Usefulness of a thermoplastic breast bra for breast cancer radiotherapy : A prospective analysis.
Despite modern techniques, in some patients receiving whole breast radiotherapy (WBI) parts of the heart and the lung might receive doses which are nowadays considered relevant for the development of late morbidity. Our aim was to analyze the usefulness of a thermoplastic breast brassiere to reduce lung and heart doses. A total of 29 patients with left-sided and 16 patients with right-sided breast cancer treated with breast conserving surgery and WBI between 2012 and 2013 were included in a prospective study analyzing the effectiveness of a thermoplastic breast bra. WBI was performed using 3D tangential fields up to 50.4 Gy. Treatment planning was performed with and without bra. Several dosimetrical parameters were analyzed comparatively focusing on the heart and ipsilateral lung. For heart dose comparisons, subvolumes like the left anterior descending artery (LAD) and a defined apical region, so-called "apical myocardial territory" (AMT), were defined. By using the bra, the mean lung dose was reduced by 30.6 % (left-sided cancer) and 29.5 % (right-sided; p < 0.001). The V20Gy for the left lung was reduced by 39.5 % (4.9 vs. 8.1 % of volume; p < 0.001). The mean and maximum heart doses were significantly lower (1.6 vs. 2.1 Gy and 30.7 vs. 39.3 Gy; p = 0.01 and p < 0.001), which also applies to the mean and maximum dose for the AMT (2.5 vs. 4.4 Gy and 31.0 vs. 47.2 Gy; p < 0.01 and p < 0.001). The mean and maximum dose for LAD was lower without reaching significance. No acute skin toxicities > grade 2 were observed. By using a thermoplastic breast bra, radiation doses to the heart and especially parts of the heart apex and ipsilateral lung can be significantly lowered without additional skin toxicity.


Assessing ecotoxicity of biomining effluents in stream ecosystems by in situ invertebrate bioassays: A case study in Talvivaara, Finland.
Mining of sulfide-rich pyritic ores produces acid mine drainage waters and has induced major ecological problems in aquatic ecosystems worldwide. Biomining utilizes microbes to extract metals from the ore, and it has been suggested as a new sustainable way to produce metals. However, little is known of the potential ecotoxicological effects of biomining. In the present study, biomining impacts were assessed using survival and behavioral responses of aquatic macroinvertebrates at in situ exposures in streams. The authors used an impedance conversion technique to measure quantitatively in situ behavioral responses of larvae of the regionally common mayfly, Heptagenia dalecarlica, to discharges from the Talvivaara mine (Sotkamo, Northern Finland), which uses a biomining technique. Behavioral responses measured in 3 mine-impacted streams were compared with those measured in 3 reference streams. In addition, 3-d survival of the mayfly larvae and the oligochaete Lumbriculus variegatus was measured in the study sites. Biomining impacts on stream water quality included increased concentrations of sulfur, sulfate, and metals, especially manganese, cadmium, zinc, sodium, and calcium. Survival of the invertebrates in the short term was not affected by the mine effluents. In contrast, apparent behavioral changes in mayfly larvae were detected, but these responses were not consistent among sites, which may reflect differing natural water chemistry of the study sites. Environ Toxicol Chem 2017;36:147-155. © 2016 SETAC.


Magnetic reduced graphene oxide functionalized with β-cyclodextrin as magnetic solid-phase extraction adsorbents for the determination of phytohormones in tomatoes coupled with high performance liquid chromatography.
A β-cyclodextrin (β-CD) functionalized magnetic reduced graphene oxide composite (Fe3O4/RGO@β-CD) has been prepared and its application as a selective adsorbent for the determination of the two naphthalene-derived phytohormones (1-naphthalene acetic acid (NAA) and 2-naphthoxyacetic acid (2-NOA)) has been investigated. Magnetic reduced graphene oxide composite (Fe3O4/RGO) was first synthesized via in situ chemical precipitation method and then β-CD was applied to further functionalize the resultant Fe3O4/RGO composite. The as-prepared Fe3O4/RGO@β-CD was characterized by Fourier transform infrared spectrometry (FT-IR), X-ray diffraction (XRD) and vibrating sample magnetometer (VSM). Compared with Fe3O4/RGO, the as-prepared Fe3O4/RGO@β-CD showed better molecular selectivity and higher extraction efficiency for NAA and 2-NOA by dint of the size complementarity brought by the introduction of β-CD. Response surface methodology (RSM), a multivariate experimental design technique, was used to optimize experimental parameters affecting the extraction efficiency in detail. Under the optimal conditions, good performance data was obtained. The calibration curves were linear over the concentration ranging from 2 to 600 ngg(-1) with correlation coefficients (R(2)) between 0.9995 and 0.9997 for all the analytes. The limits of detection (LODs) were 0.67 ngg(-1) for both NAA and 2-NOA. The intra- and inter-day relative standard deviations (RSDs) were less than 6.02% and 7.34%, respectively. The recoveries ranged from 91.45% to 95.89%. Taken together, the proposed method was an efficient pretreatment and enrichment procedure and could be successfully applied for selective extraction and determination of naphthalene-derived phytormones in complex matrices.


Consensus Guidelines of the French Society of Neuroradiology (SFNR) on the use of Gadolinium-Based Contrast agents (GBCAs) and related MRI protocols in Neuroradiology.
Gadolinium-based contrast agents (GBCAs) are used in up to 35% of magnetic resonance imaging (MRI) examinations and are associated with an excellent safety profile. Nevertheless, two main issues have arisen in the last two decades: the risk of nephrogenic systemic fibrosis and the risk of gadolinium deposition and retention. As a first step, this article reviews the different categories of GBCAs available in neuroradiology, their issues, and provides updates regarding the use of these agents in routine daily practice. Recent advances in MRI technology, as well as the development of new MRI sequences, have made GBCA injection avoidable in many indications, especially in patients with chronic diseases when iterative MRIs are required and when essential diagnostic information can be obtained without contrast enhancement. These recent advances also lead to changes in recommended MRI protocols. Thus, in a second step, this review focuses on consensus concerning brain MRI protocols in 10 common situations (acute ischemic stroke, intracerebral hemorrhage, cerebral venous thrombosis, multiple sclerosis, chronic headache, intracranial infection, intra- and extra-axial brain tumors, vestibular schwannoma and pituitary adenoma). The latter allowing the standardization of practices in neuroradiology. Recommendations were also made concerning the use of GBCAs in neuroradiology, based on evidence in the literature and/or by consensus between the different coauthors.


