bluuebunny/crossref_metadata_2025 huggingface dataset:
Circadian Rhythm Profiles in Women with Night Eating Syndrome
Authors: Goel Namni , Stunkard Albert J. , Rogers Naomi L. , Van Dongen Hans P.A. , Allison Kelly C. , O'Reardon John P. , Ahima Rexford S. , Cummings David E. , Heo Moonseong , Dinges David F.
Published: January 2009

Night eating syndrome (NES) is characterized by evening hyperphagia and frequent awakenings accompanied by food intake. Patients with NES display a delayed circadian pattern of food intake but retain a normal sleep-wake cycle. These characteristics initiated the current study, in which the phase and amplitude of behavioral and neuroendocrine circadian rhythms in patients with NES were evaluated. Fifteen women with NES (mean age ± SD, 40.8 ± 8.7 y) and 14 control subjects (38.6 ± 9.5 y) were studied in the laboratory for 3 nights, with food intake measured daily. Blood also was collected for 25 h (every 2 h from 0800 to 2000 h, and then hourly from 2100 to 0900 h) and assayed for glucose and 7 hormones (insulin, ghrelin, leptin, melatonin, cortisol, thyroid-stimulating hormone [TSH] and prolactin). Statistical analyses utilized linear mixed-effects cosinor analysis. Control subjects displayed normal phases and amplitudes for all circadian rhythms. In contrast, patients with NES showed a phase delay in the timing of meals, and delayed circadian rhythms for total caloric, fat, and carbohydrate intake. In addition, phase delays of 1.0 to 2.8 h were found in 2 food-regulatory rhythms—leptin and insulin—and in the circadian melatonin rhythm (with a trend for a delay in the circadian cortisol rhythm). In contrast, circulating levels of ghrelin, the primary hormone that stimulates food intake, were phase advanced by 5.2 h. The glucose rhythm showed an inverted circadian pattern. Patients with NES also showed reduced amplitudes in the circadian rhythms of food intake, cortisol, ghrelin, and insulin, but increased TSH amplitude. Thus, patients with NES demonstrated significant changes in the timing and amplitude of various behavioral and physiological circadian markers involved in appetite and neuroendocrine regulation. As such, NES may result from dissociations between central (suprachiasmatic nucleus) timing mechanisms and putative oscillators elsewhere in the central nervous system or periphery, such as the stomach or liver. Considering these results, chronobiologic treatments for NES such as bright light therapy may be useful. Indeed, bright light therapy has shown efficacy in reducing night eating in case studies and should be evaluated in controlled clinical trials.
Circadian Regulation of Agonistic Behavior in Groups of Parthenogenetic Marbled Crayfish, Procambarus sp.
Authors: Farca Luna Abud J. , Hurtado-Zavala Joaquin I. , Reischig Thomas , Heinrich Ralf
Published: January 2009

Crustaceans have frequently been used to study the neuroethology of both agonistic behavior and circadian rhythms, but whether their highly stereotyped and quantifiable agonistic activity is controlled by circadian pacemakers has, so far, not been investigated. Isolated marbled crayfish ( Procambarus spec.) displayed rhythmic locomotor activity under 12-h light:12-h darkness (LD12:12) and rhythmicity persisted after switching to constant darkness (DD) for 8 days, suggesting the presence of endogenous circadian pacemakers. Isogenetic females of parthenogenetic marbled crayfish displayed all behavioral elements known from agonistic interactions of previously studied decapod species including the formation of hierarchies. Groups of marbled crafish displayed high frequencies of agonistic encounters during the 1st hour of their cohabitation, but with the formation of hierarchies agonistic activities were subsequently reduced to low levels. Group agonistic activity was entrained to periods of exactly 24 h under LD12:12, and peaks of agonistic activity coincided with light-to-dark and dark-to-light transitions. After switching to DD, enhanced agonistic activity was dispersed over periods of 8-to 10-h duration that were centered around the times corresponding with light-to-dark transitions during the preceding 3 days in LD12:12. During 4 days under DD agonistic activity remained rhythmic with an average circadian period of 24.83 ± 1.22 h in all crayfish groups tested. Only the most dominant crayfish that participated in more than half of all agonistic encounters within the group revealed clear endogenous rhythmicity in their agonistic behavior, whereas subordinate individuals, depending on their social rank, initiated only between 19.4% and 0.03% of all encounters in constant darkness and displayed no statistically significant rhythmicity. The results indicate that both locomotion and agonistic social interactions are rhythmic behaviors of marbled crayfish that are controlled by light-entrained endogenous pacemakers.
RNA Interference of the Period Gene Affects the Rhythm of Sperm Release in Moths
Authors: Kotwica Joanna , Bebas Piotr , Gvakharia Barbara O. , Giebultowicz Jadwiga M.
Published: January 2009

