Calcitonin gene-related peptide antagonizes the protective effect of adrenomedullin on histamine-induced bronchoconstriction.
1. In the present study the possible relationship between adrenomedullin (AM) and calcitonin gene-related peptide (CGRP) in the regulation of airway functions in anaesthetized guinea-pigs was examined in vivo. 2. We found that AM significantly inhibited histamine-induced bronchoconstriction in a dose-dependent manner. CGRP or the CGRP receptor antagonist (CGRP [8-37]) alone did not affect pulmonary resistance and pretreatment with CGRP or CGRP [8-37] did not significantly affect histamine-induced bronchoconstriction. However, AM-induced bronchoprotection was significantly inhibited by pretreatment with CGRP or CGRP [8-37] in a dose-dependent manner. 3. It is therefore possible that CGRP may be competitive, at least in part, with binding sites of AM in the guinea-pig airway. Exogenous AM may be useful for the management of bronchial asthma, not only as a potent bronchodilator, but also as a functional antagonist of CGRP.


Uniformity of the microsymbiont population from soybean nodules with respect to buoyant density.
The microsymbiont population in soybean root nodules (Glycine max L. cv Williams 82 inoculated with Bradyrhizobium japonicum 2143) was characterized during symbiotic development to determine the extent of heterogeneity in this population. The microsymbiont population was isolated by centrifugation through a continuous sucrose gradient (44 to 57% weight to weight ratio) and appeared homogeneous at each age examined up to 26 days after planting based on the symmetrical distribution of the population, enzyme activities, poly-beta-hydroxybutyrate contents, protein contents, and viabilities. Some differences in viability, protein content, and acetylene reduction activity were observed at later ages. The population migrated to progressively lighter buoyant densities with increasing age until a density equivalent to 48% sucrose was reached. The changing density correlated directly with the increasing poly-beta-hydroxybutyrate to protein ratio. The acetylene reduction activity, based on microsymbiont concentration, followed the same developmental pattern as whole nodules. On a protein basis, the decline of acetylene reduction activity was later and reflected the decrease in protein content per cell. These results suggested that the microsymbiont population, which resulted from inoculation of B. japonicum 2143 onto Williams 82 cultivar of soybeans, developed as a homogeneous population.


H-ras-1 gene mutations in basal cell carcinoma: automated direct sequencing of clinical specimens.
Ras oncogenes are activated by point mutations occurring in codons 12, 13 or 61 and almost any base pair mutation occurring within the first two positions of any of these codons results in activation of the gene. Although ras point mutations have been reported to occur in several skin neoplasms including squamous carcinoma, keratoacanthoma and melanoma, their frequency of occurrence in basal cell carcinoma is not known. We examined basal cell carcinomas from 13 patients for activating mutations in the H-ras-1 gene by automated direct sequencing of polymerase chain reaction assay amplified targets. We amplified sequences in exon 1 that flanked codons 12 and 13 and amplified sequences in exon 2 that flanked codon 61. The PCR products were centrifuged and directly sequenced using antisense primers in an automated sequencer using fluorescent dideoxyterminators. One tumor was found to show an activating G to A transversion in codon 13 which code for aspartic acid instead of glycine. Although H-ras mutations may be found in some skin tumors, they are not frequent in basal cell carcinomas. From this study we believe that direct sequencing of clinical material is of value and has advantages over other techniques. Additional studies need to be undertaken to understand the true clinical significance of ras mutations in basal cell carcinomas when they occur.


Structures of complexes formed by HIV-1 reverse transcriptase at a termination site of DNA synthesis.
This study presents structural parameters associated with termination of human immunodeficiency virus, type 1 (HIV-1) reverse transcriptase (RT) at Ter2, the major termination site located in the center of the HIV-1 genome. DNA footprinting studies of various elongation complexes formed by RT around wild type and mutant Ter2 sites have revealed two major structural transformations of these complexes when the enzyme gets closer to Ter2. First, the interactions between RT and the DNA duplex are less extended, although the global affinity of the enzyme for this duplex is only decreased by 2-fold. Second, there is an atypical positioning of the RT RNase H domain on the DNA duplex. We interpret our data as indicating that the A(n)T(m) motif located upstream of Ter2 prevents a classical positioning of the enzyme on the double-stranded part of the DNA duplex at some precise positions of elongation downstream of this motif. Instead, novel species of binary and/or ternary complexes, characterized by atypical footprints, are formed. The new rate-limiting step of the reaction, characterized in the preceding paper (Lavigne, M., Polomack, L., and Buc, H. (2001) J. Biol. Chem. 276, 31429-31438), would be a transition leading from these new species to a catalytically competent ternary complex.


Use Of Radiological Diagnostic Modalities In Tertiary Care Hospital - How Do The Clinicians Decide About Type Of Modality And Clinician Perception Regarding Hazards Associated With Radiological Imaging Modalities?
In the past few decades there is rapid advancement in technology and hence tremendous innovations in diagnostic imaging. This has increased our ability to diagnose illness and monitor response to treatment in a manner which was not previously possible. As compared to previous times, there is also more easy availability of these diagnostic imaging modalities in our hospitals. Therefore, easy and frequent availability harbour the risk of injudicious use of these tests as well. This study is conducted to know the views of consultants about it. This cross-sectional descriptive study was conducted in Ayub Medical Institute MTI from March 2021 to July 2021. The data was collected through a self-administered anonymous questionnaire. A total of 250 clinicians participated in the study with 54% males. Majority of them (n=140) 56% answered that consultants on round and on duty in OPD decide special radiological investigations for the patients. Most of them (90%, n=225) were aware of radiation hazards in CT, X-rays and fluoroscopy . The referring physicians working at MTI ATH Abbottabad have enough basic knowledge regarding the practice of radiological modalities but were unaware of specific health hazards and radiation doses to the patients associated with the use of these imaging modalities.


The influenza virus NS1 protein binds to a specific region in human U6 snRNA and inhibits U6-U2 and U6-U4 snRNA interactions during splicing.
The influenza virus NS1 protein is a unique posttranscriptional regulator that has two activities: inhibition of the nuclear export of poly A-containing mRNAs and inhibition of pre-mRNA splicing. Here we demonstrate that this protein binds to a specific region in one of the human spliceosomal snRNAs, U6 snRNA. Using U6 deletion mutations, we show that the binding of the NS1 protein requires both chains of a stem-bulge structure encompassing nucleotides 27-46 and nucleotides 83-101 of human U6 snRNA. A chemical modification/interference assay indicated that the primary binding site is centered around a purine-containing bulge in this stem-bulge structure. These results provide strong evidence that this postulated secondary structure in U6 snRNA actually exists. The NS1 protein also binds to a model U6-U4 snRNA complex, suggesting that the U6 stem-bulge comprising the NS1 protein binding site is also present in natural U6-U4 snRNA complexes. The U6 stem-bulge includes the U6 sequence that forms helix II with U2 snRNA during splicing, an interaction that is essential for mammalian splicing. We demonstrate that the NS1 protein blocks formation of the U6-U2 helix II both in a model system and during in vitro splicing. In addition, we show that the NS1 protein inhibits formation of U6-U4 snRNA complexes during in vitro splicing, presumably because the binding site of the NS1 protein includes the 3'-terminal region of U6 snRNA that has been shown to be important for the formation of U6-U4 complexes. We postulate that the inhibition of U6-U2 and U6-U4 snRNA complex formation is largely responsible for the inhibition of pre-mRNA splicing by the NS1 protein.


Mixed Criticality Scheduling for Industrial Wireless Sensor Networks.
Wireless sensor networks (WSNs) have been widely used in industrial systems. Their real-time performance and reliability are fundamental to industrial production. Many works have studied the two aspects, but only focus on single criticality WSNs. Mixed criticality requirements exist in many advanced applications in which different data flows have different levels of importance (or criticality). In this paper, first, we propose a scheduling algorithm, which guarantees the real-time performance and reliability requirements of data flows with different levels of criticality. The algorithm supports centralized optimization and adaptive adjustment. It is able to improve both the scheduling performance and flexibility. Then, we provide the schedulability test through rigorous theoretical analysis. We conduct extensive simulations, and the results demonstrate that the proposed scheduling algorithm and analysis significantly outperform existing ones.


Relationship between burnout and performance.
This paper seeks to clarify the nature of the relationship between burnout and both perceived and actual performance. A sample was chosen for whom a clear and objective measure of actual performance was available. This was a group of 95 mid-career MBA students, for whom examination scores were obtained. A questionnaire containing items assessing burnout and perceived performance was administered. There were significant positive correlations between the measure of burnout and the items assessing perceived performance, particularly those reflecting self-esteem. There was no significant association between the measure of burnout and actual performance. It is suggested that (i) a clear distinction between actual and perceived performance be made in the burnout literature; (ii) it is premature to assume burnout will lead to an actual decline in performance; (iii) the notion of deteriorating perceived performance in relation to burnout may have more to do with general feelings of self-esteem than performance or accomplishment per se.


Eddy heat exchange at the boundary under white noise turbulence.
We prove the existence of an eddy heat diffusion coefficient coming from an idealized model of turbulent fluid. A difficulty lies in the presence of a boundary, with also turbulent mixing and the eddy diffusion coefficient going to zero at the boundary. Nevertheless, enhanced diffusion takes place. This article is part of the theme issue 'Scaling the turbulence edifice (part 2)'.


Auditory disturbances promote temporal clustering of yawning and stretching in small groups of budgerigars (Melopsittacus undulatus).
Yawning may serve both social and nonsocial functions. When budgerigars (Melopsittacus undulatus) are briefly held, simulating capture by a predator, the temporal pattern of yawning changes. When this species is observed in a naturalistic setting (undisturbed flock), yawning and also stretching, a related behavior, are mildly contagious. On the basis of these findings, we hypothesized that a stressful event would be followed by the clustering of these behaviors in a group of birds, which may be facilitated both by a standard pattern of responding to a startling stressor and also contagion. In this study, we measured yawning and stretching in 4-bird groups following a nonspecific stressor (loud white noise) for a period of 1 hr, determining whether auditory disturbances alter the timing and frequency of these behaviors. Our results show that stretching, and to a lesser degree yawning, were nonrandomly clumped in time following the auditory disturbances, indicating that the temporal clustering is sensitive to, and enhanced by, environmental stressors while in small groups. No decrease in yawning such as found after handling stress was observed immediately after the loud noise but a similar increase in yawning 20 min after was observed. Future research is required to tease apart the roles of behavioral contagion and a time-setting effect following a startle in this species. This research is of interest because of the potential role that temporal clumping of yawning and stretching could play in both the collective detection of, and response to, local disturbances or predation threats.


