Transport of Neuronal BC1 RNA in Mauthner Axons.
In neurons, localized RNAs have been identified in dendrites and axons; however, RNA transport in axons remains poorly understood. Here we analyzed axonal RNA transport in goldfish Mauthner neurons in vivo. BC1 RNA, a noncoding RNA polymerase III transcript that is targeted to dendrites in neurons of the rodent nervous system, was used as a probe for axonal RNA transport. Somata of Mauthner neurons were microinjected with various RNAs. Full-length BC1 RNA, but not control RNAs of similar length, was targeted to both axons and dendrites of Mauthner neurons. BC1 RNA was transported in the form of a rapidly advancing wave front that progressed along axons, in a microtubule-dependent manner, at a rate of 2 micrometer/sec. Whereas a BC1 5' segment of 65 nucleotides was transported to axons and dendrites in a way indistinguishable from full-length BC1 RNA, a BC1 3' segment of 60 nucleotides did not enter Mauthner cell processes to any significant extent. In the wake of the wave advancing through the axon, BC1 RNA was found localized to discrete, spatially delimited domains at the axonal surface. Such demarcated cortical concentrations of BC1 RNA could not be observed after disruption of F-actin organization in the axon. It is concluded that the specific delivery of BC1 RNA to spatially defined axonal target sites is a two-step process that requires the sequential participation of microtubules for long-range axial transport and of actin filaments for local radial transfer and focal accumulation in cortical domains.


Treatment of aseptic facial granuloma as a manifestation of pediatric rosacea with oral macrolides.
Aseptic facial granuloma is a rare pediatric disease, presenting with asymptomatic facial nodules on the cheeks or the eyelids and may represent a form of granulomatous rosacea in children. In this retrospective case series, 12 children with aseptic facial granuloma were treated with oral macrolides (erythromycin or roxithromycin) resulting in a healing of the lesions within a mean treatment time of 5.25 months with no recurrences. The treatment was mainly well tolerated. Oral macrolides may be effective in the treatment of patients with aseptic facial granuloma.


Rapid solid-state precursor synthesis of materials.
Precursor reactions based on metathetical (exchange) pathways have been found to be an effective synthetic route for the preparation of a large number of materials. These solid-solid reactions are extremely rapid (typically less than 1 second) and often can be initiated at or near room temperature. They are potentially useful for controlling product particle size and for preparing highquality cationic or anionic solid solutions. The frequently self-propagating and sometimes explosive behavior exhibited by these reactions can be attributed to the large amount of heat they release. As a consequence, thermodynamic considerations can be used to help select the best set of precursors as judged from reaction enthalpies. The factors that influence these reactions are illustrated by a discussion of MoS(2), ZrN, MoSi(2), and GaAs, examples of the many compounds accessible by this synthetic route.


[Evaluation of omethoate and fenitrothion absorption in greenhouse workers using protective equipment in confined areas].
Sprayers and workers engaged in manual operations in a greenhouse were monitored for exposure to omethoate and fenitrothion. Urinary dialkyl phosphates (dimethyl thiophosphate and dimethyl phosphate) were used as biological index of exposure to the two chemicals. Residues of fenitrothion on foliage were measured as well as levels of fenitrothion and omethoate in air samples collected in the breathing zone (personal sampling) and in the work-place near the entrance and the end of the greenhouse (static sampling). Skin exposure was estimated from pads placed on the thorax under overalls and from hand washing liquid at the end of the workshift. Sprayers wore respiratory and skin protection during the workshift. Workers engaged in manual operations did not wear respiratory protection. Re-entry to the greenhouse was permitted 48 h after spraying. Levels of omethoate and fenitrothion in air samples, on pads and on the hands, during manual operations on ornamental plants, were very low. Urine analysis shoved no significant difference between the pre- and post-exposure samples. No significant difference was found between levels of urinary dialkyl phosphates in the control group and exposed workers. Cholinesterase activity (acetyl and butyryl) showed no significant reduction at the end of the workshift compared with baseline values.


Short-term effects of intravenous benzodiazepines on autonomic neurocardiac regulation in humans: a comparison between midazolam, diazepam, and lorazepam.
To evaluate the effects of intravenously applied diazepam, lorazepam, and midazolam on autonomic neurocardiac regulation assessed by standardized measurements of heart rate variability. Prospective, randomized clinical study. University teaching hospital. Forty-five patients, who underwent a gastroscopy, were randomly assigned to intravenous premedication with midazolam (5 mg), diazepam (10 mg), or lorazepam (4 mg). Six subjects refused an injection and served as nonpremedicated controls. Serial recordings of the 5-min resting heart rate variability were obtained before and 15 and 30 mins after premedication. Seven benzodiazepine-treated patients received intravenous flumazenil (0.5 mg). The average doses applied were 0.07 mg/kg for midazolam, 0.13 mg/kg for diazepam, and 0.06 mg/kg for lorazepam. Fifteen minutes after intravenous benzodiazepines were administered, we found an increase in resting heart rate and a reduction of vagal tone compared with baseline in all three benzodiazepine-treated subgroups. Multivariate analysis (covariate age) of the changes in heart rate variability indices over the experimental course revealed a significant reduction in absolute high-frequency power with midazolam or diazepam compared with nonpremedicated subjects. Moreover, midazolam-treated subjects showed a significantly larger reduction in relative high-frequency power not only compared with nontreated subjects, but also compared with lorazepam- or diazepam-treated subjects. Vagal tone remained reduced compared with baseline even 30 mins after benzodiazepine application, however, the resting heart rate decreased toward baseline levels. After flumazenil administration, there was a linear correlation between an increase in high-frequency power and a corresponding decrease in resting heart rate. Benzodiazepines can influence autonomic neurocardiac regulation in man, probably through their interaction with the gamma-aminobutyric acidA-receptor chloride ion channel complex. The pattern of findings suggests that intravenous midazolam, diazepam, and lorazepam influence human autonomic neurocardiac regulation in a biphasic way. First, they cause a reduction of central vagal tone, and second, they may decrease the cardiac pacemaker directly. Flumazenil completely abolished the autonomic neurocardiac regulation effects of benzodiazepines.


Rituximab, plasma exchange and immunoglobulins: an ineffective treatment for chronic active antibody-mediated rejection.
Chronic active antibody-mediated rejection (c-aABMR) is an important cause of allograft failure and graft loss in long-term kidney transplants. To determine the efficacy and safety of combined therapy with rituximab, plasma exchange (PE) and intravenous immunoglobulins (IVIG), a cohort of patients with transplant glomerulopathy (TG) that met criteria of active cABMR, according to BANFF'17 classification, was identified. We identified 62 patients with active c-aABMR and TG (cg ≥ 1). Twenty-three patients were treated with the combination therapy and, 39 patients did not receive treatment and were considered the control group. There were no significant differences in the graft survival between the two groups. The number of graft losses at 12 and 24 months and the decline of eGFR were not different and independent of the treatment. A decrease of eGFR≥13 ml/min between 6 months before and c-aABMR diagnosis, was an independent risk factor for graft loss at 24 months (OR = 5; P = 0.01). Infections that required hospitalization during the first year after c-aABMR diagnosis were significantly more frequent in treated patients (OR = 4.22; P = 0.013), with a ratio infection/patient-year of 0.65 and 0.20 respectively. Treatment with rituximab, PE, and IVIG in kidney transplants with c-aABMR did not improve graft survival and was associated with a significant increase in severe infectious complications. Agencia Española de Medicametos y Productos Sanitarios (AEMPS): 14566/RG 24161. Study code: UTR-INM-2017-01.


Description of two new species of Portanus Ball, 1932 (Hemiptera: Cicadellidae: Portanini) from Northeastern Brazil.
Two new species of Portanus Ball, 1932 are described and illustrated from Brazil. P. hastatus sp. nov. from Ceará State, can be recognized by its acute pygofer apex and aedeagus with pair of apical processes directed dorsally. Portanus phoenicius sp. nov. from Piauí State, can be recognized by its rounded pygofer lobe with dorsal tooth turned inwardly, aedeagus apex with pair of elongate processes and pair of rounded flanges directed ventrally. Portanus boliviensis is newly recorded from Brazil. These findings double the number of species of Portanini recorded from Northeastern Brazil.


Mechanism of active potassium absorption and secretion in the rat colon.
To characterize and contrast the active potassium absorptive and secretory processes present in the rat colon, unidirectional 42K fluxes were performed under short-circuit conditions across isolated distal (D) and proximal (P) colonic mucosa of control rats and animals with hyperaldosteronism due to sodium depletion (aldosterone group). In the control D colon there was net potassium absorption (+0.51 +/- 0.07 mueq X h-1 X cm-2). The absorptive process appears electroneutral because net potassium flux ( JK net ) was unchanged in sodium-free Ringer solution (+0.76 +/- 0.12 mueq X h-1 X cm-2), whereas short-circuit current (Isc) was reduced to zero, and in chloride-free Ringer solution. In P colon of controls, net potassium secretion was -0.19 +/- 0.02 mueq X h-1 X cm-2 and was abolished by removal of sodium but not by removal of chloride. In both P and D colon aldosterone produced active potassium secretion (-0.39 +/- 0.06 mueq X h-1 X cm-2, P less than 0.001, and -0.90 +/- 0.07 mueq X h-1 X cm-2, P less than 0.001, respectively) that was sodium and chloride dependent. Although mucosal amiloride in D colon of aldosterone animals reduced net sodium flux to zero and reversed Isc from 4.1 +/- 0.6 to -1.1 +/- 0.1 mueq X h-1 X cm-2, net potassium secretion was not affected. Thus, in the presence of amiloride, Isc is accounted for by JK net (-0.93 +/- 0.12 mueq X h-1 X cm-2). These data indicate that 1) the active potassium absorptive process is electroneutral and could be explained by a potassium-proton exchange, and 2) the potassium secretory process is stimulated by aldosterone, is not inhibited by amiloride, and probably is electrogenic.


Choice and Constraint in the Negotiation of the Grandparent Role: A Mixed-Methods Study.
Few studies have examined how the allocation and consequences of grandchild care vary across different socioeconomic groups. We analyze qualitative data alongside data from The Irish Longitudinal Study on Ageing (TILDA), in a convergent mixed-methods approach. Regression models examined characteristics associated with grandchild care, and the relationship between grandchild care and depressive symptoms and well-being. Qualitative data shed light on processes and choices that explain patterns of grandchild care provision. Tertiary-educated grandparents provided less intensive grandchild care compared with primary educated. Qualitative data indicated that this pattern stems from early boundary-drawing among higher educated grandparents while lower socioeconomic groups were constrained and less able to say no. Intensive grandchild care was associated with more depressive symptoms and lower well-being and was moderated by participation in social activities and level of education attainment. The effect of grandchild care on well-being of grandparents depends on whether it is provided by choice or obligation.


