Allergic conjunctivitis: current concepts on pathogenesis and management.
Allergic conjunctivitis (AC) includes a wide spectrum of clinical entities characterized by different incidence, age of onset, natural course, clinical outcome and response to treatment. Taken together, they represent one of the most frequent ocular surface diseases affecting more than 30% of the young-adult population and show an increasing incidence over the years. Moreover, comorbidities with other systemic atopic conditions such as asthma, atopic dermatitis and rhinitis require a multidisciplinary approach. Recent advances in the knowledge of the pathogenic mechanism overcome the classic role of type I hyper-sensitivity and mast cells' activation, demonstrating an involvement of innate immunity and neuroinflammation in the pathogenesis of the most severe forms such as atopic keratoconjunctivitis (AKC) and vernal keratoconjunctivitis (VKC). Ocular itching, swelling and tearing are the most frequent symptoms complained by patients with all forms of AC, while photophobia and pain are typical of the most severe forms, such as VKC and AKC, due to the frequent corneal involvement. Upper tarsal papillary reaction represents the main clinical sign of AC associated with conjunctival hyperemia and mucous secretion. Diagnosis is based on clinical history and eye evaluation and can be confirmed through allergological tests. Additional ocular exams include specific allergen conjunctival provocation tests and the presence of eosinophils in the conjunctival scraping. Current treatments of AC include the use of antiallergic eye drops for mild forms, while recurrences of ocular surface inflammations with corneal involvement in severe forms require the use of topical steroids to avoid visual impairment. Novel steroid sparing therapies such as Cyclosporine A eye drops or topical Tacrolimus have been proposed to improve VKC and AKC management.


Pd-Functionalized ZnO:Eu Columnar Films for Room-Temperature Hydrogen Gas Sensing: A Combined Experimental and Computational Approach.
Reducing the operating temperature to room temperature is a serious obstacle on long-life sensitivity with long-term stability performances of gas sensors based on semiconducting oxides, and this should be overcome by new nanotechnological approaches. In this work, we report the structural, morphological, chemical, optical, and gas detection characteristics of Eu-doped ZnO (ZnO:Eu) columnar films as a function of Eu content. The scanning electron microscopy (SEM) investigations showed that columnar films, grown via synthesis from a chemical solutions (SCS) approach, are composed of densely packed columnar type grains. The sample sets with contents of ∼0.05, 0.1, 0.15, and 0.2 at% Eu in ZnO:Eu columnar films were studied. Surface functionalization was achieved using PdCl2 aqueous solution with additional thermal annealing in air at 650 °C. The temperature-dependent gas-detection characteristics of Pd-functionalized ZnO:Eu columnar films were measured in detail, showing a good selectivity toward H2 gas at operating OPT temperatures of 200-300 °C among several test gases and volatile organic compound vapors, such as methane, ammonia, acetone, ethanol, n-butanol, and 2-propanol. At an operating temperature OPT of 250 °C, a high gas response Igas/Iair of ∼115 for 100 ppm H2 was obtained. Experimental results indicate that Eu doping with an optimal content of about 0.05-0.1 at% along with Pd functionalization of ZnO columns leads to a reduction of the operating temperature of the H2 gas sensor. DFT-based computations provide mechanistic insights into the gas-sensing mechanism by investigating interactions between the Pd-functionalized ZnO:Eu surface and H2 gas molecules supporting the experimentally observed results. The proposed columnar materials and gas sensor structures would provide a special advantage in the fields of fundamental research, applied physics studies, and ecological and industrial applications.


Cloned single repeating units of 5S DNA direct accurate transcription of 5S RNA when injected into Xenopus oocytes.
Single and multiple repeating units of three types of Xenopus 5S DNA recombined with the plasmid pMB9 serve as templates for the accurate synthesis of 5S RNA after their injection into Xenopus laevis oocyte nuclei. All 15 cloned single repeating units of X. laevis oocyte 5S DNA that were tested supported 5S RNA synthesis. Three cloned fragments of X. borealis oocyte 5S DNA and one cloned single repeating unit of X. borealis somatic 5S DNA were templates for 5S RNA synthesis. We conclude that the majority of repeating units of 5S DNA in these multigene families contain the information for accurate initiation and termination of 5S RNA synthesis. The ability of this system to detect sequence changes that affect transcription is demonstrated.


Association of Timing of Biliary Drainage with Clinical Outcomes in Severe Acute Cholangitis: A Retrospective Cohort Study.
The guidelines recommend urgent biliary drainage (BD) for severe acute cholangitis, without a clear definition of "urgent". To explore the optimal time, we identified the impact of timing of BD on clinical outcomes in severe acute cholangitis. A retrospective study of patients with severe acute cholangitis was conducted based on the Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC-III) database. Multivariable regressions were used to identified the effect of timing of BD on in-hospital mortality, 30-day mortality, and the length of stay (LOS) in hospital and the intensive care unit (ICU) with adjustment for confounding factors. A total of 106 severe acute cholangitis patients underwent BD with a median time of 14.14 hours (IQR: 7.60-32.59). Among them, 67.9% were performed within 24 hours and 80.2% within 48 hours. Median length of stay was 2.65 days (IQR: 1.70-5.12) in the ICU and 7.54 days (IQR: 4.49-17.17) in hospital. The in-hospital and 30-day mortality rates were 13.2% and 14.2%, respectively. On multivariate analysis, every 1-day delay of BD increased 1.49 days of stay in hospital (P<0.0001). Delayed BD (>48 hours) was linked with 5.56 days longer ICU LOS (P = 0.0096), while urgent BD (<24 hours) did not significantly shorten the ICU stay (P = 0.0997). No significant increase was observed on in-hospital mortality (OR = 1.03; 95% CI 0.93-1.13) nor 30-day mortality (OR=1.01; 95% CI 0.87-1.14) with BD delay in this population. In severe acute cholangitis patients, delay in BD increased in-hospital LOS. BD after 48 hours was associated with longer ICU LOS. Yet, BD within 24 hours did not significantly reduce the mortality nor shortened the ICU LOS.


Could you hold the door for me? Including disability in diversity.
This article is intended to help those unfamiliar with disability studies by providing a context for disability on which psychologists can build. The 1st part presents data on disability training in graduate clinical programs and on training accessibility for graduate students with disabilities. The 2nd part is an introduction to disability studies and includes 3 core concepts of disability issues in psychology: (a) the framing of disability from 3 models (the moral, medical, and social models); (b) the ways in which disability is like and unlike other minority groups; and (c) the language that is used to describe disability. These 2 parts taken together constitute a brief introduction to disability issues within psychology.


American literature news narration based on computer web technology.
Driven by internet technology, online has become the main way of news dissemination, but redundant information such as navigation bars and advertisements affects people's access to news content. The research aims to enable users to obtain pure news content from redundant web information. Firstly, based on the narrative characteristics of literary news, the Term Frequency-Inverse Document Frequency (TF-IDF) algorithm is employed to extract pure news content from the analyzed web pages. The algorithm uses keyword matching, text analysis, and semantic processing to determine news content's boundaries and key information. Secondly, the news text classification algorithm (support vector machine, K-nearest neighbor, AdaBoost algorithm) is selected through comparative experiments. The news extraction system based on keyword feature and extended Document Object Model (DOM) tree is constructed. DOM technology analyzes web page structure and extracts key elements and information. Finally, the research can get their narrative characteristics by studying the narrative sequence and structure of 15 American literary news reports. The results reveal that the most used narrative sequence in American literary news is sequence and flashback. The narrative duration is dominated by the victory rate and outline, supplemented by scenes and pauses. In addition, 53.3% of the narrative structures used in literary news are time-connected. This narrative structure can help reporters have a clear conceptual structure when writing, help readers quickly grasp and understand the context of the event and the life course of the protagonists in the report, and increase the report's readability. This research on the narrative characteristics of American literature news can provide media practitioners with a reference on news narrative techniques and strategies.


Safety evaluation of a new anxiolytic product containing botanicals Souroubea spp. and Platanus spp. in dogs.
Separation anxiety and noise aversion are common behavioral problems in dogs. They elicit fear responses such as cowering, seeking out the owner, and attempting to escape. This can result in property damage, injury to the dog, and disruption of the owner-pet bond, possibly leading to pet abandonment or euthanasia. A novel botanical anxiolytic product was evaluated for safety in dogs as the target animal species. Its intended use is for the treatment and prevention of anxiety and noise aversion in dogs. It contains a defined mixture of Souroubea spp. vine and Platanus spp. bark, delivering the active principle, betulinic acid, at a recommended dose of 1 mg/kg body weight (BW). In the current target animal safety study, 16 healthy male beagle dogs were administered either a placebo or the newly formulated botanical tablets at 0.5×, 2.5×, or 5× the recommended dose (1 mg/kg BW) over 28 d. The dogs were monitored for occurrence of any systemic or local adverse events. In the investigation presented here, there were no clinically significant adverse effects following treatment, as determined by clinical observations, physical examinations, BW, hematology, clinical biochemistry, and urinalysis. Pharmacokinetic analysis demonstrated that the concentration of betulinic acid in serum was below 0.020 μg/mL in treated animals. Under the conditions of these studies, the formulated blend of S. sympetala and P. occidentalis, when administered up to 5× the intended dose for 28 consecutive d, showed no adverse effects on the health of dogs.


Excitation of ion-wave wakefield by the resonant absorption of a short pulsed microwave with plasma.
Unmagnetized, inhomogeneous laboratory plasma irradiated by a high power (eta=E(2)(0)/4pin(e)kT(e) approximately 5.0x10(-2)) short pulsed microwave with pulse length of the order of ion-plasma period (tau(pi) less, similar 2pi/omega(pi)) is studied. Large density perturbation traveling through the underdense plasma with a velocity much greater than the ion sound speed produced by the resonant absorption of the microwave pulse has been observed. In the beginning the density perturbation has large amplitude (deltan/n(0) approximately 40%) and propagates with a velocity of the order of 10(6) cm/s. But later its amplitude as well as the velocity decrease rapidly, and finally the velocity arrives with twice the ion sound speed. The oscillating incident electromagnetic waves enhance highly localized electric field by the resonant absorption process and develop time-averaged force field which pushes plasma electrons from the resonant layer. As the electrons are accelerated to be ejected, they pull plasma ions as a bunch with them by means of self-consistent Coulomb force. This suprathermal ion bunch can excite an ion-wave wakefield.