Turning the [Ru(bpy)2dppz]2+ light-switch on and off with temperature.
We report temperature-dependent excited-state lifetime measurements on [Ru(bpy)(2)dppz](2+) in both protic and aprotic solvents. These experiments yield a unifying picture of the excited-state photophysics that accounts for observations in both types of solvent. Our measurements support the notion of bpy-like and phz-like states associated with the dppz ligand and show that the ligand orbital associated with the bright state is similar in size to the corresponding orbital in the (3)MLCT state of [Ru(bpy)(3)](2+). In contrast to the current thinking, the experiments presented here indicate that the light-switch effect is not driven by a state reversal. Rather, they suggest that the dark state is always lowest in energy, even in aprotic solvents, and that the light-switch behavior is the result of a competition between energetic factors that favor the dark state and entropic factors that favor the bright (bpy) state.


Kinesthetic motor imagery modulates intermuscular coherence.
Intermuscular coherence can identify oscillatory coupling between two electromyographic (EMG) signals, measuring common presynaptic drive to motor neurons. Beta band oscillations (15-30 Hz) are hypothesized to originate largely from primary motor cortex, and are reduced during dynamic relative to static motor tasks. It has yet to be established whether motor imagery modulates beta intermuscular coherence. Using visual feedback, 10 unimpaired participants completed eighteen trials of pinching their right thumb and index finger at a constant force. During the 60-second trials, participants simultaneously engaged in one of three types of kinesthetic imagery: the right thumb and index finger executing a constant force pinch (static), the fingers of the right hand sequentially flexing and extending (dynamic), and the right foot pushing down with constant force (foot). Motor imagery of a dynamic motor task resulted in significantly lower intermuscular beta coherence than imagery of a static motor pinch task, without any difference in task performance or root-mean-square EMG. Thus, motor imagery affects intermuscular coherence in the beta band, even while measures of task performance remain constant. This finding provides insight for incorporation of beta band intermuscular coherence in future motor rehabilitation schemes and brain computer interface design.


Ocular vestibular evoked myogenic potentials in response to air-conducted sound in Ménière's disease.
Currently, Ménière's disease is predominantly diagnosed through clinical criteria. Additional standard vestibular testing, such as nystagmography, can show variable responses. In the last decade, the cervical vestibular evoked myogenic potential (VEMP) has shown to be of additive value in diagnosing Ménière's disease. In this study, the results of the ocular VEMP (oVEMP) in response to air-conducted sound will be discussed. To evaluate possible changes of the oVEMP in a large group (n = 37) of patients with Ménière's disease. In 55 subjects without Ménière's disease and 37 patients with Ménière's disease, oVEMPs in response to air-conducted sound stimulation (tone-burst, 500 Hz; maximum stimulus level, 120 dB sound pressure level) were studied. Recording was performed in upgaze with surface electrodes underneath both eyes. The burden of the test was scored by all subjects on a visual analogue scale. In patients with Ménière's disease the response rates are lower, the oVEMP amplitudes are smaller, and thresholds are higher than in subjects without Ménière's disease. This effect is observed in both ears of patients with Ménière's disease. The affected ear is more altered than the clinically unaffected ear. The air-conducted oVEMP can be a relevant addition to the current diagnostic workup of patients with possible Ménière's disease. A lower response rate, smaller amplitude, and higher threshold of the oVEMP indicate the pathologic disease in this population.


Mercury-induced anti-nucleolar autoantibodies can transgress the membrane of living cells in vivo and in vitro.
Treatment with HgCl2 induces a systemic autoimmune disease in certain mice and rats. The major characteristic of this disease in mice with H-2s genotype is the production of anti-nucleolar autoantibodies (ANoIA). The exact mechanism(s) for the production and the functional role of mercury-induced ANoIA are not known. We have studied the ability of mercury-induced ANoIA to enter the living cells in vivo and in vitro. We found that in highly susceptible mice, treatment with mercury induced ANoIA capable of localizing in the nucleoli of kidney and liver cells in vivo. No detectable nucleoli localization of ANoIA were found in the cells of the heart, stomach, intestine and spleen. Consistent with the in vivo studies, mercury-induced ANoIA were also able to enter and translocate in the nucleoli of certain cells in vitro. The highest degree of antibody penetration was found in A-498 cells (a human kidney cell line) followed by 3T3 cells (a mouse fibroblast cell line), whereas the cells of lymphoid origin exhibited a very low degree of antibody penetration. Penetrated ANoIA could be recovered from the nucleoli of live 3T3 cells previously treated with ANoIA. The in vitro nucleolar translocation by ANoIA did not affect the DNA synthesis, but was found to be an active process dependent on time and temperature. Furthermore, pre-treatment of living cells with trypsin markedly inhibited both cell entry and nucleolar accumulation of ANoIA. Thus, mercury-induced ANoIA have a unique ability to transgress the membrane of certain living cells in vivo and in vitro, and to localize in the nucleoli.


Effects of one-point and four-point canes on balance and weight distribution in patients with hemiparesis.
To examine the effects of one-point and four-point canes on postural sway and on the distribution of weight between the lower extremities and the walking aids in hemiparetic patients. Flieman Geriatric Rehabilitation Hospital, Haifa, Israel. Thirty hemiparetic patients following a unilateral stroke, with moderate functional impairment, and 20 age-matched healthy subjects. Subjects were tested on two forceplates, which were placed at a 30 degrees angle from each other with the heel end of the plates separated by 3 cm. Each subject was tested under three conditions: with no cane, with a one-point cane, and with a four-point cane. Testing time was 30 seconds, and order of testing was randomized. Weight borne by the lower extremities and by the walking aids expressed as a percentage of overall body weight, and Sway Index indicating vertical pressure fluctuations over both feet. In both subject groups, the one-point cane did not reduce sway significantly in comparison with no cane, while the four-point cane reduced sway significantly in comparison with both no cane and one-point cane. Neither cane type affected weight-bearing on the paretic leg, while significantly reducing weight-bearing on the uninvolved extremity. Mean percentage of body weight on the four-point cane was significantly higher than on the one-point cane A four-point cane increases stability of moderately involved hemiparetic patients during stance more than a one-point cane. The noted shift of weight toward the walking aid does not adversely affect weight-bearing on the paretic limb.


Dynamic imaging of Au-nanoparticles via scanning electron microscopy in a graphene wet cell.
High resolution nanoscale imaging in liquid environments is crucial for studying molecular interactions in biological and chemical systems. In particular, electron microscopy is the gold-standard tool for nanoscale imaging, but its high-vacuum requirements make application to in-liquid samples extremely challenging. Here we present a new graphene based wet cell device where high resolution scanning electron microscope (SEM) and energy dispersive x-rays (EDX) analysis can be performed directly inside a liquid environment. Graphene is an ideal membrane material as its high transparancy, conductivity and mechanical strength can support the high vacuum and grounding requirements of a SEM while enabling maximal resolution and signal. In particular, we obtain high resolution ([Formula: see text] nm) SEM video images of nanoparticles undergoing Brownian motion inside the graphene wet cell and EDX analysis of nanoparticle composition in the liquid enviornment. Our obtained resolution surpasses current conventional silicon nitride devices imaged in both a SEM and transmission electron microscope under much higher electron doses.


Studies on dressings for mucosa of the oral cavity. Part 3: Effect of preparation technology on the physical and chemical properties of stomatological xerogel dressings.
Adhesion of xerogel dressings prepared on Eudragit (E), methylcellulose (MC) and glycerol compositions, remaining within the range of 625-650 g, after addition polyvinylpyrolidone (PVP) amounts to 450-1250 g. Dissolution time from xerogel dressings without PVP additive both in water and in an artificial gastric juice amounts to 3 h. Addition of PVP results in reduction of the elution rate. In dependence upon the PVP/E/MC ratio elution time amounts to 3-3.5 h. Pharmaceutical availability of the Kunitz protease inhibitor in particular groups of then dressings depends upon concentration of hydrophilizing agent. The semi-liberation times amounts to 3.65-17.50 h.


Upregulation of T cell receptor gamma chain transcription by interleukin-2.
Signals involved in TcR gene rearrangement and expression are poorly understood. The ability of interleukin 2 to control TcR gamma gene expression was examined. Precursor thymocytes grown in the presence of IL-1 and Con A develop to CD3+ T cells that express either the TcR alpha/beta or gamma/delta complex on the cell surface (1). We show here that a major subpopulation of these cells are CD4-/CD8-, gamma/delta cells expressing only low levels of TcR gamma transcripts, compared to TcR delta mRnA or to TcR gamma mRNA of gamma/delta cells grown from precursor thymocytes with IL-2 and Con A. The cells cultured with IL-1 and lectin then strongly reacted to IL-2 by upregulating the steady-state level of TcR gamma mRNA. Our findings indicate that IL-2 upregulates TcR gamma transcription by transcriptional regulatory effects in this in vitro system.


Exploring self-use, attitude and interest to study complementary and alternative medicine (CAM) among final year undergraduate medical, pharmacy and nursing students in Sierra Leone: a comparative study.
CAM inclusion into the curricula of health training institutions, a strategy for its integration into the main stream healthcare delivery system is growing globally. Future healthcare professionals knowledge and perception of CAM are key determinants to its successful integration. Thus, the main objective of this study was to compare the use, attitude and interest to study CAM among final year undergraduate medical, pharmacy and nursing students at the College of Medicine and Allied Health Sciences University of Sierra Leone (COMAHS-USL). A questionnaire based cross-sectional survey was carried out among final year medical, pharmacy and nursing students enrolled at the College of Medicine and Allied Health Sciences University of Sierra Leone (COMAHS-USL). Chi square, fisher exact two tailed test and Kruskal-wallis test were used to analyze data collected. Close to two-thirds (61 %) of all the three groups of final year students used one form of CAM or the other with pharmacy (72.7 %) and nursing (55.6 %) students being the highest and least users respectively. No significant difference was observed among the three groups. In general, final year students in all three cadres demonstrated a positive attitude toward CAM (33.80 ± 3. 2) with medical students showing more positive attitude than pharmacy (p = 0.022) and nursing student (p = 0.008). No significant difference in attitude was observed between students in pharmacy and nursing programs (p = 0.354). More than three quarter (76.6 %) of the students in all the three groups indicated their interest in studying CAM, with preference for the subject to be taught as an elective module (81.6 %). An appreciable number of final year medical, pharmacy and nursing students at COMAHS-USL have used at least one CAM modality and demonstrated an overall positive attitude towards CAM. Interest to study CAM was also observed among most of them even though they preferred it to be taught as an elective module.


