The Role of Nutrients and Nutritional Signals in the Pathogenesis of Vibrio cholerae.

Vibrio cholerae, the agent of cholera, is a natural inhabitant of aquatic environments. Over the past decades, the importance of specific nutrients and micronutrients in the environmental survival, host colonization, and pathogenesis of this species has become increasingly clear. For instance, V. cholerae has evolved ingenious mechanisms that allow the bacterium to colonize and establish a niche in the intestine of human hosts, where it competes with commensals (gut microbiota) and other pathogenic bacteria for available nutrients. Here, we discuss the carbon and energy sources utilized by V. cholerae and what is known about the role of nutrition in V. cholerae colonization. We examine how nutritional signals affect virulence gene regulation and how interactions with intestinal commensal species can affect intestinal colonization.

Preferences for oral fluid rapid HIV self-testing among social media-using young black, Hispanic, and white men-who-have-sex-with-men (YMSM): implications for future interventions.

OBJECTIVES: We assessed preferences of social media-using young black, Hispanic and white men-who-have-sex-with-men (YMSM) for oral fluid rapid HIV self-testing, as compared to other currently available HIV testing options. We also identified aspects of the oral fluid rapid HIV self-test that might influence preferences for using this test instead of other HIV testing options and determined if consideration of HIV testing costs and the potential future availability of fingerstick rapid HIV self-testing change HIV testing preferences. STUDY DESIGN: Anonymous online survey. METHODS: HIV-uninfected YMSM across the United States recruited from multiple social media platforms completed an online survey about willingness to use, opinions about and their preferences for using oral fluid rapid HIV self-testing and five other currently available HIV testing options. In a pre/post questionnaire format design, participants first indicated their preferences for using the six HIV testing options (pre) before answering questions that asked their experience with and opinions about HIV testing. Although not revealed to participants and not apparent in the phrasing of the questions or responses, the opinion questions concerned aspects of oral fluid rapid HIV self-testing (e.g. its possible advantages/disadvantages, merits/demerits, and barriers/facilitators). Afterward, participants were queried again about their HIV testing preferences (post). After completing these questions, participants were asked to re-indicate their HIV testing preferences when considering they had to pay for HIV testing and if fingerstick blood sample rapid HIV self-testing were an additional testing option. Aspects about the oral fluid rapid HIV self-test associated with increased preference for using the test (post-assessment vs pre-assessment of opinion topics) were identified through multivariable regression models that adjusted for participant characteristics. RESULTS: Of the 1975 YMSM participants, the median age was 22 years (IQR 20-23); 19% were black, 36% Hispanic, and 45% white; and 18% previously used an oral fluid rapid HIV self-test. Although views about oral fluid rapid HIV self-testing test were favorable, few intended to use the test. Aspects about the oral fluid rapid HIV self-test associated with an increased preference for using the test were its privacy features, that it motivated getting tested more often or as soon as possible, and that it conferred feelings of more control over one's sexual health. Preferences for the oral fluid rapid HIV self-test were lower when costs were considered, yet these YMSM were much more interested in fingerstick blood sampling than oral fluid sampling rapid HIV self-testing. CONCLUSIONS: Despite the perceived advantages of the oral fluid rapid HIV self-test and favorable views about it by this population, prior use as well as future intention in using the test were low. Aspects about oral fluid rapid HIV self-testing identified as influential in this study might assist in interventions aimed to increase its use among this high HIV risk population as a means of encouraging regular HIV testing, identifying HIV-infected persons, and linking them to care. Although not yet commercially available in the United States, fingerstick rapid HIV self-testing might help motivate YMSM to be tested more than oral fluid rapid HIV self-testing.

The associations between fatigue, apathy, and depression in Parkinson's disease.