Role for extending hepatic resection using an aggressive approach to liver surgery.
The definition of what is unresectable in liver surgery is controversial. Problems that many believe render patients unresectable can currently be resected using advanced techniques of liver surgery. This study assesses liver resection in patients who were unresectable with standard liver resection but were potentially resectable using an aggressive approach to liver surgery. From 1997 to 2007, 830 adult patients undergoing hepatectomy were reviewed. Patients were categorized as having unresectable disease by standard resection if the disease could not be resected without resection of the IVC, hepatic vasculature, or because of tumor extent. One hundred sixteen patients were initially believed to have unresectable disease but went on to laparotomy. Eighteen patients were unresectable at operation, although 98 patients were resected. Seventy-eight trisectionectomies; 18 lobectomies; 1 mesohepatectomy; and 1 segment 5, 6 resection, combined with pancreaticoduodenectomy, nephrectomy, and colectomy, were performed. Fourteen patients also had pancreatic resections. Vascular reconstructions were performed on the IVC (n = 35), hepatic veins (n = 21), portal vein (n = 34), and hepatic artery (n = 5). Hypothermic perfusion of the liver was used in 12 patients (4 ex vivo, 8 in situ cold perfusion). Patients undergoing resection had 6% mortality with a morbidity of 35%. Median survival was 37 months (95% CI, 34-42 months). Five-year actuarial survival was 32%. Patients with liver tumors considered "unresectable" by standard liver resection should be considered for resection with an aggressive approach to liver surgery. Five-year survival of approximately one-third of patients can be expected.


Coronary angioplasty from the perspective of atherosclerotic plaque: morphologic predictors of immediate success and restenosis.
High restenosis rates continue to plague the overall efficacy of percutaneous transluminal coronary balloon angioplasty (PTCA). It is not surprising that predictions of long-term success or failure of PTCA based on coronary angiography are of limited value because these images provide only a circumscribed view of the arterial lumen and offer little insight into underlying plaque morphologic characteristics. Coronary atherosclerotic lesions are quite diverse with respect to plaque characteristics (eccentricity, concentricity, and extent of fibrosis, necrosis, and calcification) and cardiac ischemic syndromes (stable angina, unstable angina, myocardial infarction, and sudden cardiac death). It could thus be expected that dissimilar plaques will respond differently to balloon dilatation, and that plaque morphologic features may play an important role in the immediate and long-term outcome after PTCA. Histologic evaluation of de novo atherosclerotic plaques underscores the heterogeneity of coronary atherosclerosis. From pathologic examination of human coronary arteries subjected to PTCA during life, expansion of the arterial circumference via medial damage is required for an effective increase in lumen size. Eccentric plaques and plaques with a large necrotic core are more likely to be successfully dilated compared to concentric, fibrotic lesions. Intravascular ultrasound studies of PTCA have supported histologic findings. Restenosis involves the complex interaction of growth factors and cytokines, cellular elements (endothelial cells, smooth muscle cells, platelets, and inflammatory cells), and the extent of arterial injury. The effects of underlying plaque morphologic features on the vascular biology of restenosis requires further clarification.


Clinical experience with a bradycardia indicating pacemaker.
The beneficial effect of permanent pacing is controversial in certain patient groups. Once pacing has been instituted it is seldom terminated and an evaluation of pacemaker dependence is therefore not possible. An implantable pulse generator, detecting bradycardia below 30 bpm has been developed in order to broaden our knowledge about the natural history of bradyarrhythmias treated by permanent pacing. This pacemaker has been implanted in 38 patients who did not have clear-cut indications for permanent pacing. They have been followed for a mean of 13 months. Bradycardia was detected in 33 patients 1 to 21 months (4.6 mean) after implantation. Twenty-one patients did not have a detected bradycardia for long periods (months-years). Minor symptoms of lightheadedness attributable to bradycardia were reported by 15 patients during periods when the pacemaker had been activated. Holter monitoring for at least 24 hours was carried out in all patients and electronic analysis of explanted generators was performed in eleven cases. No technical failure related to the bradycardia-detecting facility was observed. The combination of diagnostic and therapeutic properties in the bradycardia-indicating pacemaker provides means for safe evaluation of pacemaker dependency over long time periods in patient groups with controversial indications for permanent pacing.


Molecular Characterization of U6 Promoters from Orange-Spotted Grouper (Epinephelus coioides) and Its Application in DNA Vector-Based RNAi Technology.
The U6 promoter, a typical RNA polymerase III promoter, is widely used to transcribe small RNAs in vector-based siRNA systems. The RNAi efficiency is mainly dependent on the transcriptional activity of the U6 promoter. However, studies have found that U6 promoters isolated from some fishes do not work well in distantly related species. To isolate a U6 promoter with high transcriptional efficiency from fish, in this study, we cloned five U6 promoters in orange-spotted grouper, of which only the grouper U6-1 (GU6-1) promoter contains the OCT element in the distant region. Functional studies revealed that the GU6-1 promoter has high transcriptional ability, which could efficiently transcribe shRNA and result in target gene knockdown in vitro and in vivo. Subsequently, the deletion or mutation of the OCT motif resulted in a significant decrease in promoter transcriptional activity, demonstrating that the OCT element plays an important role in enhancing the grouper U6 promoter transcription. Moreover, the transcriptional activity of the GU6-1 promoter showed little species specificity. It not only works in the grouper but also possesses high transcriptional activity in the zebrafish. Knockdown of the mstn gene in zebrafish and grouper through shRNA driven by the GU6-1 promoter could promote fish growth, suggesting that the GU6-1 promoter can be used as a potential molecular tool in aquaculture practice.


Resuspension of microplastics and microrubbers in a semi-arid urban environment (Shiraz, Iran).
Although airborne urban particles are a concern for air quality and human health, little information exists on the levels and characteristics of microplastics (MPs) and microrubbers (MRs) in this setting. In the present study, MPs and MRs are quantified and characterised in road dusts and accumulations captured passively (and up to elevations of 177 cm above road level) in the steps of utility poles at 18 locations throughout the city of Shiraz, southwest Iran. Dust accumulation rates were greatest at road level (median = 45 g m-2 month-1) and declined with elevation (median = 2.0 g m-2 month-1 at 177 cm). The accumulation rates and concentrations (per g of dust) of MPs and MRs were more variable between locations but accumulation declined with elevation for both particle types and MR concentration (up to ∼27,000 MR g-1) was always greater than corresponding MP concentration (up to ∼3300 MP g-1). Increasing elevation was also accompanied by an increasing proportion of fine (≤100 μm) and fibrous particles, and in particular for MPs. Fractionation in the quantities and characteristics with elevation above road level are attributed to the extent of resuspension of MPs and MRs from the road surface by wind and passing traffic, with aerodynamic considerations predicting the greatest and most widespread resuspension of fibrous MPs. The fractionation of MPs and MRs with elevation above road level also results in different exposures for adults and children.