The period ( per) gene is 1 of the core elements of the circadian clock mechanism in animals from insects to mammals. In clock cells of Drosophila melanogaster, per mRNA and PER protein oscillate in daily cycles. Consistent with the molecular clock model, PER moves to cell nuclei and acts as a repressor of positive clock elements. Homologs of per are known in many insects; however, specific roles of per in generating output rhythms are not known for most species. The aim of this article was to determine whether per is functionally involved in the circadian rhythm of sperm release in the moth, Spodoptera littoralis. In this species, as in other moths, rhythmic release of sperm bundles from the testis into the upper vas deferens occurs only in the evening, and this rhythm continues in the isolated reproductive system. S. littoralis was used to investigate the expression of per mRNA and protein in the 2 types of cells involved in sperm release: the cyst cells surrounding sperm bundles in the testes, and the barrier cells separating testicular follicles from the vas deferens. In cyst cells, PER showed a nuclear rhythm in light/dark (LD) cycles but was constitutively cytoplasmic in constant darkness (DD). In barrier cells, nuclear cycling of PER was observed in both LD and DD. To determine the role of PER in rhythmic sperm release in moths, testes-sperm duct complexes were treated in vitro with double-stranded fragments of per mRNA (dsRNA). This treatment significantly lowered per mRNA and protein in cyst cells and barrier cells and caused a delay of sperm release. These data demonstrate that a molecular oscillator involving the period gene plays an essential role in the regulation of rhythmic sperm release in this species.
Phenotyping Food Entrainment: Motion Sensors and Telemetry Are Equivalent
Authors: Mistlberger Ralph E. , Kent Brianne A. , Landry Glenn J.
Published: January 2009

Rats can anticipate a daily meal by entrainment of a circadian timekeeping mechanism that is anatomically separate from the light-entrainable circadian pacemaker located in the suprachiasmatic nucleus. The dorsomedial nucleus of the hypothalamus (DMH) has been claimed to be critical for the expression of circadian rhythms of food anticipatory activity, but efforts to confirm this finding have so far failed. Failure to confirm that DMH ablation disrupts or eliminates food anticipatory rhythms has been attributed to the use of overhead motion sensors rather than telemetry to measure locomotor activity. To examine the relationship between motion sensor and telemetric measures of locomotor activity, transponders were implanted into the peritoneal cavity of adult male rats, and activity was recorded continuously by both telemetry and infrared motion sensors. Activity counts were ~4 fold higher as detected by telemetry, but normalized activity patterns were virtually identical for the two measures during ad-lib food access, 4 h/day food restriction and total food deprivation after food restriction. Overhead motion sensors and telemetry are equivalent measures of food anticipatory activity in rats. Telemetry is an effective tool for continuous recording of body temperature but has no advantages over infrared motion sensors for measuring food anticipatory activity rhythms.
Interpretation and Rational Choice
Authors: Elster Jon
Published: January 2009

Rational choice explanation plays a critical role in the interpretation of both texts and social behavior. The interpretation of fiction benefits from the use of this type of explanation. It can inform understanding of both the author's choice and the behavior of the fictional characters the author creates. Examples of this are offered from a number of pre-modern novels and plays. The situation is somewhat more complicated when rational choice explanation is applied to the study of real human behavior. Human beings can misrepresent the reasons for their actions. This misrepresentation can render understanding more difficult. The behavior of participants in civil wars demonstrates well this misrepresentation and the problems it generates for successful theory construction.
Political Corruption and Social Trust
Authors: Rothstein Bo , Eek Daniel
Published: January 2009

The main question addressed in this paper is how the great variation in the level of social trust in different countries can be explained. Most empirical research on this question has been based on survey data which has limitations when it comes to capturing the causal mechanisms. Building on theories that point to the importance of trustworthy governmental institutions for creating social trust, two parallel experiments were conducted in two countries where the levels of corruption and social trust are very different. One group of 64 Swedish and one group of 82 Romanian undergraduate students responded to a number of scenarios which describe situations at a police station or a doctor's surgery in a foreign country. In the scenarios, the person tries to receive immediate assistance from the police/doctor at the same time as another person who lives in the `unknown' country. These encounters varied within groups in terms of (1) whether or not a bribe was used in order to receive immediate assistance, (2) whether the other person or the official took the initiative to request/offer immediate assistance in exchange for the bribe, and (3) outcome in terms of whether immediate assistance was approved or declined as a result of the offer or demand for a bribe. Type of authority (police vs. doctor) was a between-groups factor. Subsequent to each scenario, participants' levels of various aspects of vertical and horizontal trust were measured. As hypothesized, the Romanian sample had reliably lower initial levels of horizontal trust than the Swedish sample. For both samples, however, the results showed the expected effects of bribe, initiator, and outcome on all dependent trust measures. The results supported the hypothesis that trust in authorities influences the perceptions of the trustworthiness of others in general. Even though some of the effects were stronger for one sample than for the other, the influence of vertical trust on social trust was true for both the high- and the low-trusting sample.
A New Model of Wage Determination and Wage Inequality
Authors: Jasso Guillermina
Published: January 2009

This paper proposes a new model of wage determination and wage inequality. In this model, wage-setters set workers' wages; they do so either directly, as when individuals vote in a salary committee, or indirectly, as when political parties, via the myriad of social, economic, fiscal, and other policies, generate wages. The recommendations made by wage-setters (or arising from their policies) form a distribution, and all the wage-setter-specific distributions are combined into a single final wage distribution. There may be any number of wage-setters; some wage-setters count more than others; and the wage-setters may differ among themselves on both the wage distribution and the amounts recommended for particular workers. We use probability theory to derive initial results, including both distribution-independent and distribution-specific results. Fortuitously, elements of the model correspond to basic democratic principles. Thus, the model yields implications for the effects of democracy on wage inequality. These include: (1) the effects of the number of wage-setters and their power depend on the configuration of agreements and disagreements; (2) independence of mind reduces wage inequality, and dissent does so even more; (3) when leaders of democratic nations seek to forge an economic consensus, they are unwittingly inducing greater economic inequality; (4) arguments for independent thinking will be more vigorous in small societies than in large societies; (5) given a fixed distributional form for wages and two political parties which either ignore or oppose each other's distributional ideas, the closer the party split to 50–50, the lower the wage inequality; and (6) under certain conditions the wage distribution within wage-setting context will be normal, but the normality will be obscured, as cross-context mixtures will display a wide variety of shapes.
Factors Associated With Work Stress and Professional Satisfaction in Oncology Staff
Authors: Dougherty Elizabeth , Pierce Bruce , Ma Clement , Panzarella Tony , Rodin Gary , Zimmermann Camilla
Published: January 2009