Effect of Increased Neutrophil-to-Lymphocyte Ratio (NLR) and Decreased Mean Platelet Volume (MPV) Values on Inflammation in Acute Mania.
The neutrophil-to-lymphocyte ratio (NLR) and mean platelet volume (MPV) are simple, low-cost, and useful inflammatory markers detected in routine complete blood count (CBC), and their use has recently become widespread. In this study, we aimed to investigate the presence of an inflammatory state in manic patients on the basis of NLR and MPV values. This retrospective study was performed on 76 patients with acute mania who were admitted to the Inpatients Psychiatry Clinic of Afyon Kocatepe University Hospital in Turkey. Diagnoses were based on Diagnostic and Statistical Manuel of Mental disorder (DSM-IV). The control group consisted of 74 healthy individuals recruited from the community. They were age- and sex-matched with the study group. NLR values of the manic patient group were 2.2±1.4 and those of the control group were 1.6±0.5. NLR values were significantly higher (p=0.004) and MPV values were significantly lower in the manic patient group than in the control group (10.0±1.2 vs. 10.9±2.3, p=0.027). Increased NLR and decreased MPV levels may reflect inflammation in manic patients, and inflammation may play a role in the complex pathophysiology of acute mania.


Age-dependent cardiovascular effects of halothane anesthesia in neonatal pigs.
The cardiovascular effects of halothane anesthesia in a mixture of nitrous oxide and oxygen were studied on piglets 7 hr to 25 days of age. Blood pressure, heart rate and peripheral flows were recorded simultaneously in all animals. Body temperature and blood gas composition and pH were monitored and maintained within normal physiological limits for piglets. Inspired halothane concentration was kept at 1.0% during vascular surgery and then increased or decreased systematically. Halothane anesthesia depressed mean aortic pressure and increased carotid, femoral and renal resistances in piglets less than one week of age. These effects increased with increasing halothame concentrations from 0.25% to 1.5%. In older animals, mean aortic pressure changes were significant only at halothane concentrations above 1.0%, while peripheral resistances were unaffected. Although there was no concentration-dependent change in heart rate in either age group, heart rates were consistenly faster in younger animals.


Vestibular schwannoma: an unusual post radiotherapy response.
Vestibular schwannoma is a relatively uncommon tumor. Although, it is benign but locally expansile and spreads to damage the adjacent structures. Treatment strategy includes surgery, Stereotactic Radiosurgery (SRS) either by standard or hypofractionated protocols. Due to its benign nature, radiation therapy cannot remove the tumor completely, instead radiation therapy halts the growth of vestibular schwannoma and inactivates this benign tumor. Response of radiation in the form of tumor shrinkage is seen 2 - 2.5 years after the radiations. We report a case of vestibular Schwannoma in which residual tumor of 3.1 cm size following subtotal resection was irradiated of the dose of 54 Gy in 30 equal fractions on 3-Dimensional Conformal Radiation Therapy (3-DCRT). A follow-up CT scan brain after 2 months of radiotherapy showed complete disappearance of the disease categorized as complete response. This is an unusual phenomenon and is likely due to the very rarely seen malignant transformation or presence of malignant component in this benign tumor.


"Instant" new leprosy case-detection: an experience in Bihar State in India.
The National Leprosy Eradication Programme (NLEP) is based on survey, education and treatment, including coverage of all the registered cases with multi-drug therapy (MDT). The Government of India introduced MDT in all leprosy endemic districts through a vertical set-up, and through mobile leprosy treatment units in low endemic districts. Anti-leprosy work has not been uniform in all the states and needed push-start in some, such as Bihar. There have been spurts of leprosy elimination activities and the entire populations of the regions have not been covered because of various administrative reasons and logistic problems. In Singhbhum district of Bihar, a successful attempt was made to cover the maximum population by campaign approach. The strategy was to involve all the field workers of the leprosy programme in the district, supported by a small group of experienced personnel. The campaign, lasting for 39 working days, resulted in detecting leprosy cases equivalent to 64% of cases detected during the previous one full year. The entire operation helped the local staff to gain experience that would be useful for the future of the NLEP, and also provide an insight into working practices. Similar campaign approach can be used in situations where case-detection activities are feeble and the implementation of MDT is slow. If such campaigns are repeated at appropriate intervals, it will be a great support to achieving the goal of leprosy elimination.


Optimization of Taq DNA polymerase enzyme expression in Escherichia coli.
In the present study, we optimized the experimental conditions using pET15b expression vector to obtain large amounts of Taq DNA polymerase. Correct framing of the gene in the expression vector pET15b and its orientation were analyzed by digestion and sequencing. Production of Taq DNA polymerase in Escherichia coli BL21 (DE3) cells was induced by incubation with different concentrations of IPTG. Optimum production occurred with the addition of 1mM IPTG for 2h. The activity of the obtained enzyme was measured by comparing the intensities of the produced DNA bands in PCR reactions. Recombinant plasmid containing taq polymerase gene was confirmed by restriction digestion and DNA sequencing. Purified protein was identified by Western blotting. Optimum condition for the production of the enzyme was induction with 1mM IPTG for 23h. Addition of NP40 increased enzyme stability. We expressed the recombinant Taq DNA polymerase in E. coli using a T7based promoter system and obtained an active and stable enzyme.


The sound of cooperation: Musical influences on cooperative behavior.
Music as an environmental aspect of professional workplaces has been closely studied with respect to consumer behavior while sparse attention has been given to its relevance for employee behavior. In this article, we focus on the influence of music upon cooperative behavior within decision-making groups. Based on results from two extended 20-round public goods experiments, we find that happy music significantly and positively influences cooperative behavior. We also find a significant positive association between mood and cooperative behavior. Consequently, while our studies provide partial support for the relevance of affect in relation to cooperation within groups, we also show an independently important function of happy music that fits with a theory of synchronous and rhythmic activity as a social lubricant. More generally, our findings indicate that music and perhaps other atmospheric variables that are designed to prime consumer behavior might have comparably important effects for employees and consequently warrant closer investigation.


Autonomic, behavioral, and neural analyses of mild conditioned negative affect in marmosets.
Avoidance and alerting behaviors and accompanying physiological responses, including changes in heart rate (HR), are core components of negative emotion. Investigations into the neural mechanisms underlying the regulation and integration of these responses require animal models that simultaneously measure both the physiological and behavioral components of emotion. A primate model is of particular importance in view of the well developed prefrontal cortex of primates, and this region's critical role in emotion regulation and the etiology of affective disorders. Therefore, we have developed a simple aversive conditioning paradigm to assess, simultaneously, cardiovascular and behavioral responses in the marmoset (Callithrix jacchus). Validation of the paradigm was achieved by (1) comparing conditioned responses to a predictive cue with pseudoconditioned responses to a nonpredictive cue; (2) assessing the acquisition of conditioning following lesions of the amygdala, a region essential for associative learning in humans and rats; and (3) determining the contributions of the sympathetic and parasympathetic nervous system to the conditioned autonomic responses. Marmosets acquired conditioned HR and behavioral responses in the conditioned, but not the pseudoconditioned or amygdala lesioned groups. Conditioned HR accelerations were reduced by both parasympathetic and sympathetic blockade. Thus, a model of associative learning of mild negative emotion in the marmoset has been validated by psychological, neurological, and pharmacological investigation. Future studies will determine the role of the prefrontal cortex in the regulation of these negative emotional responses, to provide insights into the neuropathology of affective disorders.


New evidence for ATP binding induced catalytic subunit interactions in pig kidney Na/K-ATPase.
Pig kidney Na/K-ATPase preparations showed a positive cooperative effect for pNPP in Na-pNPPase activity. Measurements of the Na-pNPPase activity, Na-ATPase activity and the accumulation of phosphoenzyme (EP) under conditions of pNPP saturation showed several different ATP affinities. The presence of pNPP reduced both the maximum amount of EP and Na-ATPase activity to half showing a value of 4 and a 3,700-fold reduced ATP affinity for EP formation, and a 7 and 1,300-fold reduced affinity for Na-ATPase activity. The presence of low concentrations of ATP in the phosphorylation induced a 2-fold enhancement in Na-pNPPase activity despite a reduction in available pNPP sites. However, higher concentrations of ATP inhibited the Na-pNPPase activity and a much higher concentration of ATP increased both the phosphorylation and Na-ATPase activity to the maximum levels. The maximum Na-pNPPase activity was 1.7 and 3.4-fold higher without and with ATP, respectively, than the maximum Na-ATPase activity. These data and the pNPP dependent reduction in both Na-ATPase activity and the amount of enzyme bound ATP provide new evidence to show that ATP, pNPP and ATP with pNPP, respectively, induce different subunit interactions resulting a difference in the maximum Na(+)-dependent catalytic activity in tetraprotomeric Na/K-ATPase.


Nitric oxide production by cells infiltrating amphibian skin grafts.
In vivo injection of the edible frog Rana esculenta with NOS inhibitor, L-NMMA caused prolongation of skin allograft and xenograft viability, statistically significant only in the latter case. In the present studies skin allo- and xenografts at the latent or rejection phase were excised from the hosts (Bufo bufo, R. temporaria, and R. esculenta) and incubated in vitro for 24 hrs in a medium only or in the presence of competitive (L-NMMA, L-NAME, L-aminoguanidyne) and noncompetitive (dexamethasone and cycloheximide) inhibitors of NO synthesis. In some experiments graft infiltrating cells were washed out and cultured separately from the respective skin fragments. The nitrite level was measured in the culture supernatant using Griess reagent. The nitrite level was negligible in the control skins, autografts, and xenografts depleted of graft infiltrating cells, as well as in allo- and xenografts excised at the rejection phase. In the case of grafts excised at the latent phase, the nitrite amount was substantial in supernatant from allografts and significantly higher in xenografts. A high level of nitrite was also present in supernatants from graft infiltrating cells. It is concluded that the NO contributes to some stages of the rejection process of the anuran skin grafts, this contribution being especially significant in the case of xenografts. The main source of this agent are graft infiltrating phagocytic cells.


Visual optics under the wavefront perspective.
Some intriguing concepts of visual optics cannot be explained by ray tracing. However, they can be clarified using wavefront formalism. Its main advantage is in the use of the concept of vergence, which is very helpful in interpreting the optical phenomena involved in the neutralization of the ametropias. In this line of thinking, the major role of a lens is in the creation of a new light source (the image point) that orientates the refracted waves. Once the nature and position of this source is known, one can easily predict the behavior of the wavefronts. The formalism also allows for an easier understanding on how wavefronts relate to light rays and on how algebraic signs are assigned to optical distances.


