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[Botulinum toxin in the treatment of frontoglabellar and periorbital wrinkles. An initial study].

Glabellar frown lines and crow's feet are wrinkles of facial expression related to an underlying muscular activity, which is particularly strong during facial expression. Classic treatments of these wrinkles only give partially satisfactory are associated with results, and secondary effects, whether they involve skin and muscle lifting, surgical section of muscles, dermal stimulation by thread or injectable fillers, chemical or mechanical abrasion, transient or permanent soft tissue augmentation with various materials. The authors studied the efficacy and safety of intramuscular injections botulinum A Exotoxin in glabellar and crow's feet areas in 19 well-informed and consenting patients. Botulinum toxin injections have been used since 1980 in the treatment of focal dystonia (blepharospasm, oromandibular dystonia, spasmodic torticollis, spasmodic dysphonia and writer's cramp) and safety hemifacial spasm. Their wide use in these indications has highlighted their excellent and efficacy, and the need to repeat injections every 3 to 4 months. The dose required was progressively adjusted around glabellar and orbital areas, while injections of the peri-buccal and forehead areas are still being evaluated. The 19 patients were examined clinically, filmed and photographed every month over a period of 12 to 24 months, and skin prints were performed. Evaluation criteria included the percentage improvement as assessed by the patients themselves, and also evaluation by the investigators of the data of clinical examination, and blind comparison of photographic, videoscopic, and prints. The authors obtained a significant decrease of wrinkles of the areas studied, with a "smoothing" effect during the period of activity of the toxin, which lased an average of 3 to 4 months at the beginning, and 6 to 9 months after several injections. No secondary effects, either general or local, were observed. The product's specificity means that the operator must have a complete mastery of the injection technique and a thorough knowledge of its pharmacology.

Adult↗

The high cost of a nutritionally adequate diet in four Yukon communities.

The cost of purchasing a nutritionally adequate diet in four Yukon communities was examined, based on the 46 food items and quantities of the federal government's Northern Food Basket. In Old Crow, unit purchase prices were on average 250% of those in Edmonton, while in three southern Yukon communities, unit purchase prices were about 125% of those in Edmonton. In quantities needed to meet weekly nutrient needs of a family of four, the cost in Old Crow was 320% of that in Edmonton, while in three southern Yukon communities, it was 140%. It appears that due to financial necessity, Yukon aboriginal people need continuing access to traditional food resources (wild game animals, birds, fish and berries). Since the Northern Food Basket does not include any traditional foods, it alone is of limited acceptability to these people. The high cost of marketed food and the role of traditional foods in contemporary diets should be considered in giving dietary advice and in determining food allowances in social assistance programs.

Adolescent↗

[Erythrocyte superoxide dismutase (eSOD) determination in positive moments of psychosis].

Dysregulation of free radical metabolism has been supposed to be involved in schizophrenia etiopathogeny. Recently, Wang et al. showed a red blood cell super oxide dismutase increase in positive schizophrenia (Crow's type I), but neither in negative schizophrenia (Crow's type II) nor in controls. The study included 28 in-patients suffering from acute positive psychosis who were compared with 15 controls. We confirmed the results of Wang. We found a significantly red blood cell Super oxide dismutase increase in positive psychosis, in comparison to negative psychosis and controls (p = 0.0001). This SOD increase was in relationship with the degree of clinical psychomotor excitement. After 21 days of neuroleptic treatment, SOD activity decreased and reached standard values. These results support the hypothesis of striking relationships between catecholaminergic hyper-metabolism and SOD increase, in positive psychosis. These could account for psychotic positive symptoms improvement with neuroleptic treatment, which blocks dopamine pathways.

Adult↗

Teaching and learning needs of culturally diverse post-R.N. students.