ELISA for the quantification of pilsicainide.
A sensitive and specific ELISA for an antiarrhythmic drug, pilsicainide, was developed, which is capable of measuring as low as 1.6 ng/ml. Anti-pilsicainide antibody was obtained by immunizing rabbits with pilsicainide conjugated with bovine serum albumin using diazotized N-(3-amino-2,6-dimethylphenyl)-8-pyrrolizidinylacetamide (3-aminopilsicainide). Enzyme labeling of pilsicainide with beta-D-galactosidase was similarly performed using a diazotized 3-aminopilsicainide. Cross-reactivity data showed that the antibody well recognizes both the aromatic ring and the pyrrolizidine moieties, and thus specific enough to the structure of pilsicainide. The values for the pilsicainide concentrations detected using this assay were comparable with those detected using HPLC. There was a good correlation between the values determined by the two methods. Moreover, the ELISA was about 30-fold more sensitive in detecting pilsicainide at lower concentrations. Using this assay, drug levels were easily measured in the serum of rabbits after oral administration of pilsicainide at a single dose of 1 mg/kg. The ELISA should be a valuable tool in therapeutic drug monitoring (TDM) and pharmacokinetic studies of pilsicainide.


Ceftriaxone versus povidone iodine in preventing wound infections following biliary surgery.
The effect of either prophylactic antibiotic or wound antiseptic on bile bacteriology, wound and other postoperative sepsis has been studied in a controlled prospective randomised trial of 243 patients undergoing biliary surgery at a district general hospital. Wound infection rates were significantly less in patients given intravenous ceftriaxone (1%) at induction of anaesthesia when compared to povidone iodine sprayed into the wound at the completion of surgery (9%) (P = 0.02). In all but one patient infected wounds grew organisms identical to those cultured from the bile. There were also fewer chest and urinary infections in the ceftriaxone group but this was not statistically significant.


[Diagnosis and treatment of anaplastic large-cell lymphoma in children and adolescents: a retrospective multicenter survey study].
Objective: To provide a descriptive review and improve our understanding of the clinical characteristics and treatment outcome of pediatric anaplastic large cell lymphoma (ALCL) in China. Method: The clinical data and outcomes of patients under 16 years of age with newly histopathologically-confirmed ALCL in 10 large single institutions in China between January 2009 and June 2014, were retrospectively analyzed.The event-free survival (EFS) was analyzed by the Kaplan-Meier method.The risk factors of disease progression or relapse were evaluated by logistic regression analysis.Significance was defined as P<0.05. Result: Of the 80 eligible patients (52 male, 28 female), the median age was 8.4 years (range, 1.3-15.7 years). Two patients (3%) were Stage Ⅰ, 9(11%) Stage Ⅱ, 64 (80 %) Stage Ⅲ, and 5(6%) Stage Ⅳ.The median time of follow-up was 25.2 months (range, 7.1-74.8 months), 55 patients survived without disease at the last of follow-up, the 3-year EFS was (65±6)%. Sixty-five patients (81%) were treated with the Chinese Children Cancer Group-B cell-non-Hodgkin Lymphoma 2010 protocol, regimen and 15 cases (19%) were treated with other regimens.The 3-year EFS were (68±5)% vs.(65±20)% (P=0.21). The 3-year EFS was (57±7)% and (78±11)% for patients with or without B symptoms (P=0.01). Twenty-four patients experienced disease progression or relapse. The median time from initial diagnosis to tumor failure was 7.0 months (ranged, 1.5-42.6 months) (median). At the last evaluation, there were 5 patients still alive after disease progression and relapse. By univariate analysis, sex (P=0.04) and B symptoms (P=0.00) were identified as risk factors of disease progression or relapse.Nevertheless, only B symptoms (HR 5.60, 95%CI 1.47-21.27, P≤0.05) were risk factors in multivariate analysis. Conclusion: The presenting features of children and adolescents with ALCL and efficiency in this study were similar to those reported by western countries.Refinement of therapeutic strategies to improve survival for patients with disease progression or relapse should be the priority in future clinical study.


Class-modelling in food analytical chemistry: Development, sampling, optimisation and validation issues - A tutorial.
Qualitative data modelling is a fundamental branch of pattern recognition, with many applications in analytical chemistry, and embraces two main families: discriminant and class-modelling methods. The first strategy is appropriate when at least two classes are meaningfully defined in the problem under study, while the second strategy is the right choice when the focus is on a single class. For this reason, class-modelling methods are also referred to as one-class classifiers. Although, in the food analytical field, most of the issues would be properly addressed by class-modelling strategies, the use of such techniques is rather limited and, in many cases, discriminant methods are forcedly used for one-class problems, introducing a bias in the outcomes. Key aspects related to the development, optimisation and validation of suitable class models for the characterisation of food products are critically analysed and discussed.


[Regulation of tumor metastasis and invasion by fibroblasts].
Using immunodeficient mice human tumor cell lines, which metastasize to specific organs from orthotopic implantation sites but not from ectopic sites, have been established. We have been studying mechanisms of the regulation of tumor metastasis by organ specific microenvironments, and have recently found significant differences in interactions between metastatic tumor cells and fibroblasts from different tissues. Fibroblasts isolated from orthotopic organ tissues of nude mice enhanced invasion of metastatic human colon carcinoma cells. In contrast, fibroblasts derived from a subcutaneous tissue suppressed carcinoma cell invasion. These divergent effects were found in part due to differential expression of cytokines and growth factors by fibroblasts from different tissues.


Physical activity protects male patients with post-traumatic stress disorder from developing severe fibromyalgia.
Fibromyalgia syndrome (FMS) has been associated with various psychiatric and other, ill-defined disorders. We recently showed that fibromyalgia is more prevalent in men suffering from combat-related Post Traumatic Stress Disorder (PTSD). In this paper we analyze the relationship between engagement in physical activity, the psycho-metric traits of PTSD and the future development of FMS. Fifty-five male patients, all known to have combat-related PTSD, were investigated for the presence of fibro-myalgia according to the American College of Rheumatology (ACR) criteria. Each patient completed questionnaires characterizing his quality of sleep, and the Sheehan Disability Scale measuring performance in the familial, social and vocational spheres. Additionally, each of the enrollees was interviewed by an experienced psychiatrist, who then completed a Clinician Administered PTSD Scale, a Clinical Global Impression Scale, and calculated an SF-36 score. Each patient was asked whether he exercised often, occasionally or not at all. The data was analyzed by the chi2 test and by ANOVA. PTSD patients who also suffered from FMS had a more severe form of disease as measured by the Clinician Administered PTSD Scale (CAPS) score, 88.2 +/- 14.0 (n = 28) compared to 97.6 +/- 13.2 of patients with PTSD and FMS (n = 27) (p = 0.013, F(d.f 2)-6.61, ANOVA test). Interestingly, engaging in physical exercise was also associated with less severe disease. When the patients were analyzed based on their tender point count (0-5, 6-10, or > 11), the number of tender points decreased with increasing physical activity (p = 0.02, chi2(d.f.-4) = 11.3). Physical exercise in male patients with combat-related PTSD provides protection from the future development of fibromyalgia. Furthermore, physical activity is related in this group of patients to a better perception of their quality of life.


Children's temperament and teachers' decisions.
Findings from a series of studies of the educational implications of children's temperament patterns are summarized. This research has been guided by three hypotheses: (1) that there are real individual differences among children in behavioural styles or temperament; (2) that individual variations in children's patterns of temperament influence the nature of their interpersonal interactions; and (3) that perceived variations in temperament become especially powerful influences on adults' decisions when children are handicapped or at risk. Based on these assumptions, the study of temperament has followed two primary lines of research. in the first we have attempted to delineate the hypothesized link between perceived temperament variations and teachers' educational decisions. In the second we have attempted to determine the influence of perceived temperament variations on children's personal-social competence within intervention settings. Findings support a relationship between children's temperament and their achievement and adjustment in school. Temperament was related to measures of children's academic performance and to teachers' perceptions of other aspects of children's school adjustment. Further, teachers' ratings of children's temperament were related to their classroom management decisions. The results suggest that teachers' responses to children in the classroom are mediated by their perceptions of the children's temperament.


From the Cover: Disease-Induced Disparities in Formation of the Nanoparticle-Biocorona and the Toxicological Consequences.
Nanoparticle (NP) association with macromolecules in a physiological environment forms a biocorona (BC), which alters NP distribution, activity, and toxicity. While BC formation is dependent on NP physicochemical properties, little information exists on the influence of the physiological environment. Obese individuals and those with cardiovascular disease exist with altered serum chemistry, which is expected to influence BC formation and NP toxicity. We hypothesize that a BC formed on NPs following incubation in hyperlipidemic serum will result in altered NP-BC protein content, cellular association, and toxicity compared to normal serum conditions. We utilized Fe3O4 NPs, which are being developed as MRI contrast and tumor targeting agents to test our hypothesis. We used rat aortic endothelial cells (RAECs) within a dynamic flow in vitro exposure system to more accurately depict the in vivo environment. A BC was formed on 20nm PVP-suspended Fe3O4 NPs following incubation in water, 10% normal or hyperlipidemic rat serum. Addition of BCs resulted in increased hydrodynamic size and decreased surface charge. More cholesterol associated with Fe3O4 NPs after incubation in hyperlipidemic as compared with normal serum. Using quantitative proteomics, we identified unique differences in BC protein components between the 2 serum types. Under flow conditions, formation of a BC from both serum types reduced RAECs association of Fe3O4 NPs. Addition of BCs was found to exacerbate RAECs inflammatory gene responses to Fe3O4 NPs (Fe3O4-hyperlipidemic > Fe3O4-normal > Fe3O4) including increased expression of IL-6, TNF-α, Cxcl-2, VCAM-1, and ICAM-1. Overall, these findings demonstrate that disease-induced variations in physiological environments have a significant impact NP-BC formation, cellular association, and cell response.