Enhanced second-harmonic generation from magnetic resonance in AlGaAs nanoantennas.
We designed AlGaAs-on-aluminium-oxide all-dielectric nanoantennas with magnetic dipole resonance at near-infrared wavelengths. These devices, shaped as cylinders of 400nm height and different radii, offer a few crucial advantages with respect to the silicon-on-insulator platform for operation around 1.55μm wavelength: absence of two-photon absorption, high χ((2)) nonlinearity, and the perspective of a monolithic integration with a laser. We analyzed volume χ((2)) nonlinear effects associated to a magnetic dipole resonance in these nanoantennas, and we predict second-harmonic generation exceeding 10(-3) efficiency with 1GW/cm(2) of pump intensity.


Individual neurons in the caudal fastigial oculomotor region convey information on both macro- and microsaccades.
Recent studies have suggested that microsaccades, the small amplitude saccades made during fixation, are precisely controlled. Two lines of evidence suggest that the cerebellum plays a key role not only in improving the accuracy of macrosaccades but also of microsaccades. First, lesions of the fastigial oculomotor regions (FOR) cause horizontal dysmetria of both micro- and macrosaccades. Secondly, our previous work on Purkinje cell simple spikes in the oculomotor vermis (OV) has established qualitatively similar response preferences for these two groups of saccades. In this work, we investigated the control signals for micro- and macrosaccades in the FOR, the target of OV Purkinje cell axons. We found that the same FOR neurons discharged for micro- and macrosaccades. For both groups of saccades, FOR neurons exhibited very similar dependencies of their discharge strength on direction and amplitude and very similar burst onset time differences for ipsi- and contraversive saccades and, in both, response duration reflected saccade duration, at least at the population level. An intriguing characteristic of microsaccade-related responses is that immediate pre-saccadic firing rates decreased with distance to the target center, a pattern that strikingly parallels the eye position dependency of both microsaccade metrics and frequency, which may suggest a potential neural mechanism underlying the role of FOR in fixation. Irrespective of this specific consideration, our study supports the view that microsaccades and macrosaccades share the same cerebellar circuitry and, in general, further strengthens the notion of a microsaccade-macrosaccade continuum.


First report of powdery mildew on Vigna unguiculata caused by Podosphaera xanthii in China.
Vigna unguiculata belongs to the Legume family, and is an annual twining, herbaceous vine plant, which is native to Africa. V. unguiculata is the most economically beneficial type of off-season vegetables in Hainan, China because of its rich in nutrients such as protein, minerals, dietary fiber, and vitamins (Jayathilake et al. 2018). In April 2022, typical powdery mildew infection was observed on V. unguiculata leaves in Haikou, Hainan Province, China (20°3'40.428"N, 110°19'45.217"E). More than 70% leaves of 13 V. unguiculata plants displayed severe powdery mildew disease. The diseased leaves at first exhibited white rounded irregular patches, which gradually enlarged, fused and covered all the leaf as well as stems. Edges of the infected leaves crinkled upwards, and the leaves often fell off the plants at the late infection stage. On the infected leaves, many conidiophores and dense mycelium were observed by microscopic analysis. Hyphae were septate, branched, epigenous, and flexuous to straight. Hyphal appressoria were indistinct or slightly nipple-shaped, and the haustoria developed were in the shape of oval-sphere and 9 to 11μm long. Foot cells of conidiophores were straight, cylindrical, and measured 43 to 70 × 10 to 12 μm. The conidiophores arising straightly from a hyphal cell, were measured 168 to 252 (mean = 204) μm in length and produced 6 to 9 immature conidia in each chain. Conidia were ovate, pyriform or barrel-shaped, with fibrosin bodies, and measured 26 to 32 (mean = 29.4) × 16 to 20 (mean = 18.6) μm. The chasmothecia was not found in all samples. These morphological characteristics were typical of the conidial stage of the powdery mildew Podosphaera xanthii of genus Podosphaera (Braun and Cook 2012). To further confirm the identity of this causal fungus, the internal transcribed spacer (ITS) region, and the partial sequence of large subunit ribosomal RNA gene (28S rRNA), were amplified with primer pairs ITS1/ ITS4 (White et al. 1990) and NL1/NLP2 (Mori et al. 2000) from extracted genomic DNA. The obtained 563-bp ITS region and 715-bp 28S rRNA gene sequences were deposited in GenBank (ITS, OQ415534; 28S rRNA, OQ415545.1), and were compared with BLAST analysis in the GenBank nr database. The results revealed that the ITS region sequence was 99.82% identity with P. xanthii isolate HUVU-08 (MH143485.1), and the 28S rRNA gene partial sequence was 100% identity with P. xanthii isolate XHL1 (MK357442.1). On the basis of the morphological characteristics and sequence analysis, this fungus was identified as P. xanthii. Pathogenicity tests were performed by gently brushing conidia onto the leaves of six healthy potted V. unguiculata plants. Six non-inoculated plants were used as control. All plants were maintained in a greenhouse at 26 ± 2°C. After 2 weeks inoculation, similar symptoms were observed in the inoculated plants, whereas no symptoms occurred on the control plants. By microscopic observation, the fungus present on the inoculated plants was morphologically identical to those on originally diseased plants. Furthermore, ITS and 28S rRNA sequences of the re-isolated fungus individually displayed 100% identity with OQ415534 and OQ415545.1. So far, although powdery mildew disease caused by P. xanthii on different plants including Sigesbeckia orientalis (Mukhtar et al. 2022), Vigna radiata (Sheu et al. 2021), Cosmos bipinnatus (Kong et al. 2023), Verbena brasiliensis (Luecke et al. 2020), Cucurbita ficifolia (Choi et al. 2022), Glandularia tenera (Pei et al. 2023) and Verbena bonariensis (Choi et al. 2023) have been reported, to our knowledge, this is the first report of powdery mildew caused by P. xanthii on V. unguiculata in Hainan, China, which seriously threatens the utilization of V. unguiculata on off-season vegetables industry.


Seasonal variations in manifestations and activity of systemic lupus erythematosus.
The purpose of the present study was to investigate a possible seasonal pattern in various clinical and laboratory manifestations in a group of systemic lupus erythamatosus (SLE) patients. One hundred and five SLE patients were followed up during a 4 yr period. Data on each of the clinical and laboratory variables examined, as well as the results of the disease activity index (SLEDAI), were plotted against the month during which they were obtained. Photosensitivity was the only variable to show a seasonal pattern, having higher scores during the summer months (1.04 +/- 0.16 in July vs 0.58 +/- 0.12 in December). We were unable to show seasonal patterns in any of the other variables examined. As a group, SLE patients do not show any significant seasonal pattern in disease manifestations and activity, except for photosensitivity. However, such a pattern may exist for the individual patient.


A psychoeducational program to prevent aggressive behavior among Japanese early adolescents.
This study evaluates the impact of a school-based intervention program on aggressive behavior among junior high school students in Japan. One hundred and four seventh-graders were enrolled in the program and completed Time 1, Time 2, and Time 3 surveys. The program was implemented in two classes between Time 1 and Time 2 surveys (the first treatment group) and in two other classes between Time 2 and Time 3 surveys (the delayed treatment group). The program included four weekly lessons related to problem solving, stress management, and communication. The initial intervention group reported a significant increase in appropriate relationships with classmates. Aggressive behavior significantly decreased from Time 1 to Time 3 in both groups and from Time 2 to Time 3 in the delayed treatment group, but no treatment group effect was noted. Additional modification of the program may be needed to achieve decreases in aggressive behavior.


A model of hippocampal spiking responses to items during learning of a context-dependent task.
Single unit recordings in the rat hippocampus have demonstrated shifts in the specificity of spiking activity during learning of a contextual item-reward association task. In this task, rats received reward for responding to different items dependent upon the context an item appeared in, but not dependent upon the location an item appears at. Initially, neurons in the rat hippocampus primarily show firing based on place, but as the rat learns the task this firing became more selective for items. We simulated this effect using a simple circuit model with discrete inputs driving spiking activity representing place and item followed sequentially by a discrete representation of the motor actions involving a response to an item (digging for food) or the movement to a different item (movement to a different pot for food). We implemented spiking replay in the network representing neural activity observed during sharp-wave ripple events, and modified synaptic connections based on a simple representation of spike-timing dependent synaptic plasticity. This simple network was able to consistently learn the context-dependent responses, and transitioned from dominant coding of place to a gradual increase in specificity to items consistent with analysis of the experimental data. In addition, the model showed an increase in specificity toward context. The increase of selectivity in the model is accompanied by an increase in binariness of the synaptic weights for cells that are part of the functional network.


[The solvent-dried dura mater. A new dura transplant in the animal experiment].
After the excision of 7 X 5 mm abdominal muscle sections in an experiment using rats, rehydrated, solvent dried dura grafts of the same size were implanted. After three hours the tissue reaction of the transplant areas were continuously examined under a light and electron microscope for 14 months. A gradual graft decomposition advancing in a coating form from the periphery to the center and a simultaneous replacement with collagenous connective tissue of the body resulted due to an absorbent granulation tissue rich in cells and blood vessels after the initial infiltration of neutrophil granular leukocytes caused by the operation. A fibrous-rich connective tissue plate, in part forming two layers and thereby serving as a reminder of the former dura graft is decomposed in the abdominal muscles of the rats without infection or rejection and replaced with endogenous connective tissue. The duration of this decomposition and transformation process is contingent on the size of the graft and the tissue reactivity in the surrounding transplant area.


Prepregnancy body mass index and gestational weight gain with the outcome of pregnancy: a 13-year study of 292,568 cases in China.
We aimed to investigate the combined associations of prepregnancy body mass index (BMI) and gestational weight gain (GWG) with pregnancy outcomes in Chinese women. Data for 292,568 singleton term pregnancies were selected from 1993 to 2005 based on the Perinatal Health Care Surveillance System, with anthropometric measurements being collected prospectively. Prepregnancy BMI was categorized according to the definitions of the World Health Organization (WHO). Total GWG was categorized into four groups. Adjusted associations of prepregnancy BMI and GWG with outcomes of interest were estimated using logistic regression analyses. GWG was categorized as below, within and above the Institute of Medicine (IOM) (2009) recommendations. Maternal overweight and high GWG or GWG above the IOM recommendation were associated with hypertensive disorders complicating pregnancy, cesarean delivery, macrosomia and large-for-gestational-age (LGA) infants. Maternal underweight and low GWG or GWG below the IOM recommendation were risk factors for low-birth-weight (LBW) and small-for-gestational-age (SGA) infants. Moreover, being overweight [odds ratio (OR) 1.2, 95 % confidence interval (CI) 1.0-1.3) and having a low weight gain (OR 1.1, 95 % CI 1.0-1.1) increased the risk of newborn asphyxia. Being overweight/obese and having a high weight gain, as well as being underweight and having a low weight gain, were associated with increased risks for adverse pregnancy outcomes in Chinese women.