Final 5-Year Report of the Randomized BIO-RESORT Trial Comparing 3 Contemporary Drug-Eluting Stents in All-Comers.
Background In a previous trial, higher 5-year mortality was observed following treatment with biodegradable polymer Orsiro sirolimus-eluting stents (SES). We assessed 5-year safety and efficacy of all-comers as well as patients with diabetes treated with SES or Synergy everolimus-eluting stents (EES) versus durable polymer Resolute Integrity zotarolimus-eluting stents (ZES). Methods and Results The randomized BIO-RESORT (Comparison of Biodegradable Polymer and Durable Polymer Drug-Eluting Stents in an All Comers Population) trial enrolled 3514 all-comer patients at 4 Dutch cardiac centers. Patients aged ≥18 years who required percutaneous coronary intervention were eligible. Participants were stratified for diabetes and randomized to treatment with SES, EES, or ZES (1:1:1). The main end point was target vessel failure (cardiac mortality, target vessel myocardial infarction, or target vessel revascularization). Five-year follow-up was available in 3183 of 3514 (90.6%) patients. The main end point target vessel failure occurred in 142 of 1169 (12.7%) patients treated with SES, 130 of 1172 (11.6%) treated with EES, versus 157 of 1173 (14.1%) treated with ZES (hazard ratio [HR], 0.89 [95% CI, 0.71-1.12], Plog-rank=0.31; and HR, 0.82 [95% CI, 0.65-1.04], Plog-rank=0.10, respectively). Individual components of target vessel failure showed no significant between-stent difference. Very late definite stent thrombosis rates were low and similar (SES, 1.1%; EES, 0.6%; ZES, 0.9%). In patients with diabetes, target vessel failure did not differ significantly between stent-groups (SES, 19.8%; EES, 19.2%; versus ZES, 21.1% [Plog-rank=0.69 and Plog-rank=0.63]). Conclusions Orsiro SES, Synergy EES, and Resolute Integrity ZES showed similar 5-year outcomes of safety and efficacy, including mortality. A prespecified stent comparison in patients with diabetes also revealed no significant differences in 5-year clinical outcomes. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01674803.


Advances in the stability challenges of bioactive peptides and improvement strategies.
Bioactive peptides are widely used in functional foods due to their remarkable efficacy, selectivity, and low toxicity. However, commercially produced bioactive peptides lack quality stability between batches. Furthermore, the efficacies of bioactive peptides cannot be guaranteed in vivo due to gastrointestinal digestion and rapid plasma, liver, and kidney metabolism. The problem of poor stability has restricted the development of peptides. Bioactive peptide stability assessments use different stability assays, so the results of different studies are not always comparable. This review summarizes the quality stability challenges in the enzymatic hydrolysis production of bioactive peptides and the metabolism stability challenges after oral administration. Future directions on the strategies for improving their stability are provided. It was proposed that we use fingerprinting as a quality control measure using qualitative and quantitative characteristic functional peptide sequences. The chemical modification and encapsulation of bioactive peptides in microcapsules and liposomes are widely used to improve the digestive and metabolic stability of bioactive peptides. Additionally, the establishment of a universal stability test and a unified index would greatly improve uniformity and comparability in research into bioactive peptides. In summary, the reliable evaluation of stability is an essential component of peptide characterization, and these ideas may facilitate further development and utilization of bioactive peptides.


Flow injection chemiluminescence determination of naproxen based on KMnO4-Na2SO3 reaction in neutral aqueous medium.
A simple, rapid and sensitive flow injection chemiluminescence (CL) method is described for the determination of naproxen. It was found that strong CL signal was generated when naproxen was mixed with KMnO4 and Na2SO3 in neutral aqueous medium. Under the optimum experimental conditions, the CL intensity was linearly related to the concentration of naproxen from 4.0 x 10(-9) to 1.0 x 10(-6)g mL(-1) (r=0.9993). The detection limit was 2 x 10(-9)g mL(-1) naproxen, the relative standard deviation for 1.0 x 10(-7) g mL(-1) naproxen solution was 1.5% (n=11) and the sampling frequency was 120 h(-1). The method was applied to the determination of naproxen in pharmaceutical preparation with satisfactory results. The mechanism of CL reaction was discussed briefly.


Culture of peripheral monocytes in vitro in patients with renal cell carcinoma: a possible prognostic indicator.
An in vitro assay has been applied in 23 patients with renal cell carcinoma. A mononuclear cell-rich fraction was cultured from peripheral blood of patients with renal cell carcinoma. The number of monocytes maturing into macrophages was quantitated over a period of 7 days. Monocyte maturation was significantly lower in patients with renal cell carcinoma than in normal individuals. Of 10 patients tested both pre- and post-nephrectomy, 8 patients showed clinical improvement after surgery. In all 8, the posttreatment macrophage yield improved significantly from the pretreatment values to approach normal values. In 2 patients found to have metastasis postoperatively, the macrophage yield continued below normal levels. Our results suggest that the in vitro maturation of macrophages from mononuclear cells may parallel clinical events.


Inhibition of inflammatory CCR2 signaling promotes aged muscle regeneration and strength recovery after injury.
Muscle regeneration depends on a robust albeit transient inflammatory response. Persistent inflammation is a feature of age-related regenerative deficits, yet the underlying mechanisms are poorly understood. Here, we find inflammatory-related CC-chemokine-receptor 2 (Ccr2) expression in non-hematopoietic myogenic progenitors (MPs) during regeneration. After injury, the expression of Ccr2 in MPs corresponds to the levels of its ligands, the chemokines Ccl2, 7, and 8. We find stimulation of Ccr2-activity inhibits MP fusion and contribution to myofibers. This occurs in association with increases in MAPKp38δ/γ signaling, MyoD phosphorylation, and repression of the terminal myogenic commitment factor Myogenin. High levels of Ccr2-chemokines are a feature of regenerating aged muscle. Correspondingly, deletion of Ccr2 in MPs is necessary for proper fusion into regenerating aged muscle. Finally, opportune Ccr2 inhibition after injury enhances aged regeneration and functional recovery. These results demonstrate that inflammatory-induced activation of Ccr2 signaling in myogenic cells contributes to aged muscle regenerative decline.


