The application of prostate artery embolization in the management of intractable prostate bleeding.
Prostate cancer is one of the most common malignancies affecting European men. Sequelae of the advanced malignancy require invasive procedures which may not be eligible especially for old, debilitated patients. The aim of this manuscript is to review the outcomes of prostate artery embolization in the management of refractory bleeding. A PubMed database search was done for all English language articles on prostate artery embolization in prostate cancer, published between 2003 and 2019. For current review, information related to number, age of the patients, aetiology of the hematuria, bilateral or unilateral procedure, type of embolic material, technical and clinical success, complications, recurrent hematuria, hematocrit and hemoglobin levels were analyzed. A total of 10 original full-text comparative and non-comparative (case series) studies were reviewed. Minor complications described in the literature ranged from 10-50%. After prostate artery embolization, the recurrence of the haematuria occurred in 10-57% of the patients. Moreover, prostate artery embolization successfully treated lower urinary tract symptoms and urinary retention in prostate cancer patients. The procedure appears safe, burdened with low risk of complications and accomplishes technical and clinical success. It is a promising option for patients with hemorrhage, but due to the scarcity of data further investigations are needed.


Prognostic impacts of soluble immune checkpoint regulators and cytokines in patients with SARS-CoV-2 infection.
Coronavirus disease 2019 (COVID-19) has been a pandemic for the past two years. Predicting patient prognosis is critical. Although immune checkpoints (ICs) were shown to be involved in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, quantitative studies of ICs in clinical practice are limited. In this study, various soluble ICs (sICs) and cytokine levels in patients with SARS-CoV-2 infection at different time points were compared between survivors and deaths; we also examined whether sICs are useful for predicting prognosis. sICs and cytokines were measured in serum samples from 38 patients diagnosed with COVID-19 in the first and second week post-diagnosis. All assays were performed by bead-based multiplexed immunoassay system using Luminex Bio-Plex 200 system. The correlation of sICs and cytokines with laboratory markers was evaluated, and the levels of sICs in survivors were compared with those in deaths. Among the sICs, the second-week levels of soluble cluster of differentiation (sCD27, p = 0.012), sCD40 (p< 0.001), cytotoxic T-lymphocyte-associated protein 4 (sCTLA-4, p< 0.001), herpes virus entry mediator (sHVEM, p = 0.026), and T-cell immunoglobulin and mucin-domain containing-3 (sTIM-3, p = 0.002) were significantly higher in deaths than in survivors. The levels of nine cytokines assessed in the second week of deaths were significantly higher than those in survivors. The sICs sCD27, sCD40, sCTLA-4, and sTIM-3 and cytokines chemokine CC motif ligand 2 (CCL2), GM-CSF, IL-10, and IL-8 showed significant positive correlations with the levels of C-reactive protein (CRP) and procalcitonin and were negatively correlated with the absolute lymphocyte count and platelet values. Increased levels of sICs including sCD27, sCD40, sCTLA-4, and sTIM-3 and cytokines were significant factors for poor prognosis. sICs, together with cytokines and inflammatory markers, may be useful as prognostic stratification markers in SARS-CoV-2-infected patients.


Role of the Na+/K+-ATPase in regulating the membrane potential in rat peritoneal mast cells.
1. The aim of this study was to investigate the effect of the Na+/K+-ATPase on the membrane potential of peritoneal mast cells isolated from male Sprague-Dawley SPF-rats. 2. Experiments were performed at 22-26 degrees C in the tight-seal whole-cell configuration of the patch-clamp technique by use of Sylgard-coated patch pipettes (3-6 M[omega]). High-resolution membrane currents were recorded with an EPC-9 patch-clamp amplifier controlled by the 'E9SCREEN' software. In addition, a charting programme on another computer synchronously recorded at low resolution (2 Hz) membrane potential and holding current (low-pass filtered at 500 Hz). 3. Na+/K+-ATPase activity was measured as the ouabain-sensitive change in the zero-current potential. The zero-current potential in rat peritoneal mast cells measured 2 min after obtaining whole-cell configuration amounted to 1.7 +/- 2.5 mV (n = 21). Ouabain (5 mM), a Na+/K+-ATPase-inhibitor, had only a very minor effect upon the membrane potential under resting conditions (n = 3). 4. When mast cells were superfused with nominal calcium-free external solution, the cells hyperpolarized (delta mV: 20.2 +/- 3.8 mV (n = 5)). In addition, when the mast cells were preincubated in nominal calcium-free external solution for 12 +/- 1.6 min before whole-cell configuration, the membrane potential amounted to -53.7 +/- 9.8 mV (n = 8). A subsequent superfusion with ouabain (5 mM) depolarized the membrane potential (ouabain-sensitive hyperpolarization (delta mV): 23.0 +/- 8.4 mV (n = 8)). 5. A high intracellular concentration of Na+ ([Na+]i) (26.6 mM) also resulted in hyperpolarization (delta mV: 20.2 +/- 9.1 mV (n = 7)), but only when ATP was present. A subsequent superfusion with ouabain (5 mM) repolarized these cells to -1.2 +/- 14 mV (ouabain-sensitive hyperpolarization (delta mV): 19.7 +/- 7.7 mV (n = 7)). 6. The size of the [Na+]i-dependent hyperpolarization was dose-dependent. Low [Na+]i (1 mM) had no effect on membrane potential and these cells were unaffected by superfusion with calcium-free external solution. 7. These data thus directly confirm that the stimulant effect of calcium-free external solutions on the ouabain-sensitive changes in the zero-current potential, and hence the Na+/K+-ATPase, is mediated through [Na+]i and that the activity of the Na+/K+-ATPase can have an important influence on the resting membrane potential in rat peritoneal mast cells.


Pharmacological profiles of 2-carboxyphenyl-1-(4-chlorobenzoyl)-5-methoxy-2-methylindole-3-acetate and 2-[(2-carboxyphenoxy)-carbonyl]phenyl-1-(4-chlorobenzoyl)-5-meth oxy-2- methylindole-3-acetate, new antiinflammatory agents.
When the effects of new antiinflammatory drugs, 2-carboxyphenyl-1-(4-chlorobenzoyl)-5-methoxy-2-methyl-indole-3-acetate (TB 219) and 2-[(2-carboxyphenoxy)carbonyl]phenyl-1-(4-chlorobenzoyl)-5- methoxy-2-methylindole-3-acetate (TB 220), were investigated in various experiments, the following results were obtained: 1. TB 219 and TB 220 showed remarkable inhibitory effects on carrageenin edema, ultraviolet erythema and adjuvant arthritis. Although TB 219 displayed almost equipotent or slightly more potent effect than those of indometacin and acemetacin, TB 220 was slightly less effective than these two reference drugs except for the therapeutic effect on adjuvant arthritis. 2. TB 219 and TB 220 inhibited the writhing syndrome induced by acetic acid and inflammatory hyperesthesia, and they provided a significant antipyretic activity. 3. Both drugs elicited almost negligible side effects in the gastrointestinal tract even after the repeated administrations. Especially, ulcerogenic activity of TB 220 was extremely weak. LD50's of both drugs are higher than that of indometacin in rats. 4. Both drugs elicited no appreciable changes in general behavior in mice and rats after oral administration. After intraperitoneal or intravenous injection of these two drugs, no marked changes in spontaneous EEG pattern and the spinal reflex were observed.


An essential residue in the flexible peptide linking the two idiosynchratic domains of bacterial tyrosyl-tRNA synthetases.
Tyrosyl-tRNA synthetase (TyrRS) from Bacillus stearothermophilus comprises three sequential domains: an N-terminal catalytic domain, an alpha-helical domain with unknown function, and a C-terminal tRNA binding domain (residues 320-419). The properties of the polypeptide segment that links the alpha-helical and C-terminal domains, were analyzed by measuring the effects of sequence changes on the aminoacylation of tRNA(Tyr) with tyrosine. Mutations F323A (Phe323 into Ala), S324A, and G325A showed that the side chain of Phe323 was essential but not those of Ser324 and Gly325. Insertions of Gly residues between Leu322 and Phe323 and the point mutation L322P showed that the position and precise orientation of Phe323 relative to the alpha-helical domain were important. Insertions of Gly residues between Gly325 and Asp326 and deletion of residues 330-339 showed that the length and flexibility of the sequence downstream from Gly325 were unimportant but that this sequence could not be deleted. Mutations F323A, -L, -Y, and -W showed that the essential property of Phe323 was its aromaticity. The Phe323 side chain contributed to the stability of the initial complex between TyrRS and tRNA(Tyr) for 2.0 +/- 0.2 kcal x mol(-1) and to the stability of their transition state complex for 4.2 +/- 0.1 kcal x mol(-1), even though it is located far from the catalytic site. The results indicate that the disorder of the C-terminal domain in the crystals of TyrRS is due to the flexibility of the peptide that links it to the helical domain. They identified Phe323 as an essential residue for the recognition of tRNA(Tyr).


[Pharmacokinetics of pramiracetam in animals].
Pharmacokinetic rules of pramiracetam were studied here. After giving pramiracetam orally to dogs, we drew their blood at various times. The drug concentrations in blood plasma were detected by HPLC. 3p87 program was used to calculate the pharmacokinetic parameters. The time-concentration curve corresponded to one apartment model. T1/2 was about 2.3-3.9 hours in various doses. After pramiracetam was given to rats per os, high concentrations of pramiracetam were detected in the rats' tissues. The kidney had the highest concentration of pramiracetam; the liver had the next highest concentration, and then the intestine, lung, muscle, heart, gonad, spleen and sebum had the high concentration in order. The drug was also detected in the brain. 0.7% of the given dose was excreted in unchanged form in bile in 24 hours. 28.26% and 6.35% were excreted in urine and feces respectively in 72 hours. The plasma protein combining rate detected by the method of balance dialysis was 20.1-22.2%.


Polynomial-product states: A symmetry-projection-based factorization of the full coupled cluster wavefunction in terms of polynomials of double excitations.
Our goal is to remedy the failure of symmetry-adapted coupled-cluster theory in the presence of strong correlation. Previous work along these lines has taken us from a diagram-level analysis of the coupled-cluster equations to an understanding of the collective modes which can occur in various channels of the coupled-cluster equations to the exploration of non-exponential wavefunctions in efforts to combine coupled-cluster theory with symmetry projection. In this manuscript, we extend these efforts by introducing a new, polynomial product wavefunction ansatz that incorporates information from symmetry projection into standard coupled-cluster theory in a way that attempts to mitigate the effects of the lack of size extensivity and size consistency characteristic of symmetry-projected methods. We describe the new approach in detail within the context of our previous efforts, explore some illustrative calculations, and consider one route for reducing the computational cost of the new method.