Does physiotherapy after rotator cuff repair require supervision by a physical therapist?: a meta-analysis.
A supervised physiotherapy program (SPP) is a standard regimen after surgical rotator cuff repair (RCR); however, the effect of a home-based exercise program (HEP), as an alternative, on postoperative functional recovery remains unclear. Therefore, the purpose of this meta-analysis was to compare the functional effects of SPP and HEP after RCR. We searched electronic databases including Central, Medline, and Embase in April 2022. The primary outcomes included the Constant score, American Shoulder and Elbow Surgeons score, University of California Los Angeles shoulder score, and pain score. Secondary outcomes included range of motion, muscle strength, retear rate, and patient satisfaction rate. A meta-analysis using random-effects models was performed on the pooled results to determine the significance. The initial database search yielded 848 records, five of which met our criteria. Variables at 3 months after surgery were successfully analyzed, including the Constant score (mean difference, -8.51 points; 95% confidence interval [CI], -32.72 to 15.69; P=0.49) and pain score (mean difference, 0.02 cm; 95% CI, -2.29 to 2.33; P=0.99). There were no significant differences between the SPP and HEP. Other variables were not analyzed owing to the lack of data. Our data showed no significant differences between SSP and HEP with regard to the Constant and pain scores at 3 months after RCR. These results suggest that HEP may be an alternative regimen after RCR. Level of evidence: I.


Stimulated whole-blood cytokine/chemokine responses are associated with interstitial cystitis/bladder pain syndrome phenotypes and features of nociplastic pain: a multidisciplinary approach to the study of chronic pelvic pain research network study.
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a common and debilitating disease with poor treatment outcomes. Studies from the multidisciplinary approach to the study of chronic pelvic pain research network established that IC/BPS patients with chronic overlapping pain conditions (COPCs) experience poorer quality of life and more severe symptoms, yet the neurobiological correlates of this subtype are largely unknown. We previously showed that ex vivo toll-like receptor 4 (TLR4) cytokine/chemokine release is associated with the presence of COPCs, as well as widespread pain and experimental pain sensitivity women with IC/BPS. Here, we attempt to confirm these findings in the multisite multidisciplinary approach to the study of chronic pelvic pain Symptom Patterns Study using TLR4-stimulated whole blood (female IC/BPS patients with COPC n = 99; without n = 36). Samples were collected in tubes preloaded with TLR4 agonist, incubated for 24 hours, and resulting supernatant assayed for 7 cytokines/chemokines. These were subject to a principal components analysis and the resulting components used as dependent variables in general linear models. Controlling for patient age, body mass index, and site of collection, we found that greater ex vivo TLR4-stimulated cytokine/chemokine release was associated with the presence of COPCs ( P < 0.01), extent of widespread pain ( P < 0.05), but not experimental pain sensitivity ( P > 0.05). However, a second component of anti-inflammatory, regulatory, and chemotactic activity was associated with reduced pain sensitivity ( P < 0.01). These results confirm that the IC/BPS + COPCs subtype show higher levels of ex vivo TLR4 cytokine/chemokine release and support a link between immune priming and nociplastic pain in IC/BPS.


The effect of an official match on repeated sprint ability in junior basketball players.
The aim of this study was to investigate the effect of an official basketball match on repeated sprint ability indices in male junior players. Ten (16 ± 1 years old; 183.6 ± 7.0 cm; 76.6 ± 8.0 kg) starting players for their teams performed three repeated sprint ability tests, before, at half-time and immediately after an official match. Each repeated sprint ability test consisted of 10 shuttle-run sprints of 30 m (15 + 15 m) separated by 30 seconds of passive recovery. The matches were video-taped to determine the frequency of eight types of movement patterns, and blood lactate concentration was measured before and immediately after each repeated sprint ability test. Differences in total time, ideal time and percentage decrement between tests was assessed by a one-way analysis of variance (ANOVA) with repeated measures, while a two-way ANOVA with repeated measures was used to identify differences in blood lactate concentration. The main results indicated a significant decrease in total movement frequency (-9.9%), high-intensity activity frequency (-13.3%), run frequency (-13.0%) and sprint frequency (-23.3%) in the second compared to the first half, and significantly worse total time and ideal time at the end of the match, compared to the start and half-time (differences ranging from -2.1% to -2.9%, P < 0.05). The practical implications of these findings suggest that regional basketball players should participate in conditioning sessions that focus on the improvement of repeated sprint ability.


Experimental studies on bacterial product CANTASTIM derived from Pseudomonas aeruginosa. II. Protective effect in Salmonella typhimurium infection.
Stimulation of the host defense system in a nonspecific way may provide effective treatment of recurrent infections. CANTASTIM is a bacterial product that has been successfully used in cancer immunotherapy as well as in chronic infections treatment. The nonspecific protective effect of CANTASTIM was investigated in two models of experimental infection with Salmonella typhimurium in mice. Prophylactic administration of CANTASTIM (three days before challenge) enhanced peritoneal macrophages bactericidal activity and significantly increased survival of treated mice. When CANTASTIM was administered 72 h after bacterial challenge, in a sublethal infection model with Salmonella typhimurium, by activating macrophages, NK and T cells, it increased the survival rate. The cell populations and molecular mechanisms involved in the prophylactic and therapeutic protective effect CANTASTIM seem to be partially different.


Comparative evaluation of human pulp tissue dissolution by different concentrations of chlorine dioxide, calcium hypochlorite and sodium hypochlorite: An in vitro study.
Irrigation plays an indispensable role in removal of tissue remnants and debris from the complicated root canal system. This study compared the human pulp tissue dissolution by different concentrations of chlorine dioxide, calcium hypochlorite and sodium hypochlorite. Pulp tissue was standardized to a weight of 9 mg for each sample. In all,60 samples obtained were divided into 6 groups according to the irrigating solution used- 2.5% sodium hypochlorite (NaOCl), 5.25% NaOCl, 5% calcium hypochlorite (Ca(OCl)2), 10% Ca(OCl)2, 5%chlorine dioxide (ClO2) and 13% ClO2. Pulp tissue was placed in each test tube carrying irrigants of measured volume (5ml) according to their specified subgroup time interval: 30 minutes (Subgroup A) and 60 minutes (Subgroup B). The solution from each sample test tube was filtered and was left for drying overnight. The residual weight was calculated by filtration method. Mean tissue dissolution increases with increase in time period. Results showed 5.25% NaOCl to be most effective at both time intervals followed by 2.5% NaOCl at 60 minutes, 10%Ca(OCl)2 and 13% ClO2 at 60 minutes. Least amount of tissue dissolving ability was demonstrated by 5% Ca(OCl)2 and 5% ClO2 at 30 minutes. Distilled water showed no pulp tissue dissolution. Withinthe limitations of the study, NaOCl most efficiently dissolved the pulp tissue at both concentrations and at both time intervals. Mean tissue dissolution by Ca(OCl)2 and ClO2 gradually increased with time and with their increase in concentration.


A Matter of the Heart: The African Clawed Frog Xenopus as a Model for Studying Vertebrate Cardiogenesis and Congenital Heart Defects.
The African clawed frog, Xenopus, is a valuable non-mammalian model organism to investigate vertebrate heart development and to explore the underlying molecular mechanisms of human congenital heart defects (CHDs). In this review, we outline the similarities between Xenopus and mammalian cardiogenesis, and provide an overview of well-studied cardiac genes in Xenopus, which have been associated with congenital heart conditions. Additionally, we highlight advantages of modeling candidate genes derived from genome wide association studies (GWAS) in Xenopus and discuss commonly used techniques.


Formation and transformation kinetics of amorphous iron(III) oxide during the thermally induced transformation of ferrous oxalate dihydrate in air.
Focusing on the formation and transformation of amorphous Fe(2)O(3) in the course of the thermally induced transformations of ferrous oxalate dehydrate in air, the kinetics and physico-geometric mechanisms of the respective reaction steps were investigated systematically by means of thermoanalytical methods, complemented by other techniques. The final product of α-Fe(2)O(3) is produced by heating the sample to 700 K via intermediates of poorly crystalline anhydrous FeC(2)O(4) and amorphous Fe(2)O(3), where the external shape and size of the original sample particles are retained during the overall course of reactions. The initial parts of all the three distinguished reaction steps, that is, thermal dehydration of crystalline water, oxidative decomposition of anhydrous FeC(2)O(4) and crystallization of amorphous Fe(2)O(3), are controlled kinetically by the formation or reconstruction of the surface product layers. The surface product layers play important roles of regulating the physico-geometric kinetic behavior of the established parts of the reactions. The oxidative decomposition of intermediate anhydrous FeC(2)O(4), characterized as the formation process of amorphous Fe(2)O(3), arrests in the final stage of the reaction. The as-produced amorphous Fe(2)O(3), protected probably by the outer shell of the surface product layer and the residual anhydrous FeC(2)O(3), crystallizes to α-Fe(2)O(3) being induced by the surface crystallization. Aiming to contribute notably toward provision of the establishment of the novel fabrication routes of nanosized iron oxides by the controlled crystallization of amorphous Fe(2)O(3), the possible factors controlling and/or affecting the formation and transformation kinetics of amorphous Fe(2)O(3) were discussed.