Do patients receive any benefit from the addition of perioperative immunotherapy-chemotherapy for solid tumors?
Progress in the use of neoadjuvant immunotherapy combined with chemotherapy has become a highlight of cancer research. Our meta-analysis aimed to better elucidate the activity, efficacy and safety of this combination using data obtained from randomized controlled trials (RCTs). A systematic search of PubMed, Embase, Web of Science, the Cochrane Library and conference proceedings up to January 31, 2023 was carried out to identify RCTs investigating neoadjuvant immunotherapy combined with chemotherapy for the treatment of solid tumors. Using fixed- and random-effects models, pooled odds ratios (ORs) and hazard ratios with 95% confidence intervals (CIs) were calculated for pathological complete response (pCR, defined as ypT0/is pN0) and immunotherapy treatment-related adverse events. A total of 1876 studies were identified, and 6 RCTs (N = 2558 patients) were included. The pCR was significantly higher with neoadjuvant immunotherapy combined with chemotherapy than with neoadjuvant chemotherapy alone (OR = 2.30, 95% CI: 1.43-3.71, P < .001). The pCR was confirmed to be statistically significant in the PD-L1-positive subgroup (OR = 2.01; 95% CI: 1.55-2.59, P = .012). The pCR was confirmed to be statistically significant in the PD-1 inhibitor subgroup (OR = 4.17; 95% CI: 1.47-11.87, P = .000), while no statistically significant was observed in the PD-L1 inhibitor subgroup (OR = 1.52; 95% CI: 1.12-2.07, P = .308). The pooled ORs of any grade treatment-related or immunotherapy-related adverse events were significant, but the grade 3-4 immunotherapy-related adverse events were not. Our study provides comprehensive data that the addition of PD1 blockade to neoadjuvant chemotherapy resulted in better treatment efficacy than neoadjuvant chemotherapy alone in patients with solid tumors and had a similar safety profile.


Abnormal Development and Dysconnectivity of Distinct Thalamic Nuclei in Patients With 22q11.2 Deletion Syndrome Experiencing Auditory Hallucinations.
Several studies in patients with schizophrenia have demonstrated an abnormal thalamic volume and thalamocortical connectivity. Specifically, hyperconnectivity with somatosensory areas has been related to the presence of auditory hallucinations (AHs). The 22q11.2 deletion syndrome is a neurogenetic disorder conferring proneness to develop schizophrenia, and deletion carriers (22qdel carriers) experience hallucinations to a greater extent than the general population. We acquired 442 consecutive magnetic resonance imaging scans from 120 22qdel carriers and 110 control subjects every 3 years (age range: 8-35 years). The volume of thalamic nuclei was obtained with FreeSurfer and was compared between 22qdel carriers and control subjects and between 22qdel carriers with and without AHs. In a subgroup of 76 22qdel carriers, we evaluated the functional connectivity between thalamic nuclei affected in patients experiencing AHs and cortical regions. As compared with control subjects, 22qdel carriers had lower and higher volumes of nuclei involved in sensory processing and cognitive functions, respectively. 22qdel carriers with AHs had a smaller volume of the medial geniculate nucleus, with deviant trajectories showing a steeper volume decrease from childhood with respect to those without AHs. Moreover, we showed an aberrant development of nuclei intercalated between the prefrontal cortex and hippocampus (the anteroventral and medioventral reuniens nuclei) and hyperconnectivity of the medial geniculate nucleus and anteroventral nucleus with the auditory cortex and Wernicke's area. The increased connectivity of the medial geniculate nucleus and anteroventral nucleus to the auditory cortex might be interpreted as a lack of maturation of thalamocortical connectivity. Overall, our findings point toward an aberrant development of thalamic nuclei and an immature pattern of connectivity with temporal regions in relation to AHs.


Importance of genetic factors in adolescent asthma: a population-based twin-family study.
Gene-environment interactions and inheritance of asthma were studied in 16-yr-old twins and their parents who participated in the nationwide Finnish Twin Cohort Study. Between 1991 and 1994, questionnaires, including a question on physician-diagnosed asthma, were mailed to the members of 2,483 twin families. The individual response rate ranged from 82 to 93%. Information on parental asthma status allowed the genetic modeling of asthma data in two different groups of twins. In families where one of the parents was asthmatic, as much as 87% of the variation in susceptibility to asthma in twins was explained by genetic factors. On the other hand, for twins whose parents were unaffected, a model including environmental effect alone was sufficient to explain the development of asthma. Genetic influences could not be totally excluded, but their role was significantly smaller. These results indicate that the presence of asthma in successive generations is more likely caused by shared genes than shared environmental risk factors; however, substantial heterogeneity among families may exist. Genetic analysis, especially among the families with an obvious familial component in development of asthma, may enhance the chances of revealing the pathogenetic mechanisms


Emergency caesarean section delivery and puerperium in a patient with severe idiopathic pulmonary arterial hypertension - a case report.
The aim of this paper is to describe the third pregnancy trimester, delivery and puerperium in patient with idiopathic pulmonary hypertension. a 30-year-old primigravida with idiopathic pulmonary hypertension was qualified for emergency Caesarean section. In the post partum period no improvement in managing pulmonary arterial hypertension was achieved. Because of progressive respiratory and circulatory failure as well as the pulmonary artery pressure exceeding the systemic pressure the AV ECMO was applied on postoperative day 6. During the ECMO period the emergency laparotomy due to bleeding was necessary. The further course of ICU treatment was uneventful. In described case things are left to chance or goodwill of specialists and final outcome depend on happy coincidences.


The genes and enzymes for the catabolism of galactitol, D-tagatose, and related carbohydrates in Klebsiella oxytoca M5a1 and other enteric bacteria display convergent evolution.
Enteric bacteria (Enteriobacteriaceae) carry on their single chromosome about 4000 genes that all strains have in common (referred to here as "obligatory genes"), and up to 1300 "facultative" genes that vary from strain to strain and from species to species. In closely related species, obligatory and facultative genes are orthologous genes that are found at similar loci. We have analyzed a set of facultative genes involved in the degradation of the carbohydrates galactitol, D-tagatose, D-galactosamine and N-acetyl-galactosamine in various pathogenic and non-pathogenic strains of these bacteria. The four carbohydrates are transported into the cell by phosphotransferase (PTS) uptake systems, and are metabolized by closely related or even identical catabolic enzymes via pathways that share several intermediates. In about 60% of Escherichia coli strains the genes for galactitol degradation map to a gat operon at 46.8 min. In strains of Salmonella enterica, Klebsiella pneumoniae and K. oxytoca, the corresponding gat genes, although orthologous to their E. coli counterparts, are found at 70.7 min, clustered in a regulon together with three tag genes for the degradation of D-tagatose, an isomer of D-fructose. In contrast, in all the E. coli strains tested, this chromosomal site was found to be occupied by an aga/kba gene cluster for the degradation of D-galactosamine and N-acetyl-galactosamine. The aga/kba and the tag genes were paralogous either to the gat cluster or to the fru genes for degradation of D-fructose. Finally, in more then 90% of strains of both Klebsiella species, and in about 5% of the E. coli strains, two operons were found at 46.8 min that comprise paralogous genes for catabolism of the isomers D-arabinitol (genes atl or dal) and ribitol (genes rtl or rbt). In these strains gat genes were invariably absent from this location, and they were totally absent in S. enterica. These results strongly indicate that these various gene clusters and metabolic pathways have been subject to convergent evolution among the Enterobacteriaceae. This apparently involved recent horizontal gene transfer and recombination events, as indicated by major chromosomal rearrangements found in their immediate vicinity.


Photoplethysmography: a simplified method for the office measurement of ankle brachial index in individuals with diabetes.
To compare the use of photoplethysmography (PPG) and Doppler techniques to measure the ankle brachial index (ABI) for the evaluation of peripheral arterial disease (PAD) in individuals with diabetes. Consecutive patients with diabetes (n = 103) referred for PAD evaluation had ABI measured by PPG and Doppler techniques in our diabetes center. Medical records were reviewed, and the results of the Doppler and PPG testing were compared. Mean age was 60 years, 57% were female, and 79% had type 2 diabetes with an average duration of 17 years. PPG readings could not be obtained in 3 individuals. Of 200 limbs evaluated, 17 (8.5%) had noncompressible (NC) vessels by both techniques. In the remaining 183 limbs, the correlation coefficient comparing the two methods was 0.864. Mean ABI values were 1.11 ± 0.14 for Doppler and 1.12 ± 0.14 for PPG. The sensitivity of PPG compared to the Doppler technique for detection of an abnormal result was 88.2%, and the specificity was 99.4%. ABI results were classified as discordant if Doppler and PPG varied by more than 0.15, placing them in different diagnostic categories (abnormal low [≤0.9], borderline [0.91-0.99], normal [1.0-1.4], or abnormal high [>1.4 or NC vessels]). There were only 4 (2%) discordant results. We found excellent concordance between PPG and the gold standard Doppler technique for ABI measurement in individuals with diabetes. PPG requires less training and takes less time to perform, making it highly suitable for use in an office setting.


Fetuin-A is related to syndesmophytes in patients with ankylosing spondylitis: a case control study.
New bone formation is one of the hallmark characteristics of ankylosing spondylitis, which is thereby associated with syndesmophytes. Fetuin-A is a molecule that is abundantly found in calcified tissues and it shows high affinity for calcium phosphate minerals and related compounds. Considering the role of fetuin-A in the regulation of calcified matrix metabolism, we compared the fetuin-A levels in ankylosing spondylitis patients with syndesmophytes with those in patients without syndesmophytes and in healthy controls. We also studied other biomarkers that are thought to be related to syndesmophytes. Ninety-four patients (49 patients without syndesmophytes, 67.3% male, 40.7±8.7 years; 45 patients with syndesmophytes, 71.1% M, 43.9±9.9 years) and 68 healthy controls (44.2±10.6 years and 70.6% male) were included in this study. Syndesmophytes were assessed on the lateral radiographs of the cervical and lumbar spine. The serum levels of fetuin-A, dickkopf-1, sclerostin, IL-6, high-sensitivity C-reactive protein and bone morphogenetic protein-7 were measured with an enzyme-linked immunosorbent assay. Patients with syndesmophytes had significantly higher levels of fetuin-A compared with patients without syndesmophytes and controls (1.16±0.13, 1.05±0.09 and 1.08±0.13 mg/ml, respectively). However, fetuin-A was not different between the patients without syndesmophytes and controls. Bone morphogenetic protein-7 was significantly lower; dickkopf-1 was significantly higher in patients with ankylosing spondylitis compared with controls. The sclerostin concentrations were not different between the groups. In regression analysis, fetuin-A was an independent, significant predictor of syndesmophytes. Our results suggest that fetuin-A may a role in the pathogenesis of bony proliferation in ankylosing spondylitis.


Flavonoid therapy in diabetic retinopathy.
A new flavonoid, CVP (citrus vitamin P) had no beneficial effect on diabetic retinopathy in 33 patients. Minor improvement in retinal status occurred in 27 per cent of the patients. This rate of improvement is the same as that previously reported after many different therapies, and probably represents spontaneous variation in the course of this disease.


