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Botox for the eyes and eyebrows.

The forehead and crow's-feet (periorbital wrinkles) are among areas where Botox has been quite helpful. This cosmetic use is not approved by the Food and Drug Administration and is considered off-label. The effect, although temporary, is extremely popular with patients, has a very low incidence of side effects, and is a relatively easy technique to acquire.

Botulinum Toxins, Type A↗

External fixation of Charcot arthropathy.

Deformity, instability, and ulceration are present in a high percentage of patients who have Charcot arthropathy. Traditional treatment of these conditions has consisted of debridement, antibiotics, and immobilization with limited weight bearing. These measures are followed by long-term use of various foot and ankle bracing devices, such as the CROW walker, double metal upright, and the lined clam shell AFO with accommodative footwear either incorporated or attached. Sometimes these conservative measures fail and surgery is indicated for foot and ankle deformities with: (1) unbraceable deformity; (2) recurrent ulceration secondary to deformity, instability, or both; and (3) Charcot arthropathy with pain that is unresponsive to conservative measures. Certain acute traumatic situations with impending deformity also may benefit from early surgical stabilization. High deep infection rates (25%) have been reported in surgical reconstruction of feet that have a history of ulceration. The high rates of infection with internal fixation techniques and improved external fixation devices have led surgeons to consider external fixation as a viable alternative for: (1) singlestage correction of a limb with recent or current ulceration; (2) revision or salvage of previously reconstructed limbs; and (3) acute treatment of insufficiency type fractures (impending Charcot arthropathy) in the diabetic who has severe peripheral neuropathy with or without adjuvant internal fixation.

Arthropathy, Neurogenic↗

Skin ageing: a comparison between Chinese and European populations. A pilot study.

BACKGROUND: Although limited data are available, it is commonly considered that Europeans and Asians have different skin ageing features. OBJECTIVES: The present studies have been carried out to evaluate the influence of age and sun-exposure on the main clinical signs of Asian skin ageing. METHODS: One hundred and sixty Chinese and 160 French age-matched women (age range: 20-60 years old) were clinically examined and scored by the same dermatologist. Facial wrinkles (crow's-feet, glabella and perioral wrinkles) and pigmented spots (on face and hands) were assessed in situ and standardized photographs of the face were taken. Lifelong sun-exposure was estimated from answers to a questionnaire. Comparisons were made between 10-year age groups. RESULTS: Results show that, for each facial skin area, wrinkle onset is delayed by about 10 years in Chinese women as compared to French women. Facial wrinkling rate over the years is linear in French women and not linear in Chinese women who appear to experience a fast ageing process between age 40 and 50. Pigmented spot intensity is a much more important ageing sign in Chinese women (severe for 30% of women over 40) than in French women (severe for less than 8% of women, irrespective of age). CONCLUSION: These first results underline that main skin ageing features (wrinkles, spots) progress differently in the Chinese and French women we have studied. They require to be confirmed on broad multicentre studies involving larger cohorts.

Adult↗

Safety beliefs and safe behavior among midwestern college students.

PROBLEM: This study investigated the impact of safety beliefs on safe behavior and the effect of age, gender, class standing, and geographic region on these beliefs and behaviors. It also compares the level of safety beliefs and safe behavior of Midwestern college students in 1993 to those in 2002. METHOD: A total of 1,059 undergraduate students at four Midwestern universities completed the 33-item questionnaire developed by Crowe (J. Saf. Res. 26 (1995) 187) during the spring semester of 2002. RESULTS: Significant main effects for gender and age on safety beliefs and safe behavior were found as well as a significant interaction between gender and age for both outcome variables. The regression model with the independent variables of personal responsibility and gender yielded a multiple R of.58, which explained 34% of the variance of the self-reported safe behavior. Midwestern college students in 2002 were found less safety-conscious in terms of self-reported safety beliefs and safe behavior than those in 1993. DISCUSSION: The findings indicate that safety education of adolescents and young adults in the United States has not been effective, at least for the last decade, or today's social and school environment is less conducive to the students' safe behavior and beliefs than a decade ago. IMPACT ON INDUSTRY: Proactive multidisciplinary approaches to enhance safe behavior and beliefs of young adults should be made based on critical evaluation of current approaches.