Multiple phenotypically distinct smooth muscle cell populations exist in the adult and developing bovine pulmonary arterial media in vivo.
Different smooth muscle cell (SMC) functions may require different cell phenotypes. Because the main pulmonary artery performs diverse functions, we hypothesized that it would contain heterogeneous SMC populations. If the hypothesis were confirmed, we wished to determine the developmental origin of the different populations. Using specific antibodies, we analyzed the expression of smooth muscle (SM) contractile and cytoskeletal proteins (alpha-SM-actin, SM myosin, calponin, desmin, and meta-vinculin) in the main pulmonary artery of fetal (60 to 270 days of gestation), neonatal, and adult animals. We demonstrated the existence of a complex, site-specific heterogeneity in the structure and cellular composition of the pulmonary arterial wall. We found that at least four cell/SMC phenotypes, based on immunobiochemical characteristics, cell morphology, and elastic lamellae arrangement pattern, were simultaneously expressed within the mature arterial media. Further, we were able to assess phenotypic alterations in each of the four identified cell populations during development. We found that each cell population within the arterial media expressed alpha-SM-actin at least at certain stages of development, thus demonstrating its smooth muscle identity. However, each cell population progressed along different developmental pathways, suggesting the existence of multiple and distinct cell lineages. A novel anti-metavinculin antibody described in this study reliably distinguished one SMC population from the others during all the developmental stages analyzed. We conclude that the pulmonary arterial media is indeed composed of multiple phenotypically distinct cell/SMC populations with unique lineages. We speculate that these distinct cell populations may serve different functions within the arterial media and may also respond in unique ways to pathophysiological stimuli.


Hypoglycemia.
Hypoglycemia is a common, potentially avoidable consequence of diabetes treatment and is a major barrier to initiating or intensifying antihyperglycemic therapy in efforts to achieve better glycemic control. Therapy regimen and a history of hypoglycemia are the most important predictors of future events. Other risk factors include renal insufficiency, older age, and history of hypoglycemia-associated autonomic failure. Reported rates of hypoglycemia vary considerably among studies because of differences in study design, definitions used, and population included, among other factors. Although occurring more frequently in type 1 diabetes, hypoglycemia also is clinically important in type 2 diabetes. Symptoms experienced by patients vary among individuals, and many events remain undiagnosed. The incidence of severe events is unevenly distributed, with only a small proportion (∼ 5%) of individuals accounting for >50% of events. Consequently, clinicians must be conscientious in obtaining thorough patient histories, because an accurate picture of the frequency and severity of hypoglycemic events is essential for optimal diabetes management. Severe hypoglycemia in particular is associated with an increased risk of mortality, impairments in cognitive function, and adverse effects on patients' quality of life. Economically, hypoglycemia burdens the healthcare system and adversely affects workplace productivity, particularly after a nocturnal event. Ongoing healthcare reform efforts will result in even more emphasis on reducing this side effect of diabetes treatment. Therefore, improving patients' self-management skills and selecting or modifying therapy to reduce the risk of hypoglycemia will increase in importance for clinicians and patients alike.


Dopaminergic modulation of cortico-cortical functional connectivity in Parkinson's disease: an MEG study.
Recent studies have demonstrated increased resting-state cortico-cortical functional connectivity in untreated Parkinson's disease (PD). We set out to determine whether this connectivity can be modulated by dopamine replacement therapy (DRT) and explore the relationship of therapy-induced changes in connectivity with motor improvement in the relatively early stages of DRT in PD. Whole-head magnetoencephalography was performed in an eyes-closed resting-state condition in 37 patients with levodopa-treated PD (Hoehn and Yahr stages 1-3) both in a practically defined "OFF" and in the "ON" medication state. Data analysis involved calculation of three synchronisation likelihood (SL; a general measure of linear and non-linear temporal correlations between time series) measures which reflect functional coupling within and between ten major cortical areas in five frequency bands. The transition from the "OFF" to the "ON" state led to increases of SL in the 4-30 Hz range, most conspicuously with regard to local SL, in tandem with motor improvement. We found a negative correlation between the change in local beta SL and the reduction of parkinsonism after DRT. Patients presenting with relatively large motor responses (41% or better) actually showed decreases in local beta SL. The present study shows that the already elevated levels of resting-state cortico-cortical functional connectivity in the 4-30 Hz range in mild to moderate PD are on average increased even further by DRT. However, a strong motor response appears to be associated with decreases in local beta-band coupling, which may constitute a risk factor for the development of motor response fluctuations or dyskinesias.


Diagnostic transcatheter aspiration for pulmonary artery tumor embolism using an INARI Triever aspiration catheter.
Pulmonary artery tumor embolism is a rare phenomenon and its diagnosis is important because of a poor prognosis. We report a 20-year-old male with history of metastatic osteosarcoma who presented with acute pulmonary embolism. He was urgently taken to the catheterization laboratory and underwent transcatheter aspiration of pulmonary artery mass using an INARI Triever aspiration catheter. Pathology of the aspirated specimen lead to the diagnosis of pulmonary artery tumor embolism, not thrombus. This case highlights the diagnostic utility of transcatheter aspiration for the pulmonary artery tumor embolism.


[Primary graft dysfunction after lung transplantation].
Lung transplantation is a therapeutic option for pulmonary diseases in which the other treatment options have failed or in cases of rapid disease progression. However, transplantation is not free from complications, and primary graft dysfunction is one of them. Primary graft dysfunction is a form of acute lung injury. It characteristically develops during the immediate postoperative period, being associated to high morbidity and mortality, and increased risk of bronchiolitis obliterans. Different terms have been used in reference to primary graft dysfunction, leading to a consensus document to clarify the definition in 2005. This consensus document regards primary graft dysfunction as non-cardiogenic pulmonary edema developing within 72 hours of reperfusion and intrinsically attributable to alteration of the lung parenchyma. A number of studies have attempted to identify risk factors and to establish the underlying physiopathology, with a view to developing potential therapeutic options. Such options include nitric oxide and pulmonary surfactant together with supportive measures such as mechanical ventilation or oxygenation bypass.


Application of PCR-HRM method for microsatellite polymorphism genotyping in the LDHA gene of pigeons (Columba livia).
High-resolution melting (HRM) is a post-PCR method that allows to discriminate genotypes based on fluorescence changes during the melting phase. HRM is used to detect mutations or polymorphisms (e.g. microsatellites, SNPs, indels). Here, the (TTTAT)3-5 microsatellite polymorphism within intron 6 of the LDHA gene in pigeons was analysed using the HRM method. Individuals (123 homing pigeons) were genotyped using conventional PCR. Birds were classified into groups based on genotype type and the results were tested by qPCR-HRM and verified using sequencing. Based on the evaluated protocol, five genotypes were identified that vary in the number of TTTAT repeat units (3/3, 4/4, 3/4, 4/5, and 5/5). Sequencing have confirmed the results obtained with qPCR-HRM and verified that HRM is a suitable method for identification of three-allele microsatellite polymorphisms. It can be concluded that the high-resolution melting (HRM) method can be effectively used for rapid (one-step) discrimination of the (TTTAT)3-5 microsatellite polymorphism in the pigeon's LDHA gene.


The application of a Web-geographic information system for improving urban water cycle modelling.
Research in urban water management has experienced a transition from traditional model applications to modelling water cycles as an integrated part of urban areas. This includes the interlinking of models of many research areas (e.g. urban development, socio-economy, urban water management). The integration and simulation is realized in newly developed frameworks (e.g. DynaMind and OpenMI) and often assumes a high knowledge in programming. This work presents a Web based urban water management modelling platform which simplifies the setup and usage of complex integrated models. The platform is demonstrated with a small application example on a case study within the Alpine region. The used model is a DynaMind model benchmarking the impact of newly connected catchments on the flooding behaviour of an existing combined sewer system. As a result the workflow of the user within a Web browser is demonstrated and benchmark results are shown. The presented platform hides implementation specific aspects behind Web services based technologies such that the user can focus on his main aim, which is urban water management modelling and benchmarking. Moreover, this platform offers a centralized data management, automatic software updates and access to high performance computers accessible with desktop computers and mobile devices.


Control of T cell function by positive and negative regulators.
T cells are an essential element of the body's immune system. Engagement of the T cell receptor is responsible for initiating the signaling events that can activate, inactivate, or eliminate T cells, depending on the magnitude and duration of the signal. Control of T cell signaling occurs through both positive and negative regulation, as well as through the actions of molecular scaffolds that contribute to the formation of signaling complexes. The T Cell Signal Transduction Pathway at the STKE Connections Maps highlights the molecular components that are responsible for T cell activation. Understanding the mechanisms that regulate T cell responsiveness will aid in the development of therapeutic agents to treat infection, cancer, and autoimmune disease and immune deficiency.


Self-interaction corrected density functional calculations of Rydberg states of molecular clusters: N,N-dimethylisopropylamine.
Theoretical calculations of Rydberg excited states of molecular clusters consisting of N,N-dimethylisopropylamine molecules using a Perdew-Zunger self-interaction corrected energy functional are presented and compared with results of resonant multiphoton ionization measurements. The binding energy of the Rydberg electron in the monomer is calculated to be 2.79 eV and 2.27 eV in the 3s and 3p state, respectively, which compares well with measured values of 2.88 eV and 2.21 eV. Three different stable configurations of the dimer in the ground state were found using an energy functional that includes van der Waals interaction. The lowest ground state energy conformation has the two N-atoms widely separated, by 6.2 Å, while the Rydberg state energy is lowest for a configuration where the N-atoms of the two molecules come close together, separated by 3.7 Å. This conformational change is found to lower the Rydberg electron binding energy by 0.2 eV. The self-interaction corrected functional gives a highly localized hole on one of the two molecules, unlike results obtained using the PBE functional or the hybrid B3LYP functional which give a delocalized hole. For the trimer, the self-interaction corrected calculation gives a Rydberg electron binding energy lowered further by 0.13 eV as compared with the dimer. The calculated results compare well with trends observed in experimental measurements. The reduction of the Rydberg electron binding energy with cluster size can be ascribed to an effective delocalization of the positive charge of the hole by the induced and permanent dipole moments of the neighboring molecules. A further decrease observed to occur on a time scale of tens of ps can be ascribed to a structural rearrangement of the clusters in the Rydberg state where molecules rotate to orient their dipoles in response to the formation of the localized hole.


Syndrome of transient Headache and Neurological Deficits with cerebrospinal fluid Lymphocytosis (HaNDL).
A lady in her late 20s was admitted with a history of headaches and intermittent focal neurological symptoms which were greatly exacerbated by catheter angiography of the cerebral circulation. Cerebrospinal fluid analysis demonstrated a lymphocytic pleocytosis. She subsequently made a spontaneous recovery, without neurological sequelae. Her presentation fits the diagnostic criteria for the previously described syndrome of transient headache and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL). HaNDL is a probably underdiagnosed nosological entity, characterised by often dramatic clinical manifestations but ultimately a good prognosis.


