Population differentiation and behavioural association of the two 'personality' genes DRD4 and SERT in dunnocks (Prunella modularis).

Quantifying the variation in behaviour-related genes within and between populations provides insight into how evolutionary processes shape consistent behavioural traits (i.e. personality). Deliberate introductions of non-native species offer opportunities to investigate how such genes differ between native and introduced populations and how polymorphisms in the genes are related to variation in behaviour. Here, we compared the genetic variation of the two 'personality' genes, DRD4 and SERT, between a native (United Kingdom, UK) and an introduced (New Zealand, NZ) population of dunnocks, Prunella modularis. The NZ population showed a significantly lower number of single nucleotide polymorphisms (SNPs) compared to the UK population. Standardized F'st estimates of the personality genes and neutral microsatellites indicate that selection (anthropogenic and natural) probably occurred during and post the introduction event. Notably, the largest genetic differentiation was found in the intronic regions of the genes. In the NZ population, we also examined the association between polymorphisms in DRD4 and SERT and two highly repeatable behavioural traits: flight-initiation distance and mating status (promiscuous females and cobreeding males). We found 38 significant associations (for different allele effect models) between the two behavioural traits and the studied genes. Further, 22 of the tested associations showed antagonistic allele effects for males and females. Our findings illustrate how introduction events and accompanying ecological changes could influence the genetic diversity of behaviour-related genes.

The cerebellar bioenergetic state predicts treatment response in COQ8A-related ataxia.

INTRODUCTION: Primary coenzyme Q10 (CoQ10) deficiency, a recessive disorder associated with various defects of CoQ10 biosynthesis and widely varying clinical presentation, is customarily managed by oral Q10 supplementation but the benefit is debated. METHODS: To address this question, we mapped individual responses in two patients with COQ8A-related ataxia following coenzyme Q10 supplementation using noninvasive imaging. Metabolic 31phosphorus magnetic resonance spectroscopy imaging (31P-MRSI) and volumetric cerebellar neuroimaging were performed to quantify the individual treatment response in two patients with COQ8A-related ataxia, each compared with eight age- and gender-matched healthy control subjects. RESULTS: Post-treatment change in energy metabolite levels differed in the two patients, with higher energy levels and improved dysarthria and leg coordination in one, and decreased energy levels without clinical benefit in the other. CONCLUSIONS: Our results suggest that the cerebellar bioenergetic state may predict treatment response in COQ8A-related ataxia and highlight the potential of pathophysiology-orientated neuroimaging evidence to inform treatment decisions.

Separating the two polarities of the POLO contacts of an 26.1%-efficient IBC solar cell.

By applying an interdigitated back contacted solar cell concept with poly-Si on oxide passivating contacts an efficiency of 26.1% was achieved recently. In this paper the impact of the implemented initially intrinsic poly-Si region between p-type poly-Si and n-type poly-Si regions is investigated. Two recombination paths are identified: The recombination at the interface between the initially intrinsic poly-Si and the wafer as well as the recombination across the resulting p(i)n diode on the rear side which is aimed to be reduced by introducing an initially intrinsic region. By using test structures, it is demonstrated that the width of the initially intrinsic region ((i) poly-Si region) has a strong influence on the recombination current through the p(i)n diode and that this initially intrinsic region needs to be about 30 µm wide to sufficiently reduce the recombination across the p(i)n diode. Lateral and depth-resolved time of flight secondary ion mass spectrometry analysis shows that the high-temperature annealing step causes a strong lateral inter-diffusion of donor and acceptor atoms into the initially intrinsic region. This diffusion has a positive impact on the passivation quality at the c-Si/SiOx/i poly-Si interface and is thus essential for achieving an independently confirmed efficiency of 26.1% with 30 µm-wide initially intrinsic poly-Si regions.

Epithelial ovarian cancer and the ability to conceive.