Long term effects of vasectomy on experimental atherosclerosis in rhesus monkeys.
Five groups of male rhesus monkeys, Gp. I--sham-vasectomized stock diet-fed (SVS), Gp. II--vasectomized stock diet-fed (VS), Gp. III--sham-vasectomized atherogenic diet-fed (SVA), Gp. IV--vasectomized atherogenic diet-fed (VA) and Gp. V--atherogenic diet-fed vasectomized monkeys (AV) were observed for a period of 1 1/2 years. Vasectomy per se had no effect on the level of serum or tissue lipids either alone or in combination with atherogenic diet feeding. Following vasectomy the involvement of aorta by fatty lesions was significantly increased and this occurred in animals of all four experimental groups when compared with the control animals. The maximum increase was noted in group IV. Again, there was a significant increase in the frequency of aortic plaques in groups II, III and IV while it was increased in coronary arteries of all the experimental animals (Gps. II, III, IV and V). Group IV monkeys showed higher frequency of plaques as compared to group V animals. Although the plaque height was increased in all the vessels of the experimental animals, significant differences were observed only in the coronary arteries of group II monkeys and in intra-cranial cerebral vessels of group III animals. This study shows that vasectomy per se tends to increase atherosclerosis in rhesus monkeys.


Cooperative activation of the human herpesvirus 6B U79/80 early gene promoter by immediate-early proteins IE1B and IE2B.
The human herpesvirus 6B (HHV-6B) U79/80 gene belongs to the early gene class and appears as early as 3 hr postinfection. It is one of the most abundantly expressed transcripts and a useful diagnostic marker for viral reactivation. However, the expression mechanisms of the U79/80 gene remain unclear. To identify the viral factor(s) that activates the U79/80 promoter along with other HHV-6B core early gene promoters, p41, DNA polymerase, and U41, we examined the activities of U79/80 and other early gene promoters. In HHV-6B-infected MT-4 cells, U79/80 promoter activity was the highest among early gene promoters. In addition, we identified that HHV-6B immediate-early (IE)2B protein is one of the viral proteins involved in the activation of the U79/80 and other early gene promoters. Although the IE2B could independently activate these early gene promoters, the presence of IE1B significantly augmented the activities of early gene promoters. We also found that IE2B bound three human cytomegalovirus IE2-binding consensus, cis repression signal (CRS), within the U79/80 promoter. Moreover, the U79/80 promoter was activated by cellular factors, which are highly expressed in MT-4 cells, instead of HeLa cells because it was upregulated by mock infection and in the absence of IE2B. These results suggested that the activation mechanism of the U79/80 gene differs from other HHV-6B core early genes, apparently supporting its rapid and abundant expression. Therefore, the U79/80 early gene is an actually suitable biomarker of HHV-6B reactivation.


Large-area synthesis of high-quality and uniform monolayer WS2 on reusable Au foils.
Large-area monolayer WS2 is a desirable material for applications in next-generation electronics and optoelectronics. However, the chemical vapour deposition (CVD) with rigid and inert substrates for large-area sample growth suffers from a non-uniform number of layers, small domain size and many defects, and is not compatible with the fabrication process of flexible devices. Here we report the self-limited catalytic surface growth of uniform monolayer WS2 single crystals of millimetre size and large-area films by ambient-pressure CVD on Au. The weak interaction between the WS2 and Au enables the intact transfer of the monolayers to arbitrary substrates using the electrochemical bubbling method without sacrificing Au. The WS2 shows high crystal quality and optical and electrical properties comparable or superior to mechanically exfoliated samples. We also demonstrate the roll-to-roll/bubbling production of large-area flexible films of uniform monolayer, double-layer WS2 and WS2/graphene heterostructures, and batch fabrication of large-area flexible monolayer WS2 film transistor arrays.


Virtual screening and molecular simulation study of natural products database for lead identification of novel coronavirus main protease inhibitors.
3CL like protease (3CLpro or Mpro) is one of the main proteases of 2019-nCoV. The 3CLpro is a nonstructural protein of SARS-CoV and has an essential role in viral replication and transcription, thus, could be a potential target for anti-SARS drug development. The present study employed ligand- and structure-based approaches to identify the potent inhibitors of 2019-nCoV protease. The e-pharmacophore developed from 3CLpro-1 yielded virtual hits, that were subjected through drug likeliness and PAINS filters to remove interfering compounds. Further comprehensive docking studies, free energy calculations and ADMET studies resulted in two virtual leads- MolPort-000-410-348 and MolPort-002-530-156. The compounds MolPort-000-410-348 and MolPort-002-530-156 displayed good docking score of -12.09 and -13.38 Kcal/mol and free binding energy of -63.34 ± 2.03 and -61.52 ± 2.24 Kcal/mol, respectively. The compounds also exhibited satisfactory predicted ADMET profile and were subjected to molecular dynamic (MD) studies. The MD simulation produced stable complexes of these ligands with 3CLpro protein and ligand RMSD in acceptable limits. Communicated by Ramaswamy H. Sarma.


The food plant preferences of Phratora vitellinae (Coleoptera: Chrysomelinae) : B. A laboratory comparison of geographically isolated populations and experiments on conditioning.
The specialisation of the beetles from the Petite Camargue on Salix nigricans was confirmed by laboratory food-plant trials. When S. nigricans is not present in the choice offered, other Salix species are accepted and the following ranking, in decreasing order of preference, can be established: S. nigricans, S. purpurea, Populus nigra, P. tremula, S. alba, s. caprea and S. cinerea. S. nigricans leaves are the richest in salicin of the 4 most acceptable plant species. The 3 least acceptable species have the undersurface of their leaves covered with trichomes.The food-plant preferences of 2 populations from central Europe and 2 from Belgium differ both in the field and in the laboratory. The level of dietary specialisation also differs from population to population. The populations originating from localities (Oignie in Belgium and the Petite Camargue in central Europe) where their favorite food-plants in the field and in the laboratory (respectively P. tremula and S. nigricans) are abundant, show clearer preferences than the populations from localities (Grammont in Belgium and Herrliberg in central Europe) where these plants are scarcer or even absent, due to human influence.The Salicaceae tested, as seen by the more specialised beetles of Oignie and the Petite Camargue, include both a strongly preferred plant (P. tremula or S. nigricans) and two or three strongly disliked species (S. alba, S. caprea and S. cinerea). for these beetles, laboratory preferences and field observations of host plant species are in agreement. It is interesting that S. nigricans, although not present in Belgium, is the second most preferred food of the Belgian beetles in laboratory trials. Similarly, P. tremula, the preferred food of the Belgian beetles, is well accepted by the central European beetles.For the less specialised beetles of Grammont and Herrliberg, the same Salicaceae include strongly disliked speicies but no single strongly preferred species. In the Herrliberg population, with rather poorly defined preferences, preference for the favorite species of the more specific population from the same geographical area (Petite Camargue) can readily be produced in the laboratory by conditioning.