Cancer care professionals work in a stressful environment, but it is not clear what factors contribute to this stress. We surveyed 60 oncology personnel on an inpatient unit and a palliative care unit regarding levels of perceived work stress and its potential contributors. Logistic regression analyses were performed to determine predictors of staff stress. A total of 63% of staff reported experiencing ``a great deal'' of stress at work, which was predicted by greater perceived workload (odds ratio = 32.2; P < .0001), insufficient time to grieve patients' death (odds ratio = 9.75; P = .0007), lack of institutional support (odds ratio = 0.16; P = .009), perceived lack of resources (odds ratio = 0.06; P = .007), and lack of control over the choice of workplace (odds ratio = 0.10; P = .03). Measures to address work-related stress should be included in the planning of cancer programs.
Effective Hemostasis During Minor Surgery in a Case of Hereditary Combined Deficiency of Vitamin K-dependent Clotting Factors
Authors: Lapecorella Mario , Napolitano Mariasanta , Bernardi Francesco , Pinotti Mirko , Sbrighi Piero Sandro , Marchetti Giovanna , Canella Alessandro , Caruso Pierpaolo , Orecchioni Assunta , Mariani Guglielmo
Published: January 2009

Combined deficiency of the vitamin K-dependent clotting factors (VKCFD) is a rare bleeding disorder involving defective gamma-carboxylation of coagulation factors II , VII, IX and X as well as natural anticoagulants protein C and protein S. The disease is characterized by a cluster of different, often life threatening, bleeding symptoms occurring both spontaneously and in a surgical setting. In the present paper we describe two different treatment modalities to be used both in a programmed surgical procedure and in an emergency scenario. As this disease is a natural model that resembles oral anticoagulation, our experience discloses a possible rationale in the use of recombinant activated FVII for warfarin reversal.
Cerebrovascular Disease and Patterns of Cerebral Oxygenation During Sleep in Elders
Authors: Carlson Barbara Waag , Neelon Virginia J. , Carlson John R. , Hartman Marilyn , Dogra Sunil
Published: January 2009

Purpose: The aim of this descriptive exploratory study was to describe patterns of cerebral oxygen reserves during sleep and their association with cerebrovascular risk factors in elders. Method: Participants—115 elders, age 70 + years—were monitored overnight using standard polysomnography. Measures included arterial oxyhemoglobin (SaO2) and regional measures of percentage of cerebral oxyhemoglobin saturation (rcSO2) via cerebral oximetry. Participants were classified based on the magnitude of change in rcSO2 from resting baseline to the end of the first nonrapideye-movement (NREM) period. One-way ANOVA and Chi-square were used to test group differences in SaO2 and the prevalence of cerebrovascular risk factors. Findings: 20 participants (Group 1) experienced an increase in rcSO2 during sleep along with sleeping rcSO2 levels !55%; 95 participants experienced a decline in rcSO2; 72 participants (Group 2) had sleeping rcSO2 levels !55%; and 23 participants had sleeping rcSO2 levels <55% (Group 3). Although all three groups had equivalent declines in SaO2 levels during sleep, Group 3 had more cardiovascular comorbidity than Groups 1 and 2. Conclusions: Although SaO2 levels decline in most people during sleep, compensatory vascular responses to these drops in SaO2 are important for preventing rcSO2 from falling during sleep. Those entering sleep with lower baseline rcSO2 levels and those with greater declines in cerebral oxygenation during sleep may have greater cardiovascular burden and be at greater risk for stroke and other forms of disabling cerebrovascular disease.
An Evaluation of a Carbon Monoxide Poisoning Education Program
Authors: Schwartz Lauren , Martinez Luz , Louie Jean , Mercurio-Zappala Maria , Howland Mary Ann , Nokes Kathleen , Hoffman Robert S.
Published: January 2009

Carbon monoxide (CO) is the leading cause of poisoning death in the United States. Research has shown that proper use of a CO detector in the home can reduce morbidity and mortality related to unintentional CO exposure. The authors evaluated three CO education workshops that included distribution of free CO detectors for home use, and their intervention reached 133 participants. Pretest surveys and follow-up calls evaluated change in knowledge and behavior factors. Results showed that statistically significant increases were found on three out of five knowledge-based items and 91% of respondents (N = 80) reported installing CO detectors in their home. Follow-up calls provided an opportunity to clarify information and provide tailored information to participants.
Association Between Previous Concussion History and Symptom Endorsement During Preseason Baseline Testing in High School and Collegiate Athletes
Authors: Register-Mihalik Johna K. , Mihalik Jason P. , Guskiewicz Kevin M.
Published: January 2009

Background:

A graded symptom checklist is a commonly used concussion evaluation measure. Little is known about pre-season baseline symptomatology of high school and college athletes with and without a previous concussion history.