OBJECTIVES: Fatigue and apathy are two of the most common and most disabling non-motor symptoms of Parkinson's disease (PD). They have a high coincidence and can often be confused; moreover, their relationship is not fully understood. The aim of our study was to describe the coincidence of apathy with different fatigue domains in the presence/absence of depression and to separately describe the associations of different aspects of primary and secondary fatigue with apathy and other clinical and disease-related factors. MATERIALS AND METHODS: A total of 151 non-demented patients with PD were examined using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Starkstein Apathy Scale, Multidimensional Fatigue Inventory (MFI), Beck Depression Inventory-II, and Epworth Sleepiness Scale. RESULTS: The prevalence and severity of fatigue and apathy were significantly higher in depressed PD patients. However, our results show that depression, fatigue, and apathy can be clearly distinguished in PD. Apathy was associated with the MFI's-reduced motivation domain in both depressed and non-depressed patients. However, apathy was associated with mental fatigue aspects only in non-depressed patients, and it was not related to the physical aspects of fatigue in any of the studied groups. CONCLUSIONS: Although the pathophysiology of fatigue and apathy in PD is clearly multifactorial, in a proportion of PD patients, these symptoms are associated with depression, dopaminergic depletion in the mesocorticolimbic structures, and disruption of the prefrontal cortex-basal ganglia axis. Therefore, in some PD patients, adequate management of depression and optimal dopaminergic medication may improve both fatigue and apathy.

[Collaborations in publications on pediatric anesthesiology in the D-A-CH countries]. / Kollaborationen bei kinderanästhesiologischen Publikationen im D-A-CH-Raum.

BACKGROUND: Collaborations are an essential element of scientific activity and particularly important in fields such as pediatric anesthesiology, where the evidence base in general is relatively limited. A recent scientometric analysis revealed a geographic diversification of publication activity in pediatric anesthesiology within the last two decades, accompanied by a surge in international collaborations. OBJECTIVES: Given the hypothesis of a similar growth in the activity and dynamics of publications in pediatric anesthesiology, the objective of this scientometric study was to analyze the publication activity and collaboration habits in research in pediatric anesthesiology from Germany, Austria and Switzerland (D-A-CH). METHOD: This secondary analysis identified all publications on pediatric anesthesiology with an affiliation from the D­A-CH countries between 2001 and 2020 from PubMed and Web of Science. The query parameters included the timeframe 2001-2020, authors' affiliations tied to anesthesiology departments (using various forms of the term "anesthesia"), and the mention of pediatric interest in titles or abstracts. The data underwent standardization to account for linguistic variations. The publications were assigned to a state, city and institution based on the correspondence address, to a year based on the publication date and to a source based on the journal. The primary endpoint was publication activity and dynamics, represented by the number of publications and the respective growth rates (calculated as the linear regression slope). Secondary endpoints included the share of collaborations within and outside the D­A-CH region (at the country and institutional level), the distribution of publication activity and the most prominent sources of publications. RESULTS: Between 2001 and 2020 a total of 3406 publications on pediatric anesthesiology involving authors from the D­A-CH countries were identified. Of these 2807 (82.4%) had a correspondence address in D­A-CH. The average annual growth rate of publications with a correspondence address was + 2.9% for the D­A-CH countries and + 7.7% for publications with collaborations. The number of publications in which an institution from D­A-CH was named as a coauthor from a correspondence address outside D­A-CH also increased by an average of 7.4% per year during the study period. The majority of collaborations occurred between institutions within the D­A-CH region, although Swiss institutions exhibited a much higher proportion of collaborations outside the region. Of all publications with a correspondence address 90% originated from 46 cities. The most prominent source was Die Anästhesiologie for publications from Germany, and Pediatric Anesthesia for publications from Austria and Switzerland. CONCLUSION: The number of publications in pediatric anesthesiology from the D­A-CH countries has increased over the past two decades, accompanied by a surge in collaborations. It is hoped that increased collaboration will contribute to a higher level of evidence in pediatric anesthesiology care.

Condoms and developmental contexts in younger adolescent boys.