Exploring the effects of methylene blue on amyloid fibrillogenesis of lysozyme.
The 129-residue lysozyme has been shown to form amyloid fibrils in vitro. While methylene blue (MB), a compound in the phenothiazinium family, has been shown to dissemble tau fibril formation, its anti-fibrillogenic effect has not been thoroughly characterized in other proteins/peptides. This study examines the effects of MB on the in vitro fibrillogenesis of lysozyme at pH 2.0 and 55 °C. Our results demonstrated that, upon 7-day incubation, the plateau ThT fluorescence of the sample was found to be ~8.69% or ~2.98% of the control when the molar ratio of lysozyme to MB was at 1:1.11 or 1:3.33, respectively, indicating that the inhibitory potency of MB against lysozyme fibrillogenesis is positively correlated with its concentration. We also found that MB is able to destabilize the preformed lysozyme fibrils. Moreover, molecular docking and molecular dynamics simulations results revealed that MB's mechanism of fibril formation inhibition may be triggered by binding with lysozyme's aggregation-prone region. Results reported here provide solid support for MB's effect on amyloid fibrillogenesis. We believe the additional insights gained herein may pave way to the discovery of other small molecules that may have similar action toward amyloid fibril formation and its associated diseases.


The value of reality orientation with older adults who are mentally III: a study from the Republic of Ireland.
The goal of this study is to bring to the fore information that provides greater insight into the value of Reality Orientation (RO) in caring for older adults. More particularly, the author conducted this study for two reasons. First, he observed a tendency for himself and his colleagues to use RO in caring for older adults with mental illness, and second, there exists a paucity of recent research-based literature related to RO. The majority of research articles reviewed were quite old, originating in the late 1970s to early 1980s (e.g., Brook, Degun, and Mather [1975]; Zepelin, Wolfe, and Kleinplatz [1981]). Finally, this article focuses on how nurses perceived RO within an elderly mental health care setting within the Republic of Ireland.


Picolinic acid as a matrix for laser mass spectrometry of nucleic acids and proteins.
We found that picolinic acid is a very good matrix for matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry of oligonucleotides, proteins and tRNA. Among the oligonucleotides, picolinic acid was shown to be effective for homo-oligonucleotides, d(G)40 and d(C)60, and for mixed-base oligonucleotides up to 190 bases. In the case of the single-stranded oligonucleotides, and of double-stranded ones as well, only parent ions corresponding to single-stranded DNA were observed. The efficiency for MALDI of oligonucleotides using the picolinic acid matrix was superior to that using 3-hydroxypicolinic acid. MALDI of transfer RNA phenylalanine-specific (tRNA(Phe)), a 76-base ribonucleic acid, was detected with a signal-to-noise ratio of > 10. By comparison with 3-hydroxypicolinic acid the results with picolinic acid are notably superior for all oligonucleotides.


Cellulose-g-poly(2-(dimethylamino)ethylmethacrylate) Hydrogels: Synthesis, Characterization, Antibacterial Testing and Polymer Electrolyte Application.
Hydrogels have been investigated due to their unique properties. These include high water content and biocompatibility. Here, hydrogels with different ratios of poly(2-(dimethylamino)ethylmethacrylate) (PDMAEMA) were grafted onto cellulose (Cel-g-PDMAEMA) by the free radical polymerization method and gamma-ray radiation was applied in order to increase crosslinking and content of PDMAEMA. Gamma irradiation enabled an increase of PDMAEMA content in hydrogels in case of higher ratio of 2-(dimethylamino)ethyl methacrylate in the initial reaction mixture. The swelling of synthesized hydrogels was monitored in dependence of pH (3, 5.5 and 10) during up to 60 days. The swelling increased from 270% to 900%. Testing of antimicrobial activity of selected hydrogel films showed weak inhibitory activity against Escherichia coli, Pseudomonas aeruginosa, and Bacillus subtilis. The results obtained by the cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) indicate that chemically synthesized hydrogels have good characteristics for the supercapacitor application.


Factors in Predicting Failure with Medical Therapy for BPH.
Perhaps more than other common disorders, the management of benign prostatic hyperplasia (BPH) has been subject to the "reatment du jour" approach. Although pharmacotherapy has largely replaced surgery in the treatment of BPH, recommendations for optimal therapy seem to change every time a new study is published. alpha-Blockers, 5alpha-reductase inhibitors, and combination therapy with the 2 have all proved highly effective, in both trials and clinical practice. Nevertheless, medical therapy does not work for everyone, and identification of baseline factors that can help predict failure with a particular therapy is needed. Currently, the evidence supports the use of single-agent alpha-blocker therapy for patients with low prostate volumes at baseline, and combination therapy for patients with larger prostates. Symptom severity at baseline also seems predictive of success or failure.


A pulsed wire probe for the measurement of velocity and flow direction in slowly moving air.
This report describes the theory and operation of a pulsed-probe anemometer designed to measure steady three-dimensional velocity fields typical of pulmonary tracheo-bronchial airflows. Local velocities are determined by measuring the transport time and orientation of a thermal pulse initiated at an upstream wire and sensed at a downstream wire. The transport time is a reproducible function of velocity and the probe wire spacing, as verified by a theoretical model of convective heat transfer. When calibrated the anemometer yields measurements of velocity accurate to +/- 5 percent and resolves flow direction to within 1 deg at airspeeds greater than or equal to 10 cm/s. Spatial resolution is +/- 0.5 mm. Measured flow patterns typical of curved circular pipes are included as examples of its application.


In vitro and in silico evaluations of actinomycin X2and actinomycin D as potent anti-tuberculosis agents.
Multidrug-resistant tuberculosis (MDR-TB) is one of the world's most devastating contagious diseases and is caused by the MDR-Mycobacterium tuberculosis (MDR-Mtb) bacteria. It is therefore essential to identify novel anti-TB drug candidates and target proteins to treat MDR-TB. Here, in vitro and in silico studies were used to investigate the anti-TB potential of two newly sourced actinomycins, actinomycin-X2 (act-X2) and actinomycin-D (act-D), from the Streptomyces smyrnaeus strain UKAQ_23 (isolated from the Jubail industrial city of Saudi Arabia). The anti-TB activity of the isolated actinomycins was assessed in vitro using the Mtb H37Ra, Mycobacterium bovis (BCG), and Mtb H37Rv bacterial strains, using the Microplate Alamar Blue Assay (MABA) method. In silico molecular docking studies were conducted using sixteen anti-TB drug target proteins using the AutoDock Vina 1.1.2 tool. The molecular dynamics (MD) simulations for both actinomycins were then performed with the most suitable target proteins, using the GROningen MAchine For Chemical Simulations (GROMACS) simulation software (GROMACS 2020.4), with the Chemistry at HARvard Macromolecular Mechanics 36m (CHARMM36m) forcefield for proteins and the CHARMM General Force Field (CGenFF) for ligands. In vitro results for the Mtb H37Ra, BCG, and Mtb H37Rv strains showed that act-X2 had minimum inhibitory concentration (MIC) values of 1.56 ± 0.0, 1.56 ± 0.0, and 2.64 ± 0.07 µg/mL and act-D had MIC values of 1.56 ± 0.0, 1.56 ± 0.0, and 1.80 ± 0.24 µg/mL respectively. The in silico molecular docking results showed that protein kinase PknB was the preferred target for both actinomycins, while KasA and pantothenate synthetase were the least preferred targets for act-X2and act-D respectively. The molecular dynamics (MD) results demonstrated that act-X2 and act-D remained stable inside the binding region of PknB throughout the simulation period. The MM/GBSA (Molecular Mechanics/Generalized Born Surface Area) binding energy calculations showed that act-X2 was more potent than act-D. In conclusion, our results suggest that both actinomycins X2 and D are highly potent anti-TB drug candidates. We show that act-X2is better able to antagonistically interact with the protein kinase PknB target than act-D, and thus has more potential as a new anti-TB drug candidate.


[Suppression of tinnitus by electric stimulation in cochlear implant patients].
The use of electrical stimulation for the treatment of tinnitus was evaluated on 38 cochlear implant patients suffering from chronic tinnitus. In answer to a questionnaire 29 (76%) of the subjects reported a reduction of the tinnitus while using their speech processor; 15 even noted complete suppression. Sixteen patients used a processor delivering subthreshold current for 2 weeks. A placebo trial followed. Reduction of tinnitus was found in only 3 (19%) of the patients; however, 13 (81%) mentioned a substantial decrease of tinnitus when using their own device with above-threshold stimulation. The fact that tinnitus was also reduced on the contralateral side suggests that the acoustic masking effect must be the main determining factor rather than electrical stimulation. Therefore, the best therapy for the deaf seems to be the improvement of their hearing ability.


Diagnosis and treatment of patients with patellofemoral pain.
The patient-athlete with patellofemoral pain requires precise physical examination based on a thorough history. The nature of injury and specific physical findings, including detailed examination of the retinacular structure around the patella, will most accurately pinpoint the specific source of anterior knee pain or instability. Radiographs should include a standard 30 degrees to 45 degrees axial view of the patellae and a precise lateral radiograph. Nonoperative treatment is effective in most patients. Prone quadriceps muscle stretches, balanced strengthening, proprioceptive training, hip external rotator strengthening, patellar taping, orthotic devices, and effective bracing will help most patients avoid surgery. When surgery becomes necessary, indications must be specific. Lateral release is appropriate for patella tilt (abnormal rotation). Painful scar or retinaculum, neuromas, and pathologic plicae may require resection. Proximal patellar realignment may be accomplished using arthroscopic or a combined arthroscopic/mini-open approach. Symptomatic articular lesions and more profound malalignments may require medial or anteromedial tibial tubercle transfer. Clinicians should be particularly alert for symptoms of medial subluxation in postoperative patients and should use the provocative medial subluxation test followed by lateral displacement patellar bracing to confirm a diagnosis of medial patellar subluxation. This problem may be corrected in most patients using a lateral patellar tenodesis. Current thinking emphasizes precise diagnosis, rehabilitation involving the entire kinetic chain, restoration of patella homeostasis, minimal surgical intervention, and precise indications for more definitive corrective surgery.