Hypothesis:

The primary hypothesis investigated was that those individuals with a concussion history would report more symptoms at baseline testing. The effects of sex and age on symptoms were also examined.

Study Design:

Cross-sectional study.

Methods:

Subjects included 8930 high school and collegiate athletes (height, 177.79 ± 9.97 cm; mass, 75.20 ± 19.21 kg; age, 16.60 ± 1.64 years). Subjects completed a self-report graded symptom checklist and concussion history questionnaire during a preseason clinical testing session. Symptoms reported (yes or no) on the 18-item graded symptom checklist served as the dependent variables.

Results:

A significant association was observed between symptoms on the graded symptom checklist and previous concussion history ( P ≤ .001). No differences were observed between high school and college athletes regarding symptom endorsement (t8928 = 0.620; P = .535). A statistical but not clinically meaningful difference was observed between the means for males and females symptom endorsement (t8928 = −3.03; P = .002): men endorsed 1.88 ± 2.81 symptoms, and women endorsed 2.09 ± 2.90 symptoms. Headache, sleeping more than usual, difficulty concentrating, drowsiness, difficulty remembering, fatigue, difficulty sleeping, and irritability were reported by more than 10% of athletes.

Conclusion:

High school and college athletes with a history of multiple concussions may be at risk for experiencing concussion-linked symptoms well beyond the acute stage of injury. Clinicians should be mindful of previous concussion history in athletes with increased presence of base-rate symptoms as they may be predisposed to future injury.
Factors Associated With Function After Anterior Cruciate Ligament Reconstruction
Authors: Lentz Trevor A. , Tillman Susan M. , Indelicato Peter A. , Moser Michael W. , George Steven Z. , Chmielewski Terese L.
Published: January 2009

Background:

Many individuals do not resume unrestricted, preinjury sports participation after anterior cruciate ligament reconstruction, thus a better understanding of factors associated with function is needed. The purpose of this study was to investigate the association of knee impairment and psychological variables with function in subjects with anterior cruciate ligament reconstruction.

Hypothesis:

After controlling for demographic variables, knee impairment and psychological variables contribute to function in subjects with anterior cruciate ligament reconstruction.

Study Design:

Cross-sectional study; Level of evidence, 4a.

Methods:

Fifty-eight subjects with a unilateral anterior cruciate ligament reconstruction completed a standardized testing battery for knee impairments (range of motion, effusion, quadriceps strength, anterior knee joint laxity, and pain intensity), kinesiophobia (shortened Tampa Scale for Kinesiophobia), and function (International Knee Documentation Committee subjective form and single-legged hop test). Separate 2-step regression analyses were conducted with International Knee Documentation Committee subjective form score and single-legged hop index as dependent variables. Demographic variables were entered into the model first, followed by knee impairment measures and Tampa Scale for Kinesiophobia score.

Results:

A combination of pain intensity, quadriceps index, Tampa Scale for Kinesiophobia score, and flexion motion deficit contributed to the International Knee Documentation Committee subjective form score (adjusted r2 = 0.67; P < .001). Only effusion contributed to the single-legged hop index (adjusted r2 = 0.346; P = .002).

Conclusion:

Knee impairment and psychological variables in this study were associated with self-report of function, not a performance test.

Clinical Relevance:

The results support focusing anterior cruciate ligament reconstruction rehabilitation on pain, knee motion deficits, and quadriceps strength, as well as indicate that kinesiophobia should be addressed. Further research is needed to reveal which clinical tests are associated with performance testing.
The Relationship Between Lower Extremity Alignment Characteristics and Anterior Knee Joint Laxity
Authors: Shultz Sandra J. , Nguyen Anh-Dung , Levine Beverly J.
Published: January 2009

Background:

Lower extremity alignment may influence the load distribution at the knee, potentially predisposing the anterior cruciate ligament to greater stress. We examined whether lower extremity alignment predicted the magnitude of anterior knee laxity in men and women.

Hypothesis:

Greater anterior pelvic angle, hip anteversion, tibiofemoral angle, genu recurvatum, and navicular drop will predict greater anterior knee laxity.

Study Design:

Descriptive laboratory study.

Methods:

Women (n = 122) and men (n = 97) were measured for anterior knee laxity and 7 lower extremity alignment variables on their dominant stance leg. Linear regression determined the extent to which the alignment variables predicted anterior knee laxity for each sex.

Results:

Lower anterior pelvic tilt and tibiofemoral angle, and greater genu recurvatum and navicular drop were related to greater anterior knee laxity in women, explaining 28.1% of the variance ( P < .001). Lower anterior pelvic tilt and greater hip anteversion, genu recurvatum and navicular drop were predictors of greater anterior knee laxity in men, explaining 26.5% of the variance ( P < .001).

Conclusion:

Lower anterior pelvic tilt, greater knee hyperextension, and foot pronation predicted greater anterior knee laxity in both men and women, with genu recurvatum and navicular drop having the greatest impact on anterior knee laxity. Greater hip anteversion was also a strong predictor in men, while a lower tibiofemoral angle was a significant predictor in women.