Adolescent↗

Genetic diversity and genetic burden in humans.

We discuss categories of genetic diversity in humans. Neutral diversity, population differences in frequencies of genetic markers that we think are invisible to natural selection, provides a passive record of population history but is otherwise of little interest in human biology. Genetic variation related to disease can be separated into mutational noise and variation due to selection, either ongoing selection else effects of a past environment. We distinguish consequences of genetic diversity for fitness, relevant to evolution, and consequences for well-being, relevant to medicine and public health. We call genetic variation that causes impairment of health or well-being of individual humans "apparent genetic burden" and variation that has effects on fitness but not well-being "unapparent genetic burden". We use "burden" to distinguish these notions from the classical concept of "genetic load" that refers to effects on population fitness, a concept formulated by Morton et al. [Morton, N.E., Crow, J.F., Muller, H.J., 1956. An estimate of the mutational damage in man from data on consanguineous marriages. Proc. Natl. Acad. Sci. U.S.A. 42, 855-863]. We distinguish adapted genes and adapted genotypes: an adapted gene is a gene that increases fitness of its bearer either in heterozygous or homozygous state or both, while an adapted genotype is a genotype that increases fitness of its bearer but is not transmitted intact to future generations. Balanced polymorphisms in which the heterozygote is superior in fitness may generate most adapted genotypes. In the face of major rapid environmental change adapted genotypes appear first but over time they are replaced by adapted genes. The presence of adapted genotypes is a good indication of recent environmental change: for example, there are apparently many polymorphisms in domestic animals of this nature, responses to domestication, and many fewer in wild animals (and in humans).

Alleles↗

Schizophrenia-an evolutionary enigma?

The term 'schizophrenia' refers to a group of disorders that have been described in every human culture. Two apparently well established findings have corroborated the need for an evolutionary explanation of these disorders: (1) cross-culturally stable incidence rates and (2) decreased fecundity of the affected individuals. The rationale behind this relates to the evolutionary paradox that susceptibility genes for schizophrenia are obviously preserved in the human genepool, despite fundamental reproductive disadvantages associated with the disorders. Some researchers have therefore proposed that a compensatory advantage must exist in people who are carriers of these genes or in their first-degree relatives. Such advantages were hypothesised to be outside the brain (e.g. greater resistance against toxins or infectious diseases), or within the social domain (e.g. schizotypal shamans, creativity). More specifically, T.J. Crow has suggested an evolutionary theory of schizophrenia that relates the disorders to an extreme of variation of hemispheric specialisation and the evolution of language due to a single gene mutation located on homologous regions of the sex chromosomes. None of the evolutionary scenarios does, however, fully account for the diversity of the symptomatology, nor does any one hypothesis acknowledge the objection that the mere prevalence of a disorder must not be confused with adaptation. In the present article, I therefore discuss the evolutionary hypotheses of schizophrenia, arguing that a symptom-based approach to psychotic disorders in evolutionary perspective may improve upon the existing models of schizophrenia.

Adaptation, Biological↗

No association between the serotonin 1B receptor gene and schizophrenia in a case-control and family-based association study.