Breastfeeding and Mammographic Breast Density: A Cross-sectional Study.
Breastfeeding is inversely associated with breast cancer risk but the associations of breastfeeding with mammographic breast density (MBD) are not clear. We investigated the association between breastfeeding and volumetric measures of MBD [volumetric percent density (VPD), dense volume (DV), and non-dense volume (NDV)] and evaluated whether it differs by race, menopausal status, and body mass index (BMI). The study population was comprised of 964 women (67% non-Hispanic White, 29% non-Hispanic Black) who had screening mammography at Washington University School of Medicine, St. Louis, MO. VPD, DV and NDV were log10 transformed. We performed multivariable linear regression models adjusted for age, BMI, family history of breast cancer, race, and age at menarche among all participants and exclusively in parous women. Mean age was 50.7 years. VPD was 12% lower among women who breastfed 0-6 months, [10β = 0.88, 95% confidence interval (CI; 0.79-0.98)] compared with nulliparous women. Breastfeeding was not associated with VPD among women who breastfed >7 months. Breastfeeding was inversely associated with DV [parous never breastfed: 10β = 0.93; 95% CI (0.83-1.04), breastfed 0-6 months: 10β = 0.91, 95% CI (0.79-1.05), breastfed 7-12 months: 10β = 0.94; 95% CI (0.81-1.10), breastfed >12 months: 10β = 0.87, 95% CI (0.78-0.98), Ptrend = 0.03]. BMI modified the association between breastfeeding and VPD. Women who breastfed for 0-6 months and had a BMI < 25 kg/m2 had lower VPD compared with nulliparous women, but among women with a BMI ≥ 25 kg/m2 there was no association (Pinteraction = 0.04). In this diverse study population, the association of breastfeeding with VPD appears to be modified by BMI, but not by race or menopausal status. Future research exploring the associations of breastfeeding with other mammographic features are needed. Breastfeeding for up to 6 months may be associated with lower VPD among women with a BMI < 25 kg/m2. The potential role of MBD in mediating the associations of breastfeeding with breast cancer risk in a select group of women deserves further evaluation. See related Spotlight, p. 309.


Cytokines as mediators of graft-versus-host disease.
Cytokines are proteins produced mainly by lymphocytes in response to an antigenic stimulus. Originally identified and named on the basis of their biological activity, they are now called interleukins; together with the interferons, colony-stimulating factors and tumour necrosis factor/cachectin (TNF) they form a complex and overlapping network of communication between immunocompetent cells. Cytokines play a central role in T cell activation, and interleukin 2 and interferon gamma in particular are involved in the expression of graft-versus-host disease after bone marrow transplantation. Recent studies suggest that TNF is also implicated: the gene encoding TNF is situated close to the MHC gene in both mice and humans, and TNF is able to up-regulate constitutively expressed class II antigen and, with interferon gamma, to induce class II expression in previously normal cells. Bacterial lipopolysaccharide (endotoxin) is a powerful stimulus to TNF, and TNF production may be the mechanism underlying the longstanding observations on the role of the bacterial microflora of the gut in graft-versus-host disease.


Epidemiology, co-morbidities, and medication use of patients with Alzheimer's disease or vascular dementia in the UK.
Epidemiologic studies on age-specific incidence rates (IRs) separating Alzheimer's disease (AD) and vascular dementia (VaD) in the UK are scarce. We sought to assess IRs of AD and VaD in the UK and to compare co-morbidities and medication use between patients with AD, VaD, or without dementia. We identified cases aged ≥65 years with an incident diagnosis of AD or VaD between 1998 and 2008 using the General Practice Research Database (GPRD). We assessed IRs, stratified by age and gender, matched one dementia-free control patient to each demented patient, and analyzed co-morbidities and medication use. We identified 7,086 AD and 4,438 VaD cases. Overall, the IR of AD was 1.59/1,000 person-years (py) (95% CI 1.55-1.62) and the IR of VaD 0.99/1,000 py (95% CI 0.96-1.02). For AD, IRs were higher for women than for men, but not for VaD. Except for orthostatic hypotension, the prevalence of all cardiovascular (CV) co-morbidities and exposure to CV drugs was lower in patients with AD than in corresponding controls, whereas the opposite was true for VaD. The lower prevalence of CV diseases in patients with AD may be a true finding or the result of a channeling effect, i.e., the possibility that demented patients with CV diseases may be more likely diagnosed with VaD than AD.


Dihydroxy bile salt-induced secretion of rubidium ion across the rabbit distal colon.
Possible mechanisms of dihydroxy bile salt-induced K+ secretion by the mammalian colon were evaluated by studying the effects of taurochenodeoxycholate (TCDC) on 86Rb+ transport across the isolated, short-circuited rabbit distal colon. Simultaneous measurements of 86Rb+ and 42K+ unidirectional fluxes were highly correlated [r = 0.964 for serosal (s) to mucosal (m) and 0.765 for m to s], indicating that Rb+ is a suitable tracer for K+ transport across the colon. Furthermore, mucosal Ba2+ (4 mM) or serosal ouabain (0.1 mM) decreased serosal to mucosal rubidium flux (JRbs----m) (from 0.24 +/- 0.02 to 0.09 +/- 0.02, and 0.08 +/- 0.01 mu eq X h-1 X cm-2, respectively) without affecting JRbm----s. Dibutyryl cyclic adenosine monophosphate (dBcAMP, 0.5 mM serosal) specifically increased JRbs----m of controls (from 0.21 +/- 0.05 to 0.67 +/- 0.09 mu eq X h-1 X cm-2) through a barium- (4 mM, mucosal) sensitive pathway without affecting JRbs----m. Mucosal addition of 2 mM TCDC increased tissue conductance (GT), reduced short-circuit (Isc) slightly, and reversed JRbnet (from 0.13 +/- 0.05 to -0.29 +/- 0.08 mu eq X h-1 X cm-2) principally by increasing JRbs----m. The TCDC-induced increases in JRbs----m were reduced by 0.1 mM serosal ouabain (from 0.53 +/- 0.03 to 0.11 +/- 0.02 mu eq X h-1 X cm-2) or 4 mM mucosal Ba2+ (from 0.76 +/- 0.07 to 0.32 +/- 0.04 mu eq X h-1 X cm-2).(ABSTRACT TRUNCATED AT 250 WORDS)


Graphemes Sharing Phonetic Features Tend to Induce Similar Synesthetic Colors.
Individuals with grapheme-color synesthesia experience idiosyncratic colors when viewing achromatic letters or digits. Despite large individual differences in grapheme-color association, synesthetes tend to associate graphemes sharing a perceptual feature with similar synesthetic colors. Sound has been suggested as one such feature. In the present study, we investigated whether graphemes of which representative phonemes have similar phonetic features tend to be associated with analogous synesthetic colors. We tested five Korean multilingual synesthetes on a color-matching task using graphemes from Korean, English, and Japanese orthography. We then compared the similarity of synesthetic colors induced by those characters sharing a phonetic feature. Results showed that graphemes associated with the same phonetic feature tend to induce synesthetic color in both within- and cross-script analyses. Moreover, this tendency was consistent for graphemes that are not transliterable into each other as well as graphemes that are. These results suggest that it is the perceptual-i.e., phonetic-properties associated with graphemes, not just conceptual associations such as transliteration, that determine synesthetic color.


[New methods for the evaluation of bone quality. Bone quality evaluation by QCT.]
In osteoporosis, the risk of fracture is influenced by decrease of bone mineral density and deterioration of bone quality. The latter includes deterioration of the material and structural properties of bone. These changes arise from the influence of changes in hormonal balance, aging, changes in mechanical stress, lifestyle-related diseases, etc. on bone absorption and bone formation as the coupled functions of osteoclasts and osteoblasts. Deterioration of bone quality occurs at various levels ranging from the molecular to the tissue level, or even at the individual level, and leads to an increased fracture risk. In this chapter, bone quality evaluation using quantitative computed tomography is discussed among evaluation methods of various fracture risk.


Transcending death during early adulthood: symbolic immortality, death anxiety, and purpose in life.
Robert Jay Lifton has originated a comprehensive theory of development based on the human psychobiological need to symbolize death and life continuity. He calls this condition the sense of symbolic immortality and argues that life is threatened whenever death is not transcended. A Sense of Symbolic Immortality Scale was built and administered to two groups of young adults (N = 136) in order to test the hypothesis that symbolic immortality develops with age (Drolet, 1986). Templer's Death Anxiety Scale and Crumbaugh and Maholick's Purpose in Life Test also were administered. Results show that established adults have a sense of symbolic immortality and a purpose in life significantly stronger than those of young adults. They show a negative relation between death anxiety and purpose in life, while purpose in life correlates highly with the sense of symbolic immortality. Finally, the premise that the sense of symbolic immortality helps cope with the fear of death is supported.


Seated buttock contours: a pilot study of Australian senior high-school students.
Both posture and comfort of a chair are influenced by the contour and characteristics of the seat. Knowledge of seat contours of a student population could thus be useful in the design of school chairs. This study investigated seated buttock contours of senior high-school students in order to determine: (a) their general characteristics, (b) the effect of gender and sitting posture and (c) the relationship between the contours and selected anthropometric variables (stature and mass). A contour measurement device was developed and used to measure buttock contours in five sitting postures (typing, sitting up, sitting back, slumping and writing). Buttock contours were quantified by constructing anterior-posterior (AP) and lateral profiles from which six discrete profile dimension measurements were made. AP and lateral profiles were found to have a consistent shape across all participants. Five out of six profile dimensions were significantly different between genders, with just one significantly different between sitting postures (typing and sitting back). Correlations between anthropometric measures and profile dimensions were relatively low (r < 0.34) with no clear patterns evident. Overall results of this study suggest that buttock contours are influenced by gender to a greater extent than sitting posture.


Common variable immunodeficiency mimicking rheumatoid arthritis with Sjögren's syndrome.
Several autoimmune diseases have been reported to be associated with common variable immunodeficiency disease (CVID), including rheumatoid arthritis and Sjögren's syndrome. On the other hand, approximately 20-30% of patients with rheumatoid arthritis develop secondary Sjögren's syndrome. A 26-year-old woman had a 6-year history of chronic symmetric polyarthritis and 3-year history of sicca syndrome prior to admission for pneumonia. Rheumatoid arthritis with secondary Sjögren's syndrome had been diagnosed 1 year before. The patient had experienced 3 episodes of pneumonia during the previous 3 years. Markedly depressed serum immunoglobulin levels prompted a suspicion of common variable immunodeficiency, and the impression was confirmed after a series of examinations. Monthly administration of intravenous immunoglobulin (IVIG) alleviated the polyarthritis and improved the sicca syndrome. IVIG replacement therapy was ultimately successful in curing recurrent bacterial infections, chronic polyarthritis, and improving the severity of sicca syndrome.