Clinical Relevance:

The associations between lower extremity alignment and anterior knee laxity suggest that alignment of the hip, knee, and ankle may be linked to or contribute to abnormal loading patterns at the knee, potentially stressing the capsuloligamentous structures and promoting greater joint laxity.
The Function of the Human Anterior Cruciate Ligament and Analysis of Single- and Double-Bundle Graft Reconstructions
Authors: Noyes Frank R.
Published: January 2009

Context:

There exists controversy on the ability of a single or double anterior cruciate ligament graft technique to restore anterior cruciate ligament function. This article examines the published experimental and clinical data supporting these surgical procedures in the ability to restore knee stability.

Evidence Acquisition:

An analysis of anterior cruciate ligament function and single- and double-graft reconstructions defined by selected biomechanical, robotic, kinematic, anatomical, and clinical studies.

Results:

The anterior cruciate ligament resists the combined motions of anterior tibial translation and internal tibial rotation, which defines the concept of rotational stability. This function prevents anterior tibial subluxation of the lateral and medial tibiofemoral compartments that accounts for the pivot-shift phenomena. The placement of single anterior cruciate ligament grafts high and proximal at the femoral attachment and posterior at the tibial attachment results in a vertical graft orientation. This graft placement results in a limited ability to provide rotational stability and is inferior when compared to a double-bundle graft procedure. Studies show that a more oblique single-graft orientation, in the sagittal and coronal plane, achieved from a central anatomic femoral and tibial location provides rotational stability similar to a double-bundle anterior cruciate ligament graft.

Conclusion:

There exists insufficient experimental and clinical data to recommend the more complex double- bundle anterior cruciate ligament graft technique over a well-placed central anatomic single graft in terms of restoring knee rotational stability. Meticulous surgical technique for anterior cruciate ligament graft placement is necessary to avoid failure.
Titanium dioxide performance in polyethylene teraphthalate protective coatings on electrolytic chromium coated steels
Authors: Zumelzu E. , Rull F. , Ortega C.
Published: January 2009

The present study analysed the behaviour of titanium dioxide (TiO2) in polyethylene teraphthalate (PET) polymer coatings on electrolytic chromium-coated steel (ECCS) plates employed in the manufacturing of food containers. Also, the thermal source affecting rutile distribution in PET coatings was determined; i.e. whether it originated in the manufacturing processes and treatments of the composite to allow coextrusion and PET adherence on steel, or was rather a consequence of industrial canning processes. Measurements at parallel intervals from the surface to the metal interface were made by Raman and microRaman vibrational spectroscopy techniques to characterise the rutile distribution in the PET thickness. Finally, scanning and transmission electron microscopy observations determined the changes on the surface properties of the coating and provided information on the chemical and structural changes undergone by the polymer protective coating, which affect the performance and the protective capacity of polymers in contact with canned foods.
Laser gas assisted nitriding of alumina surfaces
Authors: Yilbas B. S. , Karatas C. , Arif A. F. M. , Aleem B. J. Abdul
Published: January 2009

The laser control melting can be applied to improve the structural and tribological properties of alumina surfaces. In this case, the laser remelting provides a homogeneous structure while the assisting gas diffuses into molten layer forming the nitride compounds in the irradiated region. Since the process is rapid, local heating with controllable depth and cost effective, the laser remelting provides several advantages over the conventional surface treatment techniques. In the present study, laser melting and gas assisted nitriding of alumina pellets are carried out. Morphological and metallurgical changes after the laser treatment process are examined using scanning electron microscopy (SEM), optical microscopy and X-ray diffraction (XRD), and indentation tests. It is found that two regions are formed in the laser irradiated zone. The first region below the surface is dense and composes of α-Al2O3 and AlN while in the second region, which is below the first region, randomly stacked lamellae structure is observed.
The MLL recombinome of adult CD10-negative B-cell precursor acute lymphoblastic leukemia: results from the GMALL study group
Authors: Burmeister Thomas , Meyer Claus , Schwartz Stefan , Hofmann Julia , Molkentin Mara , Kowarz Eric , Schneider Björn , Raff Thorsten , Reinhardt Richard , Gökbuget Nicola , Hoelzer Dieter , Thiel Eckhard , Marschalek Rolf
Published: January 2009

MLL translocations in adult B-cell precursor (BCP) acute lymphoblastic leukemia (ALL) are largely restricted to the immature CD10− immunophenotypes. MLL-AF4 is known to be the most frequent fusion transcript, but the exact frequencies of MLL aberrations in CD10− adult BCP-ALL are unknown. We present a genetic characterization of 184 BCR-ABL− CD10− adult ALL cases (156 cyIg−, 28 cyIg+) diagnosed between 2001 and 2007 at the central diagnostic laboratory of the GMALL study group. Patient samples were investigated by RT-PCR for MLL-AF4, MLL-ENL, and MLL-AF9 and by long-distance inverse polymerase chain reaction, thus also allowing the identification of unknown MLL fusion partners at the genomic level. MLL-AF4 was detected in 101 (54.9%) and MLL-ENL in 11 (6.0%) cases. In addition, rare MLL fusion genes were found: 2 MLL-TET1 cases, not previously reported in ALL, 1 MLL-AF9, 1 MLL-PTD, a novel MLL-ACTN4, and an MLL-11q23 fusion. Chromosomal breakpoints were determined in all 118 positive cases, revealing 2 major breakpoint cluster regions in the MLL gene. Characteristic features of MLL+ patients were significantly lower CD10 expression, expression of the NG2 antigen, a higher white blood count at diagnosis, and female sex. Proposals are made for diagnostic assessment. The clinical studies are registered at http://www.clinicaltrials.gov as NCT00199056 and NCT00198991.
Mapping of five candidate sex-determining loci in rainbow trout (Oncorhynchus mykiss)
Authors: Alfaqih Mahmoud A , Brunelli Joseph P , Drew Robert E , Thorgaard Gary H
Published: January 2009