Relationships between ovarian cancer and ability to conceive were explored in a case-control study of 188 women with histologically confirmed epithelial ovarian cancer and 539 control women in the San Francisco Bay Area. Control women consisted of two groups: those hospitalized without cancer, matched to cases by age, race, and hospital of diagnosis (n = 280); and those selected from the general population by random digital dialing, matched to cases by age, race, and telephone prefix (n = 259). Ovarian cancer risk among nulliparous (but not parous) women was positively associated with a history of unsuccessful attempts to conceive, of physician-diagnosed infertility, and of doubts about ability to conceive. Among all women, risk increased with increasing years of unprotected intercourse (P value for trend = 0.02). Risk among women having 10 or more yr of unprotected intercourse was 1.8 relative to that among women having less than 2 such yr (P = 0.01). This association was independent of parity, oral contraceptive use, and estimated years of ovulation, each associated with ovarian cancer. Further, duration of unprotected intercourse combined multiplicatively with each of these latter characteristics in increasing ovarian cancer risk. For example, while cancer risk exhibited a 2-fold range from lowest to highest years of unprotected intercourse and a 4-fold range from lowest to highest years of ovulation, risk among women in the highest joint category of these characteristics was 8 times that of women in the lowest category. We believe that some abnormality of ovulation that reduces the likelihood of conception plays a role in epithelial ovarian cancer.

Gating of hippocampal output by ß-adrenergic receptor activation in the pilocarpine model of epilepsy.

Norepinephrine acting via ß-adrenergic receptors (ß-ARs) plays an important role in hippocampal plasticity including the subiculum which is the principal target of CA1 pyramidal cells and which controls information transfer from the hippocampus to other brain regions including the neighboring presubiculum and the entorhinal cortex (EC). Subicular pyramidal cells are classified as regular- (RS) and burst-spiking (BS) cells. Activation of ß-ARs at CA1-subiculum synapses induces long-term potentiation (LTP) in burst- but not in RS cells (Wójtowicz et al., 2010). To elucidate seizure-associated disturbances in the norepinephrine-dependent modulation of hippocampal output, we investigated the functional consequences of the ß-AR-dependent synaptic plasticity at CA1-subiculum synapses for the transfer of hippocampal output to the parahippocampal region in the pilocarpine model of temporal lobe epilepsy. Using single-cell and multi-channel field recordings in slices, we studied ß-AR-mediated changes in the functional connectivity between CA1, the subiculum and its target-structures. We confirm that application of the ß-adrenergic agonist isoproterenol induces LTP in subicular BS- but not RS cells. Due to the distinct spatial distribution of RS- and BS cells in the proximo-to-distal axis of the subiculum, in field recordings, LTP was significantly stronger in the distal than in the proximal subiculum. In pilocarpine-treated animals, ß-AR-mediated LTP was strongly reduced in the distal subiculum. The attenuated LTP was associated with a disturbed polysynaptic transmission from the CA1, via the subiculum to the presubiculum, but with a preserved transmission to the medial EC. Our findings suggest that synaptic plasticity may influence target-related information flow and that such regulation is disturbed in pilocarpine-treated epileptic rats.

Evidence that anoreceptive intercourse with ejaculate exposure is associated with rapid CD4 cell loss.