Finite-time H∞ synchronization for complex dynamical networks with time-varying delays based on adaptive control.
This paper investigates the problem of finite-time H∞ synchronization (H∞FTS) for complex dynamical networks (CDNs) with time-varying delays(TVDs) and unknown internal coupling matrices. External disturbances are also considered into this model. By applying the adaptive control theory, this paper presents the adaptive control method to solve the H∞FTS of CDNs with external disturbances and TVDs. Some criteria are obtained by utilizing appropriate adaptive controllers and devising a special Lyapunov-Krasovskii function (LKF), which ensure the H∞FTS of CDNs based on passivity theory. Finally, using some effective mathematical techniques, comparative numerical example and Chua's circuit system are used to explain the advantages and applicability of the results and approaches.


Effect of end of life education on medical students' and health care workers' death attitude.
One of the goals of education in end of life care is to make communication more open by exploring critical issues related to fear of dying and death in order to reduce anxiety and improve an individual's attitude to dying patients. The aim of our research was to evaluate the effects of courses for health care workers and medical students in care at the end of life. One hundred and twenty-seven health care professionals and 41 undergraduate medical students completed the Multidimensional Fear of Death Scale (MFODS) on the first and last day of the course. The most significant factors of fear of death are: Fear for Significant Others, Fear of the Dying Process and Fear of the Unknown. Overall fear of death scores were reduced as an effect of the courses. Changes in the components and level of fear of death are influenced by the participants' gender, age and profession. Improvement was evident in the attitudes to dying patients in both groups, which was related to an increase in knowledge of high-quality care of dying patients.


Contribution of collegial support meetings (CSM) in the management of complex situations of patients with advanced cancer.
Collegial support meetings (CSM) have been set up in the Gustave Roussy Cancer Center for inpatients whose complex care requires a multi-professional approach involving many participants: oncologists but also health-caregivers, a member of the palliative care team, an intensivist, and a psychologist. This study is aimed at describing the role of this newly multidisciplinary meeting implemented in a French Comprehensive Cancer Center. Each week, the health-caregivers decide which situations should be examined, depending on the difficulty of a case. The discussion goes on to include the goal of treatment, the intensity of care, ethical and psychosocial issues, and the patient's life plan. Finally, to obtain feedback from the teams, a survey has been distributed to assess the interest in the CSM. In 2020, 114 inpatients were involved, and 91% were in an advanced palliative situation. During the CSMs, 55% of the discussions focused on whether to continue specific cancer treatment-29% about whether to continue invasive medical care-50% about optimizing supportive care. We estimate that between 65 and 75% of CSMs influenced further decisions. Death occurred during the hospitalization for 35% of the patients that were discussed. The lapse of time between last chemotherapy and death was 24 days (IQR, 28.5). CSMs were well received, since 80% of the teams find these meetings useful. CSMs reach conclusions for medical and nursing staff involved, in order to improve the management of inpatients with cancer in advanced palliative situation and to define the better goals of care.


Inactivation of Ppp1r15a minimises weight gain and insulin resistance during caloric excess in female mice.
Phosphorylation of the translation initiation factor eIF2α within the mediobasal hypothalamus is known to suppress food intake, but the role of the eIF2α phosphatases in regulating body weight is poorly understood. Mice deficient in active PPP1R15A, a stress-inducible eIF2α phosphatase, are healthy and more resistant to endoplasmic reticulum stress than wild type controls. We report that when female Ppp1r15a mutant mice are fed a high fat diet they gain less weight than wild type littermates owing to reduced food intake. This results in healthy leaner Ppp1r15a mutant animals with reduced hepatic steatosis and improved insulin sensitivity, albeit with a possible modest defect in insulin secretion. By contrast, no weight differences are observed between wild type and Ppp1r15a deficient mice fed a standard diet. We conclude that female mice lacking the C-terminal PP1-binding domain of PPP1R15A show reduced dietary intake and preserved glucose tolerance. Our data indicate that this results in reduced weight gain and protection from diet-induced obesity.


Validation of a tool to assess health practitioners' decision support and communication skills.
As patients become more involved in decisions affecting their health, it is important to monitor and improve the support clinicians provide to facilitate shared decision making. The Decision Support Analysis Tool (DSAT) was developed as a research tool to evaluate practitioners' use of decision support and related communication skills during a clinical encounter. The DSAT, consisting of six categories of decision support skills and four categories of communication skills, was tested with 34 actual transcripts of patient-physician dialogue. The patients were prepared for the clinical encounter with either a detailed decision aid plus worksheet (n=16) or a pamphlet (n=18). Pairs of raters, blinded to the intervention allocation, coded each transcript independently. The overall inter-rater agreement and kappa coefficients were, respectively 75% and 0.59 for the decision support skills and 76% and 0.68 for the communication skills categories. The frequency of DSAT skills coded: (a) were significantly correlated with three out of six patient and physician outcome measures (r>0.30, P<0.05); and (b) showed significant discrimination (P=0.05) or trends (P<0.15) in discrimination between the decision aid and pamphlet groups. The DSAT shows promise as a reliable and valid evaluation tool but requires further testing with larger samples.


Peeling skin syndrome with aminoaciduria.
A 12-year-old child presented with asymptomatic, noninflammatory, generalized peeling of the skin since early childhood. He was diagnosed as having type A continual peeling skin syndrome. Associated increased excretion of cystine and histidine in the urine has hitherto not been reported.