Cerebellar ganglioglioma--case report.
A 14-year-old boy presented with cerebellar ganglioglioma manifesting as severe headache and confusion. Computed tomographic scans showed a huge, partly enhanced cystic cerebellar tumor. The tumor was totally removed. Histological examination disclosed glial cells and mature ganglion cells. The latter were identified by Nissl's staining and immunostaining for neurofilaments. Ganglion cells were present in the cerebellum and the surrounding subarachnoid space. This heterotopic growth of ganglion cells enabled a firm diagnosis of cerebellar ganglioglioma.


[Expert consensus on PD-L1 expression testing in non-small-cell lung cancer in China].
Cancer immunotherapy, especially the programmed death 1 (PD-1) and (or) programmed death ligand 1 (PD-L1) checkpoint inhibitors, has ushered in the modern oncology era and has achieved impressive success in the treatment of different tumors, including non-small-cell lung cancer (NSCLC). Yet, only a subset of patients achieved clinical benefit. Therefore, how to effectively screen the potential beneficiaries of PD-1 and (or) PD-L1 inhibitors has become a new challenge in the era of cancer immunotherapy. Clinical studies have shown that the expression level of PD-L1 in NSCLC is positively correlated with the efficacy of PD-1 and (or) PD-L1 inhibitors, and is one of the important predictive biomarkers. However, there are many challenges in PD-L1 testing. With the approving of various PD-1 and (or) PD-L1 inhibitors for immunotherapy setting of NSCLC, expert consensus of important issues regarding clinical significance of PD-L1 testing, testing time-point, as well as the standardization of PD-L1 testing procedure, including the PD-L1 testing operation steps, results' interpretation, quality control and so on, is of great significance for improving the accuracy of detection and reducing the difference between laboratories. On account to the practical questions of PD-L1 testing, this consensus was finally reached, which is based on the combination of literature, expert experience and internal discussion among committee members, in the hope of providing the guide for standardizing the PD-L1 testing and providing accurate and reliable result to screen the potential patients and predict clinical efficacy. It must be pointed out that in view of the existence of objective and complex factors of PD-L1 testing and the fact that the clinical application of PD-L1 testing is still at the early stage in China, there are still many issues need to be updated in near future based on further practice experience and research data.


Comparative study on the immunomodulatory function of extracellular vesicles from different dairy products.
Bovine milk-derived extracellular vesicles (EVs) have been proved to have positive effects on innate immunity and intestinal health. However, the effect of different processing treatments on the biological function of EVs in dairy products remains unclear. Thus, we explored the immunomodulatory function of EVs from different dairy products (pasteurized milk, UHT milk, freeze-dried powder and organic milk powder) by constructing the RAW264.7 cell model, the most commonly used in vitro model to study immune responses and screen for anti-inflammatory active substances. The results showed that EVs from different dairy products had similar bidirectional immunomodulatory effects to EVs from raw milk, which not only promoted the normal macrophage proliferation and increased NO and cytokine (IL-1β, IL-6 and TNF-α) levels, but also inhibited the lipopolysaccharide (LPS)-induced TLR4/NF-κB pathway and inflammatory cytokines. In particular, EVs from different dairy products also could regulate the expression of immune-related miR-155, miR-223 and miR-181a, which were involved in the anti-infection response. Although the immunomodulatory effects of EVs in the pasteurized milk and freeze-dried powder groups were lower than that of the raw milk group, they were superior to the UHT milk group and significantly higher than the organic milk powder group. Therefore, we hypothesize that pasteurization and freeze-drying treatments might have less effect on the physiological activity of EVs, making the potential health benefits of the corresponding products superior to those of other dairy products.


The lateral hypothalamic area revisited: ingestive behavior.
This article discusses the role of the lateral hypothalamic area (LHA) in feeding and drinking and draws on data obtained from lesion and stimulation studies and neurochemical and electrophysiological manipulations of the area. The LHA is involved in catecholaminergic and serotonergic feeding systems and plays a role in circadian feeding, sex differences in feeding and spontaneous activity. This article discusses the LHA regarding dietary self-selection, responses to high-protein diets, amino acid imbalances, liquid and cafeteria diets, placentophagia, "stress eating," finickiness, diet texture, consistency and taste, aversion learning, olfaction and the effects of post-operative period manipulations by hormonal and other means. Glucose-sensitive neurons have been identified in the LHA and their manipulation by insulin and 2-deoxy-D-glucose is discussed. The effects on feeding of numerous transmitters, hormones and appetite depressants are described, as is the role of the LHA in salivation, lacrimation, gastric motility and secretion, and sensorimotor deficits. The LHA is also illuminated as regards temperature and feeding, circumventricular organs and thirst and electrolyte dynamics. A discussion of its role in the ischymetric hypothesis as an integrative Gestalt concept concludes the review.


Development of telemetry system in the common marmoset--cardiovascular effects of astemizole and nicardipine.
The purpose of this study was to evaluate a telemetry system for examining the cardiovascular system in the conscious common marmoset. Parameters obtained were blood pressure, heart rate, respiratory rate, ECG, body temperature and locomotor activity, and these were continuously recorded on a data recorder via the telemetry system and then processed by a computerized system. Diurnal rhythms of blood pressure, heart rate, body temperature and locomotor activity were observed in this system. We studied the effects of astemizole (antihistamine) and nicardipine (Ca2+ channel blocker) on cardiovascular parameters. Astemizole at 30 mg/kg (p.o.) and at 1 to 3 mg/kg (i.v.), prolonged QT interval and induced ventricular extrasystole. Torsades de pointes occurred in one of three cases at 3 mg/kg (i.v.) and 30 mg/kg (p.o.), while it did not affect the blood pressure, respiratory rate and body temperature. Nicardipine at 30 mg/kg (p.o.) caused sustained hypotension and tachycardia. These results demonstrate the usefulness of the telemetry system using the common marmoset for evaluating the cardiovascular effects of drugs under physiological conditions.


Outcome expectancies and ecstasy use in visitors of rave parties in The Netherlands.
The aim of this study was to examine the associations between outcome expectancies and ecstasy use in a sample of visitors of raves. The type of expectancies that people endorse were explored, as well as the differences between users and nonusers in expected outcomes of ecstasy use, and the associations between expectancies and quantity of ecstasy use within the group of users. Questionnaires were administered to 844 young visitors of 7 parties in the Netherlands, of which 543 reported to be users. Drug use on these parties was high: 65% reporting ecstasy use. Factor analyses showed 7 factors: negative consequences, enhancement, euphoria, sexiness, dancing, communication and self-insight. These factors strongly discriminated between users and nonusers. In particular those who scored high on self-insight and low on negative effects were most likely to use ecstasy. The expected outcomes of ecstasy are related to ecstasy use and patterns of use providing information for health education directed on long-term negative and positive effects of ecstasy use. Longitudinal research on random samples of visitors of raves is warranted.


Ultrastructure of bronchopulmonary lavage cells from bovines administered 3-methylindole. I. 12 hours post-treatment.
Ultrastructure of the bronchopulmonary lavage cells, viz., pulmonary alveolar macrophages (AM), neutrophils, plasma cells, ciliated epithelial cells and lymphocytes from calves 12 h following 3-methylindole (3-MI) ingestion is documented in this study. The AM had increased in number and size, and appeared stimulated as indicated by an elevated number of phagosomes and/or various combinations of structures resembling phagolysosomes. Pseudopodia on majority of the neutrophils were either sparse or absent. Morphologic parameters of heightened secretion were present in the occasionally noticed plasma cells. Ciliated epithelial cells which were only sometimes seen contained necrotic mitochondria. Lymphocytes were rarely encountered and were unaltered by the treatment. Ultrastructure of the bronchopulmonary lavage cells from the 3-MI-exposed calves demonstrates cellular response to the respiratory conditions induced by the chemical.


A new approach to kinetics study of the anhydrite crystallization at 373 K using a diamond anvil cell with Raman spectroscopy.
A new approach to the kinetics study of anhydrite (CaSO4) crystallization has been performed in situ using a hydrothermal diamond anvil cell with Raman spectroscopy in the pressure range 896-1322 MPa and a constant temperature of 373 K. Transformed volume fraction X(t) was determined from Raman peak intensity of the sulfate ion in aqueous solution. The transformation-time plots display a sigmoidal shape with time, which indicates that the reaction rate is different at each stage of anhydrite crystallization. At 373 K, the rate constant k increases from 1.14 × 10(-4) s(-1) to 1.86 × 10(-3) s(-1), demonstrating a positive effect of pressure on the overall rate at isothermal condition. We first achieved the molar volume change (ΔVm) equal to -1.82 × 10(-5) m(3)∕mol in the course of anhydrite crystallization through Avrami kinetic theory, showing a process of reduction in volume at high pressure and high temperature. According to the exponent n derived from our experiments, a grain-boundary nucleation and diffusion-controlled growth kinetically dominates the crystallization of anhydrite.


Avoiding the major complication of ophthalmic pathology: misdiagnosis. A review of three common diagnostic challenges.
Diagnostic errors in ophthalmic pathology are not uncommon. Pathology is a very subjective specialty with several biases dependent on such factors as training, experience, practice patterns, personal anecdotes, and inevitable human error. In addition to these factors, there are many cases where difficulty in diagnosis lies in differentiating between two very closely related, or similar appearing, entities that may have vastly different prognostic consequences. In this paper, we review three challenging areas wherein diagnostic dilemmas may occur. We outline some of the lessons we have learned in arriving at a correct diagnosis, which includes an admission of one's own limitations requiring consultation with other pathology subspecialists, and the use of immunohistochemistry.