Previous studies have demonstrated that polymorphisms in the putative promoter region of the human serotonin receptor 1B (HTR1B) gene affect gene expression [H.F. Sun, Y.T. Chang, C.S. Fann, C.J. Chang, Y.H. Chen, Y.P. Hsu, W.Y. Yu, A.T. Cheng, Association study of novel human serotonin 5-HT(1B) polymorphisms with alcohol dependence in Taiwanese Han, Biol. Psychiatry 51 (2002) 896-901; J. Duan, A.R. Sanders, J.E. Molen, L. Martinolich, B.J. Mowry, D.F. Levinson, R.R. Crowe, J.M. Silverman, P.V. Gejman, Polymorphisms in the 5'-untranslated region of the human serotonin receptor 1B (HTR1B) gene affect gene expression, Mol. Psychiatry 8 (2003) 901-910]. And the silent mutation G861C allele has been reported to be associated with several psychiatric disorders. Thus, we performed a case-control association study (456 cases and 557 controls) of the five variants in HTR1B gene (T-261G, -182INS/DEL-181, A-161T, C129T and G861C) with schizophrenia. The results showed that neither the allelic distribution nor the major haplotype distribution (except for a rare haplotype) of five SNPs in patients was significantly different from that in controls. A further family-based association study (229 family trios) of G861C allele suggested that HTR1B was not a susceptible gene with schizophrenia in our sample. In conclusion, these data do not support the idea that HTR1B gene plays a major role in the etiopathogenesis of schizophrenia in Chinese Han population.

Adult↗

Development of H5-RT-LAMP (loop-mediated isothermal amplification) system for rapid diagnosis of H5 avian influenza virus infection.

We developed a rapid and sensitive diagnosis system for H5N1 highly pathogenic avian influenza (HPAI) virus infection using an unique gene amplification method, reverse transcriptase loop-mediated isothermal amplification (RT-LAMP). The sensitivity of the system was found to be 100-fold higher than that of ordinary one-step RT-PCR. Moreover, by using viral RNAs extracted from influenza viruses of all 15 HA subtypes, the RT-LAMP system was confirmed to amplify only the RNA of H5 subtype virus. In the surveillance of H5N1 virus infection of wild birds, we detected two positive cases from dead crows found near the affected area with H5N1-HPAI by using RT-LAMP system, although one of two positive cases was missed by RT-PCR. These results suggested that our newly developed RT-LAMP system specific for H5 virus would be a beneficial diagnostic tool for surveillance of recent outbreaks caused by H5N1-HPAI viruses.

Animals↗

The occurrence and characterization of Campylobacter jejuni and C. coli in organic pigs and their outdoor environment.

The occurrence and species distribution of thermophilic Campylobacter was investigated in organic outdoor pigs. An increased exposure of outdoor pigs to C. jejuni from the environment may cause a shift from a normal dominance of C. coli to more C. jejuni, which may imply a concern of reduced food safety. Bacteriological methods for determination of Campylobacter excretion level were combined with colony-blot hybridization and real-time PCR for specific detection of C. jejuni in pigs. Campylobacter was isolated from pigs (n=47), paddock environment (n=126) and wildlife (n=44), identified to species by real-time PCR and sub-typed by serotyping (Penner) and pulse-field gel electrophoresis (PFGE) genotyping. All pigs excreted Campylobacter (10(3)-10(7) CFU g(-1) faeces) from the age of 8-13-weeks old. C. jejuni was found in 29% of pigs in three consecutive trials and always in minority to C. coli (0.3-46%). C. jejuni and C. coli were isolated from 10% and 29% of the environmental samples, respectively, while crow-birds and rats harboured C. jejuni. Individual pigs hosted several strains (up to nine serotypes). The paddock environment was contaminated with C. coli serotypes similar to pig isolates, while most of the C. jejuni serotypes differed. C. jejuni isolates of different origin comprised few similar serotypes, just one identical genotype was common between pigs, environment and birds. In conclusion, the occurrence of C. jejuni varied considerably between the three groups of outdoor pigs. Furthermore, transfer of C. jejuni to the outdoor pigs from the nearby environment was not predominant according to the subtype dissimilarities of the obtained isolates.

Animal Husbandry↗

Japanese domesticated chickens have been derived from Shamo traditional fighting cocks.

