The cGMP synthesis and PKG1 expression in murine lymphoid organs

Numerous reports indicate that cyclic 3',5' guanosine monophosphate (cGMP) is involved in the regulation of immune processes. However, the mechanisms responsible for the synthesis of this nucleotide and its signaling pathways in immune cells are still not well recognized. The aim of our studies was to establish: 1) which form of guanylyl cyclase (GC) synthesizes cGMP in murine lymphoid organs and 2) whether the same organs express the isoforms PKG1alpha and/or PKG1beta of protein kinase G, known as possible target for synthesized cGMP. Cells isolated from thymus, lymph nodes, and spleen were treated with activators (SNP, ANP, CNP, STa) of soluble or particulate cyclases. Sodium nitroprusside (SNP) elevated intracellular cGMP 2-fold in thymic and lymph node cells and about 10-fold in spleen cells. Atrial natriuretic peptide (ANP) caused modest but statistically significant increases of cGMP in cells of all three organs. Additionally, spleen cells elevated their cGMP content about 2-fold in response to C-type natriuretic protein (CNP). In cellular homogenates of the all analyzed organs, the antibody anti-PKG1beta stained the 78 kDa band corresponding to the molecular mass of PKG1. Only homogenates of spleen cells were stained by the antibody recognizing PKG1alpha. Our results indicate that in the investigated organs cGMP may be synthesized mainly by soluble GC in response to nitric oxide. The modest increase of cGMP upon stimulation by ANP suggests that in all these organs either exists only a small subpopulation of cells that express particulate cyclase GC-A or GC-A is expressed at very low level. In spleen cells, however, cyclase GC-B appears to be the more active enzyme. Elevated cGMP concentration may in turn activate PKG1beta in thymus, lymph node, and spleen cells and also PKG1alpha in spleen cells.     

The activity of erythrocyte enzymes in rats subjected to running exercises

Summary The studies were carried out on male Wistar rats subjected to running within an electric rotating drum. The animals were divided into four experimental groups, differing one from another as to the duration of training. Each training session lasted 30 days. In the first group the daily run lasted 3 min, in the second group 5 min; in the third group, a 1 min run on the first day, and one min longer on each successive day; in the fourth group a 2 min run on the first day and for two min longer on each successive day.The determinations made prior to and after training included the peripheral blood erythrocyte (Er) and reticulocyte (Ret.) count, the hemoglobin concentration (Hb) and packed cell volume (PCV) and, determined by spectrophotometric methods, the activity of pyruvate kinase (PK), glucose-6-phosphate dehydrogenase (G6PD) and glutathione reductase (GR). Training induced an improvement of all enzymatic activities. The heavier the physical exertion, the more intensive was the enzymatic activity of red blood cells, due to the intensification of bone marrow erythropoetic activity under physical exertion and the appearance of young red cells in peripheral blood. All the experimental groups revealed a drop in erythrocyte count (Er), hemoglobin concentration (Hb), and hematocrit values (PCV), as well as an increase in the reticulocytes count (Ret) and in the activity of all the enzymes investigated. In the fourth group anemia was detected: prolonged endurance training decreased the RBC by 24.2%, Hb by 31.1%, PCV by 26.2% and increased the reticulocyte count by 881.6%. Pronounced loading with physical effort leads to shifts in the glucose utilization ratio along particular erythrocyte metabolic pathways. This change in enzymatic activities may prove to be one of the causes of faster elimination of old RBCs.     

Immunologic defects as possible causes of therapeutic failures in children with transposition of the great arteries

Summary Recurrent and severe infections and absence of thymic shadow in X-ray examination were observed in children with the transposition of the great arteries (TGA). Among 45 children (29 boys and 16 girls) with TGA whose age ranged from 3 days to 16 years and who were hospitalized during 1 year, infectious diarrhea was observed in 77.7% cases, urinary tract infections in 44.5%, respiratory tract infections in 42.2%, sepsis in 17.5%, and meningitis in 8.8%. Nine of the children died, sepsis was a cause of death in seven children, and there were postsurgical complications in two children. Immunologic abnormalities in children with TGA included a decreased level of T-lymphocytes and T_29° subpopulation, impaired mitogen-induced lymphoproliferation in vitro, and increased nitro blue tetrazolium (NBT) reduction activity of monocytes. Impaired parameters of cellular immunity correlated with worst clinical status. No disorders of humoral immunity were observed. These observations may be important for forming opinion about proper therapy and the cause of death in children with TGA.All results have been included in T. Marek-Szydowska's doctoral dissertation and were communicated at the 65th Annual Meeting of Deutsche Gesellschaft für Rechtsmedizin, St. Gallen, Switzerland, Sept. 9–13, 1986     