Levels of chlorinated hydrocarbon residues in Canadian human breast milk and their relationship to some characteristics of the donors.
A total of 412 breast milk samples from women in all provinces of Canada were analysed for polychlorinated biphenyls, eight chlorinated benzenes, 2,3-dichloronaphthalene, Mirex, alpha, beta, gamma and delta hexachlorocyclohexane, alpha and gamma chlordane, oxychlordane, transnonachlor, p,p'-DDT and some analogues, heptachlor epoxide, dieldrin and octachlorostyrene. No delta-hexachlorocyclohexane, heptachlor or aldrin were found in any of the samples, while median levels of the 1,2,4- and 1,3,5-trichlorobenzene, 1,2,3,4- and 1,2,3,5-tetrachlorobenzenes, gamma chlordane, o,p'-DDT and octachlorostyrene were all less than the minimum detectable level (MDL). All other compounds were present at median levels ranging from < 0.1 to 7.2 ng/g whole milk, but did not occur in all samples. Di to tetrachlorobenzenes, except 1,2,4-trichlorobenzene, 2,3-dichloronaphthalene and alpha-chlordane were observed in < 50% of the samples. From 1967 to 1986 a steady decline of hexachlorobenzene, gamma-hexachlorocyclohexane, DDTs, heptachlor epoxide and dieldrin was observed in Canadian breast milk. In addition, a decrease in some chlorinated benzenes, gamma-hexachlorocyclohexane and PCBs was also observed between 1982 and 1986. Levels of oxychlordane and trans-nonachlor remained constant. Canadian breast milk contamination appears to be one of the lowest among the industrialized nations. Regional and provincial differences in residue levels appeared minimal, although more often samples from Quebec and British Columbia had higher levels of some contaminants, such as oxychlordane, than samples from other provinces. No relationship was found between maternal age and residue levels, but some contaminants, such as PCBs, were significantly higher in the milk of mothers who breastfed their first child as compared to multiparous mothers. Breast milk residue levels were not related to fish consumption.


Exploration of cotton leaf curl virus resistance genes and their screening in Gossypium arboreum by targeting resistance gene analogues.
Cotton leaf curl virus (CLCuV) disease is one of the major limiting factors in cotton production, particularly in widely cultivated Gossypium hirsutum varieties that are susceptible to attack by this virus. Several approaches have been employed to explore putative resistance genes in another cotton species, G. arboreum. However, the exact mechanisms conferring disease resistance in cotton are still unknown. In the current study, we used various approaches to identify possible resistance genes against CLCuV infection. We report the identification and isolation of a set of genes involved in the resistance response to viral infestation. PCR products containing genomic DNA gave multiple amplifications with a single primer in most reactions, and 38 fragments were cloned from G. arboreum and G. hirsutum. The sequences of cloned fragments belonged to various pathway genes and uncharacterized proteins. However, five amplified fragments (RM1, RM6, RM8, RM12 and RM31) showed similarity with R genes. Maximum homology (94 %) was observed with G. raimondii toll/interleukin receptor-like protein. BLAST search showed the homology of all resistance gene analogues (RGAs) with more than one chromosome, and multiple hits were observed on each chromosome for each RGA. Expression analysis through RT-PCR identified variable expression levels of the different RGAs in all tested genotypes. The expression level of RGAs differed between symptomatic and asymptomatic plants, with the exception of RGA 395, whose expression level was the same in both diseased and healthy plants. Knowledge of the interaction of these genes with various cotton pathogens could be utilized to improve the resistance of susceptible G. hirsutum and other plant species.


Assessment of biological responses of EpiAirway 3-D cell constructs versus A549 cells for determining toxicity of ambient air pollution.
EpiAirway™ 3-D constructs are human-derived cell cultures of differentiated airway epithelial cells that may represent a more biologically relevant model of the human lung. However, limited information is available on their utility for exposures to air pollutants at the air-liquid interface (ALI). To assess the biological responses of EpiAirway™ cells in comparison to the responses of A549 human alveolar epithelial cells after exposure to air pollutants at ALI. Cells were exposed to filtered air, 400 ppb of ozone (O3) or a photochemically aged Synthetic Urban Mixture (SynUrb54) consisting of hydrocarbons, nitrogen oxides, O3 and other secondary oxidation products for 4 h. Basolateral supernatants and apical washes were collected at 9 and 24 h post-exposure. We assessed cytotoxicity by measuring lactate dehydrogenase (LDH) release into the culture medium and apical surface. Interleukin 6 (IL-6) and interleukin 8 (IL-8) proteins were measured in the culture medium and in the apical washes to determine the inflammatory response after exposure. Both O3 and SynUrb54 significantly increased basolateral levels of LDH and IL-8 in A549 cells. No significant changes in LDH and IL-8 levels were observed in the EpiAirway™ cells, however, IL-6 in the apical surface was significantly elevated at 24 h after O3 exposure. LDH and IL-8 are robust endpoints for assessing toxicity in A549 cells. The EpiAirway™ cells show minimal adverse effects after exposure suggesting that they are more toxicologically resistant compared to A549 cells. Higher concentrations or longer exposure times are needed to induce effects on EpiAirway™ cells.


Loads and Coupling Modalities Influence the Performance of the Floating Mass Transducer as a Round Window Driver.
High loads forcing the floating mass transducer (FMT) of a single active middle ear implant toward the round window membrane (RWM) affect the backward stimulation of the cochlea. Various factors influence the backward stimulation of the cochlea. We investigated the effects of various loads applied to the FMT together with different coupling techniques at the fully exposed RWM on the vibration transmission. Experimental study on temporal bones with the FMT linked to a load cell mounted on a translation stage moving it against the fully exposed RWM with increasing loads up to 200 mN by itself, with interposed perichondrium, cartilage or connected to the round window coupler. Cochlear stimulation is measured by the volume velocities of the stapes footplate using LASER-Doppler-vibrometry. Loads ranging from 5 to 20 mN induce the highest volume velocities of the stapes footplate. Increasing loads decrease the transmission of vibration in the low-frequency range but enhance the transmission of high frequencies. The interposition of perichondrium and cartilage proved to be advantageous. The load applied to the FMT distinctly affects the backward stimulation of the cochlea. Although increasing loads have inverse effects on the transmission of low and high frequencies, high loads lead to an overall decrease of cochlear stimulation. Out of the applied coupling techniques interposed perichondrium and cartilage allow for the most efficient stimulation.


Nanosized films based on multicharged small molecules and oppositely charged polyelectrolytes obtained by simultaneous spray coating of interacting species.
Simultaneous spraying of polyelectrolytes and small multicharged molecules of opposite charges onto a vertical substrate leads to continuous buildups of organic films. Here, we investigate the rules governing the buildup of two such systems: poly(allylamine hydrochloride)/sodium citrate (PAH/citrate) and PAH/sulfated α-cyclodextrin (PAH/CD-S). Special attention is paid to the film growth rate as a function of the spraying rate ratio of the two constituents. This parameter was varied by increasing the spraying rate of one of the constituents while maintaining constant that of the other. For PAH/CD-S systems, whatever the constituent (PAH or CD-S) whose spraying rate was kept fixed, the film growth rate first increases and passes through a maximum before decreasing when the spraying rate of the other constituent is increased. For PAH/citrate, the film growth rate reaches a plateau value when the spraying rate of citrate is increased while that of PAH is maintained constant, whereas when the spraying rate of citrate is maintained constant and that of PAH is increased, a behavior similar to that of PAH/CD-S is observed. The composition of PAH/CD-S sprayed films determined by X-ray photoelectron spectroscopy is independent of the spraying rate ratio of the two constituents and corresponds to one allylamine for one sulfate group. For PAH/citrate, by increasing the PAH/citrate spraying rate ratio, the carboxylic/nitrogen ratio in the film increases and tends to 1. There is thus always a deficit of carboxylic groups (COO(-) + COOH) with respect to amines (NH2 + NH3(+)). Yet, the ratio (COO(-)/NH3(+)) is always close to 1, ensuring exact charge compensation. The film morphology determined by atomic force microscopy is granular for PAH/CD-S and is smooth and liquid-like for PAH/citrate. A model based on strong (respectively weak) interactions between PAH and CD-S (respectively citrate) is proposed to explain these features.


Ampelopsin induces apoptosis by regulating multiple c-Myc/S-phase kinase-associated protein 2/F-box and WD repeat-containing protein 7/histone deacetylase 2 pathways in human lung adenocarcinoma cells.
Ampelopsin (AMP), a plant flavonoid, has been reported to inhibit cell growth and/or induce apoptosis in various types of tumor. The aim of the present study was to assess the apoptosis-inducing activity of AMP in A549 human lung adenocarcinoma epithelial cells and the associated underlying mechanism. A549 cells were incubated with different concentrations of AMP in culture medium. Cell growth and apoptosis were evaluated by MTT assay and Annexin V/propidium iodide double staining and flow cytometry, respectively. In addition, western blotting and reverse transcription quantitative polymerase chain reaction analysis were used to examine the time-dependent changes in protein expression. Certain changes in apoptotic protein expression were detected following exposure to AMP, including X-linked inhibitor of apoptosis protein release, reduced B-cell lymphoma 2, myeloid cell leukemia 1 and survivin expression levels, increased Bcl-2-associated X protein expression levels and cleaved-poly ADP ribose polymerase expression. The results revealed that AMP was a potent inhibitor of A549 cell proliferation. The c-Myc/S-phase kinase-associated protein 2 (Skp2) and histone deacetylase (HDAC)1/2 pathways were found to exert an important role in AMP-induced A549 cell apoptosis, as increased levels of c-Myc mRNA and reduced levels of c-Myc/Skp2 and HDAC1 and 2 proteins following AMP treatment were observed. The levels of F-box and WD repeat-containing protein 7α (Fbw7α), Fbw7β, Fbw7γ, phosphorylated-(p-)c-Myc (Thr58) and glycogen synthase kinase 3β (GSK3β) proteins involved in c-Myc ubiquitin-dependent degradation were also analyzed. Following exposure to AMP, the expression levels of Fbw7α, Fbw7γ and GSK3β were reduced and p-c-Myc (Thr58) expression levels were increased. The results suggest that AMP exerts an anticancer effect, which is associated with the degradation of c-Myc, Skp2 and HDAC1 and 2. The ability of AMP to induce apoptosis independently of Fbwα and Fbw7γ suggests a possible use in drug-resistant cancer associated with Fbw7 deficiency. Understanding the exact underlying mechanism requires further investigation of the association between c-Myc and Fbw7α/γ reversal, and analysis of whether Thr58 phosphorylation of c-Myc is dependent on GSK3β.