OBJECTIVE: To determine whether ejaculate exposure through anoreceptive intercourse is associated with rapid CD4 cell loss. DESIGN: Self-reported behavioral, demographic data and blood samples were gathered longitudinally at ten semiannual visits from individuals participating in the Multicenter AIDS Cohort Study (MACS). PATIENTS/PARTICIPANTS: A group of 937 HIV-seropositive men who were continuously followed for four to ten semiannual visits. OUTCOME MEASURES: A loss of 10% or more in CD4 cells between the first two of any three consecutive semiannual visits that was followed by a 10% or greater loss between the second and third visits. RESULTS: A period of rapid CD4 cell loss over three semiannual visits occurred in 389 of the 937 (42%) HIV-seropositive men studied. Men who reported one or more anoreceptive intercourse partners with whom they were exposed to ejaculate (RAI-E) during the 12 months immediately preceding their visits were more than twice as likely to show this rapid CD4 cell loss compared with men with no such partners. CONCLUSIONS: The association between RAI-E partnerships and rapid CD4 cell loss suggests factors associated with ejaculate exposure (e.g., sexually transmitted diseases) may hasten the clinical progression of HIV disease. It is suggested that infectious diseases, which are known to be associated with ejaculate exposure, may be the causal factor underlying the association between RAI-E partnerships and rapid CD4 cell loss in these men, although the presence of these diseases was not ascertained in these data. HIV-infected individuals should be cautioned against unprotected anoreceptive intercourse.

D2 dopamine receptor and GABA(A) receptor beta3 subunit genes and alcoholism.

As the dopaminergic and GABAergic systems have been implicated in alcohol-related behaviors, variants of the D2 dopamine receptor (DRD2) and GABA(A) receptor beta3 subunit (GABRB3) genes were determined in a population-based association study of Caucasian non-alcoholic and alcoholic subjects. In severe alcoholics, compared to non-alcoholics, a significant increase was found in the prevalence (P = 1.7 x 10(-5)) and frequency (P = 1.6 x 10(-5)) of the DRD2 minor (A1) allele. Moreover, a significant progressive increase was observed in A1 allelic prevalence (P = 3.1 x 10(-6)) and frequency (P = 2.7 x 10(-6)) in the order of non-alcoholics, less severe and severe alcoholics. In severe alcoholics, compared to non-alcoholics, a significant decrease was found in the prevalence (P = 4.5 x 10(-3)) and frequency (P = 2.7 x 10(-2)) of the GABRB3 major (G1) allele. Furthermore, a significant progressive decrease was noted in G1 allelic prevalence (P = 2.4 x 10(-3)) and frequency (P = 1.9 x 10(-2)) in non-alcoholics, less severe and severe alcoholics, respectively. In sum, in the same population of non-alcoholics and alcoholics studied, variants of both the DRD2 and GABRB3 genes independently contribute to the risk for alcoholism, with the DRD2 variants revealing a stronger effect than the GABRB3 variants. However, when the DRD2 and the GABRB3 variants are combined, the risk for alcoholism is more robust than when these variants are considered separately.

Comparison of AIDS progression and survival in persons with pulmonary versus extrapulmonary tuberculosis in Los Angeles.

The objective of this research was to compare the demographics, acquired immune deficiency syndrome (AIDS) progression, and survival in persons with AIDS with pulmonary tuberculosis (PTB) versus extrapulmonary tuberculosis (EPTB), because there are limited population-based data on this topic. A population-based longitudinal study with 3 years of follow-up was performed. Data were collected every 6 months from medical records of persons with AIDS and TB treated at private and public medical facilities throughout Los Angeles County (LAC). Participants included a population-based sample of 216 persons with AIDS and PTB and 166 persons with AIDS and EPTB (including 113 persons with both PTB and EPTB), with an AIDS diagnosis reported in 1993. Compared to persons with AIDS with PTB, persons with AIDS and EPTB were 2.2 times more likely to be Latino than white (95% confidence intervals [CIs]: 1.2, 4.0) and 1.7 times more likely to be foreign-born (95% CIs: 1.1, 2.5). Compared to persons with AIDS with PTB, persons with AIDS and EPTB had similar antiretroviral and PCP prophylaxis use; lower CD4 counts at time of AIDS diagnosis (p = 0.0004); no differences in CD4 counts over the total follow-up period (p = 0.4); higher rates of total opportunistic infections (OIs) (incidence density ratio [IDR] = 2.0; 95% CIs: 1.6, 2.4); and comparable survival curves (p = 0.07). Persons with AIDS and EPTB had a more complicated medical course with lower CD4 counts at time of AIDS diagnosis and more OIs over the follow-up period than persons with AIDS and PTB, however the survival profiles for the two groups were comparable.

