the concentration of cAMP in neonatal ovaries was either elevated or reduced in vitro, the activation of primordial follicles was either accelerated or decelerated accordingly. In addition, a higher concentration of cAMP in the ovaries of puberty mice improved primordial follicle activation in vivo. Finally, cAMP promoted primordial follicle activation via canonical mTORC1-PI3K signaling cascades and PKA signaling. In conclusion, our findings reveal that the concentration of cAMP acts as a key regulator in balancing the dormancy and activation of primordial follicles in the mouse ovary.


Functional importance of Ψ38 and Ψ39 in distinct tRNAs, amplified for tRNAGln(UUG) by unexpected temperature sensitivity of the s2U modification in yeast.
The numerous modifications of tRNA play central roles in controlling tRNA structure and translation. Modifications in and around the anticodon loop often have critical roles in decoding mRNA and in maintaining its reading frame. Residues U38 and U39 in the anticodon stem-loop are frequently modified to pseudouridine (Ψ) by members of the widely conserved TruA/Pus3 family of pseudouridylases. We investigate here the cause of the temperature sensitivity of pus3Δ mutants of the yeast Saccharomyces cerevisiae and find that, although Ψ38 or Ψ39 is found on at least 19 characterized cytoplasmic tRNA species, the temperature sensitivity is primarily due to poor function of tRNA(Gln(UUG)), which normally has Ψ38. Further investigation reveals that at elevated temperatures there are substantially reduced levels of the s(2)U moiety of mcm(5)s(2)U34 of tRNA(Gln(UUG)) and the other two cytoplasmic species with mcm(5)s(2)U34, that the reduced s(2)U levels occur in the parent strain BY4741 and in the widely used strain W303, and that reduced levels of the s(2)U moiety are detectable in BY4741 at temperatures as low as 33°C. Additional examination of the role of Ψ38,39 provides evidence that Ψ38 is important for function of tRNA(Gln(UUG)) at permissive temperature, and indicates that Ψ39 is important for the function of tRNA(Trp(CCA)) in trm10Δ pus3Δ mutants and of tRNA(Leu(CAA)) as a UAG nonsense suppressor. These results provide evidence for important roles of both Ψ38 and Ψ39 in specific tRNAs, and establish that modification of the wobble position is subject to change under relatively mild growth conditions.


Medicinal Mushrooms in Guatemala.
Guatemala, located in Central America, has a long and rich history in the traditional use of edible, medicinal, and hallucinogenic mushrooms. This article describes the use of these mushrooms and presents studies on the scientific validation of native and foreign species.


Effects of periodic perturbations on the oscillatory behavior in the NO+H2 reaction on Pt(100).
The mean field model proposed by Makeev and Nieuwenhuys [J. Chem. Phys. 108, 3740 (1998)] simulates the oscillatory behavior experimentally observed in the NO+H2 reaction on the surface Pt(100). This model reproduces quite well the kinetic oscillations and the transition to chaos via the Feigenbaum route, that is to say, through bifurcations involving period doubling. From this model, we analyze the response of the natural oscillations of period-1 (P1, one maximum) to periodic perturbations superposed to the partial pressure of one of the reactants. The perturbed model reproduces the periodic states found in the autonomous model, the route to chaos through bifurcations with period doubling, and the appearance of chaos via the route of intermittency, which shows alternation of periodic oscillations with intervals of disordered oscillations in the same time evolution. Experimentally it has been observed that the reaction shows a great sensitivity to reactant partial pressures and temperature. In experimental conditions slightly different to those considered in Makeev and Nieuwenhuys (MN) model, oscillations with period-3 (P3, three maxima) have been observed. At T=457 K and certain pressures, these P3 oscillations do not appear in MN model, although they appear at T=456 K . The same effect (P3 oscillations) is obtained at T=457 K in our perturbed model, due to the modulation of pH2. In a second step we show how the modulation of the perturbing frequency influences on the oscillations P1 of the perturbed system. The results show that the periodic behavior loses its regularity at low values of the normalized amplitude and of the modulated frequency of the perturbation. Other aspect observed in the perturbed model is that the amount of products varies in relation to nonperturbed model. When the oscillations are periodic or they follow the Feigenbaum route to chaos, the production average decreases or slightly increases, whereas it always increases if there are intermittencies, the most significant percentage increase being for NH3 (nearly 10%).