Analgesic efficacy of sufentanil in dressings after surgical treatment of burn wounds

BackgroundThe aim of this study was to assess the analgesic efficacy of sufentanil in dressings after surgical treatment of burn wounds.Patients and methodsTwenty adult patients, who underwent surgical treatment of third–degree burn wounds under general anesthesia, were included. Two of the patients underwent surgery twice. During surgery, patients received 50–100 μg fentanyl every 20–30 min and, after surgery, patients received 100 mg ketoprofen twice daily. Additionally, ten patients (group 1) received 50 μg sufentanil added to the burn wound dressings soaked in octenidine and phenoxyethanol while 10 patients (group 2) received 25 μg sufentanil added to the same dressings. The rescue analgesic, which was administered when pain intensified, was 5 mg subcutaneous morphine. Plasma sufentanil concentrations were assayed at 1, 2, 3, and 6 h after surgery completion and when pain was reported, along with pain intensity evaluation.ResultsSufentanil was not detected in the serum of any patients. Rescue morphine was given during the postoperative period (24 h) in one patient in group 1 (who underwent surgery twice) and three patients in group 2. The mean sufentanil concentration in dressings was higher in group 1 (0.13 ± 0.03) than group 2 (0.06 ± 0.03 μg/mL; p < 0.001). The group 1 patient who received rescue morphine had a sufentanil concentration of 0.10 μg/mL, which was the lowest concentration in group 1. Group 2 patients who received rescue morphine had sufentanil concentrations of at least two–fold lower (0.03–0.05 μg/mL). No adverse effects were observed.ConclusionsSufentanil in dressings after burn wound surgery provides effective and safe analgesia and the sufentanil concentration in dressings should be ≥0.10 μg/mL in a solution of octenidine and phenoxyethanol.     

How Do Medical Students Perceive Diversity in Orthopaedic Surgery,and How Do Their Perceptions Change After an Orthopaedic Clinical Rotation?