Day surgery for mucosal-hemorrhoidal prolapse using a circular stapler and modified regional anesthesia.
In 1993, prolapse reduction using the circular stapler for the treatment of hemorrhoidal disease was proposed. The procedure is characterized by minimal postoperative pain. In this study we evaluated the above technique using regional anesthesia to identify the advantages and feasibility of stapled hemorrhoidectomy, with special focus on the efficacy of same-day discharge. From December 1997 to November 1999, we performed 70 consecutive reduction corrections of mucosal hemorrhoidal prolapse using the circular stapler with regional anesthesia (a technical modification of Marti's posterior perineal block). Our series included 41 males and 29 females with a mean age of 43.4 (range, 25-74) years. Three patients were affected by second-degree hemorrhoids and 67 by third-degree hemorrhoids. Sixty-two patients were discharged three hours after the operation in good general condition and without pain, whereas eight patients were discharged the day after for early complications, consisting of two cases of early bleeding, three cases of urinary retention, and three cases of persistent severe pain requiring prolonged medical treatment. Our study shows that, in selected cases, it is possible to perform day surgery for patients with hemorrhoidal disease using a circular stapler device when combined with regional anesthesia.


Magnetic resonance current density imaging of chemical processes and reactions.
Electric current density imaging was used to image conductivity changes that occur as a chemical process or reaction progresses. Feasibility was assessed in two models representing the dissolving of an ionic solid and the formation of an insoluble precipitate. In both models, temporal and spatial changes in ionic concentrations were obtained on current density images. As expected, the images showed significant signal enhancement along the ionization/dissociation sites.


A conformational epitope expressed upon association of CD3-epsilon with either CD3-delta or CD3-gamma is the main target for recognition by anti-CD3 monoclonal antibodies.
We have performed immunofluorescence analysis of COS cells transfected with human CD3 genes and detergent permeabilized to define the specificity of several anti-CD3 antibodies. We have found that the mAb OKT3, WT31, UCHT1, and Leu-4 did not stain COS cells singly transfected with the CD3-epsilon chain. However, these antibodies very strongly stained COS cells doubly transfected with a combination of CD3-epsilon plus either CD3-gamma or CD3-delta. By contrast, the antibodies SP34 and APA 1/1, which were raised against isolated SDS-denatured CD3-epsilon protein, gave a strong staining of COS cells singly transfected with CD3-epsilon as well as of the double transfectans. The recognition by this panel of anti-CD3 antibodies of CD3-gamma/epsilon and CD3-delta/epsilon complexes and not of CD3-epsilon alone was assessed by immunoprecipitation. These findings suggest that the most widely used mAb specific for the CD3 complex recognize conformational epitopes on CD3-epsilon, which are expressed when this chain is bound to either CD3-gamma or CD3-delta. It should also be highlighted that antibody WT31 clearly recognizes the CD3 moiety of the TCR/CD3 complex.


Drowning--Louisiana, 1998.
Drowning is the third leading cause of death from unintentional injuries in Louisiana. In 1998, the fatality rate from drowning for Louisiana residents was 3.1 per 100,000 population, higher than the U.S. rate of 1.9 per 100,000, and more than twice the 2000 national target of 1.3 per 100,000 population. This report describes the demographics and risk factors associated with drownings in Louisiana in 1998. Findings indicate that alcohol or illicit drug use was found in approximately 60% of tested victims aged > or = 13 years and that none of the victims of boating-related drowning were correctly wearing a personal flotation device (PFD). Prevention efforts should focus on decreasing alcohol and illicit drug use and increasing the proper use of PFDs among boaters and others involved in water recreation.


Fano signatures in the intersubband terahertz response of optically excited semiconductor quantum wells.
Absorption and transmission spectra of broadband terahertz pulses are measured to probe the intersubband response of an optically excited quantum-well heterostructure. While the terahertz absorption shows the single peak of the resonant intersubband transition, the transmission spectra display strong Fano signatures due to the phase sensitive superposition of ponderomotive and terahertz currents as predicted by our microscopic theory.


Regulated secretion of acid sphingomyelinase: implications for selectivity of ceramide formation.
The acid sphingomyelinase (aSMase) gene gives rise to two distinct enzymes, lysosomal sphingomyelinase (L-SMase) and secretory sphingomyelinase (S-SMase), via differential trafficking of a common protein precursor. However, the regulation of S-SMase and its role in cytokine-induced ceramide formation remain ill defined. To determine the role of S-SMase in cellular sphingolipid metabolism, MCF7 breast carcinoma cells stably transfected with V5-aSMase(WT) were treated with inflammatory cytokines. Interleukin-1β and tumor necrosis factor-α induced a time- and dose-dependent increase in S-SMase secretion and activity, coincident with selective elevations in cellular C(16)-ceramide. To establish a role for S-SMase, we utilized a mutant of aSMase (S508A) that is shown to retain L-SMase activity, but is defective in secretion. MCF7 expressing V5-aSMase(WT) exhibited increased S-SMase and L-SMase activity, as well as elevated cellular levels of specific long-chain and very long-chain ceramide species relative to vector control MCF7. Interestingly, elevated levels of only certain very long-chain ceramides were evident in V5-aSMase(S508A) MCF7. Secretion of the S508A mutant was also defective in response to IL-1β, as was the regulated generation of C(16)-ceramide. Taken together, these data support a crucial role for Ser(508) in the regulation of S-SMase secretion, and they suggest distinct metabolic roles for S-SMase and L-SMase.


Imperative role of trehalose metabolism and trehalose-6-phosphate signaling on salt stress responses in plants.
Sugar transport and distribution have a direct impact on the growth and development of plants. Many sugars significantly influence salt stress response. The sensing of salt stress signals triggers a wide array of complicated network transduction pathways in plants. Trehalose and its intermediate compounds effectively modulate salt response and salt tolerance. Sugars such as trehalose and its derivatives not only serve as metabolic resources and structural components of cells in plants but also exhibit hormone-like regulating properties. Trehalose has an important physiological role in improving plant tolerance against salinity stresses in different plants. Plants finely adjust their cytoplasmic compatible solute pool to cope with high salinity. Salt stress induces a variety of structural, anatomical, molecular, biochemical, and physiological changes in plants, all of which have a detrimental influence on plant growth and development. This review highlights the recent developments in understanding trehalose and trehalose-6-phosphate signaling processes in plants, especially their impacts on plants growing in salty environments.


Mean-average wall shear stress measurements in the common carotid artery.
In this study we determined mean-average wall shear stress values in the common carotid artery and assessed if there is a difference in mean-average WSS between: 1) patients with bilateral carotid bifurcation disease and 2) similar-aged volunteers with no evidence of disease. Sixteen patients with bilateral disease of the carotid bifurcation, and 8 volunteers were included in the study. Magnetic resonance phase velocity mapping was used to determine velocity, flow, vessel cross-sectional dimensions, and mean-average WSS in the common carotid artery in both the patients and volunteers. Mean-average WSS in the common carotid artery was 7.5 +/- 2.5 dynes/cm2 in patients and 8.0 +/- 4.1 dynes/cm2 in volunteers. There was no significant difference in mean-average WSS, average velocity, peak velocity, flowrate, or vessel diameter in the common carotid artery between patients and volunteers.


Host-parasite relationship of the geoduck Panopea abbreviata and the green alga Coccomyxa parasitica in the Argentinean Patagonian coast.
The association of the geoduck Panopea abbreviata and the green alga Coccomyxa parasitica is described. The identity of the green alga was confirmed by molecular studies; the alga was found within the hemocytes that infiltrate the connective tissue of the geoduck siphons. Cytological characteristics of hemocytes were not altered by algal infection; very often the algae were seen enveloped by a digestive vacuole within the hemocyte cytoplasm, evidencing diverse degrees of resorption. Connective cells of siphons were rarely infected by C. parasitica. The mean prevalence of C. parasitica was higher (82%) in San Matías Gulf (42°00'S, 65°05'W) than in San José Gulf (45%) (40°32'S, 64°02'W); except for spring, when the two locations showed no differences in prevalences (80%). Independently of location, season and host size, infected geoducks showed lower condition index values than uninfected ones. Regarding other bivalve species, only one specimen of the razor clam Ensis macha was found infected, and none of the oysters Ostrea puelchana and Pododesmus rudis and scallop Aequipecten tehuelchus was parasitized by the green alga.


Transfer of Ser7 phosphorylated CENP-A from centromere to midbody during mitosis in MCF-7 cells.
Serine 7 of centromere protein A (CENP-A) is a very important mitosis-specific phosphorylation site. In this study, we demonstrate the subcellular distribution of Ser7 phosphorylated CENP-A during mitosis in MCF-7 cells. The Ser7 phosphorylation of CENP-A was observed beginning at prophase at centromeres. Upon progression of mitosis, the fluorescence signals emerged in the central region of the metaphase plate and were maintained until anaphase at centromeres. At late anaphase, the fluorescence signals moved to the midzone gradually and transferred from the centromere to the midbody completely at telophase. They were compacted into the centre of the midbody in a thin cylinder consisting of a sandglass-like "mitotic machine" with microtubules and condensed chromosome. We also found that Ser10 phosphorylated H3 and Thr11 phosphorylated H3 were co-localized at the midbody in two bell-like symmetrical bodies with Ser7 phosphorylated CENP-A during the terminal stage of cytokinesis. Midbody isolation and immunoblotting experiments also indicated that Ser7 phosphorylated CENP-A are components of the midbody. These findings suggest that Ser7 phosphorylated CENP-A acts as a chromosomal passenger protein and may play an important role in cytokinesis.


p53 governs telomere regulation feedback too, via TRF2.
p53 takes critical part in a number of positive and negative feedback loops to regulate carcinogenesis, aging and other biological processes. Uncapped or dysfunctional telomeres are an endogenous DNA damage that activates ATM kinase (ataxia telangiectasia mutated) and then p53 to induce cellular senescence or apoptosis. Our recent study shows that p53, a downstream effector of the telomere damage signaling, also functions upstream of the telomere‐capping protein complex by inhibiting one of its components, TRF2 (telomeric repeat binding factor 2). Since TRF2 inhibition leads to ATM activation, a novel positive feedback loop exists to amplify uncapped telomere‐induced, p53‐mediated cellular responses. Siah1 (seven in absentia homolog 1), a p53‐inducible E3 ubiquitin ligase, plays a key role in this feedback regulation by targeting TRF2 for ubiquitination and proteasomal degradation. Biological significance and therapeutic implications of this study are discussed.