[Simultaneous determination of organic acids and saccharides in lactic acid fermentation broth from biomass using high performance liquid chromatography].
Abstract: A high performance liquid chromatographic method for the simultaneous determination of organic acids and saccharides in lactic acid fermentation broth from biomass was developed. A Bio-Rad Aminex HPX-87H column was used at 55 degrees C. The mobile phase was 5 mmol/L sulfuric acid solution at a flow rate of 0.6 mL/min. The samples were detected by a refractive index detector (RID). The results showed that six organic acids and three saccharides in fermentation broth were completely separated and determined in 17 min. The linear correlation coefficients were above 0.999 8 in the range of 0.15-5.19 g/L. Under the optimized conditions, the recoveries of the organic acids and saccharides in Rhizopus oryzae fermentation broth at two spiked levels were in the range of 96.91%-103.11% with the relative standard deviations (RSDs, n = 6) of 0.81%-4.61%. This method is fast and accurate for the quantitative analysis of the organic acids and saccharides in microbial fermentation broths.


Complete response of a large basosquamous carcinoma following treatment with cemiplimab and vismodegib.
The anti-PD-1 antibody cemiplimab has demonstrated effectiveness in the setting of locally advanced basal cell carcinoma (BCC) and squamous cell carcinoma. We describe a case of a large, locally invasive basosquamous carcinoma, an aggressive type of BCC, invading the left sternocleidomastoid muscle with near compression of the left internal jugular vein producing a severe anaemia secondary to ulceration and chronic blood loss. The patient was initially started on vismodegib monotherapy but failed to respond. He was then started on cemiplimab in addition to vismodegib. Improvement was noted after one cycle. After 21 cycles of cemiplimab, the left shoulder ulcerated lesion was completely re-epithelialised. He remains in complete remission after 31 cycles of cemiplimab in addition to vismodegib.


Kerogen in aquifer material and its strong sorption for nonionic organic pollutants.
Sorption of organic pollutants by subsurface materials has been found to not only correlate with the total organic carbon (TOC) content, but also depend on the types of soil and sediment organic matter (SOM). Characterization of geochemically heterogeneous SOM is key to elucidating sorption mechanisms and predicting pollutant transport in ground water systems. In this study, kerogen, a nonextractable organic material, was isolated with an acid demineralization procedure from a sandy aquifer material (Borden, Ontario, Canada) having a TOC content of approximately 0.021% (w/w). Petrographical examinations reveal that the kerogen has three major types of macerals including bituminite (Kerogen Type I and II), vitrinite (Type III), and fusinite (Type IV or charred kerogen). The solid-state 13C nuclear magnetic resonance (NMR) spectrum shows two dominant peaks, aliphatic and aromatic carbons, for the isolated material. Sorption isotherms measured using phenanthrene, naphthalene, 1,3,5-trichlorobenzene (TCB), and 1,2-dichlorobenzene (DCB) as sorbates showed that both the isolated kerogen and the original sand exhibited nonlinear sorption and that the phenanthrene and TCB isotherms measured for the kerogen material are more nonlinear than the respective isotherms for the original sand. The single-point organic carbon--normalized sorption capacity measured for the isolated kerogen can be several times greater than that measured for the original sand for a given sorbate. The study suggests that kerogen plays a major role in overall sorption isotherm nonlinearity and could yield higher-than-predicted sorption capacities for the subsurface material even though the content of this organic material is very low.


Novel solution synthesis of the overlooked cubic phase Cu2GeTe3 nanocrystals for optoelectronic devices.
Herein, for the first time, we present a novel solution method for controllable synthesis of the overlooked cubic phase Cu2GeTe3 nanocrystals. The resulting Cu2GeTe3 nanocrystals are of high quality with monodispersed size and uniform shape. Optical characterization demonstrates that Cu2GeTe3 nanocrystals have a broad absorption in the visible to near-infrared region. Furthermore, an optoelectronic device based on Cu2GeTe3 nanocrystals exhibits excellent stability, reproducibility and responsivity. The novel synthetic route presented here not only can open a new avenue for fabricating Cu2GeTe3 nanocrystals, especially at the nanoscale, but also may further expand their applications.