Despite the multicultural nature of our country, Canadian schools of nursing have generally attracted white middle-class females. The literature has identified many of the difficulties culturally diverse students experience in coping with and completing their program. The reasons noted for these difficulties include differences in learning styles, with culturally diverse students preferring visual learning (Crow, 1993; More, 1989); differences in language aptitude, particularly for those students whose first language is not English (Bowker, 1992; Harrison, 1992; Phillips & Hartley, 1990); differences in communication style (Wax & Thomas, 1961); lack of role models and social support within their cultural group (Bowker, 1992; Edwards, Smith, & French, 1989; Sedlacek, 1983); and a lack of understanding among faculty and other students regarding their lifestyles, backgrounds, and belief systems (Abu-Saad, Kaysar-Jones, & Gutierrez, 1981; Crow, 1993; Harrison, 1992).

Adaptation, Psychological↗

[Genetico-demographic characteristics of the population from three districts of the Bryansk region].

Results of genetic demographic investigation of three nations located in west Bryanskaya oblast (Klintsovskii, Klimovskii, and Starodubskii nations) are presented. A comparison is made with respect to a number of demographic parameters of "southern" (Krasnodar) and "northern" (Kirov) Russian populations. A low level of the Crow index, which is associated with a differential mortality rate, Im = 0.07, was established in the population studied. This fact significantly distinguishes the population of Bryanskaya oblast from other studied Russian populations. With respect to sex and age structure and the Crow index, the Bryansk population is comparable to the southern Krasnodar population, while in terms of level of isolation and inbreeding, the Bryansk population is similar to the northern Kirov population. Moreover, it was found that the Chernobyl meltdown in 1986 did not lead to any change in the genetic demographic situation in the three studied nations.

Demography↗

Location of the handedness gene on the X and Y chromosomes.

Accumulated data from five handedness surveys show that concordance for sex is slightly but reliably higher among siblings of the same handedness than among those of opposite handedness. This is consistent with Crow's theory that the genetic locus for handedness is in an X-Y homologous region of the sex chromosomes. The small size of the effect is predicted from genetic models in which there is a substantial random component underlying phenotypic left handedness. The findings are relevant to the putative role of cerebral asymmetry in the aetiology of psychosis.

Chromosome Mapping↗

Participation of primary motor cortical neurons in a distributed network during maze solution: representation of spatial parameters and time-course comparison with parietal area 7a.

Traditionally, primary motor cortex (M1) has been thought to be involved solely in planning and generating movements. Recent evidence suggests that the arm area of M1 plays a role in other functions, such as the representation of serial order (Pellizzer et al. 1995, Science 269:702-705; Carpenter et al. 1999, Science 283:1752-1757) and spatial processing (Georgopoulos et al. 1989, Science 243:234-236). Previous studies of such cognitive processes have used tasks in which a directed arm movement was required, raising a question as to whether this brain area is involved in cognitive processing per se, or whether such cognitive signals may be gated into the arm area of M1 only when arm movements are required. To study this question, we developed a task that required a spatial analysis of a complex visual stimulus, but required no arm movement as a response. In this task, monkeys were shown an octagonal maze. After an imposed delay of 2 to 2.5 s, they indicated whether a path that emanated from the center of the maze exited at the perimeter (exit maze) or terminated within the maze (no-exit maze) by pressing a pedal with their left or right foot, respectively. We recorded from 785 cells from the arm area of M1 from two monkeys during the delay period of the maze task. We found that cell activity was influenced by both the exit status and the direction of the path, beginning soon after the maze was displayed. This activity was not related to the activation of arm muscles, suggesting that the directional signals observed represented abstract spatial aspects of maze processing. Finally, we compared maze-related activity of M1 neurons with those recorded from posterior parietal area 7a, reported previously (Crowe et al. 2004). Interestingly, cells from each area exhibited similar properties. Both the exit status and path direction were encoded by cells in M1 and 7a, although to different extents. An analysis of the time-course of the neural representation of these factors revealed that area 7a and M1 begin to encode these factors at the same time, suggesting these brain areas are part of a distributed system performing the spatial computations involved in maze solution.