Detection of reactive oxygen metabolites in malignant and adjacent normal tissues of patients with lung cancer.
Different types of reactive oxygen metabolites (ROMs) are known to be involved in carcinogenesis. Several studies have emphasized the formation of ROMs in ischemic tissues and in cases of inflammation. The increased amounts of ROMs in tumor tissues can either be because of their causative effects or because they are produced by the tumor itself. Our study aimed to investigate and compare the levels of ROMs in tumor tissue and adjacent lung parenchyma obtained from patients with lung cancer. Fifteen patients (all male, mean age 63.6 ± 9 years) with non-small cell lung cancer were enrolled in the study. All patients were smokers. Of the patients with lung cancer, twelve had epidermoid carcinoma and three had adenocarcinoma. During anatomical resection of the lung, tumor tissue and macroscopically adjacent healthy lung parenchyma (control) that was 5 cm away from the tumor were obtained. The tissues were freshly frozen and stored at -20°C. The generation of ROMs was monitored using luminol- and lucigenin-enhanced chemiluminescence (CL) techniques. Both luminol (specific for (.)OH, H(2)O(2), and HOCl(-)) and lucigenin (selective for O(2)(.)(-)) CL measurements were significantly higher in tumor tissues than in control tissues (P <0.001). Luminol and lucigenin CL measurements were 1.93 ± 0.71 and 2.5 ± 0.84 times brighter, respectively, in tumor tissues than in the adjacent parenchyma (P = 0.07). In patients with lung cancer, all ROM levels were increased in tumor tissues when compared with the adjacent lung tissue. Because the increase in lucigenin concentration, which is due to tissue ischemia, is higher than the increase in luminol, which is directly related to the presence and severity of inflammation, ischemia may be more important than inflammation for tumor development in patients with lung cancer.


A novel family of diversified immunoregulatory receptors in teleosts is homologous to both mammalian Fc receptors and molecules encoded within the leukocyte receptor complex.
Three novel and closely related leukocyte immune-type receptors (IpLITR) have been identified in channel catfish (Ictalurus punctatus). These receptors belong to a large polymorphic and polygenic subset of the Ig superfamily with members located on at least three independently segregating loci. Like mammalian and avian innate immune regulatory receptors, IpLITRs have both putative inhibitory and stimulatory forms, with multiple types coexpressed in various lymphoid tissues and clonal leukocyte cell lines. IpLITRs have an unusual and novel relationship to mammalian and avian innate immune receptors: the membrane distal Ig domains of an individual IpLITR are related to fragment crystallizable receptors (FcRs) and FcR-like proteins, whereas the membrane proximal Ig domains are related to several leukocyte receptor complex encoded receptors. This unique composition of Ig domains within individual receptors supports the hypothesis that functionally and genomically distinct immune receptor families found in tetrapods may have evolved from such ancestral genes by duplication and recombination events. Furthermore, the discovery of a large heterogeneous family of immunoregulatory receptors in teleosts, reminiscent of amphibian, avian, and mammalian Ig-like receptors, suggests that complex innate immune receptor networks have been conserved during vertebrate evolution.


Distinct effects of CD86-mediated costimulation on resting versus activated human CD4+ T cells.
CD80 and CD86 are important in the initiation of T cell immunity. Although their costimulatory function has long been appreciated, it remains unclear whether the biological significance of the two B7 isoforms resides in their different patterns and kinetics of expression or whether differences exist in their function. We have addressed this issue using HLA-DR1 transfectants co-expressing CD80, CD86, or both molecules as stimulators for naïve, memory, and activated human CD4+ T cells. Both CD80 and CD86 efficiently costimulated alloresponses by unseparated peripheral blood CD4+ T cells; however, CD86 was substantially inferior in costimulating alloresponses by separated memory T cells, and completely incompetent in costimulating three human T cell clones. Furthermore, CD80/CD86 double transfectants stimulated lower responses by the clones than cells expressing CD80 alone. That CD86 was actively inhibitory rather than merely neutral was evidenced by the increase in response to the double CD80/CD86 APC when anti-CD86 antibody was added. Furthermore, addition of anti-CTLA-4 Fab to cultures of HLA-DR1 transfectants co-expressing CD86, fully restored the proliferative response. These results indicate that CD80 and CD86 mediate distinct signals in previously activated T cells, and demonstrate that CTLA-4 ligation may dominate the outcome of CD86-mediated costimulation of activated CD4+ T cells.


Prognostic significance of pretreatment hemoglobin for local control and overall survival in T1-T2N0 larynx cancer treated with external beam radiotherapy.
To elucidate a relationship between pretreatment hemoglobin and local control in patients with T1-T2N0 larynx cancer treated with radiotherapy. A total of 246 patients with T1-T2N0 cancer of the larynx were included in this analysis. Patients were treated using a median daily fraction of 200 cGy to a total median dose of 66 Gy within 47 days. Prognostic factors included pretreatment hemoglobin, age, gender, race, T stage, tumor subsite, beam energy, biologically equivalent dose, and therapy duration. Fifty patients developed local relapse, for an actuarial 5-year relapse-free rate of 77.3%. The actuarial 5-year survival rate was 69.8%. The pretreatment hemoglobin levels were assessed using the following hemoglobin quartiles: 10.1-13.3, 13.4-14.1, 14.2-14.9, and 15.0-18.3 g/dL. On Cox multivariate analysis, the pretreatment hemoglobin level predicted for local failure and poorer overall survival. The relative risk for 5-year local relapse by hemoglobin quartile was 2.70, 2.33, 1.91, and 1.00 (p = 0.034). The relative risk for poorer 5-year overall survival by hemoglobin quartile was 2.23 1.30, 0.80, and 1.00 (p <0.001). Pretreatment hemoglobin levels predicted for local control and overall survival for larynx cancer in a multivariate model. This relationship has potential therapeutic implications regarding correcting anemia before the initiation of radiotherapy for optimal outcome.