[Treatment of cancer pain in Denmark. A questionnaire survey].
A questionnaire survey was carried out with the aim of evaluating knowledge about and practice of cancer pain treatment in Denmark. A questionnaire was sent to a 10% random sample of Danish physicians. Of these 1411 physicians, 1068 (76%) returned the questionnaires and after the exclusion of those doctors who never treated cancer patients, 577 (54%) were analyzed. Their knowledge of the principles and practice of cancer pain treatment was evaluated by means of 14 multiple-choice and open questions. Their ability to apply their knowledge in practice was evaluated by analyzing their suggested treatment of three simulated patient cases. Ninety-seven percent of the physicians recognized difficulties in cancer pain treatment, the most frequent being side effects of drugs and inadequate pain relief. It appeared from the proposals for pain treatment of the patient cases that the majority of the physicians could treat both pain from bone metastasis (75%) and visceral pain (78%) satisfactorily, while very few suggested coanalgesics for neuropathic pain (20%). Older physicians performed less satisfactorily than did their younger colleagues. Basic pain treatment skills have been acquired by the Danish physicians. However, in the future emphasis should be placed on the treatment of neuropathic pain with coanalgesics and the management of opioid side-effects.


Quantitative analysis of myosin heavy chain expression change in laryngeal muscle after irradiation in rats.
Radiotherapy for head and neck cancer does not impair the voice quality as much as laser treatment or surgery, but it can induce muscle wasting and fibrosis and symptoms of dry mouth. We investigated the effect of irradiation on the myosin heavy chain (MyHC) expression in laryngeal muscles. Rats were irradiated with one dose of 10, 15, 20, 25, 30, or 35 Gy and other rats were irradiated with 20 Gy. The thyroarytenoid (TA), posterior cricoarytenoid (PCA), and cricothyroid (CT) muscles were subjected to reverse transcription-polymerase chain reaction (RT-PCR). Two weeks after irradiation with 10, 15, or 20 Gy, all the MyHC type expressions had decreased in a dose-dependent manner in the TA, PCA, and CT muscles, and especially the expression of MyHC IIa decreased much more than the expressions of the other MyHC isoforms in all muscles. In the 20 Gy-irradiated rats, almost all the MyHC isoform expressions declined over 12 weeks in the TA, PCA, and CT muscles, except for the MyHC I expression in the PCA and CT muscle. The MyHC IIa expression was markedly decreased in all the muscles. The laryngeal muscles responded differently to radiation, but they showed a time-dependent and long-lasting decrease in the expressions of all the MyHC isoforms in the TA, PCA, and CT muscles. In particular, the expression of the MyHC IIa isoform in all the muscles may be more sensitive to irradiation than the expressions of the other MyHC isoforms.


Effects of mitochondrial gene deletion on tumorigenicity of metastatic melanoma: reassessing the Warburg effect.
Metabolic flexibility is a hallmark of cancer. Although many tumors preferentially use glycolysis in the presence of oxygen for bioenergetic purposes (Warburg effect), the effects of glycolytic metabolism on tumor metastasis have not been investigated. We have employed an extreme model of glycolytic metabolism to investigate the ability of metastatic B16 mouse melanoma cells to grow as primary subcutaneous tumors and to form lung tumors when injected intravenously into syngeneic and immunocompromised mice. Mitochondrial gene-knockout B16rho degrees cells showed delayed subcutaneous tumor growth and, surprisingly, failed to form lung tumors. The results suggest that mitochondrial reactive oxygen species (ROS) may be required for tumor metastasis.