The role of reduced fitness to drive due to medical impairments in explaining crashes involving older drivers.
Medical conditions and associated impairments are known to be more prevalent with aging and can potentially impact the function and crash risk of older drivers. To evaluate the impact of specific medical conditions and associated impairments on older driver crash risk. A search identified reports and peer-reviewed publications evaluating the risk for medical conditions and associated crash risk. Medical conditions associated with older persons were reviewed to determine the associated relative risk of crash. The review identified three recent comprehensive reviews of medical conditions or chronic illnesses and crash risk: Dobbs (2005); Vaa (2003); Charlton et al. (2004). Comparison of the reviews reveals a relatively high agreement where medical conditions considered to be at slightly to moderately increased relative risk of crash include alcohol abuse and dependence, cardiovascular disease, cerebrovascular disease/TBI, depression, dementia, diabetes mellitus, epilepsy, use of certain medications, musculoskeletal disorders, schizophrenia, obstructive sleep apnea, and vision disorders. However, determining fitness to drive at the individual level based on diagnosis has significant limitations related to factors such as multiple medical conditions as well as varying severity of disease and associated functional impairments. Medical conditions that may affect driving can serve as "red flags" to assist health care professionals and driving administrators to identify drivers who may need further evaluation. Medical conditions overall, do impact the fitness to drive of older drivers; however, the crash risk tends to be only slightly to moderately increased. The conditions can serve as potential warnings for reduced fitness to drive, but many persons with these medical conditions would still be considered safe to continue driving.


Varicella zoster in children attending day care centers.
To describe morbidity associated to varicella in children attending day care centers. Descriptive study carried out through inquiries with parents of 664 children who acquired varicella after admission to day care centers in Taubaté (population: 244,165, census of 2004), a prosperous city in the State of São Paulo. The median age was 36 months (range 6 to 80 months); 8.4% of the children had varicella before 1 year of age. The main symptoms were: exanthema (100.0%), fever (85.4%) anorexia (39.6%), and headache (15.3%). 517 children (77.9%) had at least 1 medical visit, and 80.6% received at least 1 medication; 73 (11.0%) received nonsteroidal antiinflammatory drugs, and 52 (7.8%) received antibiotics. Complications occurred in 38 children (5.7%; 95% confidence interval: 3% - 8%); 8 (1.2%) were hospitalized, and 5 (0.7%) had sequelae. Complications and hospitalizations rates were 3 times more frequent in children with less than 1 year of age than in older children. More than half of the children and of the working parents were absent from their regular activities for more than a week. Varicella was associated with significant morbidity, affected younger children, was complicated in more than 5%, and left sequelae in 0.7% of children. More than 10% of the children received nonsteroidal antiinflammatory drugs, highlighting the need to warn the population about the risks of these drugs. Although varicella vaccination is not recommended for children younger than 12 months, vaccination of the children older than a year could avoid by herd immunity the transmission to babies. Brazilian public health authorities should be alerted to this issue and offer varicella vaccine to children attending day care centers.


Community environment moderates the relationship between older adults' need for and utilisation of home- and community-based care services: The case of China.
This study explores the moderating influence of perceived and objective community environments on the relationship between older adults' home- and community-based care (HCBC) needs and their actual utilisation of such care. We selected 5,668 older adults in two cities in China and adopted latent class analysis to descriptively explore the patterns of their HCBC need and utilisation. Structural equation modelling was used to determine factors related to the patterns of need and utilisation of HCBC services, and to explore the moderating roles that the perceived and objective community environments had on the effect of long-term care need on its utilisation. The results descriptively showed that older adults' patterns of HCBC need and utilisation appear to be embedded within two broader latent categories: a high-need/use group and a low-need/use group. Among participants who were satisfied with their community or who lived in areas with high accessibility to HCBC services, HCBC need could predict HCBC use. Our integrated conceptual framework proved to be applicable, thus enriching the theoretical models in explaining HCBC-related behaviours. The results have strong implications for urban planners, policymakers, and programme managers who seek to support older people and provide elderly care services in communities.


The development of a low-cost three-dimensional printed shoulder, arm, and hand prostheses for children.
The prosthetic options for higher level amputees are limited and costly. Advancements in computer-aided design programs and three-dimensional printing offer the possibility of designing and manufacturing transitional prostheses at very low cost. The aim of this project was to describe an inexpensive three-dimensional printed mechanical shoulder prosthesis to assist a pre-selected subject in performing bi-manual activities. The main function of the body-powered, manually adjusted three-dimensional printed shoulder prosthesis is to provide a cost-effective, highly customized transitional device to individuals with congenital or acquired forequarter amputations. After testing the prototype on a young research participant, a partial correction of the patient's spinal deviation was noted due to the counterweight of the device. The patient's family also reported improved balance and performance of some bimanual activities after 2 weeks of using the device. Limitations of the design include low grip strength and low durability. Clinical relevance The prosthetic options for higher level amputees are limited and costly. The low-cost three-dimensional printed shoulder prosthesis described in this study can be used as a transitional device in preparation for a more sophisticated shoulder prosthesis.


Interpersonal behavior profiles of eight cases of DSM-III personality disorder.
The present study used ratings of patients' interpersonal behaviors by groups of clinical trainees and undergraduates to test a priori classifications of DSM-III personality disorders onto the 1982 Interpersonal Circle. A sample of 8 videotaped personality disorder patient interviews were obtained from two psychiatric training tape series. A panel of 10 diagnosticians provided independent checks on the diagnosis assigned to the 8 patients by the training series and also rated the degree of prototypicality each case exhibited. Interpersonal characterizations of the interview behavior of the 8 patients were obtained from ratings of the tapes by undergraduate and clinical trainee observers. Findings revealed that interpersonal inventory ratings significantly differentiated the overt interpersonal behavior of the 8 patients, although the obtained interpersonal profiles appeared more complex and subtle than previous interpersonal translations suggest.


Protein turnover and resting energy expenditure in patients with undernutrition and chronic lung disease.
Whole-body protein metabolism was studied in 11 undernourished cystic fibrosis (CF) patient (7 female), 12 normally nourished CF patients (3 female), 7 anorexia nervosa (AN) patients (all female), and 15 normal control subjects (9 female). Protein turnover was studied by the single dose [15N]glycine method and the cumulative excretion of labeled urinary urea and ammonia. Energy metabolism was studied by open-circuit indirect calorimetry. Contrary to previous reports, no differences were found between the protein turnover of CF groups and the normal control group. However, patients with AN had a negative net protein deposition. Resting energy expenditure was significantly reduced in AN patients and increased in CF patients. The gender of CF patients did not affect protein and energy metabolism but fat mass was higher and fat-free mass was lower in CF females.


Import of West Nile virus infection in the Czech Republic.
We report West Nile virus infection of the central nervous system in a 69-year-old man, residing in North Moravia (Czech Republic), who visited the USA from 6 July to 31 August 2002. He developed fever with fatigue at the end of his US stay, and was hospitalized in Ostrava after his return on 3 September with fever (up to 39.5 degrees Celsius), fatigue, anorexia, moderate laryngotracheitis, dizziness, insomnia, blurred speech, and a marked bradypsychism. EEG demonstrated a slow bifrontal theta-delta activity, and CT of the brain a slight hydrocephalus. A significant increase of antibodies neutralizing West Nile virus was detected between the first (1:16) and second (1:256) blood serum sample. The patient recovered gradually and was released from hospital on 16 September. This is the first recorded human case of West Nile fever (WNF) imported to the Czech Republic. Nine similar cases of WNF import from the USA have already been reported in other European countries - France, Denmark, the Netherlands, and Germany.


Targeted inhibition in tumors with ALK dependency.
The oncogenic function of gene translocations involving the anaplastic lymphoma kinase (ALK) was first reported in rare subtypes of non-Hodgkin's lymphoma almost two decades ago. More recently, aberrant ALK signaling was found to be an oncogenic driver in subsets of non-small cell lung cancer (NSCLC), particularly in patients with little or no tobacco smoking history. The advent of molecularly targeted therapies that inhibit ALK has allowed the pairing of ALK inhibitors such as crizotinib as treatment for ALK-positive NSCLC, yielding dramatic responses and long-term disease control. The clinicopathologic features of ALK-driven NSCLC, the clinical development of ALK inhibitors, and the genetic determinants of acquired resistance to ALK inhibition are among the topics covered in this review.


Effect of collagen membrane and of bone substitute on lateral bone augmentation with titanium mesh: An experimental in vivo study.
The aim of this study was to identify the additional effects of collagen membrane (CM) and of synthetic bone substitute (BS) on lateral bone augmentation of chronic peri-implant defect with titanium mesh (TM). Atrophic alveolar ridge was induced in six canine mandibles, and 5 peri-implant defects were achieved in each hemi-mandible. Bone augmentation was attempted using the following randomly allocated modalities: (1) Control: no treatment, (2) TM only group: blood clot covered by TM, (3) TM+BS group: BS covered by TM, (4) TM+CM group: blood clot covered by TM and CM, and (5) TM+BS+CM group: BS covered by TM and CM. After 16 weeks of submerged healing, micro-CT and histomorphometric analyses were performed. TM exposure occurred in one case in the TM only group, one case in the TM+CM group, and two cases in the TM+BS+CM group. Histologically, pseudo-periosteum was observed along the inner and outer surfaces of TM, and the directions of the collagen fiber within the pseudo-periosteum differed according to the additional use of CM. In general, the TM only group rendered higher values in vertical defect fill and dimension of the augmented hard tissue in comparison with the other treatment groups. Due to the small sample size, this pilot study remains inconclusive. Within the limitations of the study, the use of CM and/or BS did not appear to have an additional benefit on lateral bone augmentation of peri-implant defect with TM.


The diagnostic and prognostic importance of ambulatory ST recording compared to a predischarge exercise test after an episode of unstable angina or non-Q wave myocardial infarction.
The diagnostic and prognostic value of ambulatory ST recordings after admission to the CCU and before discharge was compared to a symptom-limited predischarge exercise test in 170 men with unstable angina pectoris or non-Q wave myocardial infarction. ST depression in recordings before discharge identified a small group of patients (18%) out of whom 23% had a myocardial infarction within 3 months compared to 7% in those without this finding. The exercise test gave more diagnostic information, with ST depression found in 52% including 70% of those with ST depression at Holter monitoring. After 3 months, 13% of patients with ST depression at exercise test had a myocardial infarction compared to 5% in the other patients. ST depression at exercise also indicated an increased risk of myocardial and future severe angina over a longer time period. Thus ST recordings are recommended before discharge in all patients after an episode of unstable coronary artery disease as it identifies the patients with the most severe prognosis who might benefit from early revascularization. In those without ST depression at Holter a predischarge exercise test will give further information regarding the long-term risk for angina and coronary events.