Action Potentials↗

Studies on the excitability of the central program generator in the spinal cord of the terrapin Pseudemys scripta elegans.

We present observations on the multicyclic scratch reflex in spinal terrapins as produced by electrical stimuli applied to the shell at the specific regions at which a mechanical stimulus produces the reflex. EMGs and hip and knee movements are recorded. The responses to the electrical stimuli are similar to the responses to mechanical stimuli. There is a three phase EMG pattern (Stein and Grossman, 1980), to which the movement pattern is related (Bakker and Crowe, 1982). A response may consist of a series of up to 25 movement cycles with a total time course of up to about 30 sec. The initial cycles of a response are relatively fast (less than 1 sec), but the cycles at the expiration of the response may have a duration of 2-3 sec. A single electrical stimulus pulse is often insufficient to trigger a series response. Instead, a weak EMG burst of a few tenths of a second duration, together with a slight movement, is often seen. However, a second pulse can set the cycle series in motion even after an interval of 40 sec between the pulses. A further booster stimulus pulse given while a reflex response is taking place can increase the speed of the movement. If the booster pulse is given just after cessation of reflex activity it can restart the activity, but this second cycle series is often shorter than the first one. The results indicate that the excitability of the central program generator is not constant. Long duration changes in the excitability are produced within the spinal cord.

Animals↗

A single optimum degree of hemispheric specialisation in two tasks, in two UK national birth cohorts.

How differences between the two sides of the brain (or 'laterality') relate to level of function are important components of theories of the origin and purpose of hemispheric asymmetry, although different measures show different relationships, and this heterogeneity makes discerning any underlying relationships a difficult task. There are some exceptions, for example it has been concluded that increasing lateralization (eg of hand skill or planum temporale area) occurs at the expense of the non-dominant hemisphere. However, we have previously demonstrated this latter relationship to be an artefact: a consequence of plotting two variables against each other, that are not independent of each other [Leask, S. J., & Crow, T. J. (1997) How far does the brain lateralize? An unbiased method for determining the optimum degree of hemispheric specialisation. Neuropsychologia, 36, 1275-1282; Mazoyer, B. M., & Tzourio-Mazoyer, N. G. (2004). Title Planum temporale asymmetry and models of dominance for language: a reappraisal. Neuroreport, 15, 1057-1059]. Two approaches to discerning any underlying relationships are presented in data from over 20,000 10- and 11-year olds from the 1958 and 1970 UK national cohort studies. These demonstrate that maximal performance, both cognitive and hand function, is found in association with one particular degree of functional lateralization.

Adolescent↗

Phospholipid vesicles increase the survival of freeze-dried human red blood cells.

In a previous report [Z. Török, G. Satpathy, M. Banerjee, R. Bali, E. Little, R. Novaes, H. Van Ly, D. Dwyre, A. Kheirolomoom, F. Tablin, J.H. Crowe, N.M. Tsvetkova, Preservation of trehalose loaded red blood cells by lyophilization, Cell Preservation Technol. 3 (2005) 96-111.], we presented a method for preserving human red blood cells (RBCs) by loading them with trehalose and then freeze-drying. We have now improved that method, based on the discovery that addition of phospholipid vesicles to the lyophilization buffer substantially reduces hemolysis of freeze-dried RBCs after rehydration. The surviving cells synthesize 2,3-DPG, have low levels of methemoglobin, and have preserved morphology. Among the lipid species we studied, unsaturated PCs were found to be most effective in suppressing hemoglobin leakage. RBC-vesicle interactions depend on vesicle size and structure; unilamellar liposomes with average diameter of less than 300 nm were more effective in reducing the hemolysis than multilamellar vesicles. Trehalose loaded RBCs demonstrated high survival and low levels of methemoglobin during 10 weeks of storage at 4 degrees C in the dry state when lyophilized in the presence of liposomes.