Angiotensin II-receptor subtypes in human atria and evidence for alterations in patients with cardiac dysfunction.
Angiotensin II (AII) has been implicated as an important factor in the pathophysiology of heart diseases. Following the recent identification of two subtypes of the AII receptor in cardiac tissue of animals, we investigated the possible occurrence of these, or similar, subtypes in human atrial tissue. In right-atrial tissue from patients undergoing heart surgery, we determined the AII-receptor profile in receptor binding studies, using [125I]-angiotensin as radioligand and subtypes to identify and quantify AII-receptor subpopulations. In 35 patients (23 requiring coronary bypasses, 10 valvular surgery and two combined coronary and valvular surgery), the left-ventricular ejection fraction was determined in the preoperative phase, and right- and left-atrial pressure during surgery. In membranes of human right atria, AII receptors are present in high density (median: Bmax = 294 fmol.mg-1 protein, range: 111-2073) and two different subtypes can be distinguished. Type-1 receptors (AT1) accounted for 33 +/- 10% of the population whereas type-2 receptors (AT2) made up 67 +/- 10% of the population. There was no correlation between any of the measured cardiac functions and total AII-receptor density or receptor affinity. However, the percentage of AT1 receptors was higher in the atria of patients with normal right-atrial pressure; left-ventricular ejection fraction was positively and right-atrial pressure inversely correlated with the percentage of AT1 receptors (r = 0.740 and -0.901, respectively; P < 0.001, for both). Moreover, the percentage of AT2 receptors was directly correlated with the levels of left-atrial pressure (r = 0.853; P < 0.001). It is concluded that the ratio of AT1 to AT2 receptors correlates well with right-atrial pressure and left-ventricular function. This is a first indication of a possible involvement of AII-receptor subtypes in the pathophysiology of cardiac dysfunctions.


Involvement of annexin A1 in multidrug resistance of K562/ADR cells identified by the proteomic study.
Multidrug resistance (MDR) to chemotherapy is a significant barrier to the effective treatment of chromic myeloid leukemia (CML). In an attempt to identify more factors associated with MDR for an understanding of the mechanism, we first established an adriamycin (ADR)-resistant human erythroleukemia cell line K562/ADR by stepwise selection in vitro using ADR. Besides the elevated resistance to ADR, the K562/ADR cells also showed significantly increased crossed-resistance to vincristin and Gleevec, compared to the parental K562 cells. Then we compared the global protein profiles between K562 and K562/ADR cells. Following two-dimensional gel electrophoresis and image analysis, some of the proteins with different levels between the two cell lines were identified by MALDI TOF/TOF mass spectrometry and Western blot analysis. The differentially expressed proteins were classified into groups based on their functions: calcium-binding proteins, chaperones, metabolic enzymes, proteins related to protein synthesis or DNA synthesis, and proteins related to signal transduction. In particular, ANXA1, a protein that was downregulated in K562/ADR, was analyzed further for its involvement in MDR by transfection and subsequent assays. The functional validation showed that the downregulated ANXA1 expression contributes considerably to the observed drug resistance in K562/ADR cells. These data will be valuable for further study of the mechanisms of MDR and may reveal a potential new diagnostic marker to chemotherapy.


Synaptobrevin2-expressing vesicles in rat astrocytes: insights into molecular characterization, dynamics and exocytosis.
The SNARE-dependent exocytosis of glutamate-containing vesicles in astrocytes is increasingly viewed as an important signal at the basis of the astrocyte-to-neurone communication system in the brain. Here we provide further insights into the molecular features and dynamics of vesicles in cultured astrocytes. We found that immunoisolated synaptobrevin2 vesicles are clear vesicles quite heterogenous in size and contain the vesicular glutamate transporter v-Glut-2. Moreover, they are immunopositive for synaptotagmin IV, for AMPA receptor subunits GluR2,3 and, to a lesser extent, for GluR1. We also provide direct evidence for the functional expression of v-Glut-2 in astrocytes and demonstrate that synaptobrevin2-positive vesicles can specifically take up (3H)L-glutamate via a bafilomycin-sensitive mechanism. Finally, by time lapse confocal microscopy, we show that a subpopulation of vesicles (tagged with a synaptobrevin2-EGFP chimera) is highly mobile and can fuse with the plasma membrane, preferentially at the level of the astrocyte processes, in a Ca2+-dependent manner. These latter observations, together with the evidence reported here for the expression of functional v-Glut-2 in synaptobrevin2-positive vesicles, provide a molecular basis for regulated exocytosis in astrocyte.


The Prevalence of Occupational Burnout Among Ophthalmologists: A Systematic Review and Meta-Analysis.
To investigate the prevalence of occupational burnout among ophthalmologists in order to better understand the mental and physical well-being of eye physicians and surgeons in the professional workplace. A systematic review and meta-analysis. Online computer databases MEDLINE, EMBASE, CINAHL, and ProQuest Dissertations and Theses were searched systematically and thoroughly. Conferences held through Association for Research in Vision and Ophthalmology, American Academy of Ophthalmology, and Canadian Society of Ophthalmology were searched. Studies were screened using Covidence software. Data on reported burnout prevalence was extracted. STATA 15.0 was used to conduct meta-analysis.Synthesis: Our search strategy identified 318 records from online databases and 11 records from grey literature search, which were screened at 2-levels. Title and abstracts of each record were screened resulting in 24 records moving to full-text screening. Total of 9 records were utilized for quantitative analysis in the data extraction stage. Our results indicated significant professional burnout among ophthalmologists (ES = 0.41; CI: [0.26, 0.56]) with significant emotional exhaustion (ES = 0.43; CI: [0.33, 0.53]), depersonalization (ES = 0.29; CI: [0.13, 0.46]), and a low sense of personal accomplishment (ES = 0.36; CI: [0.08, 0.63]). Significant occupational burnout among ophthalmologists is concerning because burnout can have a negative effect on the physical and mental health of eye physicians and surgeons. It could impact productivity, cutbacks in work hours, or lead to early retirement from the profession. Contributing factors in ophthalmologist burnout including work overload need to be addressed in a timely manner.


Phane properties of [2.2]paracyclophane/dehydrobenzoannulene hybrids.
A series of [2.2]paracyclophane/dehydrobenzo[14]annulene (PC/DBA) hybrids (hydrocarbons 5, 6, 9, 10 b, and 10 c), [2.2]paracyclophane/dehydro[14]annulene (PC/DA) hybrids (7 and 8) and suitable model systems (11, 12, and 33) has been synthesized. Comparison of the electronic absorption spectra in each series of compounds provides further insight into the global communication between the decks in the [2.2]paracyclophane unit.


Neurosurgical developments of Thierry de Martel (1875-1940), French neurosurgery pioneer, during World Wars I and II.
Following France's entry into World War I on August 3, 1914, Thierry de Martel (1875-1940), the French neurosurgery pioneer, served on the front line and was wounded on October 3, 1914. He was then assigned as a surgeon in temporary hospitals in Paris, where he published his first observations of cranioencephalic war wounds. In 1915, de Martel met Harvey Cushing at the American Hospital in Neuilly, where de Martel was appointed chief surgeon in 1916. In 1917, he published with the French neurologist Charles Chatelin a book (Blessures du crâne et du cerveau. Clinique et traitement) with the aim to optimize the practice of wartime brain surgery. This book, which included the results of more than 5000 soldiers with head injuries, was considered the most important ever written on war neurology at that time and was translated into English in 1918 (Wounds of the Skull and Brain; Their Clinical Forms and Medical and Surgical Treatment). In this book, de Martel detailed the fundamentals of skull injuries, classified the various craniocerebral lesions, recommended exploratory craniectomy for cranioencephalic injuries, recommended the removal of metal projectiles from the brain using a magnetic nail, and advocated for the prevention of infectious complications. Between the World Wars, de Martel undertook several developments for neurosurgery in France alongside neurologists Joseph Babinski and Clovis Vincent. Following France's entry into World War II on September 3, 1939, de Martel took over as head of the services of the American Hospital of Paris in Neuilly. He updated his work on war surgery with the new cases he personally treated. Together with Vincent, de Martel presented his new approach in "Le traitement des blessures du crâne pendant les opérations militaires" ("The treatment of skull injuries during military operations") on January 30, 1940, and published his own surgical results in April 1940 in "Plan d'un travail sur le traitement des plaies cranio-cérébrales de guerre" ("Work Plan on the Treatment of Cranio-Cerebral Wounds of War"), intended for battlefield surgeons. On June 14, 1940, the day German troops entered Paris, de Martel injected himself with a lethal dose of phenobarbital. Thierry de Martel played a central role in establishing modern neurosurgery in France. His patriotism led him to improve the management of wartime cranioencephalic injuries using his own experience acquired during World Wars I and II.


What constitutes successful nurse leadership?: A qualitative approach utilizing Kanter's theory of organizational behavior.
What constitutes successful leadership in today's healthcare environment and what are the principal components of an organization that supports the role of the nurse leader? To answer these questions, 16 nurse leaders from four acute care hospitals were interviewed for their perception of leadership traits that are effective in the inpatient hospital setting and types of organizational infrastructures that create conditions for job effectiveness. Kanter's theory of organizational behavior provided the conceptual framework for this study. Leadership effectiveness is linked to having access to opportunity, resources, information, and formal and informal power in the work setting. Nurse leaders with access to these structures are empowered and successful, which leads to enhanced worth and overall organizational achievement. Also, strong central beliefs and business astuteness are considered vital attributes in today's economically oriented environment.