A20 Is Increased in Fetal Lung in a Sheep LPS Model of Chorioamnionitis.
Chorioamnionitis is associated with an increased risk of preterm birth and aggravates adverse outcomes such as BPD. Development of BPD is associated with chronic inflammatory reactions and oxidative stress in the airways which may be antenatally initiated by chorioamnionitis. A20 is an immunomodulatory protein involved in the negative feedback regulation of inflammatory reactions and is a possible regulator protein in oxidative stress reactions. The influence of chorioamnionitis on A20 gene regulation in the fetal lung is unknown. We characterized the influence of LPS and proinflammatory cytokines on A20 expression in human lung endothelial (HPMEC-ST1.6R) and epithelial (A549) cells in vitro by real-time PCR and/or western blotting and used a sheep model of LPS-induced chorioamnionitis for in vivo studies. To study the functional role of A20, endogenous A20 was overexpressed in HPMEC-ST1.6R and A549 cells. LPS induced proinflammatory cytokines in HPMEC-ST1.6R and A549 cells. Both LPS and/or proinflammatory cytokines elevated A20 at transcriptional and translational levels. Intra-amniotic LPS transiently increased IL-1β, IL-6, IL-8, and TNF-α mRNA levels in fetal lamb lungs, associated with an increase in A20 mRNA and protein levels. Overexpression of A20 reduced proinflammatory cytokines in vitro. Repeated LPS exposure induced LPS tolerance for proinflammatory cytokines and A20 in vitro and in vivo. Antenatal inflammation induced a transient increase in proinflammatory cytokines in the preterm fetal lung. The expression of proinflammatory cytokines increased expression of A20. Elevated A20 may have a protective role by downregulating chorioamnionitis-triggered fetal lung inflammation. A20 may be a novel target for pharmacological interventions to prevent chorioamnionitis-induced airway inflammation and lung damage, which can result in BPD later in life.


Breastfeeding in obstetrics residency: exploring maternal and colleague resident perspectives.
Pregnancy is becoming more common in residency, and about 80% of residents are female. This leads to questions of breastfeeding, work demands, and perception of burden by colleagues. This study was designed to assess experiences of (1) breastfeeding obstetrics residents and (2) their colleagues. This was a cross-sectional study of obstetrics and gynecology residents. Residents were categorized into experience with or no experience with breastfeeding to determine differences. Responses were obtained from 404 residents in obstetrics. Breastfeeding is common, with 90% of residents knowing a breastfeeding resident and 22% of residents reporting personal experience with breastfeeding. Breastfeeding residents (n=89) felt support from their faculty and fellow residents. More than one in three breastfeeding mothers felt they placed extra demands on colleagues, despite 80% of colleagues reporting that they did not feel that breastfeeding colleagues placed extra demands. A breastfeeding policy was important to 85% of residents, but only 7% believed their program had one. Two-thirds of breastfeeding residents struggled with low milk supply and stopped breastfeeding early. Despite high levels of perceived support from faculty/fellow residents, breastfeeding residents struggle with low milk supply and work demands that lead to early discontinuation.


Conversion of a magnesium binding site into a zinc binding site by a single amino acid substitution in Escherichia coli alkaline phosphatase.
The replacement of aspartic acid by histidine at position 153 in Escherichia coli alkaline phosphatase results in a mutant enzyme that is remarkably similar to certain mammalian alkaline phosphatases that are activated by magnesium in a time-dependent fashion. These mammalian alkaline phosphatases have histidine at the position corresponding to 153 of the E. coli sequence. Here we report the three-dimensional structure of the mutant E. coli alkaline phosphatase with histidine at position 153. The structure reveals that the octahedral magnesium binding site has been converted to a tetrahedral zinc binding site with an imidazole ring nitrogen of His-153 as one of the ligands to the zinc. The alteration in metal binding caused by the mutation could explain the origin of the magnesium activation observed with the mammalian alkaline phosphatases. The structure also reveals differences in the mode of phosphate binding, explaining the enhanced phosphate affinity and the reduced activity of the mutant enzyme in the presence of zinc.


[Androgens - a common biological marker of sleep disorders and selected sexual dysfunctions?].
The relationship between sleep disturbances and sexual dysfunctions still remains unclear. The links which indicate the importance of central nervous system and sleep mechanisms in regulations of the endocrine system seem to have bilateral character; the nature of such associations is not fully understood. The aim of the paper is to describe the influence of androgens on the relations between sexual functioning and sleep functions in patients of both sexes. The physiological role of the androgens is described with the emphasis put on the specific action of these hormones in sleep regulation, as well as the mutual relations between the regulatory role of sleep on the sexual apparatus. The newest data suggest that the androgenic hormonal profile is linked to the sleep rhythm, but not to the chronobiological diurnal rhythm in male patients. This may constitute the purpose for further research on the role of androgens in the connections between sexual and sleep disturbances. Up to date there is little known about androgens' role in sleep regulation in women. The influence of sexual activity disturbances as behavioral factors influencing the severity and the persistence of insomnia as well as their position among other factors important for the triggering of insomnia requires further scientific exploration.


[Case of callosal disconnection syndrome with a chief complaint of right-hand disability, despite presence of left-hand diagonistic dyspraxia].
e report the case of 48-year-old right-handed male patient with an infarction affecting most part of the body and the splenium of the left half of the corpus callosum. Neuropsychological examination revealed typical signs of callosal disconnection including left-sided apraxia, diagonistic dyspraxia, left-sided agraphia, left-hand tactile anomia, left hemialexia, and right-sided constructional disability. Moreover, he complained of impairment in activities involving the right hand disability and agraphia. He could not stop behaving with his right hand when he had a vague idea. For example, he involuntarily picked up a tea bottle with his right hand when he had a desire to drink, although the action was not appropriate to that occasion. The imitation and utilization behavior did not imply this case, because his right hand behaviors were not exaggerated in response to external stimuli, such as the gestures of the examiner or the subjects in front of the patient. Unexpectedly, he complained about impairment of the activity of his right hand and was unaware of left hand apraxia or diagonistic dyspraxia; this trend continued for 6 months, at the time of this writing. We argue that the patient may have been subconsciouly aware of the symptoms of his left hand but had not verbalized them.


High-Dose-Rate Brachytherapy for Primary Treatment of Refractory Proliferative Verrucous Leukoplakia of the Hard Palate.
Oral proliferative verrucous leukoplakia (PVL) is a rare, progressive form of leukoplakia with a high rate of malignant transformation. No therapies are known to lower the rate of malignant transformation and prevent a recurrence. An 84-year-old patient with a years-long history of symptomatic PVL of the hard palate refractory to CO2 laser ablation presented to the radiation oncology clinic for consideration of non-surgical management. High dose rate brachytherapy was used to deliver 36 Gy in 12 fractions to the hard palate using an Ir-192 source with a custom-molded applicator. By three months of follow-up, the patient had complete regression of the PVL and resolution of acute mucositis. With 18 months of follow-up, the patient remains disease- and symptom-free without toxicities of treatment. High dose rate surface applicator brachytherapy is a feasible and potentially effective treatment for oral PVL, yielding durable control with low long-term toxicity.


A suite of solid-state NMR experiments for RNA intranucleotide resonance assignment in a 21 kDa protein-RNA complex.
Intranucleotide resonance of the 26mer box C/D RNA in complex with the L7Ae protein were assigned by solid-state NMR (ssNMR; see picture) spectroscopy. This investigation opens the way for studying RNA in large protein-RNA complexes by ssNMR spectroscopy.


Dependence of technetium-99m red blood cell labeling efficiency on red cell surface charge.
The mechanisms by which [99mTc]pertechnetate becomes attached to stannous-primed red blood cells are not known in detail. To study the problem further, the effect of red cell surface charge on labeling efficiency was evaluated. Red cell surface charge was reduced by using the enzyme neuraminidase to remove the terminal charge-bearing sialic acid moiety of the membrane glycoprotein. Forty-five blood samples from six volunteers were treated with neuraminidase for varying lengths of time, resulting in the removal of from 11% to 99% of the normal negative surface charge, as determined from electrophoretic mobility measurements. There was excellent linear correlation between labeling efficiency and the remaining red cell surface charge for values down to 20% of normal (r = 0.89). When surface charge was less than 20% of normal, labeling efficiency was constant at 30%. Eleven blood samples from three donors were divided into two groups that were treated with neuraminidase either before or after they were labeled. The labeling efficiency was independent of the order in which the steps were performed. No evidence for shifting of the radiolabel from the cell membrane to hemoglobin was found. The results suggest that clinical conditions associated with a reduction of sialic acid on the erythrocyte membrane may be one cause of decreased red blood cell labeling efficiency, and that increased membrane permeability for reduced technetium species may be responsible for the decrease.


[Surgical Treatment of Sacral Chordoma].
PURPOSE OF THE STUDY The retrospective study of patients treated for sacral chordoma with respect of complications, clinical outcomes and longterm survival is presented. Three main hypotheses have been formulated. Hypothesis 1: survival of patients with respect to generalization of the disease, manifestation of local recurrence and metastases with a R0 resection margin achieved is longer than survival of patients with a R1 or R2 resection margin. Hypothesis 2: survival of patients with the tumor resected from low endplate of S2 distally is longer than in tumors with resection above this level. Hypothesis 3: resection of large tumors with tumor volume greater than 800 cm³ is associated with a significantly shorter survival than resection of tumors with tumor volume less than 800 cm³. MATERIAL AND METHODS A total of 12 patients (7 women, 5 men), with the mean age of 54.3 years, underwent surgical treatment at our department in 1998-2018. Sacral chordoma proximally achieved S1 level in three cases, S2 level in four cases and S3 level in five cases with volume less than 800 cm³ in eight and greater in four patients. In nine patients sacrectomy using isolated posterior approach was performed and in three patients antero-posterior approach was applied. The Kaplan-Meier survival curve was calculated to estimate the survival of patients. The patients were divided into groups and subsequently compared with respect of achieved radicality of surgical resection, i.e. R0 vs. R1 or R2 resection, secondly of the proximal margin of the tumor/resection, i.e. S1 or S2 vs. S3 distally, and thirdly of the volume of the tumor, i.e. less than 800 cm³ vs. more than 800 cm³. RESULTS At the time of evaluation, a total of seven patients were alive (58.3%), with the mean survival of 9.5 years. One patient died from complications associated with the treatment of obstructive ileus manifested 10 months after primary surgery. The remaining four patients died in relation to the generalization of the disease 14.8 years after primary surgery on average. All the patients, in whom R0 resection was achieved, at the average time of evaluation of 7.3 years (range 2.8-15.8 years) showed no signs of local recurrence or generalization of the disease, whereas in group with R1, R2 resection at the time of evaluation only two patients were still alive, both 16.8 years on average (range 15.2-18.4 years) after surgery with repeatedly treated recurrencies. Frequent postoperative complications were observed in a total of five patients (41.7%). DISCUSSION The study did not confirm any difference in patient's survival with respect of the proximal margin affection of sacrum or tumor size. The decisive factor for survival of patients with sacral chordoma is achieving the R0 resection. The size of the chordoma and proximal achievement increase the complexity of surgery, manifestation of early perioperative and subsequently postoperative complications. CONCLUSIONS In primary surgical treatment of sacral chordoma, we always try to achieve R0 resection. In the case of low-volume tumors from S3 distally, we resect the tumor using the isolated posterior approach. The anterior-posterior approach is preferred in the case of large tumors presenting in the S1/2 region. Key words: sacral chordoma, sacral cancer, wide resection, sacrectomy, vertical rectus abdominus myocutaneous (VRAM) flap.