The cell adhesion molecule E-cadherin is widely expressed in human atherosclerotic lesions.
Various cell adhesion molecules are expressed in atherogenesis and the significance of their involvement in atherosclerotic lesion formation is well appreciated. In the present work, we examined whether the Ca(2+)-dependent cell adhesion molecule E-cadherin is also involved in atherogenesis. Specimens of carotid artery and aorta were obtained at operation. Expression of E-cadherin was studied by an immunohistochemical method. The nature of E-cadherin-expressing cells was examined by comparative analysis of consecutive sections and by a double immunostaining procedure. An immunohistochemical approach was also applied to examine how the accumulation of oxidised low density lipoproteins (LDL) by intimal cells is associated with E-cadherin expression. No E-cadherin+ cells were found in normal non-atherosclerotic intima but E-cadherin+ cells were present in 96% of the atherosclerotic lesions. In atherosclerotic intima, E-cadherin was expressed by intimal cells showing varying degrees of transformation into foam cells. These E-cadherin+ cells also contained oxidised LDL in their cytoplasm. Differing numbers of CD68+ foam cells (15% to 60%) expressed E-cadherin but all the CD68+ macrophages without signs of transformation into foam cells were negative for E-cadherin. Neither smooth muscle cells nor foam cells of smooth muscle cell origin (smooth muscle alpha-actin+) were found to be positive for E-cadherin. T-cells (CD3+) and endothelial cells (von Willebrand factor+) were also negative for E-cadherin. Only a few vascular dendritic cells (S-100+) expressed E-cadherin and their expression was weak. We also found that a large proportion (40% to 85%) of E-cadherin+ cells did not stain with any cell-type specific markers. The finding that E-cadherin is expressed in atherosclerotic lesions expands our knowledge of cell adhesion molecules involved in atherogenesis. That E-cadherin is expressed in intimal cells transforming into foam cells suggests that lipid accumulation might be associated with the alteration and reorganisation of cell-to-cell interactions in atherogenesis. The present observations might assist in understanding the mechanisms associated with intracellular lipid accumulation.


Folding pathway mediated by an intramolecular chaperone: characterization of the structural changes in pro-subtilisin E coincident with autoprocessing.
Mechanisms by which many N-terminal propeptides facilitate folding of proteins are unknown. The maturation of such proteins from their precursors involve three steps, namely: (1) folding of the precursor, (2) autoprocessing of the propeptide from the N terminus and (3) degradation of the cleaved propeptide. Using subtilisin E we have analyzed the mechanism of propeptide-mediated protein folding. Two active site mutations allow us to trap intermediates at stages of autoprocessing and degradation. An analysis of these intermediates has shown the existence of a molten-globule-like intermediate on the folding pathway. After autoprocessing of the propeptide, this intermediate undergoes a structural reorganization which reduces solvent-accessible hydrophobic surface area and increases the amount of its tertiary structure. Removal of the propeptide from the mature enzyme in this intermediate state occurs only by proteolytic degradation and contributes to the stability of the active enzyme.


[Seropositivity to leptospiras in sera from patients suspected of viral hepatitis negative to serological markers].
The prevalence of leptospirosis found in icteric patients negative to serological markers for hepatitis was described. 15.99 % of them were positive patients. It was observed a predominance of serovars canicola, pomona and icterohaemorrhagiae.


Phylogeny and diversification of planthoppers (Hemiptera: Fulgoromorpha) based on a comprehensive molecular dataset and large taxon sampling.
Our understanding of the evolution of Fulgoromorpha (Insects, Hemiptera) has relied on molecular studies that have only considered either a limited number of taxa where all the families were not represented simultaneously, or a reduced number of genes.The absence of a global analysis comparing all the available data has thus led to significant biases in the analyzes, as evidenced by the incongruence of the results reported for planthopper phylogeny. Here we provide a phylogenetic and dating analysis of the Fulgoromorpha with a large sampling of 531 ingroup taxa, representing about 80% of the currently described suprageneric taxonomic diversity in this group. This study is based on most of the molecular sequences available to date and duly verified, for a set of nuclear and mitochondrial genes from a taxonomic sampling as complete as possible. The most significant results of our study are: (1) the unexpected paraphyly of Delphacidae whose Protodelphacida seem more related to Cixiidae than to other Delphacidae;(2) the group Meenoplidae-Kinnaridae recovered sister to the remaining Fulgoroidea families; (3) the early branching node of Tettigometridae sister of all the other families;(4) the Achilidae-Derbidae clade with Achilidae Plectoderini including Achilixiidae recovered as monophyletic as well as theFulgoridae-Dictyopharidae clade; and (5) the Tropiduchidae placed sister to the other so called 'higher' families (sec. Shcherbakov, 2006).Our divergence times analysis, calibrated with a set of duly verified fossils, suggests that the first diversification of planthoppers occurred in the Early Triassic around 240 Mya and those of the superfamilies Delphacoidea and Fulgoroidea in the Middle-Late Triassic around 210 Mya and 230 Mya, respectively. By the end of the Jurassic, all major planthopper lineages were originated, and all families, around 125 Mya, might havebeen driven in their distribution and evolution (in their first subfamilial divisions) by the geographical constraints of the Gondwanan break-up.Rapid evolutionary radiations occurred particularly in Fulgoridae around 125-130 Mya. Our results stress the importance of the good quality of the sequences used in the molecular analyzes and the primordial importance of a large sampling when analyzing the phylogeny of the group.


Development of Parkinson's disease in patients with Narcolepsy.
Although amphetamine drugs can damage dopaminergic axons, it is unknown whether chronic treatment with amphetamine increases the risk of developing Parkinson's disease (PD). Of 1,152 consecutive PD patients, 3 had a prior diagnosis of narcolepsy. This rate is five times higher than expected (p = 0.02). These patients had typical onset of narcolepsy and underwent treatment with amphetamine. Although preliminary, this observation raises the possibility that some factors intrinsic to narcolepsy or its treatment may be a risk factor for PD.


Durable viral suppression in an HIV-infected patient in the absence of antiretroviral therapy.
We describe the case of a young woman with an acute HIV infection characterized at onset by neurological features. The patient spontaneously controlled her HIV infection and recovered in a short period of time. The patient's clinical and virological history showed a peculiar evolution of HIV infection, with an MDR HIV-1 in CSF and a wild HIV strain in PBMCs. The patient's PBMC showed a rapid shift from a wild type to an MDR strain in few days.