BACKGROUND: Condom use is a key part of sexually transmitted infection (STI) prevention for young men. Yet little is known about how younger adolescent boys initially learn about and use condoms. We examined sources of information, attitudes towards, acquisition, practice and early use of condoms among 14-16-year-old boys. METHODS: Thirty 14-16-year-old boys were recruited from a teen clinic serving a community with high STI rates and were asked open-ended questions about condoms, such as, "Where did you learn about condoms?" and "In what situations would you/would you not, use condoms." Interviews were audio recorded, transcribed and coded. Qualitative analysis focused upon key concepts and shared social cognitions related to condom use. RESULTS: Both sexually inexperienced and experienced participants perceived that sex feels or would feel less pleasurable with condoms. For almost all participants, families were the primary source of both information about condoms and of condoms themselves. This information focused on pregnancy prevention, with STIs secondary. Participants' views of condoms fell into three developmental groups: not interested in condoms and equating their use with interest in sex; exploring condoms out of either curiosity or in preparation for sex; and experienced with condom use. Exploring included behaviours such as checking condoms out and trying them on. CONCLUSIONS: Our findings of existing negative perceptions of condoms, the importance of families in learning about condoms and the developmental need to test and try on condoms before use have implications for adolescent STI prevention programmes.

Field collection of rectal samples for sexually transmitted infection diagnostics among men who have sex with men.

Rectal sexually transmitted infections (STIs) are common in men at risk for urethral infections with these pathogens, particularly men who have sex with men (MSM). However, for those individuals not regularly seen by a clinician, screening for rectal STI is not currently a widespread option. Qualitative data and samples (i.e. self-obtained rectal specimens) were collected from 75 MSM in a variety of venues. Upon completion of the rectal self-sampling, each participant completed a brief interview regarding their overall experience with the process. Participants reported an overall high level of acceptability and comfort-level involved with self-sampling for rectal STI. Of the majority of men who agreed to provide a rectal self-sample, all reported that they would provide a sample again in the future. However, many men also appreciated the interaction with a health-care provider that a clinical setting offered. In conclusion, self-sampling is a feasible and acceptable option when offered to MSM in a range of community-based venues. Further research is needed to determine which combinations of STI testing and treatment methods (including self-sampling) are most appropriate for diverse groups of men.

Surface Activity Profiling (SAP): A potential means of predicting intestinal membrane permeability.

Early characterization of new drug substances intended for oral application includes not only physicochemical properties and stability but also the ability of the substance to permeate through the intestinal mucosa. In this work, a rapid screening method, surface activity profiling (SAP), is proposed as an alternative to animal studies and screening in cell cultures. Measurements are made with a multichannel tensiometer and require only 50 µl of stock solution for the complete permeability analysis. Correlation of SAP results with human absorption was demonstrated for marketed drugs and with absorption in rats for development compounds of Boehringer Ingelheim. Cross-laboratory results for marketed drugs showed excellent agreement. For early stage investigations of lead compounds, where only small amounts of the compound are available, the SAP method appears to be an effective and fast tool to accurately predict fa, provided the compound is amphiphilic.

Stage of goose embryo development at oviposition depending on genotype, flock age, and period of laying.

Embryo development and chick quality are influenced by parental genotype, age, nutrition, environment, and flock management. The aim of study was to determine if genotype, age of goose or eggs laid near the onset of egg production vs. eggs laid near the end of reproduction influence the stage of embryo at oviposition. Three experiments were undertaken. To compare genotypes (Experiment 1) 150 eggs were collected from 3-year-old commercial line White Koluda (WK) geese and from two breeds involved in a genetic resources conservation program, Zatorska (Za) and Bilgoraj (Bi). Age comparison (Experiment 2) was conducted with 200 eggs collected from 1-, 2-, 3-, and 4-year-old WK geese. To compare laying periods (Experiment 3), 150 WK eggs were collected at the first week of March and 100 at the second half of June. Eggs were stored for 72 h at 16°C, staged using Eyal-Giladi and Kochav (EGK, Roman numerals) and Hamburger and Hamilton (HH, Arabic numerals) procedures. Experiment 1: Individual breed differences were evident with Stage X EGK embryos comprising 42.4, 33.3, and 38.7% in the eggs examined from the WK, Bi, and Za, respectively. For all breeds combined, 38.8% of the embryos were in Stage X, but in the next order in WK there was stage XI (18.2%), while in geese from the genetic reserve it was stage XIII (Bi - 33.3; Za - 29.0%). Experiment 2: In eggs of 1-, 2-, and 3-year-old WK geese, the majority of embryos (38.7, 32.4 and 42.2%, respectively) were in Stage X. In contrast, in 4-year-old geese the embryos were in Stage XI (36.1%). Experiment 3: In eggs collected in March and in June most of embryos were in Stage X (33.7% and 43.6%, respectively). In addition, more developmentally advanced stages (XI-XIII) were similar in both periods. However, embryos in Stage 2 HH were only observed in eggs collected at the end of laying season. Interestingly, earlier stages (VI-IX) were observed exclusively in the eggs collected in March.