[Extra-bulbar primary olfactory projection in teleost fishes].
Immunohistochemical investigations with anti-substance P antiserum demonstrate the existence of an extensive extrabulbar primary olfactory projection in several gymnotid teleost fish. This projection, never described before, originates in particular primary olfactory bundles which enter with the olfactory nerve into the olfactory bulb. While the bulk of the olfactory fibers end with glomeruli in the glomerular layer of the olfactory bulb, two particular bundles penetrate into the telencephalon and end, without forming glomeruli, in several telencephalic and diencephalic regions. A few fibers run as far as to the hypothalamus. In the light of these findings, the general notion that the primary olfactory projection is limited to the olfactory bulb and forms only glomeruli-like terminals, should be reconsidered.


Oxidative stress induces coordinated remodeling of RNA-enzyme interactions.
RNA-binding proteins (RBPs) are key post-transcriptional regulators that play a substantial role during stress adaptation. Recent proteome-wide surveys have uncovered a large number of new and "unconventional" RBPs such as metabolic enzymes, yet little is known about the reconfiguration of the RNA-binding proteome (RBPome) and RNA-enzyme interactions in response to cellular stress. Here, we applied RNA-interactome capture to monitor the dynamics of the mRBPome upon mild oxidative stress in the yeast Saccharomyces cerevisiae. Among the 257 proteins that significantly changed RNA associations, we observed the coordinated remodeling of RNA-binding enzymes - particularly of the central carbon metabolism - that complemented known metabolic responses. Furthermore, we recognized the propensity for paralogous specific alterations of enzyme-RNA interactions. Our results suggest coordinated cross talk between RNA-enzyme interactions and intermediary metabolism to maintain the physiological and molecular balance upon oxidative stress, perhaps through specialization of paralogous during evolution.


Mutually exclusive neuronal expression of peptides encoded by the FMRFa gene underlies a differential control of copulation in Lymnaea.
An innovative method, direct peptide profiling of small samples of nervous tissue by matrix-assisted laser desorption ionization mass spectrometry, in combination with peptide characterization, immunocytochemistry in conjunction with specific neuronal labeling by backfilling of the penis nerve, and bioassay of peptides was used to study the intrinsic neuronal expression patterns of distinct sets of related FMRFa peptides and their significance for the organization of male copulation behavior in the mollusk, Lymnaea stagnalis. Previous studies indicate that the sets of FMRFa-related and GDPFLRFa-related peptides are encoded by two alternatively spliced transcripts of the single FMRFa gene. Direct mass spectrometry revealed that both FMRFa-related and GDPFLRFa-related peptides are present in the penis nerve, the sole nerve that innervates the penis complex. Accordingly, authentic FMRFa, GDPFLRFa, and related peptides were purified from the penis complex. The loci of synthesis of FMRFa and related peptides could be traced to the right cerebral ventral lobe, those of GDPFLRFa and related peptides to the B group neurons in the right parietal ganglion and to a few unidentified neurons in the right pleural ganglion. Notwithstanding their related structures, the two sets of peptides have distinctly different actions on the penis retractor muscle.


Crystal structures of a yeast 14-3-3 protein from Lachancea thermotolerans in the unliganded form and bound to a human lipid kinase PI4KB-derived peptide reveal high evolutionary conservation.
14-3-3 proteins bind phosphorylated binding partners to regulate several of their properties, including enzymatic activity, stability and subcellular localization. Here, two crystal structures are presented: the crystal structures of the 14-3-3 protein (also known as Bmh1) from the yeast Lachancea thermotolerans in the unliganded form and bound to a phosphopeptide derived from human PI4KB (phosphatidylinositol 4-kinase B). The structures demonstrate the high evolutionary conservation of ligand recognition by 14-3-3 proteins. The structural analysis suggests that ligand recognition by 14-3-3 proteins evolved very early in the evolution of eukaryotes and remained conserved, underlying the importance of 14-3-3 proteins in physiology.


Comparison of propofol and methohexitone in anaesthesia for ECT: effect on seizure duration and outcome.
The effect of the induction agents propofol and methohexitone on seizure duration and clinical outcome was assessed in a prospective, randomised, double blind study in 32 depressed patients receiving electroconvulsive therapy (ECT). Assessments comprised Hamilton rating scales pre-ECT, weekly during the course, and at one month follow-up. Patients showed a significant improvement in depression as measured by the Hamilton rating scale across the course of the ECT treatment. This improvement was not significantly different in the propofol and methohexitone groups. Nor was the amount of improvement related to either the total duration of seizure experienced by the patient during the ECT series or the use of tricyclic antidepressants by some patients.


Promoter methylation and large intragenic rearrangements of DPYD are not implicated in severe toxicity to 5-fluorouracil-based chemotherapy in gastrointestinal cancer patients.
Severe toxicity to 5-fluorouracil (5-FU) based chemotherapy in gastrointestinal cancer has been associated with constitutional genetic alterations of the dihydropyrimidine dehydrogenase gene (DPYD). In this study, we evaluated DPYD promoter methylation through quantitative methylation-specific PCR and screened DPYD for large intragenic rearrangements in peripheral blood from 45 patients with gastrointestinal cancers who developed severe 5-FU toxicity. DPYD promoter methylation was also assessed in tumor tissue from 29 patients Two cases with the IVS14+1G > A exon 14 skipping mutation (c.1905+1G > A), and one case carrying the 1845 G > T missense mutation (c.1845G > T) in the DPYD gene were identified. However, DPYD promoter methylation and large DPYD intragenic rearrangements were absent in all cases analyzed. Our results indicate that DPYD promoter methylation and large intragenic rearrangements do not contribute significantly to the development of 5-FU severe toxicity in gastrointestinal cancer patients, supporting the need for additional studies on the mechanisms underlying genetic susceptibility to severe 5-FU toxicity.


Molecular architecture and function of the Omp85 family of proteins.
Omp85 is a protein found in Gram-negative bacteria where it serves to integrate proteins into the bacterial outer membrane. Members of the Omp85 family of proteins are defined by the presence of two domains: an N-terminal, periplasmic domain rich in POTRA repeats and a C-terminal beta-barrel domain embedded in the outer membrane. The widespread distribution of Omp85 family members together with their fundamental role in outer membrane assembly suggests the ancestral Omp85 arose early in the evolution of prokaryotic cells. Mitochondria, derived from an ancestral bacterial endosymbiont, also use a member of the Omp85 family to assemble proteins in their outer membranes. More distant relationships are seen between the Omp85 family and both the core proteins in two-partner secretion systems and the Toc75 family of protein translocases found in plastid outer envelopes. Aspects of the ancestry and molecular architecture of the Omp85 family of proteins is providing insight into the mechanism by which proteins might be integrated and assembled into bacterial outer membranes.


Cytopathologic findings and differential diagnostic considerations of primary clear cell carcinoma of the lung.
Primary clear cell carcinoma (CLCC) of the lung is an extremely rare disease and is a subtype of large cell carcinoma, according to the World Health Organization (WHO) classification. A case is presented here in which intraoperative squash smears in a 53-year-old man revealed sheet and small clusters or tumor cells with prominent nucleoli and fine granular chromatin. Abundant translucent cytoplasm with occasional cytoplasmic vacuoles and intracytoplasmic eosinophilic inclusions was also identified. A cytopathologic diagnosis of a CLCC was suggested. Further evaluation and immunohistochemical studies were conducted on formalin-fixed, paraffin-embedded material. Nests of slightly acidophilic clear tumor cells with a prominent cellular membrane and an alveolar growth pattern were identified on H&E sections. Immunohistochemically, the tumor cells showed diffuse and strong membranous staining for CK(AE1/AE3), CK7, and CA19-9 but were negative for Napsin A, CK20, CDX2, TTF-1, alpha-fetoprotein, chromogranin A, synaptophysin, CD10, and CD56. The diagnosis of primary CLCC of the lung was confirmed based on cytopathologic, histopathologic, immunohistochemical results, and a detailed systemic examination to exclude a possible extrapulmonary origin. We report here the cytopathological features of CLCC of the lung with an emphasis on differential diagnostic considerations.


Potential release pathways, environmental fate, and ecological risks of carbon nanotubes.
Carbon nanotubes (CNTs) are currently incorporated into various consumer products, and numerous new applications and products containing CNTs are expected in the future. The potential for negative effects caused by CNT release into the environment is a prominent concern and numerous research projects have investigated possible environmental release pathways, fate, and toxicity. However, this expanding body of literature has not yet been systematically reviewed. Our objective is to critically review this literature to identify emerging trends as well as persistent knowledge gaps on these topics. Specifically, we examine the release of CNTs from polymeric products, removal in wastewater treatment systems, transport through surface and subsurface media, aggregation behaviors, interactions with soil and sediment particles, potential transformations and degradation, and their potential ecotoxicity in soil, sediment, and aquatic ecosystems. One major limitation in the current literature is quantifying CNT masses in relevant media (polymers, tissues, soils, and sediments). Important new directions include developing mechanistic models for CNT release from composites and understanding CNT transport in more complex and environmentally realistic systems such as heteroaggregation with natural colloids and transport of nanoparticles in a range of soils.