African-American physicians and smoking cessation counseling.

While African American physicians can play a key role in encouraging black patients who smoke to quit, little is known about the views and activities of these physicians with respect to antitobacco programming. In the process of developing a protocol for encouraging physicians' smoking cessation intervention, 96 African-American physicians completed a survey indicating their knowledge, attitudes, and practices relating to stop smoking counseling. Few physicians reported patient help-seeking behavior and 47.9% cited lack of patient motivation as a key barrier to intervention. Only 46.8% believed that it is possible to accomplish a lot of cessation help in a few minutes time, and 34.4% believed that setting up and maintaining an office protocol would require a great deal of effort. Explaining health risks (71.9%) and enrolling patients in programs (66.6%) were perceived as keys to patient cessation; fewer than half of the physicians surveyed discuss specific strategies for quitting with their patients. Physicians indicated a willingness to offer more counseling in the future and were open to a range of strategies for learning more about effective approaches. Our findings support the need for dissemination of such information, particularly among specialists, to support antitobacco efforts among African-American physicians.

[Value of color-coded duplex sonography in diagnosis of acute and chronic venous diseases of the lower extremity]. / Stellenwert der farbkodierten Duplexsonographie bei der Diagnostik von akuten und chronischen venösen Erkrankungen der unteren Extremität.

In a prospective study we compared colour duplex ultrasound to venography in 325 patients with clinically suspected acute lower extremity deep vein thrombosis. In 269 cases of proven thrombosis overall sensitivity and specificity of colour duplex ultrasound were 98% and in calf vein thrombosis 96%. Investigations by both methods after fibrinolytic urokinase therapy of phlebothrombosis in 53 patients revealed no significant diagnostic differences between the two methods. In 115 patients with clinically suspected chronic venous insufficiency colour duplex ultrasound allowed to differentiate between occluded, partially recanalised or normal deep veins with or without venous valve incompetence and superficial venous insufficiency. In this study colour duplex ultrasound in diagnosis of acute or chronic lower limb venous disease attained results that were comparable to those obtained by phlebography.

Postpartum and nonpostpartum depression: differences in presentation and response to pharmacologic treatment.

Following childbirth, major depression (postpartum depression) affects approximately 8-12% of new mothers. However, little is known about the pharmacological management of postpartum depression, and no studies to date have assessed differences in treatment response between women with postpartum and nonpostpartum major depression. The authors reviewed the records of 26 women with postpartum major depression and 25 women with major depression unrelated to childbearing (nonpostpartum depression) who presented to them for treatment over a 4-year period. Compared with the nonpostpartum depressed patients, the postpartum depressed women were significantly more likely to present with anxious features. Also, cases of postpartum depression were more severe than cases of nonpostpartum depression. While the postpartum patients were equally as likely to recover (as defined by a Clinical Global Impression score of 1 or 2) compared to the nonpostpartum-depressed patients, their time to response was significantly longer. By 3 weeks of pharmacotherapy, 75% of the nonpostpartum cases had recovered, in contrast to only 36% of the postpartum cases. Further, postpartum patients were significantly more likely to be receiving more than one antidepressant agent at the time of response to treatment. Length of depression prior to treatment did not explain the difference in treatment response. Presence of depressive symptoms during pregnancy and timing of onset of the depression (before vs. after 4 weeks of delivery) did not affect likelihood of treatment response in this sample. Women with postpartum depression appear to be significantly more likely than the nonpostpartum women to present with anxious features, take longer to respond to pharmacotherapy for depression, and require more antidepressant agents at the time of response to treatment.

Pharmacokinetics in low dose extrapolation using animal cancer data.