Mastery, functional disability and perceived health status in patients with multiple sclerosis.

BACKGROUND AND PURPOSE: Multiple sclerosis (MS) is a chronic disease that is difficult to predict and to cope with. Mastery refers to the extent to which patients see themselves as being in control of the forces that affect their lives. It may play an important role in perceived health status and well-being. The purpose of this study was to clarify whether mastery is associated with functional disability and perceived health status in MS patients and how such an association might function. METHODS: Two hundred and three MS patients completed the Short-Form-36 Health Survey as well as the Pearlin-Schooler Mastery Scale. Functional disability was assessed using the Kurtzke Expanded Disability Status Scale. Hierarchical multiple linear regression analyses were performed on the data from two MS age groups: <45 and > or =45 years of age. RESULTS: Functional disability was negatively associated with perceived physical health status in both age groups and with perceived mental health status in younger age group. Mastery was positively associated with perceived health status in older age group. DISCUSSION: The findings confirm that mastery might be helpful for older MS patients. Education strategies for MS patients aimed at personal empowerment for the maintaining of physical and mental well-being may be important.

Impact of fatigue on quality of life in patients with Parkinson's disease.

BACKGROUND AND PURPOSE: Fatigue is frequent and important in the lives of Parkinson's disease (PD) patients. It is multidimensional, with physical and mental aspects. The aim of our study was to explore the impact of fatigue on quality of life (QoL) for PD patients. METHODS: The sample consisted of 175 PD patients from Eastern Slovakia (52% males, mean age 68.2 +/- 9.2, mean disease duration 7.4 +/- 6.7). The Multidimensional Fatigue Inventory (five dimensions), the Parkinson's Disease Quality of Life Questionnaire (eight dimensions) and the Unified Parkinson's Disease Rating Scale were used. Demographic data were obtained in a structured interview. Fisher's exact test, t-test, and multiple linear regression analysis were used. RESULTS: Different aspects of fatigue selectively explained different domains of QoL - physical dimensions of fatigue were connected with Mobility and Activities of daily living; mental fatigue dimensions affected Cognition, Emotional well-being, Communication and Activities of daily living; general fatigue was related to Bodily discomfort. The explained variances varied from 5% (Social support) to 65% (Activities of daily living). CONCLUSION: Fatigue combined with worse functional status appears to be a significant contributor to poor quality of life. Its multidimensional construct can be used to develop strategies for improving specific aspects of fatigue to improve QoL for PD patients.

Virulence of low pathogenicity H7N2 avian influenza viruses from the Delmarva peninsula for broiler and leghorn chickens and turkeys.

The virulence of low pathogenicity (LP) type A H7N2 avian influenza virus (AIV) isolates recovered from chickens in Delaware and the eastern shore of Maryland in 2004 was evaluated. Three-week-old leghorn- and broiler-type chickens and turkeys were inoculated via the conjunctival sac with 10(3.5)-10(4.0) 50% embryo infections dose (EID50) of virus per bird with A/ chicken/Delaware/Viva/04, A/chicken/Delaware/Hobo/04, and A/chicken/Maryland/Minh Ma/04. In broilers, the viruses produced respiratory signs, airsacculitis, and microscopic lesions in the trachea and lung. In contrast, signs and lesions were less severe in turkeys, and they were rarely observed in specific-pathogen-free (SPF) leghorns. In broilers and SPF leghorns, AIV peaked on day 3 postinoculation (PI), based on virus isolation and real-time reverse transcription-polymerase chain reaction, and antigen capture testing. Infection in turkeys peaked on day 7 PI. Serum antibodies generally were detected earlier in broilers (day 7 PI) than in turkeys or SPF leghorns (day 14 PI) using agar gel immunodiffusion, hemagglutination-inhibition, and the enzyme-linked immunosorbent assay. A second trial was performed to further examine the disease susceptibility of the leghorn chicken given the comparatively mild responses noted in the first trial. A 10-fold higher dose of 10(4.5)-10(5.0)EID50 per chick given via the conjunctival sac was used. In addition, commercial-type leghorns were tested as were chicks from the SPF leghorn source. The higher AIV dose resulted in more rapid and consistent rates of infection and higher serum antibody responses in both types of leghorn chickens. However, as observed in the first trial, clinical signs and microscopic lesions in both types of leghorns were infrequent and very mild. These findings indicate leghorn-type chickens, which are commonly used for pathogenicity assessments because of their availability, may not be the most suitable host for evaluating the virulence potential of LP AIV.