Diaphragmatic dysfunction in neuralgic amyotrophy: an electrophysiologic evaluation of 16 patients presenting with dyspnea.
We report 16 adult men (age, 41 to 75 yr) with neuralgic amyotrophy (NA) who presented with dyspnea due to involvement of the diaphragm. All patients developed breathlessness after a prodrome of acute severe neck and shoulder pain. Bilateral diaphragm paralysis (BDP) was confirmed in 12 patients and unilateral diaphragm paralysis (UDP) in four by the absence of electrical and mechanical responses to percutaneous phrenic nerve stimulation. Global expiratory muscle strength was well preserved in all patients, but inspiratory muscle strength was reduced in proportion to the extent of diaphragmatic involvement. Lung function showed low lung volumes with preservation of carbon monoxide transfer coefficient in all patients. Two BDP patients were hypoxic (PaO2 = 67 and 54 mm Hg, respectively) on daytime arterial blood gas analysis; the latter patient with pre-existing chronic obstructive pulmonary disease and marked obesity also had borderline hypercapnia (PaO2 = 49 mm Hg). Overnight sleep studies in three BDP and two UDP patients showed frequent intermittent arterial oxygen desaturations apparently caused by obstructive sleep apneas, but there was no evidence of alveolar hypoventilation. Follow-up muscle studies in five BDP and four UDP patients between 2 and 4 yr after initial referral showed complete recovery of diaphragmatic function in only two UDP patients, one of whom relapsed a year later. We postulate that NA may be an important but underrecognized cause of diaphragmatic paralysis in otherwise normal patients. Diaphragmatic strength returns very slowly, if at all.


How do infants start learning object names in a sea of clutter?
Infants are powerful learners. A large corpus of experimental paradigms demonstrate that infants readily learn distributional cues of name-object co-occurrences. But infants' natural learning environment is cluttered: every heard word has multiple competing referents in view. Here we ask how infants start learning name-object co-occurrences in naturalistic learning environments that are cluttered and where there is much visual ambiguity. The framework presented in this paper integrates a naturalistic behavioral study and an application of a machine learning model. Our behavioral findings suggest that in order to start learning object names, infants and their parents consistently select a set of a few objects to play with during a set amount of time. What emerges is a frequency distribution of a few toys that approximates a Zipfian frequency distribution of objects for learning. We find that a machine learning model trained with a Zipf-like distribution of these object images outperformed the model trained with a uniform distribution. Overall, these findings suggest that to overcome referential ambiguity in clutter, infants may be selecting just a few toys allowing them to learn many distributional cues about a few name-object pairs.


Activation of the anterior cingulate cortex by thalamic stimulation in patients with chronic pain: a positron emission tomography study.
Deep brain stimulation (DBS) of the sensory thalamus has been used to treat chronic, intractable pain. The goal of this study was to investigate the thalamocortical pathways activated during thalamic DBS. The authors compared positron emission tomography (PET) images obtained before, during, and after DBS in five patients with chronic pain. Two of the five patients reported significant DBS-induced pain relief during PET scanning, and the remaining three patients did not report any analgesic effect of DBS during scanning. The most robust effect associated with DBS was activation of the anterior cingulate cortex (ACC). An anterior ACC activation was sustained throughout the 40 minutes of DBS, whereas a more posteriorly located ACC activation occurred at a delay after onset of DBS, although these activations were not dependent on the degree of pain relief reported during DBS. However, implications specific to the analgesic effect of DBS require further study of a larger, more homogeneous patient population. Additional effects of thalamic DBS were detected in motor-related regions (the globus pallidus, cortical area 4, and the cerebellum) and visual and association cortical areas. The authors demonstrate that the ACC is activated during thalamic DBS in patients with chronic pain.


University-assisted community school program of West Philadelphia: democratic partnerships that make a difference.
The university-assisted community school model is showing results for children and youth in West Philadelphia. The University of Pennsylvania's (Penn's) Center for Community Partnerships has coordinated universitywide efforts, in partnership with the community, in order to create and develop community school programs. The Sayre program aims to become a university-assisted community school, with a comprehensive community problem-solving curriculum and communitywide program that is fully integrated across both the Sayre curriculum and the curriculum of a number of Penn's schools. The Penn-Sayre project demonstrates that higher education can be a permanent anchor for revitalizing schools and communities if the vast resources it possesses, particularly its faculty, students, and staff, are brought to bear in a coordinated fashion.


Supportive needs of informal caregivers of people with amyotrophic lateral sclerosis in Switzerland: a qualitative study.
This study explores the supportive needs of informal caregivers of people with amyotrophic lateral sclerosis (ALS) in Switzerland. We conducted semi-structured interviews with nine informal caregivers currently providing care to a person with ALS, 14 bereaved informal caregivers, and 13 healthcare professionals. Interviews were recorded on digital audio and analysed using an inductive thematic analysis within a realist framework. Informal caregivers discussed five themes of support needs relating to being overburdened by administrative demand, in contact with healthcare providers, home support, especially during the terminal phase, and having or lacking social support. Healthcare professionals discussed three themes of support needs of informal caregivers which related to the general institutional support for informal caregivers, their own work as caring for informal caregivers, and the challenges in healthcare for families with ALS they encountered. Informal caregiving for people with ALS can be demanding. This study provides evidence for improvements in supporting informal caregivers. It shows administrative needs of informal caregivers, stresses their needs regarding advance care planning early in the context of ALS, and underlines the importance of social support, be it in peer-groups or community care.


[The influence of rheumatoid and degenerative disease on hospital resources in the operative treatment of cervical spine instability].
The aim of this study was to compare perioperative diagnostic and therapeutic measures in the treatment of cervical spine instability in patients with rheumatoid arthritis or degenerative disease. Twenty patients (ten in each group) were evaluated and compared with regard to age, sex, surgery time, total operating room time, intensive care time, extent of physical therapy, nursing requirements, costs of medication and radiography. Rheumatoid arthritis patients required more resources with regard to surgery, nursing and rehabilitation than the patients with degenerative disease. Significant differences existed with regard to patient age (P=0.0005), surgery time (P=0.0021), total operating room time (P=0.0001), duration of intensive care (P=0.0005), nursing requirements (P=0.0000), costs of medication (P=0.0000), costs of radiography (P=0.0015) and the duration of hospitalisation (P=0.0115). The data suggest that it is necessary to distinguish patients with rheumatoid or degenerative cervical spine instability from an economic point of view, as the treatment of the rheumatoid cervical spine requires more resources.


Top-down therapy for Crohn's disease: rationale and evidence.
Several trials have shown that early treatment of Crohn's disease with immunomodulators and anti-TNF agents leads to superior clinical outcome including healing of the mucosa. Evidence is mounting that this endpoint is associated with a reduced risk of complications and a reduced need for surgeries and hospitalizations. In the SONIC trial, treatment with the combination of azathioprine and infliximab was the most potent anti-inflammatory therapy in Crohn's disease patients with evidence of active inflammation who had never been exposed to immunomodulators or biologics. These findings have introduced a trend towards earlier initiation of immunomodulator therapy, comparable to what is being done in rheumatoid arthritis. Given the fact that subsets of patients have a favorable disease course without immunomodulator therapy and given the significant potential toxicity of these medications, however, it is becoming a challenge to the gastroenterologists to try and identify patients with an unfavorable disease prognosis and treat these early and aggressively. The key to successful management of Crohn's disease appears to lie in careful timing and selection of the appropriate interventions.


Assessing intrinsic renal sodium avidity in acute heart failure: implications in predicting and guiding decongestion.
Intrinsic renal sodium avidity (IRSA) is a hallmark feature of acute heart failure (AHF) and can be measured by evaluating the urinary sodium (UNa) concentration. The aim of this study is to assess the role of measuring IRSA through a random Una-sample and its association with decongestive response. A post-hoc analysis of the ROSE-AHF trial was performed in all patients with a random UNa spot sample before randomization (n = 339/360). Patients were categorized according to tertiles of UNa as high (range 19-40 mmol/L), intermediate (range 41-68 mmol/L), or low (range 69-139 mmol/L) IRSA. Linear mixed effect models and ANCOVA were used to assess the relation with decongestive effectiveness measured by: (i) weight change, (ii) visual analogue scale (VAS) improvement, (iii) N-terminal pro-B-type natriuretic peptide (NT-proBNP) change, (iv) natriuretic response (UNa in mmol/L), (v) 72 h natriuresis (mmol), (vi) oedema resolution, and (vii) length of stay. High IRSA patients had less improvement in decongestive metrics, including weight loss (p = 0.028), VAS improvement, NT-proBNP decrease, natriuretic response (p-time interaction <0.001 for all), had lower total natriuresis (high IRSA 438 ± 141 mmol, intermediate IRSA 526 ± 320 mmol, and low IRSA 603 ± 276 mmol; p < 0.001), exhibited more oedema at 72 h (p = 0.005), and had a longer length of stay (p = 0.015). Incremental loop diuretic dose titration (± 4 times home dose) after >24 h, resulted in an increase in natriuretic response in the high IRSA group, however cumulative natriuresis still remained lower at 72 h (p < 0.001). Longitudinal UNa profiling of patients with low IRSA showed physiologic breaking in the UNa pattern, associated with attaining decongestion and slight increase in creatinine and cystatin C, forming a potential signal of complete decongestion. A simple random UNa sample at the time of AHF, gives insight into IRSA which is consistently associated with decongestive effectiveness across multiple metrics, offering an opportunity for early AHF care improvement.


Theory and computer simulation for the cubatic phase of cut spheres.
The phase behavior of a system of hard-cut spheres has been studied using a high-order virial theory and by Monte Carlo simulation. The cut-sphere particles are disks of thickness L formed by symmetrically truncating the end caps of a sphere of diameter D . The virial theory predicts a stable nematic phase for aspect ratio LD=0.1 and a stable cubatic phase for LD=0.15-0.3 . The virial series converges rapidly on the equation of state of the isotropic and nematic phases, while for the cubatic phase the convergence is slower, but still gives good agreement with the simulation at high order. It is found that a high-order expansion (up to B8 ) is required to predict a stable cubatic phase for LD> or =0.15 , indicating the importance of many-body interactions in stabilizing this phase. Previous simulation work on this system has focused on aspect ratios LD=0.1 , 0.2, and 0.3. We expand this to include also LD=0.15 and 0.25, and we introduce a fourth-rank tensor to measure cubatic ordering. We have applied a multiparticle move which dramatically speeds the attainment of equilibrium in the nematic phase and therefore is of great benefit in the study of the isotropic-nematic phase transition. In agreement with the theory, our simulations confirm the stability of the nematic phase for LD=0.1 and the stability of the cubatic phase over the nematic for LD=0.15-0.3 . There is, however, some doubt about the stability of the cubatic phase with respect to the columnar. We have shown that the cubatic phase found on compression at LD=0.1 is definitely metastable, but the results for LD=0.2 were less conclusive.