With the aim of elucidating the evolutionary origin of Japanese domesticated chickens, this study evolutionarily analyzed 85 chicken mtDNA sequences. Thirty-four various ornamental chickens, 42 fighting cocks (Shamo), and nine long-crowing chickens (Naganakidori) were included. Of the Shamo, 18 were sampled from Okinawa, while the remaining 24 were collected in other islands around Japan. In addition, three Southeast Asian Junglefowls were used as a reference to determine the common ancestor of Japanese domesticated chickens. A phylogenetic tree was constructed for the 88 mtDNA sequences revealing that the Shamo group from Okinawa clearly diverged from the other Japanese domesticated chickens studied. This strongly suggests that all Japanese domesticated chickens, including the ornamental varieties and Naganakidori, derived from the ancestors of the Shamo in Okinawa. To create novel varieties of ornamental chickens, intensive artificial selection is imposed on ancestral Shamo populations, resulting in profoundly differentiated Japanese domesticated chickens.

Animals↗

Vertical banded gastroplasty as an antireflux procedure.

Vertical banded gastroplasty creates a channel by two applications of the TA-90 stapler from an end-to-end anastomosis window above the crow's foot to the angle of His, against a 32 F. tube along the lesser curvature. The caudad end of the channel is restricted by a 5 cm collar. Thirty-one obese patients more than 45 kg overweight were studied by interview, barium swallow, endoscopy, and manometry. These procedures were repeated 13 +/- 5.5 weeks postoperatively, after resolution of operative edema and before extensive weight loss. Preoperative symptoms included heartburn in 24 patients, regurgitation in 17 patients, and aspiration in 2 patients, and barium swallow demonstrated hiatal hernia in 7 patients and reflux in 7 patients (5 with hiatal hernia). In addition, endoscopy detected mild esophagitis in 3 patients, and hiatal hernia in 11 patients. Postoperatively, the incidence of heartburn decreased in all patients, barium swallow showed slow channel emptying but no hiatal hernia or reflux, and endoscopy did not identify any esophagitis. Preoperative lower esophageal sphincter pressure was 14.5 +/- 7.2 mm Hg. Postoperatively, the vertical banded gastroplasty channel had an initial peak (collar) pressure of 19.2 +/- 7.8 mm Hg (p less than 0.01 compared with preoperative lower esophageal sphincter pressure), a channel pressure of 9.5 +/- 6 mm Hg, a lower esophageal sphincter pressure of 20.1 +/- 7.7 mm Hg (p less than 0.005), and a channel length of 6.8 +/- 1.4 cm. Vertical banded gastroplasty creates a high pressure channel, inhibiting reflux of gastric juice without the need for any additional procedure.

Adult↗

Detection of monoclonal proteins by capillary electrophoresis using a zwitterion in the running buffer.

Some cases have been reported in which a small monoclonal protein (M-protein) cannot be detected by conventional cellulose acetate membrane electrophoresis (CAE) or capillary zone electrophoresis (CZE) using a short fused-silica capillary. This is probably because these methods do not have the necessary sensitivity or resolution. To overcome this problem, we improved the CZE system by using a longer capillary and adding a zwitterion to the running buffer (pH 10.0). A comparison of CZE and CAE demonstrated that with the exception of alpha(1)- and alpha(2)-globulin, the correlation was satisfactory in serum samples from 34 patients with M-proteins which had been detected by immunoelectrophoresis. In addition, a comparison of CZE electropherograms with those from CAE showed that small M-proteins that went undetected by CAE could be detected by CZE in four patients whose diseases included epipharyngeal carcinoma, solitary plasmacytoma, Crow-Fukase syndrome and macroglobulinemia. The improved resolution produced by a longer capillary may be effective for the detection of small M-proteins.

Antibodies, Monoclonal↗

The amniotic band disruption complex: timing of amniotic rupture and variable spectra of consequent defects.

Seventy-nine patients with the amniotic band disruption complex, including 54 infants with multiple system involvement and 25 with affected limbs alone, were evaluated. No two cases of the disorder were exactly alike. Defects varied from simple digital band constrictions to major craniofacial and visceral defects; fetal death may also occur. Amniotic rupture appeared to cause injury through three basic mechanisms: (1) interruption of normal morphogenesis; (2) crowing of fetal parts; and (3) disruption of previously differentiated structure. Comparison of 35 cases in which the timing of amniotic rupture could be estimated suggests that early amniotic rupture results in multiply affected infants who are frequently aborted or stillborn, whereas later rupture results primarily in limb involvement. Our findings indicate that both the spectrum of the developmental pathology and the nature of fetal outcome are determined by the timing of amniotic rupture. Appreciation of the mechanism which explains the disparate appearances of infants with the amniotic band disruption complex will allow more acurate diagnosis and appropriate counseling with respect to the sporadic nature of the disorder.