2,3-Diphosphoglycerate↗

Host cell killing by the West Nile Virus NS2B-NS3 proteolytic complex: NS3 alone is sufficient to recruit caspase-8-based apoptotic pathway.

The West Nile Virus (WNV) non-structural proteins 2B and 3 (NS2B-NS3) constitute the proteolytic complex that mediates the cleavage and processing of the viral polyprotein. NS3 recruits NS2B and NS5 proteins to direct protease and replication activities. In an effort to investigate the biology of the viral protease, we cloned cDNA encoding the NS2B-NS3 proteolytic complex from brain tissue of a WNV-infected dead crow, collected from the Lower Merion area (Merion strain). Expression of the NS2B-NS3 gene cassette induced apoptosis within 48 h of transfection. Electron microscopic analysis of NS2B-NS3-transfected cells revealed ultra-structural changes that are typical of apoptotic cells including membrane blebbing, nuclear disintegration and cytoplasmic vacuolations. The role of NS3 or NS2B in contributing to host cell apoptosis was examined. NS3 alone triggers the apoptotic pathways involving caspases-8 and -3. Experimental results from the use of caspase-specific inhibitors and caspase-8 siRNA demonstrated that the activation of caspase-8 was essential to initiate apoptotic signaling in NS3-expressing cells. Downstream of caspase-3 activation, we observed nuclear membrane ruptures and cleavage of the DNA-repair enzyme, PARP in NS3-expressing cells. Nuclear herniations due to NS3 expression were absent in the cells treated with a caspase-3 inhibitor. Expression of protease and helicase domains themselves was sufficient to trigger apoptosis generating insight into the apoptotic pathways triggered by NS3 from WNV.

Amino Acid Sequence↗

Apoptosis repressor with caspase recruitment domain protects against cell death by interfering with Bax activation.

Myocardial ischemia/reperfusion (I/R) is associated with an extensive loss of myocardial cells. The apoptosis repressor with caspase recruitment domain (ARC) is a protein that is highly expressed in heart and skeletal muscle and has been demonstrated to protect the heart against I/R injury (Gustafsson, A. B., Sayen, M. R., Williams, S. D., Crow, M. T., and Gottlieb, R. A. (2002) Circulation 106, 735-739). In this study, we have shown that transduction of TAT-ARCL31F, a mutant of ARC in the caspase recruitment domain, did not reduce creatine kinase release and infarct size after I/R. TAT-ARCL31F also failed to protect against hydrogen peroxide-mediated cell death in H9c2 cells, suggesting that the caspase recruitment domain is important in mediating ARC's protective effects. In addition, we report that ARC co-immunoprecipitated with the pro-apoptotic protein Bax, which causes cytochrome c release when activated. TAT-ARC, but not TAT-ARCL31F, prevented Bax activation and cytochrome c release in hydrogen peroxide-treated H9c2 cells. TAT-ARC was also effective in blocking cytochrome c release after ischemia and reperfusion, whereas TAT-ARCL31F had no effect on cytochrome c release. In addition, recombinant ARC protein abrogated Bax-induced cytochrome c release from isolated mitochondria. This suggests that ARC can protect against cell death by interfering with activation of the mitochondrial death pathway through the interaction with Bax, preventing mitochondrial dysfunction and release of pro-apoptotic factors.

Animals↗

An update on the potential of north American mosquitoes (Diptera: Culicidae) to transmit West Nile Virus.