The iron-regulated surface proteins IsdA, IsdB, and IsdH are not required for heme iron utilization in Staphylococcus aureus.
The iron-regulated surface determinant proteins (Isd) of Staphylococcus aureus are expressed during iron limitation and have been proposed to be involved in the scavenging of iron from heme. In this study, the genes encoding the surface proteins IsdA, IsdB, and IsdH were inactivated in order to determine their combined role. The triple mutant was found to have no defect in growth under any conditions of iron limitation tested. Also using a mouse septic arthritis model of S. aureus systemic disease, no significant difference in bacterial load was observed for the triple mutant, compared with its otherwise isogenic parent.


The use of low- dose intrathecal fluorescein in endoscopic repair of cerebrospinal fluid rhinorrhea.
Intrathecal injection of fluorescein is a useful adjuvant method for localization of fistulas in endoscopic endonasal repair of cerebrospinal fluid (CSF) leakage. Although being neurotoxic in commercial doses, a low dose of diluted fluorescein seems to be safe on the basis the existing data in the literature. The purpose of this study was to investigate the role of a low- dose intrathecal fluorescein injection in detection of CSF fistula and potential adverse effects of this technique. CSF rhinorrhea was repaired in 20 patients with an endoscopic endonasal technique. Intraoperative intrathecal fluorescein injection was used for localization of the site of the CSF leak. The accuracy rate of leakage site identification and the incidence of complications and recurrences were recorded. Intrathecal administration of fluorescein demonstrated CSF leakage in 18 of the 20 patients (90%). There were no intraoperative complications. Definitive closure of the CSF leakage site was achieved in 16 patients (80%) after the initial reconstruction. Recurrence occurred in four cases and all patients were free of CSF leakage after the second surgical attempt. The present study suggested that a low dose of intraoperative intrathecal fluorescein administration is a safe and sensitive method for localization of CSF leakage sites.


Species traits elucidate crop pest response to landscape composition: a global analysis.
Recent synthesis studies have shown inconsistent responses of crop pests to landscape composition, imposing a fundamental limit to our capacity to design sustainable crop protection strategies to reduce yield losses caused by insect pests. Using a global dataset composed of 5242 observations encompassing 48 agricultural pest species and 26 crop species, we tested the role of pest traits (exotic status, host breadth and habitat breadth) and environmental context (crop type, range in landscape gradient and climate) in modifying the pest response to increasing semi-natural habitats in the surrounding landscape. For natives, increasing semi-natural habitats decreased the abundance of pests that exploit only crop habitats or that are highly polyphagous. On the contrary, populations of exotic pests increased with an increasing cover of semi-natural habitats. These effects might be related to changes in host plants and other resources across the landscapes and/or to modified top-down control by natural enemies. The range of the landscape gradient explored and climate did not affect pests, while crop type modified the response of pests to landscape composition. Although species traits and environmental context helped in explaining some of the variability in pest response to landscape composition, the observed large interspecific differences suggest that a portfolio of strategies must be considered and implemented for the effective control of rapidly changing communities of crop pests in agroecosystems.


The impact of the United Nations Convention on the Rights of Persons with Disabilities (CRPD) on Victorian guardianship practice.
Article 12 of the United Nations Convention on the Rights of Persons with Disabilities (CRPD) emphasises full and equal legal capacity of all citizens to participate in decisions. This paper examines whether the principles of Article 12, also reflected in other reform documents, were evident within 12 guardianship hearings conducted in Victoria, Australia from 2001 to 2016 involving adults with cognitive disability. The issues this study raises resonate loudly across the globe as multiple signatory nations to the CRPD grapple with the complexities of implementing Article 12. Reports of VCAT decisions with written reasons of Guardianship List hearings from 2001 to 2016 were selected from the Australasian Legal Information Institute site and analysed thematically. Thematic analysis of proceedings revealed three consistent trends. Firstly, a presumption of incapacity based on disability excluded Proposed Represented Persons (PRP) from involvement in decision-making. Secondly, external perceptions of PRPs best interest were dominated by safeguarding concerns and conflict between supporters. Finally, in multiple cases, although a PRP's preference had been established, it was considered immaterial to the final decision. The paper concludes with a promising discussion of the new Guardianship and Administration Act 2019 (Vic), which came into force on 1 March 2020, and recommendations for guardianship practice both locally and internationally.IMPLICATIONS FOR REHABILITATIONLegal capacity should be recognised as inherent in all people, and therefore decision making incapacity should not be assumed based on a person's cognitive and/or communication disability;The supported decision making mechanisms, born from Article 12 of the CRPD, that facilitate acknowledgment, interpretation and acting upon a person's expression of will and preference need to be recognised and promoted within the context of Guardianship proceedings and by health professionals when assessing decision making capacity of people with cognitive disability;Significant knowledge and attitudinal changes are required within the Tribunal and incorporated into the practice of health professionals informing the Tribunal, in order to counter many conceptual underpinnings embedded within current guardianship legislation across the globe;Ascertaining the will and preference of the proposed represented person should be prioritised by Guardianship tribunal members' rather than the management of conflict between interested parties.


[Clinical experiences with the Gianturco-Z stent in endotracheal and -bronchial stenoses].
We inserted Gianturco-Z stents in 17 patients with tracheobronchial stenoses on 18 occasions. Three patients had benign, all others malignant stenoses due to compression of the tracheobronchial tree by metastasising malignancies. In all cases the stents could be easily positioned and the patients experienced relief of their severe dyspnea. In one case there was fatigue breakage of the stent. The patient was therefore given a silicone tracheal stent.


Observation of Solute Transport between Articular Cartilage and Subchondral Bone in Live Mice.
To establish a method for investigating the permeability of calcified cartilage zone (CCZ) and to observe solute transport between articular cartilage (AC) and subchondral bone (SB) through intact CCZ in vivo. We developed a novel fixing device combined with un-decalcified fluorescence observation method to address the permeability of CCZ in live mice. Twenty-four Balb/c female mice aged 1 to 8 months were used to observe the development of CCZ. Eighty-four Balb/c female mice (aged 1 or 6 months) with mature or immature CCZ of distal femur were used to investigate the permeability of intact CCZ in vivo. Diffusivity of rhodamine B (476 Da) and tetramethyl-rhodamine isothicyanate-dextran (TRITC-Dextran, 20 kDa) was tested from AC to SB in 0 minutes, 1 minute, 15 minutes, 30 minutes, 1 hour, and 2 hours. None diffused knee joints (0 minutes) served as blank control, while in vitro immersion of distal femurs in rhodamine B or TRITC-Dextran for 72 hours served as positive control. CCZ was well developed in 6-month mice. Both tracers penetrated immature CCZ down to SB in less than 1 hour in live mice, while the diffusion of both tracers decreased rapidly at tidemark in all testing time points. Current study provided direct evidence of blocking effect of CCZ in solute transportation during short diffusion period in live animal, indicating the important role of CCZ in joint development and microenvironment maintenance.


Study of influenza A virus in wild boars living in a major duck wintering site.
Wild birds, which are reservoirs of influenza viruses, are believed to be the original source of new influenza viruses-including highly pathogenic ones-that can be transmitted to domestic animals as well as humans and represent a potential epizootic and/or pandemic threat. Despite increasing knowledge on influenza A virus dynamics in wild birds, the viral circulation in wild boars remains largely unknown. This is of particular interest since pigs can be infected with both human and avian viruses; upon co-infection, they can act as a mixing vessel through reassortment, a mechanism that resulted in the emergence of the pandemic H1N1 virus in 2009. The Camargue (Southern France) appears as an ideal study area to investigate inter-species transmission of influenza A viruses from wild birds and possibly humans to wild boars. Indeed, the important local wild boar population shares wetland use with humans and the largest concentration of wintering ducks in France, that are both susceptible to infection by influenza A viruses. Additionally, wild boars occasionally prey on ducks. We conducted a virological and serological survey on wild boars in the Camargue (Southern France) between September 2009 and November 2010. No influenza A virus was detected in the collected nasal swabs (n=315) and no influenza specific antibodies were observed in the serological samples (n=20). As the study was mainly focused on viral excretion, which is limited in time, we cannot exclude that low or occasional influenza A virus circulation took place during the study period. Although, wild boars did not seem to be a key element in the dynamics of influenza A virus circulation in the Camargue, wild boar influenza A virus infections should be more widely studied to determine if the pattern observed here represents the normal situation or an exceptional one.


GPR35 promotes neutrophil recruitment in response to serotonin metabolite 5-HIAA.
Rapid neutrophil recruitment to sites of inflammation is crucial for innate immune responses. Here, we reveal that the G-protein-coupled receptor GPR35 is upregulated in activated neutrophils, and it promotes their migration. GPR35-deficient neutrophils are less recruited from blood vessels into inflamed tissue, and the mice are less efficient in clearing peritoneal bacteria. Using a bioassay, we find that serum and activated platelet supernatant stimulate GPR35, and we identify the platelet-derived serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) as a GPR35 ligand. GPR35 function in neutrophil recruitment is strongly dependent on platelets, with the receptor promoting transmigration across platelet-coated endothelium. Mast cells also attract GPR35+ cells via 5-HIAA. Mice deficient in 5-HIAA show a loss of GPR35-mediated neutrophil recruitment to inflamed tissue. These findings identify 5-HIAA as a GPR35 ligand and neutrophil chemoattractant and establish a role for platelet- and mast cell-produced 5-HIAA in cell recruitment to the sites of inflammation and bacterial clearance.


Controlling pathogenic risks of water treatment biotechnologies at the source by genetic editing means.
Antimicrobial-resistant pathogens in the environment and wastewater treatment systems, many of which are also important pollutant degraders and are difficult to control by traditional disinfection approaches, have become an unprecedented treat to ecological security and human health. Here, we propose the adoption of genetic editing techniques as a highly targeted, efficient and simple tool to control the risks of environmental pathogens at the source. An 'all-in-one' plasmid system was constructed in Aeromonas hydrophila to accurately identify and selectively inactivate multiple key virulence factor genes and antibiotic resistance genes via base editing, enabling significantly suppressed bacterial virulence and resistance without impairing their normal phenotype and pollutant-degradation functions. Its safe application for bioaugmented treatment of synthetic textile wastewater was also demonstrated. This genetic-editing technique may offer a promising solution to control the health risks of environmental microorganisms via targeted gene inactivation, thereby facilitating safer application of water treatment biotechnologies.