Development of orofacial praxis of children from 4 to 8 years of age.
Orofacial praxis is the ability to plan and execute movements or sequences of voluntary movements, meaningful or not, using the muscles of the pharyngo-buccofacial system or the orofacial region. An original test was developed, the Orofacial Praxis Test, consisting of 36 gestures, 24 single and 12 complex, elicited through verbal and imitative request. The test was administered to 93 normally developing Italian children ages 4 to 8 yr. to assess development of orofacial praxis. Analysis showed a progressive development of the orofacial praxic ability by type of gesture and examiner's request: (1) the imitation modality is more facilitating than a verbal request modality, especially for children ages 4 or 5 years; (2) a consistent mastery of sequences of gestures and oroverbal movements is in place by age 6 years. The analysis of the orofacial region may be helpful in identifying persistent speech difficulties and developmental coordination disorders.


[Perception of parental attitudes and the level of female adolescents' self-esteem affected with anorexia nervosa].
The article's aim is to look for correlation between a parent - child relationship and the level of self-esteem in the perception of girls affected with anorexia nervosa (who meet the criteria of DSM-IV-TR). The differences in the perception of parental attitudes (of mothers and fathers) and self-esteem of girls suffering from anorexia nervosa and their healthy peers were also analyzed. Two equally numbered groups of girls: the clinical group (30 persons affected with anorexia nervosa) and control group (30 healthy girls) in the 15-20 age range were examined. Two test were applied: Parent-Child Relations Questionnaire (PCR) A. Roe and M. Siegelman in the authorized translation by W. S. Kowalski to investigate characteristic behavior of parents of small children as perceived by youth or adults and a Questionnaire "What are you like?" by P. Sears in adaptation of J. Kostrzewski, which is used to study self-esteem. The results confirmed the expected relationship between perception of parental attitudes and the level of self-esteem of girls affected with anorexia nervosa. Parental attitudes characterized by love and protection promote higher self-esteem of their daughters and the experience of higher demands and rejection by both parents lowers their self-esteem. The comparison of average attitudes of mothers and fathers in perception of their daughters diagnosed with anorexia nervosa did not confirm significant statistical differences. Comparison of maternal attitudes in the perception of their daughters from the group affected by anorexia and the healthy group revealed significant differences in full range of attitudes. The differences in perception of the attitudes of their fathers were statistically substantial regarding the attitudes concerning love and rejection. Self-esteem of persons treated for anorexia is significantly lower than of their healthy peers.


Uremia causes endothelial progenitor cell deficiency.
Circulating bone marrow-derived endothelial progenitor cells (EPCs) promote vascular repair. Their number in peripheral blood correlates with endothelial function and cardiovascular risk in humans. We explored whether uremia influences the number of EPCs. We assessed circulating CD34+ hematopoietic progenitor cells in whole blood using flow cytometry and EPCs (in vitro assay) in 46 patients with advanced renal failure and in 46 age- and gender-matched healthy subjects. Further, the effect of uremia on EPC differentiation was studied in vitro and in vivo. Both in renal patients (r= 0.34, P < 0.02) and in healthy subjects (r= 0.32, P= 0.04) the number of EPCs was significantly correlated to the absolute number of CD34+ hematopoietic progenitor cells. Renal patients had significantly fewer EPCs than healthy subjects, however (167 +/- 15 cells/high power field vs. 235 +/- 17 cells/high power field; P < 0.05). Uremic serum significantly (P < 0.05) inhibited EPC differentiation and functional activity in vitro. Amelioration of uremia after institution of renal replacement therapy in patients with terminal renal failure also significantly (P < 0.05) increased the number of EPCs. Uremia inhibits differentiation of EPCs. This may impair cardiovascular repair mechanisms in patients with renal failure.


Interaction of low-energy electrons with the purine bases, nucleosides, and nucleotides of DNA.
The authors report results from computational studies of the interaction of low-energy electrons with the purine bases of DNA, adenine and guanine, as well as with the associated nucleosides, deoxyadenosine and deoxyguanosine, and the nucleotide deoxyadenosine monophosphate. Their calculations focus on the characterization of the pi* shape resonances associated with the bases and also provide general information on the scattering of slow electrons by these targets. Results are obtained for adenine and guanine both with and without inclusion of polarization effects, and the resonance energy shifts observed due to polarization are used to predict pi* resonance energies in associated nucleosides and nucleotides, for which static-exchange calculations were carried out. They observe slight shifts between the resonance energies in the isolated bases and those in the nucleosides.


Striking similarity in the gene expression levels of individual Myc module members among ESCs, EpiSCs, and partial iPSCs.
Predominant transcriptional subnetworks called Core, Myc, and PRC modules have been shown to participate in preservation of the pluripotency and self-renewality of embryonic stem cells (ESCs). Epiblast stem cells (EpiSCs) are another cell type that possesses pluripotency and self-renewality. However, the roles of these modules in EpiSCs have not been systematically examined to date. Here, we compared the average expression levels of Core, Myc, and PRC module genes between ESCs and EpiSCs. EpiSCs showed substantially higher and lower expression levels of PRC and Core module genes, respectively, compared with those in ESCs, while Myc module members showed almost equivalent levels of average gene expression. Subsequent analyses revealed that the similarity in gene expression levels of the Myc module between these two cell types was not just overall, but striking similarities were evident even when comparing the expression of individual genes. We also observed equivalent levels of similarity in the expression of individual Myc module genes between induced pluripotent stem cells (iPSCs) and partial iPSCs that are an unwanted byproduct generated during iPSC induction. Moreover, our data demonstrate that partial iPSCs depend on a high level of c-Myc expression for their self-renewal properties.


Possible involvement of circulating fibroblast growth factor 23 in the development of secondary hyperparathyroidism associated with renal insufficiency.
Fibroblast growth factor 23 (FGF-23) is a recently identified polypeptide that promotes renal phosphate excretion and decreases serum 1,25-dihydroxyvitamin D3 (1,25D) levels. Serum FGF-23 levels are extraordinarily elevated in patients with end-stage renal failure. Blood and urine samples were obtained from 62 predialysis patients (age, 51.3 +/- 14.0 years; range, approximately 18 to 76 years; 32 men, 30 women). Serum FGF-23 levels were determined by means of a sandwich enzyme-linked immunosorbent assay system using 2 kinds of monoclonal antibodies that does not detect biologically inactive N-terminal and C-terminal fragments derived from an identified internal cleavage site to date. Serum FGF-23 levels increased with the decrease in creatinine clearance (Ccr). Both intact parathyroid hormone (PTH) and 1-84 PTH levels correlated closely with FGF-23 levels (r2 = 0.857; r2 = 0.860). A negative correlation between serum concentrations of FGF-23 and 1,25D (r2 = 0.255) was found. The maximum tubular reabsorptive rate of phosphate correlated negatively with serum FGF-23 concentrations (r2 = 0.460). However, the amount of daily urinary phosphate excretion was significantly less in patients with a Ccr less than 30 mL/min (<0.50 mL/s; P < 0.01), whereas their circulating FGF-23 levels were significantly greater (P < 0.001). Circulating FGF-23 levels increase with the decrease in renal function. FGF-23 is a likely candidate to lead the reduction in serum 1,25D levels. FGF-23 becomes a potential uremic toxin to decrease 1,25D levels when it loses its hypophosphatemic action because of a decreased number of viable nephrons in patients with advanced renal failure. As such, FGF-23 may be an important determinant in the regulation of mineral metabolism with renal insufficiency.


Physiological study of pH stability and sensitivity to pepsin of human gastric lipase.
The aim of this study was to exactly determine the pH stability of human gastric lipase (HGL) and to investigate the mechanism underlying the inactivation of HGL which occurs in gastric juice. Samples of human gastric juice and purified HGL were incubated at various pH values ranging from 0.5 to 8.0, and the residual HGL activity was measured as a function of time using the pHstat technique. Samples of purified HGL were also incubated in the presence of human pepsin. Electrophoresis and Western blot analysis were performed on all the samples in which HGL was inactivated. HGL was found to be stable in gastric juice at pH values ranging from 2.0 to 7.0, especially between pH 3.0 and 5.0 (half-inactivation time >24 h). HGL activity decreased rapidly below pH 2.0 and above pH 7.0. The inactivation half times were only 43 +/- 9 and 24 +/- 18 min at pH 1 and pH 8, respectively. The pH stability of purified HGL was much lower than that of HGL in gastric juice. Acid or alkaline inactivation of HGL could occur without any prior proteolytic degradation, and this inactivation was irreversible. However, proteolytic degradation of HGL by pepsin also occurred at very low pH values, probably because the acid-denatured HGL is more sensitive to proteolytic cleavage by pepsin. An ex vivo study of HGL activity in several gastric juice samples showed that the HGL activity decreased with the pH of the sample, in both basal and pentagastrin-stimulated gastric juice. Although HGL is not as stable as it was previously thought to be under acidic conditions, it is nevertheless the most stable acid lipase and constitutes a good candidate tool for enzyme substitution therapy.


[What is established in the therapy of kidney diseases?].
The established therapy for glomerular disorders of the kidney is outlined in a short review. Before initiating therapy, the physician must decide if the underlying disease is of primary or secondary type. The nephrotic syndrome and progressive renal insufficiency can result in both conditions. The necessary dietary and pharmacological principles in the therapy of these syndromes are discussed. Finally, the clinical and therapeutic aspects of secondary glomerulopathy are described with selected examples.


Septuagenarian Sydenham's with secondary hypomania.
A 74-year-old man with a remote history of Sydenham's chorea but no personal or family history of mood disorder had simultaneous onset of severe, generalized chorea and a mild manic syndrome in clear consciousness. Both chorea and hypomania improved after treatment with sodium valproate and clonazepam. Agitated delirium or mood lability have been described in Sydenham's, but this case is the first report of criteria-based secondary mania with probable Sydenham's chorea, as well as the longest reported remission between symptomatic Sydenham's episodes. The parallel course of this patient's hypomania and chorea supports current pathophysiologic theories of idiopathic mania.


[Unusual aspects in the creative pictures of a retarded, ineducable boy].
Drawings and sculptures of an 11-year-old retarded boy are presented, who was not capable of school education. His low-level of lingual-logic thinking contrasts with his almost age-corresponding capability of optic differentiation. His pictorial creations are impressive in their accurate presentation of animals, which are reminiscent of the artistic figures of paleolithic big game hunters. Parallels with the paleolithic hunting magics as characterized by Mirimanow are obvious. The presentation of men in the form of acting head-feeters might be based on an undifferentiated idea of their own body, of partially disabled children with impaired sensorial recognition.