ABSTRACT Since first discovered in the New York City area in 1999, West Nile virus (WNV) has become established over much of the continental United States and has been responsible for >10,000 cases of severe disease and 400 human fatalities, as well as thousands of fatal infections in horses. To develop appropriate surveillance and control strategies, the identification of which mosquito species are competent vectors and how various factors influence their ability to transmit this virus must be determined. Therefore, we evaluated numerous mosquito species for their ability to transmit WNV under laboratory conditions. This report contains data for several mosquito species not reported previously, as well as a summary of transmission data compiled from previously reported studies. Mosquitoes were allowed to feed on chickens infected with WNV isolated from a crow that died during the 1999 outbreak in New York City. These mosquitoes were tested approximately 2 wk later to determine infection, dissemination, and transmission rates. All Culex species tested were competent vectors in the laboratory and varied from highly efficient vectors (e.g., Culex tarsalis Coquillett) to moderately efficient ones (e.g., Culex nigripalpus Theobald). Nearly all of the Culex species tested could serve as efficient enzootic or amplifying vectors for WNV. Several container-breeding Aedes and Ochlerotatus species were highly efficient vectors under laboratory conditions, but because of their feeding preferences, would probably not be involved in the maintenance of WNV in nature. However, they would be potential bridge vectors between the avian-Culex cycle and mammalian hosts. In contrast, most of the surface pool-breeding Aedes and Ochlerotatus species tested were relatively inefficient vectors under laboratory conditions and would probably not play a significant role in transmitting WNV in nature. In determining the potential for a mosquito species to become involved in transmitting WNV, it is necessary to consider not only its laboratory vector competence but also its abundance, host-feeding preference, involvement with other viruses with similar transmission cycles, and whether WNV has been isolated from this species under natural conditions.

Animals↗

Avian virulence and thermostable replication of the North American strain of West Nile virus.

The NY99 genotype of West Nile virus (WNV) introduced into North America has demonstrated high virulence for American crows (AMCRs), whilst a closely related WNV strain (KEN-3829) from Kenya exhibits substantially reduced virulence in AMCRs [Brault, A. C., Langevin, S. A., Bowen, R. A., Panella, N. A., Biggerstaff, B. J., Miller, B. R. & Nicholas, K. (2004). Emerg Infect Dis 10, 2161-2168]. Viruses rescued from infectious cDNA clones of both the NY99 and KEN-3829 strains demonstrated virulence comparable to that of their parental strains in AMCRs. To begin to define parameters that might explain the different virulence phenotypes between these two viruses, temperature-sensitivity assays were performed for both viruses at the high temperatures experienced in viraemic AMCRs. Growth curves of the two WNV strains were performed in African green monkey kidney (Vero; 37-42 degrees C) and duck embryonic fibroblast (DEF; 37-45 degrees C) cells cultured at temperatures that were tolerated by the cell line. Unlike the NY99 virus, marked decreases in KEN-3829 viral titres were detected between 36 and 120 h post-infection (p.i.) at temperatures above 43 degrees C. Replication of KEN-3829 viral RNA was reduced 6500-fold at 72 h p.i. in DEF cells incubated at 44 degrees C relative to levels of intracellular virus-specific RNA measured at 37 degrees C. In contrast, replication of virus derived from the NY99 infectious cDNA at 44 degrees C demonstrated only a 17-fold reduction in RNA level. These results indicated that the ability of WNV NY99 to replicate at the high temperatures measured in infected AMCRs could be an important factor leading to the increased avian virulence and emergence of this strain of WNV.

Animals↗

The conformation of the mature dimeric human immunodeficiency virus type 1 RNA genome requires packaging of pol protein.