Importance of a Lys113-Glu195 intermonomer ionic bond in F-actin stabilization and regulation by yeast formins Bni1p and Bnr1p.
Proper actin cytoskeletal function requires actin's ability to generate a stable filament and requires that this reaction be regulated by actin-binding proteins via allosteric effects on the actin. A proposed ionic interaction in the actin filament interior between Lys(113) of one monomer and Glu(195) of a monomer in the apposing strand potentially fosters cross-strand stabilization and allosteric communication between the filament interior and exterior. We interrupted the potential interaction by creating either K113E or E195K actin. By combining the two, we also reversed the interaction with a K113E/E195K (E/K) mutant. In all cases, we isolated viable cells expressing only the mutant actin. Either single mutant cell displays significantly decreased growth in YPD medium. This deficit is rescued in the double mutant. All three mutants display abnormal phalloidin cytoskeletal staining. K113E actin exhibits a critical concentration of polymerization 4 times higher than WT actin, nucleates more poorly, and forms shorter filaments. Restoration of the ionic bond, E/K, eliminates most of these problems. E195K actin behaves much more like WT actin, indicating accommodation of the neighboring lysines. Both Bni1 and Bnr1 formin FH1-FH2 fragment accelerate polymerization of WT, E/K, and to a lesser extent E195K actin. Bni1p FH1-FH2 dramatically inhibits K113E actin polymerization, consistent with barbed end capping. However, Bnr1p FH1-FH2 restores K113E actin polymerization, forming single filaments. In summary, the proposed ionic interaction plays an important role in filament stabilization and in the propagation of allosteric changes affecting formin regulation in an isoform-specific fashion.


Inactivation of Salmonella Enteritidis in chicken breast fillets by single-cycle and multiple-cycle high pressure treatments.
The effect of single-cycle and multiple-cycle high hydrostatic pressure (HHP) treatments on the survival of three Salmonella Enteritidis strains in chicken breast fillets was investigated. The surface of fillets was inoculated with a cocktail of three Salmonella strains at approximately 10(7) colony-forming units (CFU)/g, and held at 4 degrees C for 20 hours before HHP treatments. Reduction of Salmonella counts on tryptic soy agar (TSA) by single-cycle treatments at 300 MPa and 12 degrees C ranged from 0.58 log CFU/g for a 0-minute (no dwell time) cycle to 3.35 log CFU/g for a 20-minute cycle, whereas with 400 MPa treatments the decline ranged from 0.93 log CFU/g to more than 5 log CFU/g, respectively. The 4.8 log unit reduction in Salmonella counts on TSA achieved by a 15-minute treatment at 400 MPa should suffice to eliminate the pathogen naturally present in contaminated chicken meat. When plated on Salmonella Shigella agar (SSA), the reduction of Salmonella counts by single-cycle treatments at 300 MPa and 12 degrees C ranged from 0.69 log CFU/g for a 0-minute cycle to 4.21 log CFU/g for a 20-minute cycle, and with 400 MPa treatments from 1.25 log CFU/g to more than 5 log CFU/g, respectively. From the comparison of Salmonella counts on SSA and TSA it was concluded that not only the lethality but also the proportion of injured Salmonella cells increased with the length of HHP treatments. The use of multiple-cycle treatments instead of single-cycle treatments of the same HHP time for the inactivation of Salmonella Enteritidis inoculated on chicken breast fillets showed to be more advantageous at 400 MPa than at 300 MPa. No recovery of injured Salmonella cells was observed when fillets treated at 300 or 400 MPa for 5 minutes were held for 72 hours at 4 degrees C.


Peer, substance use, and race-related factors associated with recidivism among first-time justice-involved youth.
Peer deviancy and substance-related consequences are dynamic criminogenic needs associated with increased risk of recidivism for justice-involved youth. Most prior research in this area, however, is based on samples of primarily male youth charged with delinquent offenses. Because identification of dynamic criminogenic needs is essential to delinquency risk reduction efforts, the purpose of this study was to examine the role of peer deviancy and substance-related consequences in a sample of youth at first contact with the juvenile justice system, with relatively equal representation of males and females and youth charged with delinquent and status offenses. We hypothesized that higher levels of peer deviancy and more severe alcohol- and cannabis-related consequences would predict recidivism. We also hypothesized that Black and brown youth would be more likely to recidivate than non-Latinx White participants. First-time justice-involved youth (N = 401) aged 12-18 and their caregivers reported independent variables at baseline (demographic, legal, psychiatric, and peer factors). Official records of recidivism (i.e., number of new charges 2 years later) was the dependent variable for nested multivariate negative binomial regression models. Peer deviancy reported by caregivers, but not by youth, predicted recidivism 2 years later. Consequences related to alcohol, but not cannabis, increased recidivism risk. Finally, participants who were younger, male, charged with a delinquent offense, and Black, multiracial, and/or Latinx were more likely to recidivate than non-Latinx White participants after controlling for covariates. Results highlight the influence of institutionalized racism on later court involvement for youth of color at first court contact, regardless of individual risk. Deviant peers and consequences of alcohol are salient intervention targets for this population. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Liquid-liquid emulsification by static mixers for use in microencapsulation.
4e report a feasibility study on liquid-liquid emulsification by static mixers for use in microencapsulation. This study was concerned with developing a quantitative correlation between the size of the microspheres and process parameters. The process parameters considered included operational variables and physical properties associated with both the dispersion and dispersed phases. The effect of mixing element design on mixing efficiency and particle-size distribution was evaluated using three different static mixers. The performance of static mixers and conventional continuously stirred-tank reactors was assessed in several different aspects. Dimensional analysis was used to establish a correlation based on protein-free poly(lactic acid-co-glycolid acid) and poly(methyl methacrylate) microspheres in an oil-in-water emulsion using 1/4", 1/2" and 1" static mixers. This correlation accurately described the preparation of protein-loaded microspheres and provided large-scale microsphere production with a empirical basis.


mRNA expression of MMP-28 (Epilysin) in gingival tissues of chronic and aggressive periodontitis patients: a reverse transcriptase PCR study.
Matrix metalloproteinases degrade extracellular membrane and also release bioactive fragments and growth factors, thus influencing fundamental biological and pathological processes. Epilysin (MMP-28) differs from most other MMPs as it is expressed in a number of normal tissues, suggestive of functions in tissue homeostasis. The aim of the present study was to quantitatively evaluate and compare the mRNA expression of epilysin (MMP-28) in gingival tissues of healthy patients and of patients affected by chronic or aggressive periodontitis. A total of 60 subjects, 20 periodontally healthy subjects, 20 with chronic periodontitis, and 20 with aggressive periodontitis, were included in this study. Periodontal status was evaluated by measuring gingival index, probing depth and clinical attachment level. mRNA expression of MMP-28 was determined by quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR) in gingival tissue samples collected. Relative quantification of mRNA expression of MMP-28 was highest in healthy tissues (RQ = 0.97) when compared to subjects with chronic periodontitis (RQ = 0.37) and aggressive periodontitis (RQ = 0.23), but the difference was not statistically significant. mRNA expression of MMP-28 was highest in healthy tissues when compared to diseased periodontal tissues suggesting that MMP-28 could act as a biomarker for periodontal health.


Assessing the progression of renal disease in clinical studies: effects of duration of follow-up and regression to the mean. Modification of Diet in Renal Disease (MDRD) Study Group.
Many clinical studies of the effects of low-protein and low-phosphorus diets on the course of chronic renal disease have used the rate of decline in renal function to assess the rate of progression. In this report, data from the feasibility phase of the Modification of Diet in Renal Disease Study were used to analyze methods used in other studies. The focus is particularly on the effects of duration of follow-up and of regression to the mean. The findings are summarized as follows. (1) During the mean follow-up period of 14.1 months, rates of decline in glomerular filtration rate, creatinine clearance, and the reciprocal of the serum creatinine concentration were highly variable among individuals, and mean rates of decline were slow. (2) Precision of estimates of individual rates of decline in renal function were relatively low and improved with increasing duration of follow-up. (3) Correlations between rates of decline in creatinine clearance and the reciprocal of the serum creatinine concentration with glomerular filtration rate in individuals were significant but weak and became stronger with increasing duration of follow-up. (4) After entry into the study, mean rate of decline in the reciprocal of the serum creatinine concentration became less negative. The change predicted simply from regression to the mean was 68.4% of the observed change.(ABSTRACT TRUNCATED AT 250 WORDS)


Computer-aided quantification of RNA levels detected by in situ hybridization of tissue sections.
A semi-automatic program, designed for non-computer scientists, was developed for quantification of RNA levels detected by in situ hybridization in heterogeneous tissues. A video camera was used to acquire microscopic images of autoradiographed tissue sections which are then digitized on a video monitor for semi-automated quantification of silver grains. We describe a data entry and analysis procedure for systematic quantification of RNA levels in which about 300 cells per tissue sample can be analysed within 10 min. When compared with visual counting, computer-aided quantification was found to be more objective and reliable, with the highest variation coefficient between individuals being 7.5% using computer-aided quantification, compared to 24% with manual counting of the same section areas. A comparative study of c-myc oncogene expression in 11 mammary adenocarcinomas from 3 independent experiments showed the good reproducibility of results using the computer-aided method, with an 18% maximum variation between experiments. The program, with its simple user-interface, reliability and rapidity, is convenient for measuring specific genetic expression levels in clinical studies requiring large numbers of specimens.