Modeling of pharmaceuticals mixtures toxicity with deviation ratio and best-fit functions models.
The present study deals with assessment of ecotoxicological parameters of 9 drugs (diclofenac (sodium salt), oxytetracycline hydrochloride, fluoxetine hydrochloride, chloramphenicol, ketoprofen, progesterone, estrone, androstenedione and gemfibrozil), present in the environmental compartments at specific concentration levels, and their mutual combinations by couples against Microtox® and XenoScreen YES/YAS® bioassays. As the quantitative assessment of ecotoxicity of drug mixtures is an complex and sophisticated topic in the present study we have used two major approaches to gain specific information on the mutual impact of two separate drugs present in a mixture. The first approach is well documented in many toxicological studies and follows the procedure for assessing three types of models, namely concentration addition (CA), independent action (IA) and simple interaction (SI) by calculation of a model deviation ratio (MDR) for each one of the experiments carried out. The second approach used was based on the assumption that the mutual impact in each mixture of two drugs could be described by a best-fit model function with calculation of weight (regression coefficient or other model parameter) for each of the participants in the mixture or by correlation analysis. It was shown that the sign and the absolute value of the weight or the correlation coefficient could be a reliable measure for the impact of either drug A on drug B or, vice versa, of B on A. Results of studies justify the statement, that both of the approaches show similar assessment of the mode of mutual interaction of the drugs studied. It was found that most of the drug mixtures exhibit independent action and quite few of the mixtures show synergic or dependent action.


LncRNA ZNF667-AS1 alleviates rheumatoid arthritis by sponging miR-523-3p and inactivating the JAK/STAT signalling pathway.
Rheumatoid arthritis (RA) is an autoimmune disease, which compromises the synovial membrane resulting in chronic inflammation. Increasing evidence has demonstrated that long non-coding RNAs (lncRNAs) are implicated in the pathogenesis of RA. This study investigated the role of lncRNA ZNF667-AS1 in RA progression. Synovial tissues and fibroblast-like synoviocytes (FLSs) were obtained from patients with RA. Gene expression was measured using RT-qPCR. Chondrocytes were treated with lipopolysaccharide (LPS) to establish in vitro models of OA. Cell counting kit-8 (CCK-8), western blot, and enzyme-linked immunosorbent assay (ELISA) were used to examine the proliferation and inflammatory cytokine production in chondrocytes. Animal models of OA were established in SD rats. Peripheral blood mononuclear cells (PBMCs) were isolated from the OA rats. Flow cytometry was used to measure the changes of the inflammatory T-helper cell 17 (Th17) cells. The relationship between ZNF667-AS1 and miR-523-3p was verified by luciferase reporter assay. ZNF667-AS1 was downregulated in RA-FLSs and LPS-stimulated chondrocytes. ZNF667-AS1 overexpression significantly promoted cell proliferation and inhibited the production of IL-6, IL-17 and TNF-α in LPS-stimulated chondrocytes. Additionally, ZNF667-AS1 overexpression reduced the generation of CD4 + IL-17+ cells. In mechanism, ZNF667-AS1 acted a sponge for miR-523-3p. MiR-523-3p overexpression reversed the ZNF667-AS1-mediated regulation of cell proliferation and inflammation. Furthermore, miR-523-3p overexpression abolished the inhibitory effects of ZNF667-AS1 on the JAK/STAT signalling activation. ZNF667-AS1 exerts protective effects during RA development by sponging miR-523-3p and inactivating the JAK/STAT signalling.


[A study on the effect of Tanshinone II A against human breast cancer in vivo].
To confirm Tanshinone II A's (Tan II A) anti-cancer activity on nude mice bearing human breast cancer cells with estrogen receptor (ER) positive and negative and to elucidate the mechanism of its activity in vivo. Established the animal model of nude mices bearing human breast cell, both ER positive MCF-7 and ER negative MDA-MB-231, each group was divided into 3 subgroups, respectively by intraperitoneal injection of Tan II A at a dose of 30 mg/kg 4 times/week, by gavage of Tamoxifen at a dose of 1 mg/kg 7 times/ week and by solvent control for 4 weeks. All animals were tested for anti-cancer activity including the weights and the volumes of the tumor, apoptosis index by flow cytometry and expression of p53, bcl-2, cerbB-2 by immunohistochemistry method after the treatment. In MCF-7 group, there were a 33.64% tumor mass volume reduction and a 32.24% tumor mass weight reduction after Tan II A treatment; in MDA-MB-231 group, a 38.34% tumor mass volume reduction and a 39.82% tumor mass weight reduction were observed in Tan II A subgroups; the differences between Tan II A and Tamoxifen or solvent control were statistically significant in both groups (P < 0.05); increase of apoptosic fiction by flow cytometry examination in Tan II A subgroups in both MCF-7 (48.31% +/- 5.84%) and MDA-MB-231(50.25% +/- 5.03%) groups were observed, there were both significant differences between Tan II A and the other subgroups (P < 0.05). Statistically significant decrease of p53 and bcl-2 expression were observed in Tan lI A between solvent control subgroup in both MCF-7 and MDA-MB-231 groups (P < 0.05) while cerbB-2 had no significant difference with control group (P > 0.05). Tan lI A can inhibit both breast cancer cell MCF-7 and MDA-MB-231 growth in vivo, which had better anti-cancer effect than Tamoxifen. The mechanism may be associated with the induction of apoptosis, down regulation of the expression level of gene bcl-2 and p53, but may not with the expression level of cerbB-2.


Long-term GERD management: the individualized approach.
Gastroesophageal reflux disease (GERD) is a complex condition, and both mucosal lesions and symptoms are important parameters in evaluating disease severity and the impact of treatment. An individualized approach in which treatment is tailored to each patient is the appropriate strategy. Treatment with a standard dose of a proton pump inhibitor (PPI) should be continued until symptoms resolve in the case of nonerosive reflux disease (NERD), or until complete remission is achieved (resolution of symptoms and endoscopically confirmed healing) in patients with erosive disease. Maintenance treatment with a half-dose PPI is effective in both erosive esophagitis and NERD. If NERD patients remain in remission with the half-dose PPI, therapy can continue in an on-demand basis. A relapse of symptoms often needs to be treated by a return to a full-dose PPI. Studies of long-term treatment with PPIs show that they are a safe and effective means of maintaining remission in patients with GERD.


Chronic phencyclidine treatment increases dendritic spine density in prefrontal cortex and nucleus accumbens neurons.
We examined whether repeated exposure to the noncompetitive NMDA receptor antagonist phencyclidine (PCP) produces enduring changes in dendritic structure in a manner similar to the stimulants cocaine and amphetamine. Adult rats were treated with i.p. injections of PCP (5 mg/kg) or saline, twice a day, for 5 consecutive days, for a total of 4 weeks. One month after the last injection, their brains were removed and processed for Golgi-Cox staining. Prior exposure to PCP increased dendritic spine density in the mPFC and NAcc core, but not in the parietal cortex. These findings, which are similar to those observed after chronic treatment with cocaine and amphetamine, raise the possibility that, despite differences in their mechanisms of action, PCP and stimulant drugs may induce some of their enduring effects via common processes.


Yttrium ethyl-enediammonium squarate tetra-hydrate.
The title compound, {(C(2)H(10)N(2))(1.5)[Y(C(4)O(4))(3)(H(2)O)(4)]}(n) {system-atic name: catena-poly[sesqui(ethyl-enediammonium) [[tetra-aquabis-(squarato-κO)yttrium(III)]-μ-squarato-κ(2)O:O']]}, was synthesized by slow evaporation of an acid solution. The asymetric unit contains one yttrium cation in an anti-prismatic environnement, three squarate groups, one and a half protonated ethyl-enediamine mol-ecules and four water mol-ecules. YO(8) polyhedra are connected through bis-(mono-dentate) squarates, leading to infinite zigzag chains, in between which are located ammonium groups. A framework of hydrogen bonds between protonated amine N atoms, water mol-ecules and squarate anions ensures the cohesion of the structure.


Comparison of clinical and microbiological profiles in smear-positive and smear-negative cases of suspected microbial keratitis.
To examine the hypothesis that initial smear examination results have a significant bearing on the management and outcome of suspected microbial keratitis. One hundred and seventy consecutive patients with suspected microbial keratitis were included in a prospective nonrandomized comparative study and their detailed clinical and microbiological data (smears and cultures of corneal scrapings) were captured on a predesigned corneal ulcer database. Patients were divided into two groups: Group 1 included 68 patients with corneal scrapings negative in smears while Group 2 included 102 patients with corneal scrapings positive in smears. The two groups were compared for their clinico-microbiological profile, management and clinical outcome. The outcome was noted at three months. Fisher's exact test was applied for statistical analysis. Cultures were sterile in 57.3% of patients in Group 1 compared to 17.6% in Group 2. Scrapings that grew S. pneumoniae, gram-negative organisms, fungi and Acanthamoeba were more often positive in smears (18.6%, 11.8%, 19.6% and 2.9% respectively). While data on duration of prior treatment was not available, prior medication made no significant difference to smear results. More (79.3%) patients of Group 1 had small infiltrate size ( Initial smear examination helps in instituting specific therapy thereby improving the outcome in cases of microbial keratitis. Positive smears indicate greater severity of disease and prior medication may not be a significant cause of smear negativity.


Tolerance of combined radiochemotherapy in cervical cancer patients.
Radiochemotherapy in cervical cancer was implemented to clinical practice based on 5 randomized clinical trials, published at the end of the 20th century, which showed improvement in the total and symptomless survivals by about 10-18%. The increase of therapeutic index of such treatment can take place only when the efficiency of the treatment outweighs the increase of its toxicity. Thus, it is necessary to monitor treatment reaction during radiochemotherapy. The aim of this study was to assess the acute post-radiation reaction during radiochemotherapy for cervical cancer and the to analyze the reasons of the unplanned course of combined treatment. A group of consecutive 176 cervical cancer patients in the clinical stage from IB to IIIB acc. to FIGO classification who underwent radiochemotherapy were taken under prospective observation in Clinical Gynecologic Radiotherapy Ward of the Lower Silesian Cancer Center in Wrocław between April 2010 and September 2012. Early post-radiation reaction was assessed in RTOG/EORTC scale once a week. During the treatment early post-radiation reaction of upper part of alimentary duct was observed in 74.4% of the patients, the reaction of lower part of gastrointestinal tract in 51.2%, and in bladder 44.8%. The most frequent symptoms of post-radiation reaction are: nausea (73.3% of the patients), diarrhea (51.2%) and vomiting (20.9%). Leucopenia was observed in 97.1% of the patients, granulocytopenia in 70.4%, anemia in 69.2%, and thrombocytopenia in 25.5%. The planned dose of radiotherapy was administered completely in 90.1% of the patients. A break in radiotherapy was necessary in 15.7% of the patients. In total, 44.8% of the patients did not receive radiochemotherapy according to the plan, because of the side effects of the treatment (most often leucopenia, thrombocytopenia and gastrointestinal reaction). The presented data shows that radiochemotherapy causes the intensification of acute side effects of treatment and may cause unplanned course of treatment and prolongation of the total treatment time.