MR angiography of the aortic arch vessels and upper extremities.
MR angiography of the aortic arch vessels and upper extremities is a noninvasive alternative to conventional catheter angiography without the risks of stroke or the potential toxicity of iodinated contrast. The use of optimized, breath hold gadolinium-enhanced three-dimensional MR angiography provides excellent image quality with the capability of display options not available with conventional angiography. This article demonstrates the utility of this new technique in the diagnosis of congenital and acquired conditions of the supraaortic vascular system.


Autoantibody production by patients infected with Leishmania.
Sera from 29 patients with visceral leishmaniasis and 14 patients with cutaneous leishmaniasis were tested against a panel of nine nuclear antigens employing an enzyme-linked immunosorbent assay (ELISA). Anti- Sm, RNP, SS-A and SS-B antibodies were present in high titres in 83, 86, 36 and 73 per cent of the patients with visceral leishmaniasis and in 7, 14, 25 and 25 per cent of the patients with cutaneous leishmaniasis. One serum from a patient with visceral leishmaniasis which reacted strongly with Sm, RNP, SS-A and SS-B was examined by immunoblotting on extractable nuclear antigen from Hela cells. This serum binds to nine different antigenic bands (16, 23, 29, 30, 40, 50, 58, 100 and 115 kD). These same antigens were recognized by serum from a patient with systemic lupus erythematosus. The binding of visceral leishmaniasis serum antibodies to ribonucleoproteins was inhibited by prior incubation of serum with either leishmanial membrane antigens, from four different species of Leishmania, or intact cells of Leishmania donovani, implying molecular resemblance between common leishmanial antigens and ribonuclear antigens. It seems that appearance of autoantibodies to ribonucleoproteins in sera of patients infected with Leishmania is not only due to simply polyclonal activation of lymphocytes, but is also the result of a molecular mimicry between leishmanial antigens and ribonucleoproteins.


Georeferenced evaluation of genetic breeding value patterns in Brazilian Holstein cattle.
The aim of this study was to analyze the relationship between environmental and genetic values for milk production and type traits in Holstein cattle in Brazil. The genetic value of 65,383 animals for milk production and 53,626 for type classification were available. Socioeconomic and environmental data were obtained from the Brazilian Institute of Geography and Statistics, the Food and Agriculture Organization of the United Nations, the National Aeronautics and Space Administration, and the National Institute of Meteorology. Five to six clusters were generated for each of the groups of type traits and production levels. The relationships between these traits were assessed using the STEPDISC, DISCRIM and CANDISC procedures in SAS(®). Traits within the clusters behaved differently, but, in general, animals with lower genetic values were found in environments that were more stressful for animal production. These differences were mainly associated with temperature, humidity, precipitation and the Normalized Difference Vegetative Index. Genetic values for milk production showed best discrimination between different environments, while type traits showed poor discrimination, possibly because farmers mainly select for milk production. Environmental variations for genetic values in dairy cattle in Brazil should be further examined.


Differences between the Craig's test and computed tomography in measuring femoral anteversion in patients with anterior cruciate ligament injuries.
[Purpose] This study aimed to compare the Craig's test and computed tomography (CT) in measuring the femoral anteversion angle (FAA) in patients with anterior cruciate ligament (ACL) injuries. The relationship between the FAA measured on CT, and the range of axial rotation of the hip joint and muscle tightness around the hip joint was also investigated. [Participants and Methods] Twenty-six patients who received CT examination within 3 months after ACL reconstruction were enrolled in this study. The Craig's test, internal and external rotation of the hip, the Ely test, Ober's test, and FAA on the CT were assessed. [Results] The FAA on the Craig's test and CT in female patients was 24.3 ± 3.9° and 23.0 ± 10.3°, respectively on the uninjured side and 25.0 ± 5.2° and 20.3 ± 11.2°, respectively on the injured side, indicating no significant correlation between the 2 measurement techniques. In contrast, the FAA on the CT was significantly correlated with the range of internal rotation of the hip, which was 40.5 ± 6.1° on the uninjured side and 37.8 ± 5.6° on the injured side. [Conclusion] The results suggest that measuring the internal hip rotation range rather than the Craig's test, provides more reliable estimates of the magnitude of FAA, and may help to evaluate the risk of ACL injuries in female athletes.


Transcription factor SP1 mediates hyperglycemia-induced upregulation of roundabout4 in retinal microvascular endothelial cells.
Roundabout4 (Robo4) is a gene that is expressed specifically in vasculature and is involved in the angiogenesis and integrity of blood vessels. The expression level of Robo4 increases gradually along with the development of diabetic retinopathy (DR). In this study, we explored the mechanism of transcriptional regulation of Robo4 in retinal endothelial cells, and investigated the effects of this regulation on cellular functions under hyperglycemic conditions. Human retinal endothelial cells (HREC) exposed to hyperglycemia were used to detect the expression levels of specificity protein 1 (SP1) and Robo4 by RT-qPCR and western blotting. Small interfering RNA (SiRNA) transfection technology was used to analyze the regulatory relationship between SP1 and Robo4. The effect of transcription factor SP1 on Robo4 promoter activity and the location of SP1 binding sites were investigated using chromatin immunoprecipitation (ChIP) and luciferase assay. Cell migration, monolayer permeability and tube formation assays were performed to demonstrate the role of SP1/Robo4 in regulating HREC functions in hyperglycemic conditions. The results showed that hyperglycemia upregulated the mRNA and protein levels of SP1 and Robo4 in HREC. Depletion of SP1 by siRNA transfection inhibited the hyperglycemia induced overexpression of Robo4. ChIP combined with luciferase assay showed that under hyperglycemic conditions, SP1 significantly increased the transcriptional level of Robo4 via an additional SP1 binding site at -1912/-1908 in the Robo4 promoter. Repressing the SP1/Robo4 pathway effectively mitigated the abnormity in HREC migration, permeability and angiogenesis induced by hyperglycemia. All these findings indicate that hyperglycemia-induced upregulation of Robo4 is mediated by enhanced transcription of SP1. The SP1/Robo4 signaling pathway can regulate the migratory ability, monolayer permeability and angiogenesis of HREC under hyperglycemic conditions, suggesting that it may play an important role in microvascular dysfunction during DR.


Sub-high Temperature and High Light Intensity Induced Irreversible Inhibition on Photosynthesis System of Tomato Plant (Solanum lycopersicum L.).
High temperature and high light intensity is a common environment posing a great risk to organisms. This study aimed to elucidate the effects of sub-high temperature and high light intensity stress (HH, 35°C, 1000 μmol⋅m-2⋅s-1) and recovery on the photosynthetic mechanism, photoinhibiton of photosystem II (PSII) and photosystem I (PSI), and reactive oxygen (ROS) metabolism of tomato seedlings. The results showed that with prolonged stress time, net photosynthetic rate (Pn), Rubisco activity, maximal photochemistry efficiency (Fv/Fm), efficient quantum yield and electron transport of PSII [Y(II) and ETR(II)] and PSI [Y(I) and ETR(I)] decreased significantly whereas yield of non-regulated and regulated energy dissipation of PSII [Y(NO) and Y(NPQ)] increased sharply. The donor side limitation of PSI [Y(ND)] increased but the acceptor side limitation of PSI [Y(NA)] decreased. Content of malondialdehyde (MDA) and hydrogen peroxide (H2O2) were increased while activity of superoxide dismutase (SOD) and peroxidase (POD) were significantly inhibited compared with control. HH exposure affected photosynthetic carbon assimilation, multiple sites in PSII and PSI, ROS accumulation and elimination of Solanum lycopersicum L.


Novel diagnostic assays for heparin-induced thrombocytopenia.
Laboratory testing for heparin-induced thrombocytopenia (HIT) has important shortcomings. Immunoassays fail to discriminate platelet-activating from nonpathogenic antibodies. Specific functional assays are impracticable due to the need for platelets and radioisotope. We describe 2 assays that may overcome these limitations. The KKO-inhibition test (KKO-I) measures the effect of plasma on binding of the HIT-like monoclonal antibody KKO to platelet factor 4 (PF4)/heparin. DT40-luciferase (DT40-luc) is a functional test comprised of a B-cell line expressing FcγRIIa coupled to a luciferase reporter. We compared these assays to polyspecific and immunoglobulin (Ig)G-specific PF4/heparin enzyme-linked immunosorbent assays (ELISAs) in samples from 58 patients with suspected HIT and circulating anti-PF4/heparin antibodies. HIT was defined as a 4Ts score ≥ 4 and positive (14)C-serotonin release assay. HIT-positive plasma demonstrated greater mean inhibition of KKO binding than HIT-negative plasma (78.9% vs 26.0%; P < .0001) and induced greater luciferase activity (3.14-fold basal vs 0.96-fold basal; P < .0001). The area under the receiver-operating characteristic curve was greater for KKO-I (0.93) than for the polyspecific (0.82; P = .020) and IgG-specific ELISA (0.76; P = .0044) and for DT40-luc (0.89) than for the IgG-specific ELISA (P = .046). KKO-I and DT40-luc showed better discrimination than 2 commercially available immunoassays, are simple to perform, and hold promise for improving the specificity and feasibility of HIT laboratory testing.


Permeation energetics in a model potassium channel.
Known structures of selective ion channels share a common property: a narrow constriction, presumably crucial for ionic discrimination. This region can be fairly long, imposing single file motion on waters and ion(s). We apply the semi-microscopic Monte Carlo approach to study permeation in the KcsA channel, decomposing energetics into a three-step process: cation dehydration; ion transfer into a uniform low epsilon dielectric; and transfer from the uniform dielectric into the channel. The influence of individual channel structural features is separately assessed. The aqueous cavity has only a modest stabilizing effect on nearby ions in the filter. Ionic solvation in the filter reflects the combined influence of the single file waters, the binding pockets' carbonyls, the alpha helices directed at the cavity and the negative residues near the extracellular surface of the channel; no one feature dominates. At all sites along the permeation pathway there is substantial discrimination favouring K+ over Na+; conversely, there is little discrimination among the larger alkali cations. Selectivity for K+ over Na+ appears due to the inability of the filter's carbonyl oxygens to ideally coordinate Na+.


Sublethal contaminant exposure alters behavior in a common insect: important implications for trophic transfer.
This study examined the effects of sub-lethal exposure of the ubiquitous pesticide malathion on the behavior of the model orthopteran species, the house cricket (Acheta domesticus). Increasing concentrations of malathion caused male crickets to increase periods of non-directional movement, such as twitching and grooming, directional movement, and to seek out shelter less. These are all behavioral alterations that may increase the cricket's chances of being preyed upon, and thus have the potential for serious ecological consequences through trophic transfer. This study also revealed that female crickets appeared to be less affected by malathion than their male conspecifics, indicating a potential sex-bias in both susceptibility and possible predator attack.