The packaging of a mature dimeric RNA genome is an essential step in human immunodeficiency virus type 1 (HIV-1) replication. We have previously shown that overexpression of a protease (PR)-inactive HIV-1 Gag-Pro-Pol precursor protein generates noninfectious virions that contain mainly monomeric RNA (M. Shehu-Xhilaga, S. M. Crowe, and J. Mak, J. Virol. 75:1834-1841, 2001). To further define the contribution of HIV-1 Gag and Gag-Pro-Pol to RNA maturation, we analyzed virion RNA dimers derived from Gag particles in the absence of Gag-Pro-Pol. Compared to wild-type (WT) dimeric RNAs, these RNA dimers have altered mobility and low stability under electrophoresis conditions, suggesting that the HIV-1 Gag precursor protein alone is not sufficient to stabilize the dimeric virion RNA structure. The inclusion of an active viral PR, without reverse transcriptase (RT) and integrase (IN), rescued the stability of the virion RNA dimers in the Gag particles but did not restore the mobility of the RNAs, suggesting that RT and IN are also required for virion RNA dimer maturation. Thin-section electron microscopy showed that viral particles deficient in RT and IN contain empty cone-shaped cores. The abnormal core structure indicates a requirement for Gag-Pro-Pol packaging during core maturation. Supplementing viral particles with either RT or IN via Vpr-RT or Vpr-IN alone did not correct the conformation of the dimer RNAs, whereas expression of both RT and IN in trans as a Vpr-RT-IN fusion restored RNA dimer conformation to that of the WT virus and also restored the electron-dense, cone-shaped virion core characteristic of WT virus. Our data suggest a role for RT-IN in RNA dimer conformation and the formation of the electron-dense viral core.

Cell Line↗

Schizophrenia and temporal lobe asymmetry. A post-mortem stereological study of tissue volume.

BACKGROUND: A previous report by Crow of a left-sided increase in temporal horn volume in schizophrenia implies a left-sided loss of tissue. AIMS: To elucidate the structural nature of schizophrenia. METHOD: The volume of grey matter in the temporal pole and inferior, middle and superior temporal gyri was measured, in addition to the total volume of grey and white matter, in the temporal lobes of the brains of 29 patients with schizophrenia and 27 controls. RESULTS: We found a significant left-sided reduction in the superior temporal gyrus in both males and females with schizophrenia, which was related to increasing age of onset in the males. The total volume of temporal lobe grey and white matter was also significantly reduced. Although being more marked on the left than the right, the lateralisation for these total grey and white measures (by contrast with the superior temporal gyrus alone) did not attain formal statistical significance. CONCLUSIONS: Confirmation of a lateralised reduction in the superior temporal gyrus, which is differentially related to age of onset according to gender, adds to evidence that the changes in schizophrenia are in systems that are lateralised. The findings implicate language as the relevant function.

Adult↗

Evaluation of a model of adjustment to an iatrogenic hepatitis C virus infection.

OBJECTIVE: The aim of this study was to evaluate a model of adjustment to an iatrogenic hepatitis C(HCV) infection in a cohort of women. PARTICIPANTS: Eighty-three women diagnosed with an iatrogenic HCV infection were recruited; 49 women had chronic infection (PCR positive) and the remaining 34 women were considered to have a self-limiting HCV infection (PCR negative). MEASURES: The Hepatitis C Survey Questionnaire (HCSQ; Coughlan, Sheehan, Carr, & Crowe, unpublished) and the General Health Questionnaire (GHQ30; Goldberg & Williams, 1988) were used in this study. RESULTS: Structural equation modelling (SEM) was carried out to evaluate and modify a recursive path model using Moos and Schaefer's (1984) model of coping with illness as the basis for developing a multivariate model of adjustment to an iatrogenic HCV infection. The final model fit, chi(2)(30) = 21.9 p =.86, CFI = 1.00, RMSEA = 0.000, was judged to be theoretically acceptable, indicating that positive illness appraisal, ability to work and negative behaviour as a consequence of feelings of anger and blame are directly related to adjustment. CONCLUSION: This model has provided support for the following general relationships, namely that, adjustment to an iatrogenic HCV infection is related to: (1) illness and social factors; (2) cognitive appraisals; (3) adaptive tasks; and (4) coping skills thus emphasizing the need to develop a biopsychosocial model of treatment.

Adaptation, Psychological↗

Rapid West Nile virus antigen detection.

We compared the VecTest WNV antigen assay with standard methods of West Nile virus (WNV) detection in swabs from American Crows (Corvus brachyrhynchos) and House Sparrows (Passer domesticus). The VecTest detected WNV more frequently than the plaque assay and was comparable to a TaqMan reverse transcription-polymerase chain reaction.

Animals↗