A modified Fasanella-Servat procedure for ptosis.
This procedure was first suggested for "minimal ptosis of 3-4 mm." However, since the amount of ptosis varies widely with the etiological factors, the true indication in any given case is not the amount of ptosis but the amount of levator action. Hence, unless there is at least 10 mm of levator action, this operation is contraindicated. Since the levator (except that part of the aponeurosis that is adherent to the tarsus) is not involved, the procedure has been simplified accordingly.


From nonpeptide toward noncarbon protease inhibitors: metallacarboranes as specific and potent inhibitors of HIV protease.
HIV protease (PR) represents a prime target for rational drug design, and protease inhibitors (PI) are powerful antiviral drugs. Most of the current PIs are pseudopeptide compounds with limited bioavailability and stability, and their use is compromised by high costs, side effects, and development of resistant strains. In our search for novel PI structures, we have identified a group of inorganic compounds, icosahedral metallacarboranes, as candidates for a novel class of nonpeptidic PIs. Here, we report the potent, specific, and selective competitive inhibition of HIV PR by substituted metallacarboranes. The most active compound, sodium hydrogen butylimino bis-8,8-[5-(3-oxa-pentoxy)-3-cobalt bis(1,2-dicarbollide)]di-ate, exhibited a K(i) value of 2.2 nM and a submicromolar EC(50) in antiviral tests, showed no toxicity in tissue culture, weakly inhibited human cathepsin D and pepsin, and was inactive against trypsin, papain, and amylase. The structure of the parent cobalt bis(1,2-dicarbollide) in complex with HIV PR was determined at 2.15 A resolution by protein crystallography and represents the first carborane-protein complex structure determined. It shows the following mode of PR inhibition: two molecules of the parent compound bind to the hydrophobic pockets in the flap-proximal region of the S3 and S3' subsites of PR. We suggest, therefore, that these compounds block flap closure in addition to filling the corresponding binding pockets as conventional PIs. This type of binding and inhibition, chemical and biological stability, low toxicity, and the possibility to introduce various modifications make boron clusters attractive pharmacophores for potent and specific enzyme inhibition.


Oncocytic carcinoid of the lung. An ultrastructural observation.
A case of a 55-year-old female patient with an oncocytic variety of carcinoid tumor of the lung is reported. Electron microscopic observation of marked hyperplasia and increase in number of mitochondria in the tumor cells suggested it to be of oncocytic variety and membrane bound electron dense granules were characteristically found in the tumor cells which were histologically diagnosed as carcinoid.


Intraoperative diagnosis of an unsuspected ruptured left ventricular aneurysm using transesophageal echocardiography: A case report.
Transesophageal echocardiography (TEE) enables a more accurate visualization of left ventricular posterior aneurysms than transthoracic echocardiography due to the close proximity of the esophagus to the posterior ventricular wall. Therefore, TEE is essential for the accurate diagnosis of posterior aneurysm, particularly in urgent settings where preoperative assessments may be insufficient.


Thyrotropin stimulation of a thyroid contractile protein phosphorylation.
Contractile proteins were isolated from preincubated dog thyroid slices by a procedure identical to the one used for the preparation of muscle actomyosin. At least two of these proteins (molecular weight = 26000 and 15000) were phosphorylated in the intact cell system. After one hour of incubation of the slices with thrytropin (10 mU/ml) and [32P]phosphate, the specific activity of the 26000-Mr protein was increased by a factor of three while no significant change in specific activity was observed in the 1500-Mr contractile protein. This effect of thyrotropin was already observed after 30 min of action, was elicited at hormone concentrations of the same order as those required to induce secretion and has been reproduced by dibutyryl adenosine 3':5'-monophosphate. Cycloheximide (0.35 mM) which almost totally inhibited protein synthesis in thyroid slices, did not affect the thyrotropin stimulation of the phosphorylation of the 26000-Mr protein. The phosphorylation of serine residue(s) has been demonstrated in this protein but the presence of radioactive phosphothreonine could not be detected. On the basis of its molecular weight, the 26000-Mr protein could be similar to the inhibitory component of muscle troponin complex (TN-I).


Enrichment of Ly6Chi monocytes by multiple GM-CSF injections with HBV vaccine contributes to viral clearance in a HBV mouse model.
Adjuvants are considered a necessary component for HBV therapeutic vaccines but few are licensed in clinical practice due to concerns about safety or efficiency. In our recent study, we established that a combination protocol of 3-day pretreatments with GM-CSF before a vaccination (3 × GM-CSF+VACCINE) into the same injection site could break immune tolerance and cause over 90% reduction of HBsAg level in the HBsAg transgenic mouse model. Herein, we further investigated the therapeutic potential of the combination in AAV8-1.3HBV-infected mice. After 4 vaccinations, both serum HBeAg and HBsAg were cleared and there was a 95% reduction of HBV-positive hepatocytes, in addition to the presence of large number of infiltrating CD8+ T cells in the livers. Mechanistically, the HBV-specific T-cell responses were elicited via a 3 × GM-CSF+VACCINE-induced conversion of CCR2-dependent CD11b+ Ly6Chi monocytes into CD11b+CD11c+ DCs. Experimental depletion of Ly6Chi monocytes resulted in a defective HBV-specific immune response thereby abrogating HBV eradication. This vaccination strategy could lead to development of an effective therapeutic protocol against chronic HBV in infected patients.


American Indian historical trauma: Anticolonial prescriptions for healing, resilience, and survivance.
The American Indian historical trauma (HT) concept is an important precursor to racial trauma (RT) theory that reflects the distinct interests of sovereign Indigenous nations but shares much of the same promise and challenge. Here, that promise and challenge is explored by tracing HT's theoretical development in terms of its anticolonial ambitions and organizing ideas. Three predominant modes of engaging HT were distilled form the literature (HT as a clinical condition, life stressor, and critical discourse), each informing a research program pursuing a different anticolonial ambition (healing trauma, promoting resilience, practicing survivance) organized by distinct ideas about colonization, wellness, and Indigeneity. Through critical reflection on these different ambitions and dialogue of their organizing ideas, conflict between research programs can be mitigated and a more productive anticolonialism realized in psychology and related health fields. Key recommendations emphasized clarifying clinical concepts (e.g., clinical syndrome vs. idiom of distress), disentangling clinical narratives of individual pathology (e.g., trauma) from social narratives of population adversity (e.g., survivance stories), attending to features of settler-colonialism not easily captured by heath indices (e.g., structural violence), and encouraging alignment of anticolonial efforts with constructive critiques establishing conceptual bridges to disciplines that can help to advance psychological understandings of colonization and Indigenous wellness (e.g., postcolonial studies). This conceptual framework was applied to the RT literature to elaborate similar recommendations for advancing RT theory and the interests of ethnic/racial minority populations through engagement with psychology and related health fields. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


[Study of compression resistance of conventional or passive post and core reconstructed roots].
The object of this study is to estimate if the reconstructed roots with passive post and core have a greater resistance to compression in relation to reconstructed roots with traditional post and core. Experimental situations have been reproduced as close as possible to real clinical situations simulating the cervical edge of the crown with a supporting cervical ring. A comparative analysis of the resistance to compression has been carried out using three groups of roots: the first group constructed from reconstructed roots with traditional post and core; the second group of reconstructed roots with passive post and core; the third group of roots were not reconstructed. Our results have shown that if the root reconstruction includes a metallic support ring that goes beyond the root plate by at least 1 mm there is no difference in the resistance to compression of statistical significance between reconstructed roots with passive post and core and reconstructed roots with traditional post and core. It turns out instead that there is a significant increase in resistance to compression of the reconstructed roots (because of the presence of the cervical support ring) in respect of the third group of unreconstructed roots.


The cocaine trail: levamisole-induced leukocytoclastic vasculitis in a cocaine user.
Two million Americans use cocaine on a regular basis. Sixty-nine percent of cocaine in the United States is adulterated with levamisole, a veterinary antihelminthic drug. In 2008, the first cases of levamisole-induced agranulocytosis and vasculopathy associated with adulterated cocaine were reported in the southwestern United States. Since then, reports of levamisole-associated toxicity have become increasingly common. The authors present the case of a 47-year-old woman from Michigan with purpuric lesions likely secondary to levamisole-induced leukocytoclastic vasculitis.


Structural basis of the substrate specificity and instability in solution of a glycosidase from Lactobacillus plantarum.
Statistics from structural genomics initiatives reveal that around 50-55% of the expressed, non-membrane proteins cannot be purified and therefore structurally characterized due to solubility problems, which emphasized protein solubility as one of the most serious concerns in structural biology projects. Lactobacillus plantarum CECT 748T produces an aggregation-prone glycosidase (LpBgl) that we crystallized previously. However, this result could not be reproduced due to protein instability and therefore further high-resolution structural analyses of LpBgl were impeded. The obtained crystals of LpBgl diffracted up to 2.48Å resolution and permitted to solve the structure of the enzyme. Analysis of the active site revealed a pocket for phosphate-binding with an uncommon architecture, where a phosphate molecule is tightly bound suggesting the recognition of 6-phosphoryl sugars. In agreement with this observation, we showed that LpBgl exhibited 6-phospho-β-glucosidase activity. Combination of structural and mass spectrometry results revealed the formation of dimethyl arsenic adducts on the solvent exposed cysteine residues Cys211 and Cys292. Remarkably, the double mutant Cys211Ser/Cys292Ser resulted stable in solution at high concentrations indicating that the marginal solubility of LpBgl can be ascribed specifically to these two cysteine residues. The 2.30Å crystal structure of this double mutant showed no disorder around the newly incorporated serine residues and also loop rearrangements within the phosphate-binding site. Notably, LpBgl could be prepared at high yield by proteolytic digestion of the fusion protein LSLt-LpBgl, which raises important questions about potential hysteretic processes upon its initial production as an enzyme fused to a solubility enhancer.


Centrifugal analysis for plasma kallikrein activity, with use of the chromogenic substrate S-2302.
The amidolytic activity of activated kallikrein in plasma can be measured by use of the chromogenic substrate, S-2302 (H-D-Pro-Phe-Arg-pNA). Plasma prekallikrein was activated to kallikrein by exposure to 50 mg/L dextran sulfate in acetone/water (35/65 by vol) at 0 degrees C for 15 min. The acetone slows anti-kallikrein activity and increases the kallikrein activity by 30%. The 37 degrees C reaction mixture contained 0.54 mmol of S-2302 substrate per liter of Tris buffer (pH 7.5 at 37 degrees C). We monitored the change in absorbance at 405 nm for 60 s. The specificity of the substrate for kallikrein was demonstrated by using plasma deficient in prekallikrein (Fletcher trait) diluted with pooled normal human plasma. We recommend collecting blood specimens with sodium citrate as the anticoagulant and with use of a double-syringe technique and all-plastic containers. Plasma kallikrein activity with Chromozym-PK (Bz-Pro-Phe-Arg-pNA) as substrate (y-axis) compared with S-2302 as substrate (x-axis) gave the relation: y = 0.28x + 0.82 (r = 0.94). Day-to-day analytical variation was 2.4% for a pooled plasma with a mean value of 85.9 mukat/L. The mean (and 2 SD) for 50 healthy adults was 86.4 (32.4) mukat/L.