A bone-targeting drug delivery vehicle of a metal-organic framework conjugate with zoledronate combined with photothermal therapy for tumor inhibition in cancer bone metastasis.
Chemotherapy is a conventional treatment method for metastatic bone cancer, but it has limitations, such as lower drug-targeting of bone tissues and serious side effects. Bone metastasis almost always occurs in advanced cancer, and most patients in this period have strong drug resistance, which further worsens the curative effect. To address the above-mentioned difficulties, a drug delivery platform is proposed in this paper that accomplishes the bone-targeting of drugs to efficiently inhibit tumors. First, the anti-cancer drugs 5-fluorouracil (5-Fu) and indocyanine green (ICG) were loaded into a zeolitic imidazolate framework (ZIF-90) to form 5-Fu/ICG@ZIF-90. Polyethylene glycol with zoledronic acid (ZOL) was encapsulated using 5-Fu/ICG@ZIF-90 to synthesize 5-Fu/ICG@ZIF-90-PEG-ZOL nanoparticles, which showed dimensional stability, good thermal stability, and bone-targeting ability. Second, the in vitro anti-cancer activity of the designed platform was investigated using cytotoxicity, apoptosis, live-dead staining, cell cycle, and cell ultrathin section analysis. The results indicated that the nanoparticles inhibited MCF-7 cell activity when chemotherapy was combined with PTT. Finally, H&E staining and TUNEL detection were performed in mouse organs and tumors. The nanoparticles combined with photothermal therapy (PTT) and triggered by near-infrared irradiation induce apoptosis of tumor cells in vivo, displaying a better efficacy of combined chemotherapy and photothermal therapy. Experiments conducted on the 5-Fu/ICG@ZIF-90-PEG-ZOL nanoparticles demonstrated their promising performance for cancer bone metastasis inhibition.


Dartos reflex: a sympathetically mediated scrotal reflex.
The dartos muscle is a sympathetically innervated dermal muscle layer within the scrotum, distinct from the somatically innervated cremasteric muscle. We electrophysiologically demonstrate the presence of a dartos reflex (DR), which can be used to evaluate the thoracolumbar sympathetic and genitofemoral nerve pathways. In 20 healthy men, we evoked the DR by cutaneous stimulation of the thigh and recorded the resultant scrotal skin contraction. We recorded hand, foot, and perineal sympathetic skin responses (SSRs) as controls. The DR was reliable and reproducible, as were the SSRs. The mean left DR latency was 4.8 s (SD, 2.7 s) and right DR latency was 5.4 s (SD, 3 .4), both of which were longer than the mean hand, foot, and perineal SSRs (P < 0.05). An intact reflex arc reflects the integrity of the afferent and efferent branches of the genitofemoral nerve (T12-L2). The DR test can also be used to assess scrotal autonomic innervation. Abnormalities of dartos innervation may impact testis thermoregulation and spermatogenesis.


Endoplasmic reticulum glucosidase II is inhibited by its end products.
The calnexin/calreticulin cycle is a quality control system responsible for promoting the folding of newly synthesized glycoproteins entering the endoplasmic reticulum (ER). The association of calnexin and calreticulin with the glycoproteins is regulated by ER glucosidase II, which hydrolyzes Glc 2Man X GlcNAc 2 glycans to Glc 1Man X GlcNAc 2 and further to Glc 0Man X GlcNAc 2 ( X represents any number between 5 and 9). To gain new insights into the reaction mechanism of glucosidase II, we developed a kinetic model that describes the interactions between glucosidase II, calnexin/calreticulin, and the glycans. Our model accurately reconstructed the hydrolysis of glycans with nine mannose residues and glycans with seven mannose residues, as measured by Totani et al. [Totani, K., Ihara, Y., Matsuo, I., and Ito, Y. (2006) J. Biol. Chem. 281, 31502-31508]. Intriguingly, our model predicted that glucosidase II was inhibited by its nonglucosylated end products, where the inhibitory effect of Glc 0Man 7GlcNAc 2 was much stronger than that of Glc 0Man 9GlcNAc 2. These predictions were confirmed experimentally. Moreover, our model suggested that glycans with a different number of mannose residues can be equivalent substrates of glucosidase II, in contrast to what had been previously thought. We discuss the possibility that nonglucosylated glycans, existing in the ER, might regulate the entry of newly synthesized glycoproteins into the calnexin/calreticulin cycle. Our model also shows that glucosidase II does not interact with monoglucosylated glycans while they are bound to calnexin or calreticulin.


Massive Hemorrhage: The Role of Whole Blood Viscoelastic Assays.
Viscoelastic whole blood tests are increasingly used to guide hemostatic therapy in bleeding patients in the perioperative, trauma, and obstetric settings. Compared with standard laboratory tests of hemostasis, they have a shorter turnaround time and provide simultaneous information on various aspects of clot formation and lysis. The two available brands TEG (thromboelastography) and ROTEM (rotational thromboelastometry) provide devices that are either manually operated or fully automated. The automation allows for the assays to be used as point-of-care tests increasing their usefulness in massively bleeding patients with rapidly changing hemostatic profiles. While the number of research papers on the subject and the number of published treatment algorithms increase rapidly, the influence of the use of these devices on patient outcome needs yet to be established. In this article, we first review the technology of these devices and the parameters provided by the assays. Next, we present the problems encountered when choosing cut-off values that trigger intervention. Furthermore, we discuss the studies examining their influence on clinical outcomes, and finally, we briefly highlight some of the most important limitations and pitfalls inherent to these assays.


Effect of starvation and insulin-induced hypoglycemia on oxidative stress scavenger system and electron transport chain complexes from rat brain, liver, and kidney.
Considerable evidence suggests that oxidative stress plays an important role in tissue damage associated with hypoglycemia and other metabolic disorders. The altered brain neurotransmitters metabolism, cerebral electrolyte contents, and impaired blood-brain barrier function may contribute to CNS dysfunction in hypoglycemia. The present study elucidates the effect of starvation and insulin-induced hypoglycemia on the free radical scavanger system--reduced glutathione (GSH) content, glutathione S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR), gamma-glutamyl transpeptidase (gamma-GTP), gamma-glutamyl cystein synthetase (gamma-GCS), catalase and superoxide dismutase (SOD), and mitochondrial electron transport chain (ETC) complexes I-IV from three different regions of rat brain, namely cerebral hemispheres (CH), cerebellum (CB), and brainstem (BS). Peripheral organs, such as liver and kidney, were also studied. Significant changes in these enzymic activities were observed. The analysis of such alterations is important in ultimately determining the basis of neuronal dysfunction during metabolic stress conditions, such as hypoglycemia, and also defining the nature of these changes may help to develop therapeutic means to cure metabolically stressed tissues.


Molecular cloning and characterization of a human carboxylesterase gene.
A cDNA encoding human liver carboxylesterase and its gene were isolated. Nucleotide sequence analyses of the cDNA revealed that the predicted enzyme protein consists of 567 amino acids, including 18 amino acids of a putative signal peptide. Comparison of the deduced amino acid sequences of this enzyme with those of seven other carboxylesterases in various mammalian species, together with experimental data from several other laboratories, showed that these enzymes can be classified into three groups depending on the sequences at their carboxyl terminals and the presence or absence of one exon. A human carboxylesterase gene was found to span approximately 30 kb and to have 14 small exons. Alignments of this gene with those of human cholinesterase and rat cholesterol esterase indicated insertional sites at some introns and homologous amino acid sequences around them, although these genes have different numbers of exons. Thus the results supported the conclusion that these esterases evolved from a common ancestral gene.


Density matrix embedding in an antisymmetrized geminal power bath.
Density matrix embedding theory (DMET) has emerged as a powerful tool for performing wave function-in-wave function embedding for strongly correlated systems. In traditional DMET, an accurate calculation is performed on a small impurity embedded in a mean field bath. Here, we extend the original DMET equations to account for correlation in the bath via an antisymmetrized geminal power (AGP) wave function. The resulting formalism has a number of advantages. First, it allows one to properly treat the weak correlation limit of independent pairs, which DMET is unable to do with a mean-field bath. Second, it associates a size extensive correlation energy with a given density matrix (for the models tested), which AGP by itself is incapable of providing. Third, it provides a reasonable description of charge redistribution in strongly correlated but non-periodic systems. Thus, AGP-DMET appears to be a good starting point for describing electron correlation in molecules, which are aperiodic and possess both strong and weak electron correlation.


Peripheral Neuropathic Facial/Trigeminal Pain and RANTES/CCL5 in Jawbone Cavitation.
Introduction. In this study, we elucidate the possible causative role of chronic subclinical inflammation in jawbone of patients with atypical facial pain (AFP) and trigeminal neuralgia (TRN) in the local overexpression of the chemokine regulated on activation and normal T-cell expressed and secreted (RANTES/C-C motif ligand 5 CCL5). Neurons contain opioid receptors that transmit antipain reactions in the peripheral and central nervous system. Proinflammatory chemokines like RANTES/CCL5 desensitize μ-opioid receptors in the periphery sensory neurons and it has been suggested that RANTES modifies the nociceptive reaction. Materials and Methods. In 15 patients with AFP/TRN, we examined fatty degenerated jawbone (FDOJ) samples for the expression of seven cytokines by multiplex analysis and compared these results with healthy jawbones. Results. Each of these medullary jawbone samples exhibited RANTES as the only highly overexpressed cytokine. The FDOJ cohort with AFP/TRN showed a mean 30-fold overexpression of RANTES compared to healthy jawbones. Conclusions. To the best of our knowledge, no other research has identified RANTES overexpression in silent inflamed jawbones as a possible cause for AFP/TRN. Thus, we hypothesize that the surgical clearing of FDOJ might diminish RANTES signaling pathways in neurons and contribute to resolving chronic neurological pain in AFP/TRN patients.


Do Endocannabinoids Cause the Runner's High? Evidence and Open Questions.
The runner's high is an ephemeral feeling some humans experience during and after endurance exercise. Recent evidence in mice suggests that a runner's high depends on the release of endocannabinoids (eCBs) during exercise. However, little is known under what circumstances eCBs are released during exercise in humans. This systematic review sampled all data from clinical trials in humans on eCB levels following exercise from the discovery of eCBs until April 20, 2021. PubMed/NCBI, Ovid MEDLINE, and Cochrane library were searched systematically and reviewed following the PRISMA guidelines. From 278 records, 21 met the inclusion criteria. After acute exercise, 14 of 17 studies detected an increase in eCBs. In contrast, after a period of long-term endurance exercise, four articles described a decrease in eCBs. Even though several studies demonstrated an association between eCB levels and features of the runner's high, reliable proof of the involvement of eCBs in the runner's high in humans has not yet been achieved due to methodological hurdles. In this review, we suggest how to advance the study of the influence of eCBs on the beneficial effects of exercise and provide recommendations on how endocannabinoid release is most likely to occur under laboratory conditions.