BackgroundA diverse physician workforce improves the quality of care for all patients, and there is a need for greater diversity in orthopaedic surgery. It is important that medical students of diverse backgrounds be encouraged to pursue the specialty, but to do so, we must understand students’ perceptions of diversity and inclusion in orthopaedics. We also currently lack knowledge about how participation in an orthopaedic clinical rotation might influence these perceptions.Questions/purposes(1) How do the perceptions of diversity and inclusion in orthopaedic surgery compare among medical students of different gender identities, races or ethnicities, and sexual orientations? (2) How do perceptions change after an orthopaedic clinical rotation among members of demographic groups who are not the majority in orthopaedics (that is, cis-gender women, underrepresented racial minorities, other racial minorities, and nonheterosexual people)?MethodsWe surveyed students from 27 US medical schools who had completed orthopaedic rotations. We asked about their demographic characteristics, rotation experience, perceptions of diversity and inclusion in orthopaedics, and personal views on specialty choice. Questions were derived from diversity, equity, and inclusion climate surveys used at major academic institutions. Cis-gender men and cis-gender women were defined as those who self-identified their gender as men or women, respectively, and were not transgender. Forty-five percent (59 of 131) of respondents were cis-men and 53% (70 of 131) were cis-women; 49% (64 of 131) were white, 20% (26 of 131) were of underrepresented racial minorities, and 31% (41 of 131) were of other races. Eighty-five percent (112 of 131) of respondents were heterosexual and 15% (19 of 131) reported having another sexual orientation. We compared prerotation and postrotation perceptions of diversity and inclusion between majority and nonmajority demographic groups for each demographic domain (for example, cis-men versus cis-women). We also compared prerotation to postrotation perceptions within each nonmajority demographic group. To identify potential confounding variables, we performed univariate analysis to compare student and rotation characteristics across the demographic groups, assessed using an alpha of 0.05. No potential confounders were identified. Statistical significance was assessed at a Bonferroni-adjusted alpha of 0.0125. Our estimated response percentage was 26%. To determine limitations of nonresponse bias, we compared all early versus late responders and found that for three survey questions, late responders had a more favorable perception of diversity in orthopaedic surgery, whereas for most questions, there was no difference.ResultsBefore rotation, cis-women had lower agreement that diversity and inclusion are part of orthopaedic culture (mean score 0.96 ± 0.75) compared with cis-men (1.4 ± 1.1) (mean difference 0.48 [95% confidence interval 0.16 to 0.81]; p = 0.004), viewed orthopaedic surgery as less diverse (cis-women 0.71 ± 0.73 versus cis-men 1.2 ± 0.92; mean difference 0.49 [95% CI 0.20 to 0.78]; p = 0.001) and more sexist (cis-women 1.3 ± 0.92 versus cis-men 1.9 ± 1.2; mean difference 0.61 [95% CI 0.23 to 0.99]; p = 0.002), believed they would have to work harder than others to be valued equally (cis-women 2.8 ± 1.0 versus cis-men 1.9 ± 1.3; mean difference 0.87 [95% CI 0.45 to 1.3]; p < 0.001), and were less likely to pursue orthopaedic surgery (cis-women 1.4 ± 1.4 versus cis-men 2.6 ± 1.1; mean difference 1.2 [95% CI 0.76 to 1.6]; p < 0.001). Before rotation, underrepresented minorities had less agreement that diversity and inclusion are part of orthopaedic surgery culture (0.73 ± 0.72) compared with white students (1.5 ± 0.97) (mean difference 0.72 [95% CI 0.35 to 1.1]; p < 0.001). Many of these differences between nonmajority and majority demographic groups ceased to exist after rotation. Compared with their own prerotation beliefs, after rotation, cis-women believed more that diversity and inclusion are part of orthopaedic surgery culture (prerotation mean score 0.96 ± 0.75 versus postrotation mean score 1.2 ± 0.96; mean difference 0.60 [95% CI 0.22 to 0.98]; p = 0.002) and that orthopaedic surgery is friendlier (prerotation 2.3 ± 1.2 versus postrotation 2.6 ± 1.1; mean difference 0.41 [95% CI 0.14 to 0.69]; p = 0.004), more diverse (prerotation 0.71 ± 0.73 versus postrotation 1.0 ± 0.89; mean difference 0.28 [95% CI 0.08 to 0.49]; p = 0.007), less sexist (prerotation 1.3 ± 0.92 versus postrotation 1.9 ± 1.0; mean difference 0.63 [95% CI 0.40 to 0.85]; p < 0.001), less homophobic (prerotation 2.1 ± 1.0 versus postrotation 2.4 ± 0.97; mean difference 0.27 [95% CI 0.062 to 0.47]; p = 0.011), and less racist (prerotation 2.3 ± 1.1 versus postrotation 2.5 ± 1.1; mean difference 0.28 [95% CI 0.099 to 0.47]; p = 0.003). Compared with before rotation, after rotation cis-women believed less that they would have to work harder than others to be valued equally on the rotation (prerotation 2.8 ± 1.0 versus postrotation 2.5 ± 1.0; mean difference 0.31 [95% CI 0.12 to 0.50]; p = 0.002), as did nonheterosexual students (prerotation 2.4 ± 1.4 versus postrotation 1.8 ± 1.3; mean difference 0.56 [95% 0.21 to 0.91]; p = 0.004). Underrepresented minority students saw orthopaedic surgery as less sexist after rotation compared with before rotation (prerotation 1.5 ± 1.1 versus postrotation 2.0 ± 1.1; mean difference 0.52 [95% CI 0.16 to 0.89]; p = 0.007).ConclusionEven with an estimated 26% response percentage, we found that medical students of demographic backgrounds who are not the majority in orthopaedics generally perceived that orthopaedic surgery is less diverse and inclusive than do their counterparts in majority groups, but these views often change after a clinical orthopaedic rotation.Clinical RelevanceThese perceptions may be a barrier to diversification of the pool of medical student applicants to orthopaedics. However, participation in an orthopaedic surgery rotation is associated with mitigation of many of these negative perceptions among diverse students. Medical schools have a responsibility to develop a diverse workforce, and given our findings, schools should promote participation in a clinical orthopaedic rotation. Residency programs and orthopaedic organizations can also increase exposure to the field through the rotation and other means. Doing so may ultimately diversify the orthopaedic surgeon workforce and improve care for all orthopaedic patients.     