Osteochondral Allograft Transplantation and Opening Wedge Tibial Osteotomy: Clinical Results of a Combined Single Procedure.
Objective To evaluate the outcome of patients who have undergone simultaneous osteotomy and osteochondral allograft (OCA) transplantation. Our hypothesis is that use of high tibial osteotomy and fresh OCA in a combined procedure is safe and effective without increasing morbidity in comparison to OCA alone. Design A case series of 17 patients underwent tibial osteotomy and simultaneous OCA during a single surgery. Osteotomy was indicated when axial alignment was within the affected compartment. Patients had a minimum of 2 years of follow-up after surgery. The mean graft size was 8.7 cm2, with 82% located on the medial femoral condyle alone and 18% involving the medial femoral condyle and one or more other sites. Data collection included demographics, osteotomy correction, graft site(s) and area, and clinical evaluation. Failure was defined as conversion to arthroplasty. Results Two of 17 patients (12%) failed at a mean of 9.3 years. The remaining 15 patients (88%) had intact allografts with mean survival of 8.1 years (SD 3.3). Five patients (29%) had an additional procedure, all undergoing osteotomy hardware removal. Of those with surviving allografts, mean pain and function scores improved significantly from the preoperative to postoperative assessment and International Knee Documentation Committee total scores improved significantly from 40.9 ± 15.4 preoperative to 75.5 ± 24.0 at latest follow-up ( P = 0.003); 92% of patients were satisfied with the results of the surgery. No postoperative complications occurred. Conclusion Combining high tibial osteotomy and OCA in properly selected patients is safe and effective.


Inlaying Radiosensitizer onto the Polypeptide Shell of Drug-Loaded Ferritin for Imaging and Combinational Chemo-Radiotherapy.
Rationale: Ferritin with unique hollow cavity is an emerging protein-based nanoplatform for anticancer-drug delivery, but the in vivo chemotherapeutic effectiveness is still unsatisfactory with such a monotherapy modality, which is urgently in need of improvement. Methods: Here a novel ferritin nanotheranostic with anticancer-drug doxorubicin encapsulated into its hollow interior and nanoradiosensitizer bismuth sulfide nanocrystals inlayed onto its polypeptide shell was synthesized for combinational therapeutic benefits. The formation mechanism of bismuth sulfide nanocrystals based on ferritin has been analyzed. The in vitro and in vivo treatment effects were carried out on HeLa cancer cells and tumor-bearing mice, respectively. The biocompatibility and excretion of the ferritin nanotheranostic have also been evaluated to guarantee their biosafety. Results: The polypeptide shell of ferritin provides nucleation sites for the bismuth sulfide nanocrystals through coordination interaction, and simultaneously inhibits the further growth of bismuth sulfide nanocrystals, rendering the bismuth sulfide nanocrystals like rivets inlaying onto the polypeptide firmly, which can not only strengthen the architectural stability of ferritin to prevent drug burst leakage during systemic circulation, but also act as excellent computed tomography contrast agents and nanoradiosensitizers for in vivo imaging-guided cancer combinational treatments. Conclusions: The design concept of inlaying bismuth sulfide nanocrystals onto the polypeptide shell of doxorubicin-encapsulated ferritin significantly inhibits the tumor growth and simultaneously further broadens the application of ferritin in nanomedicine.


Neonatal septic arthritis.
To assess and correlate the microbiology of neonatal septic arthritis with the clinical presentation, we reviewed the records of nine infants with neonatal septic arthritis (NSA) diagnosed at Edmonton hospitals between 1964 and 1981, and evaluated 92 other cases reported in the English literature since 1960. Our analysis revealed that the microbiology of NSA seemed to be dependent on whether it was hospital or community acquired. In the hospital-acquired cases, staphylococci were the predominant isolates (62%), followed by Candida species (17%) and gram-negative enteric bacilli (15%). Community-acquired arthritis was caused most often by streptococci (52%), followed by staphylococci (26%) and gonococci (17%). Since 1970, the relative infrequency of staphylococcal (5%) in favor of streptococcal (75%) isolates in community-acquired NSA is even more pronounced.