Delete or Not: A Game-Theoretical Model for Soft Censorship of Rumor.
Rumor censorship of social media platforms has become an important issue in the academia and in practice. However, most studies focus on the complete rumor censorship behavior rather than the soft censorship behavior of (social media) platforms. To characterize soft censorship behavior, we conduct analytical, numerical, and experimental analyses using game theory to determine the specific strategies of platforms and rumormongers. Given that (1) the censorship behavior of platforms is costly and (2) platforms have a limited accuracy rate to identify rumors correctly, the platform may identify rumors as true information or identify true information as rumors; moreover, (3) rumormongers decide whether to publish rumors or not to avoid been deleted by the platforms. We found that (1) if deleting true information mistakenly has benefits rather than cost (the platform may cost less by not improving their rumor identification algorithms if the public pays less attention to the freedom of their speech), then platforms are more likely to censor rumormongers and delete the information they published; (2) if deleting true information is costly, then platforms become more cautious about their deleting behavior. This study explains why censoring is accepted by the public in some countries but is highly questionable in others. Using these findings can help platforms understand the rumor publishing behavior of rumormongers and make decisions based on certain situations.


Quality of life of patients with sarcoma postchemotherapy.
This study was designed to describe the effects of a 96-hour doxorubicin hydrochloride/dacarbazine chemotherapy protocol for soft-tissue sarcoma on patients' functioning, life-style, and quality of life (QOL). Patients from the surgical oncology clinic of a large, midwestern university completed the Quality of Life Index--Cancer Version (QLI) and Functional Living Index: Cancer (FLIC). Additional information obtained regarded response to chemotherapy and demographic data. Patients were most satisfied with faith in God, family health, health care, long life, and their spouse. Patients were least satisfied with sex life, stress or worries, unemployment, financial independence, and government influence. QOL in the family domain was found to be significantly higher than QOL in the health, functioning, and socioeconomic domains (p less than 0.05). Functional living assessment indicated that patients were confident in their prescribed course of treatment, optimistic about the future, generally felt well, and felt that their QOL had improved since treatment. Aspects of chemotherapy that most interfered with patients' lives were the length of treatment and the financial burden. The patients reported a high confidence level in the medical and nursing care that they received.


[Tortuous retinal vessels].
The authors observed an occurrence of tortuosity of retinal vessels from the group of 5,000 investigations of an ocular fundus. Elimination of all local reasons or symptoms of general diseases, even in spite of the great possibility of modification of this feature, three characteristic types were found. In two of them the familiar and hereditary occurrence was proved.


Macrophage activation syndrome in a patient affected by Plasmodium falciparum Aeroport malaria.
Malaria is a worldwide problem. Infection with Plasmodium. falciparum that may cause a multi-organ-failure, especially if the diagnose wasn't at time. Macrophage activation syndrome is a clinical and biological syndrome caused by an excessive proliferation of T lymphocytes. Plasmodium falciparum infection was rarely reported as a cause of this syndrome reported in the literature. We report a case of severe airport malaria in a 62-year-old man complicated by Macrophage activation syndrome. The patient was treated with intravenous quinine for 7days, catecholamine, volume expansion, mechanical ventilation, sedation and dialysis. But the evolution was marked by a multi-organ failure leading to the death of the patient. The occurrence of airport malaria stresses the need for sensitization of clinicians for considering malaria in febrile individuals even when they have not traveled to an endemic area. Clinicians should be aware of Macrophage activation syndrome when malaria does not respond to conventional therapy, since early diagnosis and prompt treatment may dramatically reduce the mortality associated with this condition.


Microsatellite instability in acute myelocytic leukaemia developed from A-bomb survivors.
Genetic alterations, including microsatellite instability (MSI), are ultimate steps toward malignant process. To investigate MSI in A-bomb survivors, leukaemic cells were analysed from 13 acute myelocytic leukaemia patients with a history of radiation exposure and also in 12 de novo patients. To assess the microsatellite changes, a fluorescent system in 10 loci (BAT40, D3S643, D5S107, IRF1, MYC, D9S171, WT1, TP53, DM, D17S855) was used. MSI analysis revealed a high frequency of multiple microsatellite changes in the exposed patients (84.6%) compared with non-exposed patients (8.3%). There was a significant difference (p < 0.001) between the two groups. These analyses clearly demonstrate that leukaemic cells from heavily exposed patients contain a number of genetic instabilities that may strongly influence the development of leukaemia among people exposed to the Hiroshima A-bomb radiation.


A Multidisciplinary Approach to Verbal Communication Interventions for Mechanically Ventilated Adults With a Tracheostomy.
There is developing evidence with regard to the feasibility, utility, and safety of verbal communication interventions with patients with tracheostomy who are invasively ventilated. In the past 2 decades, research efforts have focused on establishing evidence for communication interventions, including introducing an intentional leak into the ventilatory circuit such as with a fenestrated tube, leak speech or ventilator-adjusted leak speech, the use of a one-way valve in-line with the ventilator, and above cuff vocalization. This narrative review describes the benefits of a multi-disciplinary approach, summarizes verbal communication interventions, and provides guidance on the indications, contraindications and considerations for patient selection. Our clinical procedures based on collective clinical experience are shared. A multidisciplinary team approach enables holistic management across acuity, ventilation, airway, communication, and swallowing parameters. This collaborative approach is recommended to maximize the chance of successful opportunities for patients to communicate safely and effectively.


Fluid motions in the Earth's core inferred from time spectral features of the geomagnetic field.
The aim of this work is to investigate the time spectral features of the main geomagnetic field fluctuations as measured on the Earth's surface in connection with a nontraditional turbulent dynamics of the fluid motions in the outer layers of the Earth's liquid core. The average geomagnetic field spectrum is found to be a power law, characterized by a spectral exponent alpha approximately -11/3, on time scales longer than 5 yr. We discuss the spectral exponent in connection with an intense magnetic field in the Earth's core and with a vortex coalescence process in a regime of drift-wave turbulence.


The mTOR inhibitor RAD001 potentiates autophagic cell death induced by temozolomide in a glioblastoma cell line.
We have studied the consequences of the combination of the mammalian target of rapamycin (mTOR) inhibitor RAD001 and temozolomide on the growth and cell death of the glioblastoma cell line U-87 in vitro. A progressive decrease of cell proliferation was recorded with increasing concentrations of temozolomide, which was markedly reinforced and prolonged by the addition of RAD001. While this combination treatment resulted in only a low level of apoptosis, it led to a pronounced enhancement of autophagic cell death. When combined with γ-ray irradiation, a significant reinforcement of the overall cytotoxicity was obtained, suggesting the efficacy of such a multipronged approach for the treatment of glioblastoma. RAD001 strongly contributes to the reinforcement of temozolomide-induced autophagy, which appears to represent a major form of cell death in glioblastoma. The association of such combined chemotherapies with radiotherapy could be useful for the management of these hard-to-treat malignancies.


Fluctuating selection by water level on gynoecium colour polymorphism in an aquatic plant.
It has been proposed that variation in pollinator preferences or a fluctuating environment can act to maintain flower colour polymorphism. These two hypotheses were tested in an aquatic monocot Butomus umbellatus (Butomaceae) with a pink or white gynoecium in the field population. Pollinator visitation was compared in experimental arrays of equivalent flowering cymes from both colour morphs. Seed set was compared between inter- and intramorph pollination under different water levels to test the effect of fluctuating environment on seed fertility. Overall, the major pollinator groups did not discriminate between colour morphs. Compared with the white morph, seed production in the pink morph under intermorph, intramorph and open pollination treatments was significantly higher when the water level was low but not when it was high. Precipitation in July was correlated with yearly seed production in the pink morph but not in the white morph. The results indicated that the two colour morphs differed in their tolerance to water level. Our study on this aquatic plant provides additional evidence to support the hypothesis that flower colour polymorphism can be preserved by environmental heterogeneity.


Developing the Intergenerational Community Survey for older adults: Assessing neighborhood environments, social and physical activities, and health.
Many survey instruments have been developed to assess neighborhood environments for their impacts on people's health and daily activities. However, no instruments are available for capturing social interactions with different age groups among older populations. This study introduces a four-phase process of developing a comprehensive Intergenerational Community Survey (ICS) covering six domains: (1) physical activities, walking, and sedentary activities; (2) mental health and quality of life; (3) social activities (e.g. intergenerational and peer interactions) in and outside the neighborhood; (4) neighborhood environments (e.g. safety, streets and sidewalks); (5) supportive services or programs (e.g. intergenerational programs, transportation services); and (6) personal characteristics. Test-retest reliability assessments among 38 community-dwelling older adults (aged 65+) showed fair to good reliability results. ICS can serve as a useful tool to facilitate future research on intergenerational communities and interactions for older adults.


Zeaxanthin and the Heat Dissipation of Excess Light Energy in Nerium oleander Exposed to a Combination of High Light and Water Stress.
Upon termination of watering of plants of Nerium oleander exposed to high light, photochemical efficiency became reduced as leaf water content decreased. Evidence is presented that this type of photoinhibition reflects to a substantial degree radiationless dissipation of excitation energy, probably mediated by the carotenoid zeaxanthin. During the imposition of water stress, the zeaxanthin content of leaves increased at the expense of violaxanthin and beta-carotene as a water deficit developed over a period of several days. The increase in zeaxanthin content was linearly related to an increase in the rate of radiationless energy dissipation in the antenna chlorophyll as calculated from the characteristics of chlorophyll a fluorescence measured with a pulse amplitude modulated fluorometer at room temperature. The increase in the rate of radiationless dissipation was also linearly related to a decrease in PSII photochemical efficiency as indicated by the ratio of variable to maximum fluorescence. Leaves of well-watered shade plants of N. oleander exposed to strong light showed a similar increase in zeaxanthin content as sun leaves of the same species subjected to drought in strong light. Shade leaves possessed the same capacity as sun leaves to form zeaxanthin at the expense of both violaxanthin and beta-carotene. The resistance of this species to the destructive effects of excess light appears to be related to interconversions between beta-carotene and the three carotenoids of the xanthophyll cycle.