Data on rodents exposed to carcinogens indicate that their tumor probabilities are proportional to effective concentrations of parent compound or metabolites at the target tissues. This proportionality suggests that observed nonlinear dose-response curves reflect dose-dependent kinetics between applied dose rate and effective concentrations. Therefore low dose extrapolation procedures that include pharmacokinetic data could improve extrapolation accuracy. To test such procedures, we simulated bioassay and pharmacokinetic "data." Then, ignoring the mechanisms generating the data, we used four extrapolation procedures to estimate tumor probability at a low applied dose rate. Two of the procedures use a pharmacokinetic model and simulated pharmacokinetic data, and two do not. The pharmacokinetic model used for extrapolation was only an approximation to the one used to generate the pharmacokinetic data. The procedures that include pharmacokinetics often performed better and never did much worse than those that ignore them, regardless of the relations used to generate the data, the amount of experimental error in the pharmacokinetic data, and the appropriateness of the pharmacokinetic and extrapolation models used. Moreover they performed substantially better when effective concentration and tumor probability were concave-up functions of applied dose rate.

Recruitment to a school-based adult smoking-cessation program: do gender and race/ethnicity make a difference?

BACKGROUND: Recruitment to interventional research, clinical trials, and community-based health programs remains a central public health challenge, particularly among low-income and multi-ethnic populations. Utilizing existing community institutions and "opportunistic" communication channels within these settings for recruitment seems an optimal strategy for overcoming barriers to participation. However, such institutions frequently serve heterogeneous populations, and little is known regarding intra-community variations in program uptake. METHODS: This paper reports the gender and race/ethnic differences in subject characteristics and enrollment patterns among 435 Latino and African American participants in a smoking-cessation program delivered through one such community institution, an inner-city school district in Los Angeles County. RESULTS: Enrollees were more likely to be female and Latino. Recruitment strategies tailored specifically to this program were more effective then recruitment through channels such as regular school activities, particularly among African Americans. CONCLUSIONS: Intragroup variations need to be carefully considered in the design and implementation of such programs if they are to receive acceptance and to succeed.

Censored survival data with misclassified covariates: a case study of breast-cancer mortality.

PIP: A number of alternative models are used to examine the relationship of survival among breast-cancer patients to the time since diagnosis and to the stage of the disease at diagnosis. The data concern 2,495 women aged 55-64 diagnosed with breast cancer in the San Francisco Bay area of California. In particular, the authors examine the extent to which the bad fit of simple models for breast-cancer survival is due to measurement error in the covariates.^ieng

[Prosthesis implantation of the rheumatoid arthritis shoulder]. / Endoprothetik der rheumatischen Schulter.

Omarthritis occurs frequently during the early course of rheumatoid arthritis. Many rheumatoid patients ignore omarthritis because of the good compensation mechanism of the shoulder. Sonography and tomography enable early diagnosis of omarthritis before deterioration is radiologically visible. Arthroplasty gives better results when the musculotendinous rotator cuff is still intact. Therefore, arthroplasty should be performed before severe damage develops. Early indication for cup arthroplasty of the humeral head is justified because of better options in revision surgery. Glenoid components show a high incidence of radiolucency and loosening in rheumatoid patients. Cemented hemiarthroplasties show the lowest rate of loosening.

Oxygen consumption and resting metabolic rate in sepsis, sepsis syndrome, and septic shock.