Impact of diet on faecal output and caecotroph consumption in rabbits.
To assess the impact of four rabbit diets (hay only, extruded diet with hay, muesli with hay and muesli only) on faecal pellet size, faecal output and caecotrophy. Thirty-two Dutch rabbits were studied over 17 months. Faecal pellet size and weight were measured in weeks 3, 9, 21 and 43 and faecal output in weeks 10, 22 and 45. Number of uneaten caecotrophs was recorded weekly. Faecal pellets were consistently smaller and lighter in rabbits fed muesli only, and the size of pellets produced by those fed muesli with hay decreased over the course of the study. Faecal output was greatest in rabbits with the highest hay intake. Uneaten caecotrophs were found in greatest frequency in rabbits fed muesli. Muesli diets have a negative effect on faecal output and caecotroph ingestion and may therefore predispose to digestive disorders. Higher hay intake is associated with greater faecal output and fewer uneaten caecotrophs and may assist in preventing the gastrointestinal stasis.


Communicating with Daughters About Familial Risk of Breast Cancer: Individual, Family, and Provider Influences on Women's Knowledge of Cancer Risk.
Women facing complex and uncertain situations such as cancer in their families may seek information from a variety of sources to gain knowledge about cancer risk and reduce uncertainty. We describe and assess the relative importance of information sources about familial breast cancer at the individual, family, and healthcare provider levels influencing women's reporting they had enough information to speak with daughters about breast cancer. This outcome we refer to as being informed about breast cancer. Sister Study participants, a cohort of women with a family history of breast cancer, were surveyed on family cancer history, family communication, social support, and interactions with healthcare providers (n = 11,766). Adjusted percentages and 95% confidence intervals for being informed about breast cancer versus not being informed were computed for individual-, family-, and provider-level characteristics in three steps using multivariate logistic regression models. We found 65% of women reported being informed about breast cancer while 35% did not. Having a trusted person with whom to discuss cancer concerns, having a lower versus higher perceived risk of breast cancer, having undergone genetic counseling, and being satisfied with physician discussions about breast cancer in their families were predictors of being informed about breast cancer. Although acquiring objective risk information, such as through genetic counseling, may contribute to a basic level of understanding, communication with providers and within other trusted relationships appears to be an essential component in women's reporting they had all the information they need to talk with their daughters about breast cancer.


Polycystin-2 activation by inositol 1,4,5-trisphosphate-induced Ca2+ release requires its direct association with the inositol 1,4,5-trisphosphate receptor in a signaling microdomain.
Autosomal dominant polycystic kidney disease is characterized by the loss-of-function of a signaling complex involving polycystin-1 and polycystin-2 (TRPP2, an ion channel of the TRP superfamily), resulting in a disturbance in intracellular Ca(2+) signaling. Here, we identified the molecular determinants of the interaction between TRPP2 and the inositol 1,4,5-trisphosphate receptor (IP(3)R), an intracellular Ca(2+) channel in the endoplasmic reticulum. Glutathione S-transferase pulldown experiments combined with mutational analysis led to the identification of an acidic cluster in the C-terminal cytoplasmic tail of TRPP2 and a cluster of positively charged residues in the N-terminal ligand-binding domain of the IP(3)R as directly responsible for the interaction. To investigate the functional relevance of TRPP2 in the endoplasmic reticulum, we re-introduced the protein in TRPP2(-/-) mouse renal epithelial cells using an adenoviral expression system. The presence of TRPP2 resulted in an increased agonist-induced intracellular Ca(2+) release in intact cells and IP(3)-induced Ca(2+) release in permeabilized cells. Using pathological mutants of TRPP2, R740X and D509V, and competing peptides, we demonstrated that TRPP2 amplified the Ca(2+) signal by a local Ca(2+)-induced Ca(2+)-release mechanism, which only occurred in the presence of the TRPP2-IP(3)R interaction, and not via altered IP(3)R channel activity. Moreover, our results indicate that this interaction was instrumental in the formation of Ca(2+) microdomains necessary for initiating Ca(2+)-induced Ca(2+) release. The data strongly suggest that defects in this mechanism may account for the altered Ca(2+) signaling associated with pathological TRPP2 mutations and therefore contribute to the development of autosomal dominant polycystic kidney disease.