An Innovative Approach for Biocontrol of Meloidogyne incognita in Ginger Using Potential Bacteria Isolated from Indian Himalayas.
The prevalence of Meloidogyne incognita, a severe root-knot nematode, is alarmingly high in the production of ginger-a main cash crop of Himachal Pradesh, a Himalayan state of India. In order to control this through natural means, the nematicidal potential of plant growth-promoting rhizobacteria (PGPR) against M. incognita was analyzed. This is an effective alternative solution to manage nematode incidence as compared to hazardous chemicals under protected and field cultivation of ginger. In the present study an attempt has been made to isolate, characterize, and identify potential rhizobacteria associated with ginger rhizosphere and endosphere. In total, 169 bacterial isolates were isolated from ginger (Zingiber officinale) rhizosphere and endosphere of 4 different sites of Sirmaur district, screened out for multifarious PGP traits showing positive results. The combined cluster analysis and 16S rRNA genotypic analysis of selected bacterial isolates revealed that Serratia marcescens FS-23, Pseudochrobacter sp. GS-15, Stonotrophomonas pavanii HER-9, Pseudomonas brassicacearum HER-20 and Serratia marcescens IS-2 exhibited highest PGP traits. All tested bacterial isolates were capable of exerting a significant effect on mortality of juvenile M. incognita ranging upto 40-90% in laboratory experiments. Further a consortium of these screened isolates showed 86.67% reduction in gall formation by M. incognita in lab conditions. The remarkable increase to 93.24% with 138.73 q/ha with application of charcoal based bio-formulation of consortium without adding any chemical fertilizer was observed in field trials of Nohradhar of Sirmaur district. An alternative choice as a biocontrol agent as well as for PGP activities, the novel and most robust isolate Serratia marcescens IS-2 had revealed to have a variety of bioactive metabolic products with abilities against nematodes, bacteria, and fungi.


GM-CSF expression is preferential to multi-CSF (IL-3) expression in murine T lymphocyte clones.
The expression of the lymphokines GM-CSF and Multi-CSF (IL-3) has been studied in three IL-2-dependent CD4+ T lymphocyte clones. By contrast with the widely held view that lymphokine genes are coordinately expressed, the present study revealed a marked preference for GM-CSF compared with Multi-CSF expression. Preferential expression of GM-CSF was evident in a number of situations: early after stimulation via the T cell antigen receptor; in a proportion of low-producing cells of a clone; and in response to IL-2. There was a clear hierarchy of the three clones studied, each being ranked in the same order in all situations, suggesting that a common mechanism underlies each phenomenon. The possibility that the GM-CSF gene is responsive to lower doses of intercellular signal than the Multi-CSF gene was rendered unlikely, since in only one clone was GM-CSF preferentially expressed at low doses of stimulus. Since GM-CSF expression occurred more rapidly after stimulation, the possibility that Multi-CSF expression is dependent upon that of GM-CSF was considered. However, GM-CSF production was neither necessary nor sufficient for Multi-CSF expression: A retroviral construct expressing a GM-CSF cDNA was introduced into one of the clones, leading to constitutive GM-CSF expression, but Multi-CSF expression was not induced. The possibility is discussed that Multi-CSF expression is dependent on transcriptional activation of the GM-CSF locus and that positive feedback occurs between these two tightly linked genes at the chromosomal level.


Effective chemotherapy for esophageal cancer with methotrexate, bleomycin, and cis-diamminedichloroplatinum II.
Ten patients with squamous cancer of the esophagus were treated with an outpatient regimen combining cis-diamminedichloroplatinum (II), methotrexate and bleomycin. Nine of these had metastatic disease or recurrence after radiotherapy. Objective responses were noted in 50%, regardless of performance status or metastatic site. None of three patients with prior radiation therapy responded, however. Median duration of response was six months. Responders survived a median of eight months versus five months for nonresponders. Three patients had severe hematologic toxicity. A single patient with massive disease confined to the esophagus had an excellent response to six weeks of chemotherapy before radical irradiation. He is disease-free after two years but is paraplegic from radiation myelitis. This chemotherapy program is an effective palliative therapy for metastatic esophageal cancer. Its safety and efficacy as part of the initial treatment of local disease should be further investigated.


Skew-normal/independent linear mixed models for censored responses with applications to HIV viral loads.
Often in biomedical studies, the routine use of linear mixed-effects models (based on Gaussian assumptions) can be questionable when the longitudinal responses are skewed in nature. Skew-normal/elliptical models are widely used in those situations. Often, those skewed responses might also be subjected to some upper and lower quantification limits (QLs; viz., longitudinal viral-load measures in HIV studies), beyond which they are not measurable. In this paper, we develop a Bayesian analysis of censored linear mixed models replacing the Gaussian assumptions with skew-normal/independent (SNI) distributions. The SNI is an attractive class of asymmetric heavy-tailed distributions that includes the skew-normal, skew-t, skew-slash, and skew-contaminated normal distributions as special cases. The proposed model provides flexibility in capturing the effects of skewness and heavy tail for responses that are either left- or right-censored. For our analysis, we adopt a Bayesian framework and develop a Markov chain Monte Carlo algorithm to carry out the posterior analyses. The marginal likelihood is tractable, and utilized to compute not only some Bayesian model selection measures but also case-deletion influence diagnostics based on the Kullback-Leibler divergence. The newly developed procedures are illustrated with a simulation study as well as an HIV case study involving analysis of longitudinal viral loads.


Parental eligibility and enrollment in state children's health insurance program: the roles of parental health, employment, and family structure.
We examined eligibility and enrollment among parents of children in New Jersey's State Children's Health Insurance Program following expansion of parental eligibility for NJ FamilyCare coverage. Data were from the 2003 NJ FamilyCare Family Health Survey (n = 416 families). Parental eligibility was higher in households without a full-time employed parent (odds ratio [OR] = 5.50; 95% confidence interval [CI] = 2.72, 11.14) and lower among single parents (OR = 0.38; 95% CI = 0.23, 0.61). Enrollment was higher among single parents (OR = 2.24; 95% CI = 1.17, 4.31). Roughly one third of eligible parents did not enroll, suggesting the need to increase awareness of parental eligibility and reduce barriers to enrollment.


Roentgenographically occult lung cancer: pathologic findings and frequency of multicentricity during a 10-year period.
During the first 10 years of the Mayo Lung Project, 68 roentgenographically inapparent ("occult") lung cancers were localized and apparently completely resected. A pathologic classification was developed based on depth of tumor infiltration. The five categories were (1) in situ carcinoma confined to surface epithelium or ducts of mucous glands or acini (23 cancers), (2) intramucosal invasion not greater than 0.1 cm from mucosal surface (12 cancers), (3) invasion to bronchial cartilages (11 cancers), (4) invasion to full thickness of bronchial wall (10 cancers), and (5) extrabronchial invasion (12 cancers). Multicentricity of lung cancer was studied in 54 patients, none of whom had a history of cancer of the respiratory tract, and all of whom had had "complete" surgical resection of the initial occult lung cancer (or cancers). Neoplasms that were initially multicentric occurred in 4 patients, and a subsequent primary lung cancer developed in 11. The rate of detection of second primary lesions was 42 per 1,000 person-years of observation. A high incidence of unresectable cancers and a low survival rate were noted among patients who had a subsequent primary tumor. These findings were primarily attributable to invasiveness of the subsequent primary cancer or to respiratory insufficiency that resulted from obstructive lung disease or previous pulmonary resection. Because of the high risk of development of a second primary cancer after initial surgical resection, it is important to treat the initial occult cancer as conservatively as possible consistent with "cure."


Tolerance to LSD and DOB induced shaking behaviour: differential adaptations of frontocortical 5-HT(2A) and glutamate receptor binding sites.
Serotonergic hallucinogens, such as lysergic acid diethylamide (LSD) and dimethoxy-bromoamphetamine (DOB), provoke stereotype-like shaking behaviour in rodents, which is hypothesised to engage frontocortical glutamate receptor activation secondary to serotonin2A (5-HT2A) related glutamate release. Challenging this hypothesis, we here investigate whether tolerance to LSD and DOB correlates with frontocortical adaptations of 5-HT2A and/or overall-glutamate binding sites. LSD and DOB (0.025 and 0.25 mg/kg, i.p.) induce a ketanserin-sensitive (0.5 mg/kg, i.p., 30-min pretreatment) increase in shaking behaviour (including head twitches and wet dog shakes), which with repeated application (7× in 4 ds) is undermined by tolerance. Tolerance to DOB, as indexed by DOB-sensitive [(3)H]spiroperidol and DOB induced [(35)S]GTP-gamma-S binding, is accompanied by a frontocortical decrease in 5-HT2A binding sites and 5-HT2 signalling, respectively; glutamate-sensitive [(3)H]glutamate binding sites, in contrast, remain unchanged. As to LSD, 5-HT2 signalling and 5-HT2A binding, respectively, are not or only marginally affected, yet [(3)H]glutamate binding is significantly decreased. Correlation analysis interrelates tolerance to DOB to the reduced 5-HT2A (r=.80) as well as the unchanged [(3)H]glutamate binding sites (r=.84); tolerance to LSD, as opposed, shares variance with the reduction in [(3)H]glutamate binding sites only (r=.86). Given that DOB and LSD both induce tolerance, one correlating with 5-HT2A, the other with glutamate receptor adaptations, it might be inferred that tolerance can arise at either level. That is, if a hallucinogen (like LSD in our study) fails to induce 5-HT2A (down-)regulation, glutamate receptors (activated postsynaptic to 5-HT2A related glutamate release) might instead adapt and thus prevent further overstimulation of the cortex.


Challenges for the formulation, implantation and implementation of a National Health Surveillance Policy in Brazil.
This article examines the evolution of health surveillance policies as actions, models and systems, as well as contributing to the debate about the constitution of the National Health Surveillance Policy (PNVS). The article discusses conceptual elements regarding the notion of health surveillance and its evolution in Brazil and a trajectory is provided in relation to the construction of care models, particularly after the creation of the Unified Health System (SUS). The possibility of using the framework of public policies based on evidence, and methods for analyzing health situations, such as spatial analysis and time series, are highlighted. To conclude, questions are raised regarding the effective creation of the PNVS, and the challenges that the federal executive faces in driving this process.