Background

Rainbow trout have an XX/XY genetic mechanism of sex determination where males are the heterogametic sex. The homology of the sex-determining gene (SDG) in medaka to Dmrt1 suggested that SDGs evolve from downstream genes by gene duplication. Orthologous sequences of the major genes of the mammalian sex determination pathway have been reported in the rainbow trout but the map position for the majority of these genes has not been assigned.

Results

Five loci of four candidate genes (Amh, Dax1, Dmrt1 and Sox6) were tested for linkage to the Y chromosome of rainbow trout. We exclude the role of all these loci as candidates for the primary SDG in this species. Sox6i and Sox6ii, duplicated copies of Sox6, mapped to homeologous linkage groups 10 and 18 respectively. Genotyping fishes of the OSU × Arlee mapping family for Sox6i and Sox6ii alleles indicated that Sox6i locus might be deleted in the Arlee lineage.

Conclusion

Additional candidate genes should be tested for their linkage to the Y chromosome. Mapping data of duplicated Sox6 loci supports previously suggested homeology between linkage groups 10 and 18. Enrichment of the rainbow trout genomic map with known gene markers allows map comparisons with other salmonids. Mapping of candidate sex-determining loci is important for analyses of potential autosomal modifiers of sex-determination in rainbow trout.
Optical mapping of the Mycobacterium avium subspecies paratuberculosis genome
Authors: Wu Chia-wei , Schramm Timothy M , Zhou Shiguo , Schwartz David C , Talaat Adel M
Published: January 2009

Background

Infection of cattle with Mycobacterium avium subspecies paratuberculosis (M. ap) causes severe economic losses to the dairy industry in the USA and worldwide. In an effort to better examine diversity among M. ap strains, we used optical mapping to profile genomic variations between strains of M. ap K-10 (sequenced strain) and M. ap ATCC 19698 (type strain).

Results

The assembled physical restriction map of M. ap ATCC 19698 showed a genome size of 4,839 kb compared to the sequenced K-10 genome of 4,830 kb. Interestingly, alignment of the optical map of the M. ap ATCC 19698 genome to the complete M. ap K-10 genome sequence revealed a 648-kb inversion around the origin of replication. However, Southern blotting, PCR amplification and sequencing analyses of the inverted region revealed that the genome of M. ap K-10 differs from the published sequence in the region starting from 4,197,080 bp to 11,150 bp, spanning the origin of replication. Additionally, two new copies of the coding sequences > 99.8% were identified, identical to the MAP0849c and MAP0850c genes located immediately downstream of the MAP3758c gene.

Conclusion

The optical map of M. ap ATCC 19698 clearly indicated the miss-assembly of the sequenced genome of M. ap K-10. Moreover, it identified 2 new genes in M. ap K-10 genome. This analysis strongly advocates for the utility of physical mapping protocols to complement genome sequencing projects.
Perception of primary health professionals about Female Genital Mutilation: from healthcare to intercultural competence
Authors: Kaplan-Marcusan Adriana , Torán-Monserrat Pere , Moreno-Navarro Juana , Fàbregas Ma Jose Castany , Muñoz-Ortiz Laura
Published: January 2009

Background

The practice of Female Genital Mutilation (FGM), a deeply-rooted tradition in 28 countries in Sub-Saharan Africa, carries important negative consequences for the health and quality of life of women and children. Migratory movements have brought this harmful traditional practice to our medical offices, with the subsequent conflicts related to how to approach this healthcare problem, involving not only a purely healthcare-related event but also questions of an ethical, cultural identity and human rights nature.

Methods

The aim of this study was to analyse the perceptions, degree of knowledge, attitudes and practices of the primary healthcare professionals in relation to FGM. A transversal, descriptive study was performed with a self-administered questionnaire to family physicians, paediatricians, nurses, midwives and gynaecologists. Trends towards changes in the two periods studied (2001 and 2004) were analysed.

Results

A total of 225 (80%) professionals answered the questionnaire in 2001 and 184 (62%) in 2004. Sixteen percent declared detection of some case in 2004, rising three-fold from the number reported in 2001. Eighteen percent stated that they had no interest in FGM. Less than 40% correctly identified the typology, while less than 30% knew the countries in which the practice is carried out and 82% normally attended patients from these countries.