[Disorder of lipid metabolism in visceral fat syndrome--relation to familial combined hyperlipidemia].
'Visceral fat syndrome' is a clinical entity compatible with Syndrome X, Deadly quartet, and insulin resistance syndrome. All of these entities express the pathophysiology of multiple risk factor syndrome in which multiple risks of arteriosclerosis, i.e., hypertension, hyperlipidemia, and glucose intolerance, cluster in an individual. The accumulation of visceral fat plays a crucial role in the pathogenesis of visceral fat syndrome. On the other hand, familial combined hyperlipidemia (FCHL) is a common hyperlipidemia associated with premature arteriosclerosis. The pathogenesis of FCHL is not fully elucidated but the visceral fat accumulation may play an important role in the pathophysiology of FCHL. In this review, we will discuss the relationship between visceral fat syndrome and FCHL.


Adsorption of plasma proteins on hydrophobic surfaces. IV. Contact angle studies on implanted polymers.
Contact angle studies have been carried out on plasma protein layers adsorbed on selected polymer surfaces under buffered saline at 37 degrees, in an attempt to demonstrate directly a recent suggestion that the interfacial free energy between such protein layers and surrounding liquid phase should be zero at equilibrium. Although an initial contact angle of 180 degrees was always obtained, the angle decayed slowly to a stationary value which varied for any one drop on each polymer surface. The stationary values could be reasonably correlated with the reversible work of adhesion predicted for each polymer/protein combination, suggesting that protein desorption from the solid surface is a dominant event in the contact angle decay process. It is concluded that the data bear more relevance to the protein layer/polymer interface than to the protein layer/solution interface, and that the contact angle technique is not a suitable technique for studying the latter on biomaterials.


Can older adults accurately judge their learning of emotional information?
Prior research suggests that older adults judge their learning as well as young adults, but given age-related differences in the processing of emotional materials, older adults may show deficits in their judgment accuracy when they study emotionally charged words. In 2 experiments, we evaluated this possibility by having young and older adults study negative, positive, and neutral words. They made a judgment of learning (JOL) after studying each word and then later had a free recall test. In Experiment 1, young and older adults' JOLs were sensitive to negative words (higher JOLs for negative than neutral words). By contrast, whereas young adults' JOLs were sensitive to positive emotion (higher for positive than neutral words), older adults' JOLs were insensitive. In Experiment 2, we replicated this age-related deficit in sensitivity to positive emotion, as well as evaluated possible explanations for it. As important, in both experiments, JOLs were plotted as a function of input serial position, and the shape of these curves were not influenced by emotional valence or age group. Taken together, these results indicate that healthy aging largely leaves judgments of learning intact for negatively charged words.


[Middle meningeal artery embolization for refractory chronic subdural hematoma: 3 case reports].
The authors present three cases of refractory chronic subdural hematoma (CSDH) treated by embolization of the middle meningeal artery (MMA) after several unsuccessful drainage procedures. The patients were initially treated by the usual method of burr hole and irrigation of the hematoma. After recurrence, several percutaneous puncture and drainage procedures were unable to prevent re-collection of the hematoma. Then the authors embolized the MMA which was thought to be the feeding artery of the outer membrane of the hematoma cavity. No enlargement of the hematoma was seen after embolization and, gradually, complete resolution of the hematoma was obtained. The outcome of the patients was excellent in all three cases. This new therapeutic approach to recurrent CSDH is discussed.


Prognostic significance of primary site after radiotherapy in non-Hodgkin's lymphomata.
In contrast to Hodgkin's lymphomata, non-Hodgkin's lymphomata originate in approximately a fourth of the cases in extranodal organs and sites. The prognosis of patients with primary extranodal organ involvement of the non-Hodgkin's lymphomata is similar to that of patients with primary lumph node involvement of the Hodgkin's and non-Hodgkin's lymphomata, dependent on the special spreading of the disease corresponding to the 4 stages of the Ann Arbor classification. This applies to the primary involvement of a single lymph node region (Stage I) or a single extralymphatic organ or site (stage IE) as well as to further stages of spreading within the lymphatic system (Stages II and III) including secondary localized involvement of an extralymphatic organ and site (Stages IIE and IIIE). The same qualitative dependence of the prognosis of Hodgkin's and non-Hodgkin's lymphomata on the spatial spreading, corresponding to the Ann Arbor concept, legitimizes, in spite of some quantitative differences, the application of the Ann Arbor classification system to all malignant lymphomata.