Introduction to the OrBiTo decision tree to select the most appropriate in vitro methodology for release testing of solid oral dosage forms during development.

The EU research initiative OrBiTo (oral biopharmaceutics tools) involving partners from academia, pharmaceutical industry, small medium enterprises and a regulatory agency was launched with the goal of improving tools to predict the absorption of drugs in humans and thereby accelerating the formulation development process. The OrBiTo project was divided into four work packages (WP), with WP2 focusing on characterization of drug formulations. The present work introduces the OrBiTo WP2 Decision Tree, which is designed to assist the investigator in choosing the most appropriate in vitro methods for optimizing the oral formulation design and development process. The WP2 Decision Tree consists of four stages to guide the investigator. At the first stage, the investigator is asked to choose the formulation type of interest. At the second stage, the investigator is asked to identify which type of equipment (compendial/modified/noncompendial) is preferred/available. At the third stage, characteristics of the active pharmaceutical ingredient (API) are evaluated and in the fourth stage of the decision tree, suitable experimental protocols are recommended. A link to the living Decision Tree document is provided, and we now invite the pharmaceutical sciences community to apply it to current research and development projects and offer suggestions for improvement and expansion.

Goose embryonic development from oviposition through 16 hours of incubation.

Normal tables provide an objective step-wise description of the morphological development of an embryo. Such tables have been described for the chicken, turkey, quail, and duck embryos, but there is no such staging table for goose embryos. As the goose has one of the longest incubation periods of all the poultry species and embryo mortality during incubation is relatively high, a normal table of goose embryo development would be useful in assessing the morpho-genetic status of the goose embryo before and during incubation. In this study, embryos were isolated from commercial White Koluda goose eggs stored no longer than four days in a cool room (18°C) prior to incubation and after 4, 8, 12, and 16 h of incubation. Embryo staging was based on the normal tables described for the chicken by Eyal-Giladi and Kochav (EGK) and Hamburger and Hamilton (HH). Goose embryos from unincubated eggs were at Stage X and XI EGK and after 16 h of incubation the majority of embryos were between Stages 2 and 4 HH. Our results suggest that while the stage of development of the embryo in the unincubated goose egg is similar to that reported for the chicken, although the diameter of goose embryo is slighter larger. Following incubation, a goose embryo advances more slowly than a chicken embryo up to 16 h of incubation.

Incidence of Diabetes Mellitus After Kidney Transplantation in Slovakia: Multicentric, Prospective Analysis.

BACKGROUND: The incidence rate of post-transplant diabetes mellitus (PTDM) after kidney transplantation (KT) is 5% to 40%. The objective of this analysis was to identify the risk factors of PTDM after KT in the Slovak Republic (SR). METHODS: In the group of 133 patients/non-diabetics, we identified the risk factors of PTDM in the monitored period of 12 months from transplantation. RESULTS: The incidence of PTDM in the SR in 2014 was 38.3%. By logistic regression, we discovered that the age at the time of KT [odds ratio, 1.0885; 95% CI, 1.0222-1.1592; P = .0082], the value of body mass index (BMI) at the time of KT [odds ratio, 1.4606; 95% CI, 1.0099-2.1125; P = .0442], and the value of insulin resistance index (homeostatic model assessment for insulin resistance) at the time of KT [odds ratio, 2.5183; 95% CI, 1.7119-3.4692; P < .0001] represented predictive factors of PTDM. The independent risk factors of PTDM in our group were age at the time of KT of more than 60 years [HR 0.3871; 95% CI 0.1659-1.7767; P = .0281], waist circumference at the time of KT in men more than 94 cm and in women more than 80 cm [HR, 3.4833; 95% CI, 1.2789-9.4878 (P = .0146)], BMI at the time of KT [HR 3.0011; 95% CI 1.0725-8.3977 (P = .0363)], and triacylglycerols at the time of KT more than 1.7 mmol/L [HR, 2.9763; 95% CI, 1.0141-8.7352; P = .0471]. CONCLUSIONS: In the group of Slovak patients after kidney transplantation, the dominating risk factor for PTDM development was insulin resistance prior to KT.