Detection of Mycobacterium avium subsp. paratuberculosis in reproductive tissue and semen of naturally infected rams.
Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of paratuberculosis (PTB), disease that causes a syndrome of bad nutrient absorption, weight loss and eventually death. The intestine is the main target organ where the infection develops; however, there is evidence of infection by MAP in extra-intestine sites of sheep, including mesenteric nodes and semen. The aim of the study was to identify the presence of MAP in reproductive tissue and semen of infected Pelibuey rams in clinical state of PTB. Seven rams were used in clinical PTB state and a non-infected ram by MAP of the Pelibuey breed, confirmed by serology, nPCR and bacteriological culture, with average weight and age of 57.23 ± 1.73 kg and 2.91 ± 0.17 years, respectively. The presence of MAP was identified in different tissue samples: spleen (1/7, 14.3% and 2/7, 28.6%), small intestine (3/7, 42.9% and 4/7, 57.1%) and mesenteric lymph nodes (3/7, 42.9% and 3/7, 42.9%), with nPCR and culture, respectively. It was also identified in epididymis tissue (1/7, 14.3%), Cowper gland (2/7, 28.6%) and prostate (1/7, 14.3%), using nPCR, although without detection in culture. It was identified in testicular tissue in 42.8% (3/7; culture or nPCR technique), but in 28.6% (2/7) with both techniques. Finally, the presence of MAP was identified in 42.9% (3/7) of semen samples with nPCR; however, it was not detected through culture. In conclusion, the presence of MAP was identified in lymphatic, digestive tissue, and semen; the presence of MAP was reported for the first time in epididymis, Cowper gland, prostate and testicles of infected Pelibuey rams.


Traumatic muscle injury.
Traumatic muscle injury represents a collection of skeletal muscle pathologies caused by trauma to the muscle tissue and is defined as damage to the muscle tissue that can result in a functional deficit. Traumatic muscle injury can affect people across the lifespan and can result from high stresses and strains to skeletal muscle tissue, often due to muscle activation while the muscle is lengthening, resulting in indirect and non-contact muscle injuries (strains or ruptures), or from external impact, resulting in direct muscle injuries (contusion or laceration). At a microscopic level, muscle fibres can repair focal damage but must be completely regenerated after full myofibre necrosis. The diagnosis of muscle injury is based on patient history and physical examination. Imaging may be indicated to eliminate differential diagnoses. The management of muscle injury has changed within the past 5 years from initial rest, immobilization and (over)protection to early activation and progressive loading using an active approach. One challenge of muscle injury management is that numerous medical treatment options, such as medications and injections, are often used or proposed to try to accelerate muscle recovery despite very limited efficacy evidence. Another challenge is the prevention of muscle injury owing to the multifactorial and complex nature of this injury.


Ca(2+)-binding proteins S100A6 and S100B in primary cutaneous melanoma.
Commercially available polyclonal antibodies against a mixture of bovine brain S100 proteins have become an established marker for immunohistochemical characterization of malignant melanoma. However, the commercially available antibodies used are undefined and to date, 13 different human S100 proteins are known. The purpose of this study was to examine the expression of 4 newly available polyclonal antibodies against the human recombinant Ca(2+)-binding S100 proteins, S100A1, S100A2, S100A4 and S100A6, in cutaneous melanoma and to correlate these findings with the standard S100 staining as well as with the metastatic potential of the primary. 39 formalin-fixed paraffin-embedded primary cutaneous melanomas were incubated with polyclonal antibodies against recombinant human S100 proteins using the APAAP method. The extent of staining was qualitatively assessed and a staining index was calculated. Findings were correlated to the metastatic potential and the overall survival in all patients. Staining with antibodies against human S100A6 as well as with antibodies against conventional bovine S100 proteins was positive in all specimens. No correlation was found between the extent of protein expression and patients' outcome for standard S100 staining as well as for S100A6. S100A1, S100A2 and S100A4 staining could not be used for statistical analysis due to their low expression in melanoma. Staining was positive using S100A6 antibodies in all specimens, the quality being inferior to the commercially available S100 antibody. Highly specific and well characterized antibodies against the individual S100 proteins are now available for future immunohistochemical characterization studies in melanomas.


Flow cytometric analysis of chicken NK activity and its use on the effect of restraint stress.
Immune system is organized by the influence of both neural and endocrine systems. NK activity plays an important role in the innate immunity. In this study, we observed the effects of restraint stress on chicken peripheral blood NK activity. Viability of FITC-labeled RP9 was measured with PI after treatment with the effector cells. Chicken peripheral blood CD8alpha+ cells expressed strong cytotoxic activity, in contrast to thrombocytes, while peripheral blood CD3+ CD8alpha+ cells and CD4+ cells had little cytotoxic activity. Con A supernatant enhanced the cytotoxic activity of CD8alpha+ cells. Therefore, it is considered that these cytotoxic activities measured by flow cytometry (FCM) analysis are NK activity. When chickens were exposed to restraint stress, the levels of serum corticosterone increased transiently over a short period of time while the NK activity decreased. The decreased NK activity, however, did not recover to the intact levels for a long time, even once the serum corticosterone levels had recovered. These data indicate that chicken NK activity is able to be measured by flow cytometric analysis and that restraint stress causes severe damage to the chicken NK activity.


Expanded double negative T cells in patients with systemic lupus erythematosus produce IL-17 and infiltrate the kidneys.
Double negative (DN) T cells are expanded in patients with systemic lupus erythematosus (SLE) and stimulate autoantibody production as efficiently as CD4(+) T cells. In this study, we demonstrate that DN T cells from patients with SLE produce significant amounts of IL-17 and IFN-gamma, and expand when stimulated in vitro with an anti-CD3 Ab in the presence of accessory cells. Furthermore, IL-17(+) and DN T cells are found in kidney biopsies of patients with lupus nephritis. Our findings establish that DN T cells produce the inflammatory cytokines IL-17 and IFN-gamma, and suggest that they contribute to the pathogenesis of kidney damage in patients with SLE.


Carcinosarcoma ex pleomorphic adenoma of the parotid gland: a case report.
Carcinosarcoma ex pleomorphic adenoma is an extremely rare malignant neoplasm of the salivary gland that originates from a pre-existing benign tumor. Malignant transformation of the pleomorphic adenoma is extremely rare. The management of carcinosarcoma ex pleomorphic adenoma remains challenging because of its rarity, behavioral aggressiveness and resemblance to benign pleomorphic adenoma. Herein, we present the case of a 75-year-old male resident of Saudi Arabia with a history of a swelling in the right parotid gland for more than 25 years, which grew slowly with time. He underwent surgical removal with superficial parotidectomy. Afterward, histological examination of the resected tumor revealed features of carcinosarcoma, and he was diagnosed with carcinosarcoma ex pleomorphic adenoma. He presented again with recurrence of the tumor, which was managed with total parotidectomy and a combination of radiotherapy and chemotherapy. At 12-month follow-up, the patient showed no evidence of disease recurrence or distant metastasis.


Expression of Exogenous E-cadherin Regulates Anchorage-independent Growth in Human Lung Adenocarcinoma Cells.
To explore the suppressive effects of E-cadherin on aggregation and anchorage-independent growth of human lung adenocarcinoma cells, a mammalian expression vector containing full E-cadherin cDNA was constructed and transfected into a metastatic human lung adenocarcinoma cell line A549. RT-PCR and Western blot were used to analyse expression levels of E-cadherin. Cells aggregation and anchorage-independent growth of the tumor cells before and after gene transfection were assessed respectively. The results indicated that stable transfectants showed markedly increased levels of expressed E-cadherin compared with the corresponding sham transfectants. The transfections showed more intense cellular aggregation and anchorage-independent growth.


GENES AND GINI: WHAT INEQUALITY MEANS FOR HERITABILITY.
Research has established that genetic differences among people explain a greater or smaller proportion of the variation in life outcomes in different environmental conditions. This review evaluates the results of recent educationally relevant behavioural genetic studies and meta-analyses in the context of recent trends in income and wealth distribution. The pattern of results suggests that inequality and social policies can have profound effects on the heritability of educational attainment and achievement in a population (Gene-Gini interplay). For example, heritability is generally higher at greater equality levels, suggesting that inequality stifles the expression of educationally relevant genetic propensities. The review concludes with a discussion of the mechanisms of Gene-Gini interplay and what the findings mean for efforts to optimize education for all people.


Marginal nature of DNA solutions.
We adapt a scanning fluorescence correlation spectroscopy technique to measure the structure factor of complex fluid systems and present the first measurements of the structure of semidilute solutions of long DNA polymers. The measured structure factors exhibit screening effects which, as expected for semidilute polymer solutions, grow stronger with increasing DNA concentration c. The measured concentration dependence of the screening length xi proportional to c{0.53+/-0.02} is unusual, but can be understood within the framework of a marginal solutions theory for semiflexible polymers.


Screening Students and Staff for Asymptomatic Coronavirus Disease 2019 in Chicago Schools.
To assess rates of asymptomatic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) positivity in K-8 schools with risk mitigation procedures in place, and to evaluate SARS-CoV-2 transmission in school and household contacts of these positive individuals. In this prospective observational study, screening testing for SARS-CoV-2 was performed by oropharyngeal swabbing and polymerase chain reaction (PCR) analysis in students and staff at K-8 private schools in high-risk Chicago ZIP codes. New coronavirus disease 2019 (COVID-19) diagnoses or symptoms among participants, household contacts, and nonparticipants in each school were queried. Among 11 K-8 private schools across 8 Chicago ZIP codes, 468 participants (346 students, 122 staff members) underwent screening testing. At the first school, 17 participants (36%) tested positive, but epidemiologic investigation suggested against in-school transmission. Only 5 participants in the subsequent 10 schools tested positive for an overall 4.7% positivity rate (1.2% excluding school 1). All but 1 positive test among in-person students had high PCR cycle threshold values, suggesting very low SARS-CoV-2 viral loads. In all schools, no additional students, staff, or household contacts reported new diagnoses or symptoms of COVID-19 during the 2 weeks following screening testing. We identified infrequent asymptomatic COVID-19 in schools in high-risk Chicago communities and did not identify transmission among school staff, students, or their household contacts. These data suggest that COVID-19 mitigation procedures, including masking and physical distancing, are effective in preventing transmission of COVID-19 in schools. These results may inform future strategies for screening testing in K-8 schools.