Abnormalities, Multiple↗

An evaluation of marine bird population trends following the Exxon Valdez oil spill, Prince William Sound, Alaska.

We examined post-spill trends (1989-1998) of marine bird populations in Prince William Sound (PWS) following the Exxon Valdez oil spill (EVOS) to evaluate recovery of injured taxa. Two criteria were employed. First, we examined population trends of injured taxa only in the oiled area of PWS using regression models. Second, we examined population trends of injured taxa in the oiled area relative to the unoiled area using homogeneity of the slopes tests. We considered a population recovering if there was a positive trend using either criteria. We considered a population not recovering if there was no trend using either criteria or a negative trend in the oiled area. A significant negative trend in the oiled area relative to the unoiled area was considered a continuing and increasing effect. Most taxa for which injury was previously demonstrated were not recovering and some taxa showed evidence of increasing effects nine years after the oil spill. Four taxa (loons Gavia spp, Harlequin Duck Histrionicus histrionicus, Bufflehead Bucephala spp, and North-western Crow Corvus caurinus) showed weak to very weak evidence of recovery. None of these taxa showed positive trends in both winter and summer. Nine taxa (grebes Podiceps spp, cormorants Phalacrocorax spp, Black Oystercatcher Haematopus bachmani, Mew Gull Larus canus, Glaucous-winged Gull Larus glaucescens, terns Sterna spp, murres Uria spp, Pigeon Guillemot Cepphus columba, and murrelets Brachyramphus spp) showed no evidence of recovery during summer or winter. Four taxa (scoters Melanitta spp, mergansers Mergus spp, goldeneyes Bucephala spp, and Black-legged Kittiwaka Rissa tridactyla) showed evidence of continuing, increasing effects. We showed evidence of slow recovery, lack of recovery, and divergent population trends in many taxa which utilize shoreline and nearshore habitats where oil is likely to persist. Potential lingering spill effects and natural variability appear to be acting in concert in delaying recovery of many PWS bird populations.

Alaska↗

Mutation load and human longevity.

Since paternal age at reproduction is considered to be the main factor determining human spontaneous mutation rate (Crow, J. (1993) Environ. Mol. Mutagenesis, 21, 122-129), the effect of paternal age on human longevity was studied on 8,518 adult persons (at age 30 and above) from European aristocratic families with well-known genealogy. The daughters born to old fathers (50-59 years) lose about 4.4 years of their life compared to daughters of young fathers (20-29 years) and these losses are highly statistically significant, while sons are not significantly affected. Since only daughters inherit the paternal X chromosome, this sex-specific decrease in daughters' longevity might indicate that human longevity genes (crucial, house-keeping genes) sensitive to mutational load might be located in this chromosome.

Adult↗

Genetic toxicities of human teratogens.