Response of rat pituitary anterior lobe prodynorphin products to changes in gonadal steroid environment.

The total content of rat pituitary anterior lobe (AL) immunoreactive (ir) dynorphin A (ir-Dyn A) and ir-dynorphin B (Dyn B) increased in male rats between 15 and 58 days of age, but there was little alteration in the concentration of ir-Dyn A or B expressed relative to protein content. Adult rats (90 days of age) had lower concentrations of these peptide immunoreactivities in the AL. Castration of 58-day-old male rats produced a testosterone-reversible loss of ir-Dyn A and B by 50-60% 3 days after surgery. Thereafter, the levels of these peptides gradually increased to 2.5 times the levels found in control animals at 1 month after castration. These effects of castration on AL dynorphin were not seen in 15-day-old rats and were much less marked in adults. Similar changes were seen in the levels of other prodynorphin products, alpha- and beta-neo-endorphin (ir-alpha-nEnd and ir-beta-nEnd), and ir-[Leu5]enkephalin (ir-LE). Administration of testosterone (100 micrograms/100 g BW) to castrated rats for 2 days largely prevented the drop in the levels of AL ir-Dyn A and B. Ovariectomy produced an increase in the levels of ir-Dyn A, Dyn B, alpha-nEnd, beta-nEnd, and LE 2 weeks after surgery, but, in contrast to castration, no significant decrease was seen 3 days after ovariectomy. These changes in AL content of dynorphin-related peptides after castration or ovariectomy directly reflect those previously reported for AL content of LH. The mechanisms regulating storage (and perhaps secretion) of AL peptides derived from prodynorphin may be similar to those regulating storage and secretion of LH and FSH in rat AL. AL ir-LE could potentially arise from proenkephalin A or prodynorphin (proenkephalin B). Ir-LE levels in AL were approximately 10 times higher than the levels of ir-[Met5]-enkephalinyl-Arg-Gly-Leu (ME-RGL) in male rat AL, and changes in ir-LE content after castration were very similar to those observed in other prodynorphin-derived peptides, but different from the effects of castration on ir-ME-RGL. It is possible that prodynorphin is a major source of AL ir-LE.

Characterization of binding of [3H]GBR 12935 (1-[2-(diphenylmethoxy)ethyl]-4-(3-phenylpropyl)-piperazine) to membranes and to solubilized membrane extracts from terminal field regions of mesolimbic, mesocortical and nigrostriatal dopamine pathways.

The binding characteristics of [3H]GBR 12935 (1-[2-(diphenylmethoxy)ethyl]-4-(3-phenylpropyl)piperazine), a selective dopmaine uptake inhibitor, were examined in intact membrane preparations and solubilized extracts of terminal field regions of dopamine pathways in the brain of the rats. There were many similarities in the properties of binding sites for [3H]GBR 12935 in the striatum, nucleus accumbens and olfactory tubercle. The binding of [3H]GBR 12935 was saturable and the affinity constants were not significantly different between regions of the brain. The binding of [3H]GBR 12935 was inhibited by amfonelic acid, GBR 12909, mazindol, methylphenidate and cocaine, with comparable affinities in each region of the brain and with the same order of potency in both preparations. Furthermore, the rank order of potencies for inhibiting the binding of [3H]GBR 12935 was the same as for inhibiting the uptake of [3H]dopamine in these regions of the brain. There did appear to be some degree of heterogeneity of binding sites for [3H]GBR 12935 in each of these regions of the brain, as both amfonelic acid and mazindol were best fitted by two-site models. Whether this apparent heterogeneity was due to the existence of two distinct binding sites or to two components of a single site is unclear. It did not, however, appear to be due to binding to uptake sites for norepinephrine or serotonin, as neither nisoxetine nor fluoxetine, selective inhibitors of the uptake of norepinephrine and serotonin, respectively, inhibited the binding of [3H]GBR 12935, at concentrations which inhibit the uptake of norepinephrine or serotonin.