OBJECTIVE: To test the hypothesis that variations in oxygen consumption (VO2) and resting metabolic rate reflect the severity of bacterial infections and reflect the development of sepsis syndrome and septic shock. DESIGN: Observational study with sequential measurements of VO2 and resting metabolic rate by expiratory gas analysis. SETTING: Medical intensive care unit. PATIENTS: Thirty patients, treated primarily for presumed bacterial infection, were examined on 118 treatment days. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: VO2 and resting metabolic rate were measured by expiratory gas analysis. For mechanically ventilated patients, a measurement system was developed, based on a paramagnetic oxygen sensor, an infrared CO2 sensor, and digital signal averaging. Measurements in spontaneously breathing patients were performed with a metabolic monitor. Patients were assigned by clinical criteria to the following groups: sepsis, sepsis syndrome, and septic shock. The lowest VO2 value of each patient in each stage was evaluated. Mean VO2 in 15 patients with sepsis was 180 +/- 19 (SD) mL/min/m2, in 11 patients with sepsis syndrome 156 +/- 22 mL/min/m2, and in eight patients with septic shock 120 +/- 27 mL/min/m2 (p < .001). Mean resting metabolic rate in sepsis was +55 +/- 14%, in sepsis syndrome +24 +/- 12%, and in septic shock +2 +/- 24% (p < .001). Mean oxygen delivery (DO2) was 501 +/- 116 mL/min/m2 in sepsis, 515 +/- 186 mL/min/m2 in sepsis syndrome, and 404 +/- 96 mL/min/m2 in septic shock. Oxygen extraction (VO2/DO2) was highest in sepsis (0.39 vs. 0.33 in sepsis syndrome and 0.29 in septic shock). During recovery from sepsis syndrome or septic shock, a significant increase in resting metabolic rate to +61 +/- 22% was measured in nine patients. CONCLUSIONS: In sepsis syndrome, VO2 and resting metabolic rate are enhanced by 30% compared with normal basal metabolism, but they are markedly reduced compared with uncomplicated sepsis. The higher VO2 in uncomplicated sepsis is flow independent. The noninvasive measurement of VO2 and resting metabolic rate by expiratory gas analysis therefore can be used as a quantitative staging and monitoring parameter for the development of sepsis syndrome and septic shock.

[Sporotrichosis as the cause of a leg ulcer]. / Sporotrichose als Ursache eines Ulcus cruris.

A young man presented at Lugala Lutheran Hospital (Tanzania) with an ulcer on his lower leg which had developed over the past 9 weeks. Subcutaneous nodules and plaques were found all the way up to his groin; this observation prompted a strong suspicion that the patient had the lymphocutaneous form of sporotrichosis which had not been seen at this hospital before. The diagnosis was confirmed histopathologically. The patient was then treated with saturated solution of potassium iodide.

[High-dosage cotrimoxazole therapy of disseminated Nocardia brasiliensis infection]. / Hochdosierte Cotrimoxazol-Therapie einer disseminierten Nocardia-brasiliensis-Infektion.

After a scraping injury to the skin a 47-year-old man developed a generalized Nocardia brasiliensis infection with cutaneous, pulmonary and cerebral dissemination. There was no predisposing underlying illness. High-dosage cotrimoxazol and short-term intrathecal and systemic gentamycin administration achieved extensive healing. This form of treatment would thus seem capable of reversing the otherwise poor prognosis of generalized N. brasiliensis infection.

[Comparative measurement of oxygen uptake and cardiac output at rest and during stress--evaluation of a new monitor for continuous determination of oxygen uptake and carbon dioxide release]. / Vergleichende Messungen von Sauerstoffaufnahme und Herzzeitvolumen in Ruhe und unter Belastung--Evaluierung eines neuen Monitors zur kontinuierlichen Bestimmung der Sauerstoffaufnahme und Kohlendioxydabgabe.

A new device for the continuous monitoring of oxygen uptake and carbon dioxide delivery is presented, which is based on a continuous expired gas analysis using a paramagnetic oxygen and an infrared-absorption carbon dioxide sensor. To validate the results, data of measured oxygen uptake and cardiac output calculated by the Fick principle were compared to synchronous thermodilution measurements at rest and during exercise. Measurements were performed at rest on 18 patients, additionally 13 of the patients were exercised with either 25 W or 50 W workload. The results indicate, for both measurement series, a significant correlation (r greater than 0.95, p less than 0.001) and exemplify that the measurement of oxygen uptake by expired gas analysis permits a precise analysis of the cardiovascular transport function during exercise.