Birth defects cause a myriad of societal problems and place tremendous anguish on the affected individual and his or her family. Current estimates categorize about 3% of all newborn infants as having some form of birth defect or congenital anomaly. As more precise means of detecting subtle anomalies become available this estimate, no doubt, will increase. Even though birth defects have been observed in newborns throughout history, our knowledge about the causes and mechanisms through which these defects are manifested is limited. For example, it has been estimated that around 20% of all birth defects are due to gene mutations, 5-10% to chromosomal abnormalities, and another 5-10% to exposure to a known teratogenic agent or maternal factor [D.A. Beckman, R.L. Brent, Mechanisms of teratogenesis. Ann. Rev. Pharmacol. Toxicol. 24 (1984) 483-500; K. Nelson, L.B. Holmes Malformations due to presumed spontaneous mutations in newborn infants, N. Engl. J. Med. 320 (1989) 19-23.]. Together, these percentages account for only 30-40%, leaving the etiology of more than half of all human birth defects unexplained. It has been speculated that environmental factors account for no more than one-tenth of all congenital anomalies [D.A. Beckman, R.L. Brent, Mechanisms of teratogenesis, Ann. Rev. Pharmacol. Toxicol. 24 (1984) 483-500]. Furthermore, since there is no evidence in humans that the exposure of an individual to any mutagen measurably increases the risk of congenital anomalies in his or her offspring' [J.F. Crow, C. Denniston, Mutation in human populations, Adv. Human Genet. 14 (1985) 59-121; J.M. Friedman, J.E. Polifka, Teratogenic Effects of Drugs: A Resource for Clinicians (TERIS). The John Hopkins University Press, Baltimore, 1994], the mutagenic activity of environmental agents and drugs as a factor in teratogenesis has been given very little attention. Epigenetic activity has also been given only limited consideration as a mechanism for teratogenesis. As new molecular methods are developed for assessing processes associated with teratogenesis, especially those with a genetic or an epigenetic basis, additional environmental factors may be identified. These are especially important because they are potentially preventable. This paper examines the relationships between chemicals identified as human teratogens (agents that cause birth defects) and their mutagenic activity as evaluated in one or more of the established short-term bioassays currently used to measure such damage. Those agents lacking mutagenic activity but with published evidence that they may otherwise alter the expressions or regulate interactions of the genetic material, i.e. exhibit epigenetic activity, have likewise been identified. The information used in making these comparisons comes from the published literature as well as from unpublished data of the U.S. National Toxicology Program (NTP).

Animals↗

Assessment of handedness using a digitizing tablet: a new method.

The assessment of handedness is of interest in some psychiatric populations, above all in schizophrenic patients, because there may be a relationship between neurodevelopmental, hemispheric damage and psychiatric disease processes (Crow TJ. Schizophrenia Bulletin 1990;16:433-443; Tyler M, Diamond J, Lewis S. Schizophrenia Research 1995;18:37-41). Various methods to assess handedness have been proposed. In order to detect the most precise instrument for the assessment of handedness, two different measures, a questionnaire and a computational procedure for movement analysis, were compared in a group of healthy subjects. The ability of the methods to discriminate not only between the groups of right-handers (n=12) and left-handers (n=23), but also between left-handers trained in school to use the non-dominant right hand ('inconsistent' left-handers; n=11) and those allowed to use their left hand for writing ('consistent' left-handers; n=12) was investigated. For future investigations, our main concern was to determine if one method had superiority over the other. The results revealed that the Edinburgh Handedness Inventory (EHI) distinguishes just as well as the computational method between right-handers and non-right-handers. However, more precise discrimination between the subgroups of 'consistent' and 'inconsistent' left-handers is possible using digitized analysis of hand-motor performance. According to our results handedness should be assessed not only with the EHI, but also with the computer-aided analysis of hand-movements.

Adult↗

Neural correlates of naming animals from their characteristic sounds.

The neural correlates of naming stimuli presented through the auditory modality have scarcely been studied. Using a PET experiment in 10 normal subjects, we began to address this issue by testing the hypothesis that naming animals from their characteristic sounds will engage bilateral primary auditory and auditory association cortices, bilateral early visual association cortices, left inferotemporal (IT) cortices, and left frontal operculum. Subjects listened to characteristic animal sounds (e.g. a rooster crowing), and named the animals making the sounds. When contrasted with a baseline task that involved saying up/down to the direction of pitch change in tone sequences, the naming task produced activation in mesial occipital cortices, the left ventral IT region, and the left frontal operculum. We interpret the activation in visual association cortices to reflect the process of retrieving conceptual knowledge (e.g. physical structure) pertinent to the animals being named, as in visual images. The left IT activation is interpreted to reflect activation of a mediation system for word retrieval, that operates to link conceptual knowledge retrieval to word production, and whose triggering is independent of the sensory modality in which a stimulus is presented.

Acoustic Stimulation↗