Advances in Electrochemical Detection Electrodes for As(III).
Arsenic is extremely abundant in the Earth's crust and is one of the most common environmental pollutants in nature. In the natural water environment and surface soil, arsenic exists mainly in the form of trivalent arsenite (As(III)) and pentavalent arsenate (As(V)) ions, and its toxicity can be a serious threat to human health. In order to manage the increasingly serious arsenic pollution in the living environment and maintain a healthy and beautiful ecosystem for human beings, it is urgent to conduct research on an efficient sensing method suitable for the detection of As(III) ions. Electrochemical sensing has the advantages of simple instrumentation, high sensitivity, good selectivity, portability, and the ability to be analyzed on site. This paper reviews various electrode systems developed in recent years based on nanomaterials such as noble metals, bimetals, other metals and their compounds, carbon nano, and biomolecules, with a focus on electrodes modified with noble metal and metal compound nanomaterials, and evaluates their performance for the detection of arsenic. They have great potential for achieving the rapid detection of arsenic due to their excellent sensitivity and strong interference immunity. In addition, this paper discusses the relatively rare application of silicon and its compounds as well as novel polymers in achieving arsenic detection, which provides new ideas for investigating novel nanomaterial sensing. We hope that this review will further advance the research progress of high-performance arsenic sensors based on novel nanomaterials.


Eosinophilia as a diagnostic value in patients suffering from schistosomiasis haematobium comparing to eosinophiluria and egg count in the urine.
Sixty cases ranging in age between 18-30 years old, 50 of them were suffering from schistosomiasis haematobium, they were selected from in- and out-patient clinic of Theodor Bilharz Research Institute. Patients were divided into three groups, 20 infected and not treated, 20 infected and treated then exposed again to infection and 10 were completely treated. The authors have a fourth group to serve healthy control. Blood samples were collected to count eosinophil percentage and absolute eosinophil count. Urine samples were collected to 1-study eosinophiluria by slide film staining with Leishman's stain, and 2- to count number of ova excreted in 10 ml urine by urine filtration technique. Eosinophila and eosinophiluria > 5% were considered as a diagnostic value for schistosomiasis haematobium as well as it correlation between them and intensity of infection by number of ova in urine.


The role of trophoblastic binucleate cells in implantation in the goat: a morphological study.
In the goat conceptus individual intra-epithelial trophectodermal binucleate cells first appear 18 days post coitum and their incidence rapidly increases where the trophectoderm is apposed to the caruncular and intercaruncular sites of initial attachment to the uterine epithelium. Special staining techniques reveal that these cells, when mature, contain prominent Golgi bodies and numerous characteristic granules. Our evidence shows that at 19 days post coitum the binucleate cells migrate to the microvillar junction and fuse with individual uterine epithelial cells to form hybrid feto-maternal trinucleate cells. It is proposed that subsequent continued binucleate cell migration and fusion with trinucleate cells produce the syncytial plaques typical of the remainder of pregnancy. It is further suggested that the fusion is important in facilitating the delivery of the characteristic granules to the base of the uterine epithelial layer with subsequent exocytosis of their contents into maternal tissue.


Dual targeting of Osh1p, a yeast homologue of oxysterol-binding protein, to both the Golgi and the nucleus-vacuole junction.
Oxysterol binding protein (OSBP) is the only protein known to bind specifically to the group of oxysterols with potent effects on cholesterol homeostasis. Although the function of OSBP is currently unknown, an important role is implicated by the existence of multiple homologues in all eukaryotes so far examined. OSBP and a subset of homologues contain pleckstrin homology (PH) domains. Such domains are responsible for the targeting of a wide range of proteins to the plasma membrane. In contrast, OSBP is a peripheral protein of Golgi membranes, and its PH domain targets to the trans-Golgi network of mammalian cells. In this article, we have characterized Osh1p, Osh2p, and Osh3p, the three homologues of OSBP in Saccharomyces cerevisiae that contain PH domains. Examination of a green fluorescent protein (GFP) fusion to Osh1p revealed a striking dual localization with the protein present on both the late Golgi, and in the recently described nucleus-vacuole (NV) junction. Deletion mapping revealed that the PH domain of Osh1p specified targeting to the late Golgi, and an ankyrin repeat domain targeting to the NV junction, the first such targeting domain identified for this structure. GFP fusions to Osh2p and Osh3p showed intracellular distributions distinct from that of Osh1p, and their PH domains appear to contribute to their differing localizations.


[Borderline ovarian tumors--10-year clinical series and literature review].
Analysis of 10-year clinical series of borderline ovarian tumors (BLT) and literature review. Retrospective clinical study. Department of Obstetrics and Gynaecology, 1st Medical Faculty, Charles University and General Faculty Hospital, Prague. Analysis of 38 patients from years 1994-2003 regarding age, histological types, tumor duplicities, role of frozen section, Ca125 levels, operation methods, adjuvant treatment, relaps occurrence, follow-up and survival. Median follow-up was 18.5 months (3-122), median age 51 (16-78). 23 serous, 12 mucinous (1 microinvasion), 2 cystadenofibromas and 1 endosalpingiosis. 26 patients of stage IA, 3 of IB, 6 of IC, 1 of IIA, 1 of IIC and 1 IIIB. 3 cases were underestimated by frozen section. 6 tumor duplicities were revealed. Ca125 marker was elevated in 10/23 (43.5%) cases. 12 patients underwent conservative surgery, 3 of them with complete staging including lymphadenectomy. 26 patients had radical operation, 9 of them with full staging. No one lymphonode was positive. 7 patients had primary laparoscopic approach, 6 had more than one operation. Adjuvant chemotherapy was indicated in 3 cases: PTX-CBDCA (IC and IIC) and CBDCA-CFA (IC). 4 patients were lost of evidence. 2/34 evaluated patients (5.9%) had a frank carcinoma recurrence after 3 and 7 years. Both relapsed patients and all 34 evaluable patients live without evidence of disease at present. Our results as well as literature date generate some controversies. Do we need staging lymphadenectomy in all cases (inclusive T1a)? Which parameters identify high-risk group and which patients will benefit from adjuvant (and which one) therapy? Are there not recurrencies of BLT rather second primary malignancies? In spite of 2 recurrences in a group of 34 evaluated cases all patients live without evidence of disease at present. Some management questions are therefore raised.


Multi-access drug delivery network and stability.
A novel design of a multi-drug delivery network and diagnosis using a molecular network is proposed. By using a pair of tweezers to generate the intense optical vortices within the PANDA ring resonator, the required molecules (drug volumes) can be trapped and moved dynamically within the molecular bus networks, in which the required drug delivery targets can be achieved within the network. The advantage of the proposed system is that the diagnostic method can be used within a tiny system (thin film device or circuit), which is available as an embedded device for diagnostic use in patients. In practice, the large molecular networks such as ring, star, and bus networks can be integrated to form a large drug delivery system. The channel spacing of the trapped volumes (molecules) within the bus molecular networks can be provided by using the appropriate free spectrum range, which is analyzed and discussed in the terms of crosstalk effects. In this work, crosstalk effects of about 0.1% are noted, which can be neglected and does not affect the network stability.


Brain death: ethical challenges to palliative care concepts of family care.
Brain death is a controversial issue that is often difficult for families to understand or accept. Palliative care interventions can help families to accept the death. However, delaying pronouncement of brain death may be detrimental to the family and lead to financial, ethical, and legal complications, including the potential for insurance fraud. We describe a case of brain death in which the passage of time along with continuation of life support without concomitant testing for brain death led to decreased acceptance of the patient's death by the family. Clinicians should weigh the risks and benefits of harm to the family when deciding how long to keep a brain dead patient on a ventilator. Pronouncement of death, which is good basic medical care regardless of the cause or mechanism of death, should not be delayed for family considerations. Risk management should be involved early in the decision process, if life support is withdrawn without the family's assent.


A Web-Based system for interactive visualization and exploration of time-oriented clinical data and their abstractions.
In this theater-style demonstration, the speakers will demonstrate KNAVE-II, a Web-based distributed system for interactive visualization and exploration of large amounts of time-oriented clinical data from multiple sources, and of clinically meaningful concepts (abstractions) derivable from these data. The KNAVE-II system and its complete underlying architecture provide a solution to the data overload problem.


Regulation of acetylcholinesterase during the lipopolysaccharide-induced inflammatory responses in microglial cells.
The non-classical function of acetylcholine (ACh) has been reported in neuroinflammation that represents the modulating factor in immune responses via activation of α7 nicotinic acetylcholine receptor (α7 nAChR), i.e., a cholinergic anti-inflammatory pathway (CAP). Acetylcholinesterase (AChE), an enzyme for ACh hydrolysis, has been proposed to have a non-classical function in immune cells. However, the involvement of AChE in neuroinflammation is unclear. Here, cultured BV2 cell, a microglial cell line, and primary microglia from rats were treated with lipopolysaccharide (LPS) to induce inflammation and to explore the regulation of AChE during this process. The expression profiles of AChE, α7 nAChR, and choline acetyltransferase (ChAT) were revealed in BV2 cells. The expression of AChE (G4 form) was induced significantly in LPS-treated BV2 cells: the induction was triggered by NF-κB and cAMP signaling. Moreover, ACh or α7 nAChR agonist suppressed the LPS-induced production of pro-inflammatory cytokines, as well as the phagocytosis of microglia, by activating α7 nAChR and followed by the regulation of NF-κB and CREB signaling. The ACh-induced suppression of inflammation was abolished in AChE overexpressed cells, but did not show a significant change in AChE mutant (enzymatic activity knockout) transfected cells. These results indicate that the neuroinflammation-regulated function of AChE may be mediated by controlling the ACh level in the brain system.


[Progress in biology of dendritic cells].
As the most potent antigen-presenting cells (APC), dendritic cells are important in launching both humoral and cellular immune responses against tumor. Although the high evaluation of DC in immunotherapy for cancer by means of DC vaccines, more studies have indicated DC is a heterogeneous population and proved that DC subsets are prominent determinants for the effectiveness of immune responses. Different DC subsets display different receptors and surface molecules, and express different sets of cytokines/chemokines, which result in distinct immunological outcomes. Clinical trials with ex vivo generated DC vaccines also manifest unexpected immunological tolerance as well as allergic response. It is essential to study the biological aspects of human DC subsets, which may be a key to the generation of novel DC-based vaccines. In this article, the progress of studies on biology of dendritic cells including their origins, differentiation, function and application of DC subsets is reviewed.


Photoinduced effects in the vicinity of the smectic-C(*)(alpha)-smectic-A transition.
We report the first results of photoinduced effects near the smectic-C(*)(alpha)-smectic-A transition in a binary liquid crystalline material. Dielectric dispersion measurements show that the softening of the tilt fluctuation mode in the vicinity of the transition gets enhanced in the presence of the UV light.