Conclusion

Female genital mutilations are present in primary healthcare medical offices with paediatricians and gynaecologists having the closest contact with the problem. Preventive measures should be designed as should sensitization to promote stands against these practices.
The consequence of fetal ethanol exposure and adolescent odor re-exposure on the response to ethanol odor in adolescent and adult rats
Authors: Eade Amber M , Sheehe Paul R , Molina Juan C , Spear Norman E , Youngentob Lisa M , Youngentob Steven L
Published: January 2009

Background

An epidemiologic predictive relationship exists between fetal ethanol exposure and the likelihood for adolescent use. Further, an inverse relationship exists between the age of first experience and the probability of adult abuse. Whether and how the combined effects of prenatal and adolescent ethanol experiences contribute to this progressive pattern remains unknown. Fetal ethanol exposure directly changes the odor attributes of ethanol important for both ethanol odor preference behavior and ethanol flavor perception. These effects persist only to adolescence. Here we tested whether adolescent ethanol odor re-exposure: (Experiment 1) augments the fetal effect on the adolescent behavioral response to ethanol odor; and/or (Experiment 2) perpetuates previously observed adolescent behavioral and neurophysiological responses into adulthood.

Methods

Pregnant rats received either an ethanol or control liquid diet. Progeny (observers) experienced ethanol odor in adolescence via social interaction with a peer (demonstrators) that received an intragastric infusion of either 1.5 g/kg ethanol or water. Social interactions were scored for the frequency that observers followed their demonstrator. Whole-body plethysmography evaluated the unconditioned behavioral response of observers to ethanol odor in adolescence (P37) or adulthood (P90). The olfactory epithelium of adults was also examined for its neural response to five odorants, including ethanol.

Results

Experiment 1: Relative to fetal or adolescent exposure alone, adolescent re-exposure enhanced the behavioral response to ethanol odor in P37 animals. Compared to animals with no ethanol experience, rats receiving a single experience (fetal or adolescent) show an enhanced, yet equivalent, ethanol odor response. Fetal ethanol experience also increased olfactory-guided following of an intoxicated peer. Experiment 2: Combined exposure yielded persistence of the behavioral effects only in adult females. We found no evidence for persistence of neurophysiological effects in either sex.

Conclusion

Fetal ethanol exposure influences adolescent re-exposure, in part, by promoting interactions with intoxicated peers. Re-exposure subsequently enhances ethanol odor responsivity during a key developmental transition point for emergent abuse patterns. While persistence of behavioral effects occurred in females, the level of re-exposure necessary to uniformly yield persistence in both sexes remains unknown. Nonetheless, these results highlight an important relationship between fetal and adolescent experiences that appears essential to the progressive pattern of developing ethanol abuse.
TheTalpid3gene (KIAA0586) encodes a centrosomal protein that is essential for primary cilia formation
Authors: Yin Yili , Bangs Fiona , Paton I. Robert , Prescott Alan , James John , Davey Megan G. , Whitley Paul , Genikhovich Grigory , Technau Ulrich , Burt David W. , Tickle Cheryll
Published: January 2009

The chicken talpid3 mutant, with polydactyly and defects in other embryonic regions that depend on hedgehog (Hh) signalling(e.g. the neural tube), has a mutation in KIAA0568. Similar phenotypes are seen in mice and in human syndromes with mutations in genes that encode centrosomal or intraflagella transport proteins. Such mutations lead to defects in primary cilia, sites where Hh signalling occurs. Here, we show that cells of talpid3 mutant embryos lack primary cilia and that primary cilia can be rescued with constructs encoding Talpid3. talpid3 mutant embryos also develop polycystic kidneys,consistent with widespread failure of ciliogenesis. Ultrastructural studies of talpid3 mutant neural tube show that basal bodies mature but fail to dock with the apical cell membrane, are misorientated and almost completely lack ciliary axonemes. We also detected marked changes in actin organisation in talpid3 mutant cells, which may explain misorientation of basal bodies. KIAA0586 was identified in the human centrosomal proteome and, using an antibody against chicken Talpid3, we detected Talpid3 in the centrosome of wild-type chicken cells but not in mutant cells. Cloning and bioinformatic analysis of the Talpid3 homolog from the sea anemone Nematostella vectensis identified a highly conserved region in the Talpid3 protein, including a predicted coiled-coil domain. We show that this region is required to rescue primary cilia formation and neural tube patterning in talpid3 mutant embryos, and is sufficient for centrosomal localisation. Thus, Talpid3 is one of a growing number of centrosomal proteins that affect both ciliogenesis and Hh signalling.
Pitx3 potentiates Nurr1 in dopamine neuron terminal differentiation through release of SMRT-mediated repression
Authors: Jacobs Frank M. J. , van Erp Susan , van der Linden Annemarie J. A. , von Oerthel Lars , Burbach J. Peter H. , Smidt Marten P.
Published: January 2009

In recent years, the meso-diencephalic dopaminergic (mdDA) neurons have been extensively studied for their association with Parkinson's disease. Thus far, specification of the dopaminergic phenotype of mdDA neurons is largely attributed to the orphan nuclear receptor Nurr1. In this study, we provide evidence for extensive interplay between Nurr1 and the homeobox transcription factor Pitx3 in vivo. Both Nurr1 and Pitx3 interact with the co-repressor PSF and occupy the promoters of Nurr1 target genes in concert. Moreover, in vivo expression analysis reveals that Nurr1 alone is not sufficient to drive the dopaminergic phenotype in mdDA neurons but requires Pitx3 for full activation of target gene expression. In the absence of Pitx3, Nurr1 is kept in a repressed state through interaction with the co-repressor SMRT. Highly resembling the effect of ligand activation of nuclear receptors, recruitment of Pitx3 modulates the Nurr1 transcriptional complex by decreasing the interaction with SMRT, which acts through HDACs to keep promoters in a repressed deacetylated state. Indeed, interference with HDAC-mediated repression in Pitx3-/- embryos efficiently reactivates the expression of Nurr1 target genes, bypassing the necessity for Pitx3. These data position Pitx3 as an essential potentiator of Nurr1 in specifying the dopaminergic phenotype, providing novel insights into mechanisms underlying development of mdDA neurons in vivo, and the programming of stem cells as a future cell replacement therapy for Parkinson's disease.
Two ParaHox genes,SpLoxandSpCdx, interact to partition the posterior endoderm in the formation of a functional gut
Authors: Cole Alison G. , Rizzo Francesca , Martinez Pedro , Fernandez-Serra Montserrat , Arnone Maria I.
Published: January 2009