Ontogeny of growth hormone (GH) binding in the domestic turkey: evidence of sexual dimorphism and developmental changes in relationship to plasma GH.

The post-hatch ontogeny of hepatic GH binding and its relationship to GH plasma profile characteristics in male and female turkeys of slow- (RBC-2) and fast-growing (F; selected from RBC-2) genetic lines were determined. Specific binding of 125I-labelled recombinant chicken GH to crude hepatic membrane preparations (100,000 g pellet) was determined at 2, 4, 8, 14 and 24 weeks of age for both total (occupied plus free; 4 mol MgCl2/l pretreatment) and free (without MgCl2 pretreatment) binding sites. Characteristics of the plasma GH profile were measured at each age by serial blood sampling through indwelling jugular vein catheters. When specific binding to either free or total sites was expressed on a whole organ basis (i.e. hepatic GH-binding capacity/bird), binding increased dramatically (P less than 0.0001) with increasing age over both lines and sexes. Total binding capacity (free plus occupied sites) per bird was greater for females than for males at 24 weeks of age (P less than 0.04), as birds reached sexual maturity, but did not differ between fast- and slow-growing lines at any age. Available binding capacity (free sites) per bird was greater for the faster growing F than RBC-2 line at the older ages when body size was most divergent (14 and 24 weeks of age; P less than 0.01, P less than 0.06 respectively), but did not differ between sexes. Correlation analysis at individual ages revealed a progressive change in the nature of the relationship between hepatic GH binding, plasma GH and somatic growth.(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnostic specificity of synovial lesions.

Sections of synovium from 393 operations on diseased joints were re-examined without knowledge of the clinical findings. Specimens were scored for each of 37 histopathologic features. Independently, patients were assigned to one of 10 diagnostic groups after review of all available clinical data. Computer analysis revealed statistically significant differences in the incidence of one or more histologic parameters between the members of all except three of the possible disease pairs. The possibility of exploiting these differences to increase diagnostic precision was examined.

A statistical approach to the histopathologic diagnosis of synovitis.

Synovial tissue from 393 operations on diseased joints were scored for each of 37 histopathologic variables; the patients fell into 10 clinically defined diagnostic categories. The five most populous of these diagnostic groups provided a data set for calculating diagnoses based on histopathologic findings. For each pair of clinical diagnostic categories we derived a linear discriminant function dependent solely on the histopathologic assessments. The functions gave a numerical score for segregating each case into one of the diagnostic categories. The histopathology based diagnoses agreed with the clinical diagnoses in 54 to 78 per cent of the cases. Illustrations of the application of this technique are presented.

Mu and delta opioid receptor gene expression after chronic treatment with opioid agonist.

Levels of mRNA coding for mu and delta opioid receptors were evaluated by competitive PCR in regions of rat brain where adaptive changes in opioid regulation of adenylyl cyclase occur following chronic morphine treatment. Correlation between receptor protein and mRNA levels after exposure to full and partial agonists were also investigated in NG108-15 cells. Different basal gene expression levels of mu and delta opioid receptors were found in the caudate-putamen, nucleus accumbens, thalamus and periaquaductal gray. After continuous morphine treatment for 7 days both mu and delta opioid receptor mRNA levels were unchanged in all four regions compared with saline-treated controls. In NG108-15 cells marked down-regulation of delta opioid receptors as measured by radioligand binding was observed after 5 or 24 h full agonist (D-Ser3-Leuenkephalin; DSLET) treatment. Morphine, a partial agonist at delta receptors, did not reduce receptor number at either time point. The reduction in delta receptor binding after DSLET treatment was not accompanied by significantly diminished levels of delta receptor mRNA. Unaltered mu and delta receptor mRNA levels in brain after chronic morphine exposure make it unlikely that adaptive changes in the transcription of these genes play a role in the observed tolerance in opioid regulation of adenylyl cyclase.