Social Perception of Non-Binary Individuals

People can express their identity in different ways, one of which is through language. Non-binary individuals often speak in a gender-neutral way and use specific language forms. Language use not only reveals their identity but also can shape how others perceive them. The present study’s purpose was to analyze how non-binary people are perceived through the language they use. The research was conducted in Polish, a language that is especially challenging for non-binary individuals because it has many gender markers. To avoid using gendered forms, they often use a specific form of passive voice. In an experiment, participants (N?=?130, 102 women, 28 men) read a gendered (feminine or masculine) text and a gender-neutral text with passive voice. Most gave a masculine name to the person in the neutral text, but addressed them in a gender-neutral way when asked to react to them in presented scenarios. The gender-neutral text was evaluated as being less comprehensible than the gendered texts, and the non-binary person was rated less competent and colder than a man or a woman and was less socially accepted. Furthermore, the negative evaluation of non-binary people seemed to be attributable to unfamiliarity with gender-neutral language and its lower comprehensibility. More research is needed to understand these perceptions better and to be able to prevent their potential negative consequences.

     

Good practices in health promotion for older people – Significance for evidence in health policy

This article is devoted to convincing policy makers to use good practices in encouraging older people to pursue adequate and effective health policies. Long-term scientific research focused on the effects of health promotion programmes is rarely undertaken, although its scope is still expanding. At the same time, it is strongly desirable to form health policy based on scientific evidence. In this situation, an indication of good practices characterised by precisely defined features and their systematic evaluation could be an alternative to an insufficient number of empirical studies. The first step of the methodology was a literature review on health promotion for older people, aimed at defining good practices and criteria used for their selection. The authors searched the following databases: PubMED, Embase and Cochrane Library, as well as international databases dedicated to health promotion programmes for older people (e.g. Age-friendly World ( https://extranet.who.int/agefriendlyworld/age-friendly-practice-database-launched ); HealthProElderly ( www.healthproelderly.com/database/index.php?id=16 ); JA-CHRODIS ( www.chrodis.eu ); EuroHealthNet ( www.eurohealthnet.eu ) and ProFouND; ( www.profound.eu.com ). As relevant health policy information is usually available in national languages, the authors then approached national experts in 10 European countries, who filled in a dedicated survey on health promotion programmes for older people and indicated examples of good practices from their countries. Practical evidence, based on real implemented programmes, is valuable as inspiration for health promotion programmes, their planning and management. Selecting good practices from among implemented and evaluated actions makes it possible to establish their value. The significance of good practices in health promotion is to deliver real benefits and health effects for a target group, which, in the case of evident benefits, renders the practices credible and worthy of further dissemination. The EU already successfully shares good practices in migrant health and environmental protection. Creating databases on good practices helps policy makers promote the sustainability of already implemented activities and enhances their applicability by other organisations and in different settings.     

Recovery of hindlimb motor functions after spinal cord transection is enhanced by grafts of the embryonic raphe nuclei

In this study, a piece of embryonic tissue from the raphe nucleus was transplanted into the spinal cord below the lesion 1 month after transection. Two months later the recovery of hindlimb motor function in rats which had received a transplant of neural tissue (ST rats) was much better than in spinal control animals without the graft (SC rats). Analysis of the electromyographic (EMG) activity showed that the timing of muscle activity during locomotor-like movement of hindlimbs in ST rats was more regular than in SC rats. In SC rats the relationships between EMG burst duration (soleus, tibialis anterior) and step cycle duration were significantly altered. The restoration of hindlimb motor function of ST rats was also reflected in the better interlimb coordination during locomotor-like hindlimb movements. The results of several behavioural tests demonstrated that the responses to stimulation of various receptors, such as tactile or proprioceptive, in ST rats were more complex than in SC rats. Additionally, unlike in SC animals, in ST rats long-lasting spontaneous episodes of air stepping movement of hindlimbs accompanied by a relatively high amplitude of EMG activity were obtained. These results confirm that grafted embryonic raphe nuclei which contain serotoninergic cells are likely to increase the excitability of neuronal circuitry in the injured spinal cord. Moreover, transplantation of embryonic raphe nuclei encourages the recovery of hindlimb motor function in adult rats even when the grafting is carried out several weeks after spinal cord injury.     

Imidazopyrimidodiazepines--new heterocyclic system; synthesis and properties

The synthesis of the new tricyclic system ring 6-methyl-2,3,10,11-tetrahydroimidazo (1',2',3'-CD) pyrimido (5,4-b) (1,4) diazepinediones-5,8 is described. The 4-aryl- and 5-amino-imidazopyrimidodiazepines have also been obtained. The synthesis started from derivatives of 2-hydroxy-6-methyl-5-pyrimidine carboxylic acids. Some of the chemical and biological properties of new compounds are described.