We report the characterization of the ortholog of the Xenopus XlHbox8 ParaHox gene from the sea urchin Strongylocentrotus purpuratus, SpLox. It is expressed during embryogenesis, first appearing at late gastrulation in the posterior-most region of the endodermal tube,becoming progressively restricted to the constriction between the mid- and hindgut. The physiological effects of the absence of the activity of this gene have been analyzed through knockdown experiments using gene-specific morpholino antisense oligonucleotides. We show that blocking the translation of the SpLox mRNA reduces the capacity of the digestive tract to process food, as well as eliminating the morphological constriction normally present between the mid- and hindgut. Genetic interactions of the SpLox gene are revealed by the analysis of the expression of a set of genes involved in endoderm specification. Two such interactions have been analyzed in more detail: one involving the midgut marker gene Endo16,and another involving the other endodermally expressed ParaHox gene, SpCdx. We find that SpLox is able to bind Endo16cis-regulatory DNA, suggesting direct repression of Endo16 expression in presumptive hindgut territories. More significantly, we provide the first evidence of interaction between ParaHox genes in establishing hindgut identity, and present a model of gene regulation involving a negative-feedback loop.
The long noncoding RNA Kcnq1ot1 organises a lineage-specific nuclear domain for epigenetic gene silencing
Authors: Redrup Lisa , Branco Miguel R. , Perdeaux Elizabeth R. , Krueger Christel , Lewis Annabelle , Santos Fátima , Nagano Takashi , Cobb Bradley S. , Fraser Peter , Reik Wolf
Published: January 2009

Long noncoding RNAs are implicated in a number of regulatory functions in eukaryotic genomes. The paternally expressed long noncoding RNA (ncRNA)Kcnq1ot1 regulates epigenetic gene silencing in an imprinted gene cluster in cis over a distance of 400 kb in the mouse embryo, whereas the silenced region extends over 780 kb in the placenta. Gene silencing by the Kcnq1ot1 RNA involves repressive histone modifications, including H3K9me2 and H3K27me3,which are partly brought about by the G9a and Ezh2 histone methyltransferases. Here, we show that Kcnq1ot1 is transcribed by RNA polymerase II, is unspliced,is relatively stable and is localised in the nucleus. Analysis of conditional Dicer mutants reveals that the RNAi pathway is not involved in gene silencing in the Kcnq1ot1 cluster. Instead, using RNA/DNA FISH we show that the Kcnq1ot1 RNA establishes a nuclear domain within which the genes that are epigenetically inactivated in cis are frequently found, whereas nearby genes that are not regulated by Kcnq1ot1 are localised outside of the domain. The Kcnq1ot1 RNA domain is larger in the placenta than in the embryo, consistent with more genes in the cluster being silenced in the placenta. Our results show for the first time that autosomal long ncRNAs can establish nuclear domains, which might create a repressive environment for epigenetic silencing of adjacent genes. Long ncRNAs in imprinting clusters and the Xist RNA on the inactive X chromosome thus appear to regulate epigenetic gene silencing by similar mechanisms.
Policy on the rebound: trends and causes of delayed discharges in the NHS
Authors: Godden S , McCoy D , Pollock AM
Published: January 2009

Summary

Objectives

The Community Care (Delayed Discharges, etc.) Act, 2003 was aimed at reducing the number of patients whose discharge from hospital was delayed, incorporating financial incentives based on a model from Sweden. The Act permitted NHS hospital trusts to charge local authority Social Service Departments for delays they were deemed responsible for and was accompanied by grants aimed at supporting improvements in the transfer of care. This study aims to assess how far the subsequent reduction in delays has been due to the operation of the Act, and to evaluate the extent that the legislation increased efficiency across health and social care.

Design

Analysis and interpretation of a range of official routine health statistics plus unpublished performance data.

Setting

Data on patients delayed in hospital in England from 2001–2002 to 2006–2007 and trends in hospital activity.

Main outcome measures

Trend analysis of health statistics and performance data relating to delayed discharges and other relevant indicators.

Results

Althought there has been an overall reduction in delayed discharges, this trend predates the implementation of the Act. Overall, bed- days lost to delayed discharges accounted for only a small proportion of all bed-days – 1.6% in 2006–2007, and over the period studied the causes of the majority of delays were attributed to the NHS (68%).

Conclusions

These findings indicate lttle evidence to support the policy of charging social services to improve public sector efficiency. The focus on reducing delays should be set in the context of the wider health economy. There are a number of pressures to reduce the time patients spend in hospital including fewer beds and increasing numbers of admissions, plus a rise in emergency readmission rates is noted. There are few good data available to monitor the impact of earlier discharge, such as on the quality and availability of post-discharge care.