Clinical and Echocardiographic Predictors of Outcomes in Patients With Moderate (Mean Transvalvular Gradient 20 to 40 mm Hg) Aortic Stenosis.
Risk factors for adverse clinical outcomes in patients with moderate aortic stenosis are not well defined. Previous studies have suggested that certain patients with moderate AS may be at an increased risk of heart failure (HF) or death. All patients with moderate AS seen in our institution during the study period (6/1/2014 to 6/30/2017) with a minimum 1-year follow-up were included. Clinical and echocardiographic data were collected retrospectively. End points were defined as HF hospitalization, aortic valve replacement (AVR), or death. Kaplan-Meier and multivariable Cox proportional hazard models analyses were conducted using composite outcomes of (1) HF hospitalization or AVR and (2) HF hospitalization, AVR, or all-cause death. A total of 151 subjects met the inclusion criteria. The most significant risk factors associated with the composite outcomes were an ejection fraction (EF) <50% ((1) hazard ratio [HR]: 4.1; 95% confidence interval [CI]: 2.34, 7.12; (2) HR: 3.8; 95% CI: 2.2, 6.6), atrial fibrillation ((1) HR: 2.0; 95% CI: 1.2, 3.2; (2) HR: 2.1; 95% CI: 1.43, 3.2), left ventricular hypertrophy ((1) HR: 5.85; 95% CI: 2.0, 15.8; (2) HR: 3.2; 95% CI: 1.4, 7.4), aortic valve area ((1) HR: 0.3; 95% CI: 0.1, 0.6; (2) HR: 0.32; 95% CI: 0.1, 0.65), and abnormal right ventricular function ((1) HR: 4.3; 95% CI: 2.5, 7.5; (2) HR: 5.5; 95% CI: 3.0, 9.8). In conclusion, presence of reduced ejection fraction, atrial fibrillation, left ventricular hypertrophy, and abnormal right ventricular function are associated with an increased risk of HF hospitalization, AVR, and death in patients with moderate aortic stenosis.


Effects of adverse childhood experiences on the Charlson comorbidity index in US adults.
The aim of this article was to explore the association between adverse childhood experiences (ACEs) and the Charlson comorbidity index (CCI) and to provide valuable information for public health professionals and policymakers to improve quality of life and reduce mortality. A cross-sectional analysis was conducted using data pooled from the 2020 Behavioral Risk Factor Surveillance System (BRFSS). This study involved 102,393 US adult participants from the 2020 BRFSS. The zero-inflated negative binomial (ZINB) and mixed graphical model (MGM) models were used to explore the effect of ACEs on CCI and the interaction between ACEs. In the count part of the model (CCI ≥0), sexual abuse had the strongest association with CCI (relative risk [RR] = 1.111, P < 0.001). In the logit part of the model (CCI = 0), the likelihood of having CCI equal to 0 decreased by 23.0% for household substance abuse, which was the highest percentage decrease for all ACEs. Compared to those with ACE scores equal to 0, individuals with ACE scores ≥4 have an expected CCI RR of 1.222, and the likelihood of having CCI equal to 0 decreased by 50.2%. Household substance abuse and incarceration history in the home had the strongest association among interactions of ACEs (0.85). Associations between ACEs and CCI were observed in this study, and these associations differed between genders. The findings of this study provide data to design strategies for disease prevention and improvement of quality of life.


Arthroscopic treatment of type I and II greater trochanteric pain syndrome.
The goal of this study was to describe and evaluate endoscopic bursectomy combined with fascia lata lengthening in the treatment of type I and II greater trochanteric pain syndrome recalcitrant to conservative management. This was a retrospective study of 20 patients (7 type I, 13 type II) reviewed with a minimum follow-up of 2 years. The mean follow-up was 44±11 [26-65] months. While significant improvements in pain, mHHS and NAHS were found, 80% of patients still had hip pain graded at≥3 on VAS. The satisfaction rate was 7/10±2 [3-10]. Snapping in the hip had been eliminated in 100% of cases. No complications were observed. This is a minimally invasive surgery that is feasible in patients who have failed an optimal course of conservative treatment. But patients must be informed that pain might not be completely eliminated by this procedure. LEVEL OF EVIDENCE: IV; retrospective, case series.


Study of gene polymorphisms as predictors of treatment efficacy and toxicity in patients with indolent non-hodgkin lymphomas and mantle cell lymphoma receiving bendamustine and rituximab.
Bendamustine is used in combination with rituximab (BR) to treat indolent non-Hodgkin lymphomas (iNHL) and mantle cell lymphoma (MCL). The variability in treatment efficacy and toxicity could be related to single nucleotide polymorphisms (SNPs) in immune response genes. We would like to show a correlation between SNPs and treatment outcome in iNHL and MCL patients receiving BR. We investigated some SNPs that had already been associated with NHL outcome. Samples were genotyped for the IL2 (rs2069762), IL10 (rs1800890, rs10494879), VEGFA (rs3025039), IL8 (rs4073), CFH (rs1065489) and MTHFR (rs1801131) SNPs by allelic discrimination assays. We enrolled 70 patients that received rituximab 375 mg/m2 and bendamustine 90 mg/m2 every 28 days, both as first-line treatment and ≥ second-line regimens. Overall response rate was 97·1% (complete response [CR] rate 73·9%). Treatment toxicity included grade 3-4 neutropenia (24/70 patients), infections (21/70 patients; 1/70 grade 3), skin rash (26/70 patients; 2/70 grade 3). After a median follow-up of 24 months we did find any correlation between the analysed SNPs, CR rate and PFS. However, we demonstrated an association between the SNP in IL2 (rs2069762) and the onset of skin rash (P = 0·0001). Our study suggests a role for cytokine SNPs in bendamustine-related toxicity, which could represent a promising research field.


Omentin-regulated proteins combine a pro-inflammatory phenotype with an anti-inflammatory counterregulation in human adipocytes: A proteomics analysis.
Experimental and epidemiological studies reported controversial data on the role of omentin in type 2 diabetes and cardiovascular diseases. This study aimed to characterise the impact of omentin on the secretome of human adipocytes to analyse the enrichment of these proteins in metabolic and cellular signalling pathways underlying its physiological function. Differentiated primary human adipocytes were treated without or with 500 or 2000 ng/mL omentin for 24 hours. The secretome was analysed by liquid chromatography coupled tandem-mass spectrometry. Differences in protein secretion between untreated and omentin-treated adipocytes were compared using a paired t-test. Other potential upstream regulators and the overrepresentation in canonical pathways of omentin-stimulated proteins were analysed using Ingenuity Pathway Analysis. The supernatant of adipocytes contained 3493 proteins, of which 140 were differentially secreted by both concentrations of omentin compared with untreated adipocytes. Among the most strongly increased proteins, tumour necrosis factor-inducible gene 6 protein (TNFAIP6) was increased by 140-fold in the supernatant. Omentin-regulated proteins were overrepresented in seven canonical pathways including eukaryotic initiation factor 2 signalling, complement system, and inhibition of matrix metalloproteases. We further identified 25 other potential upstream activators of omentin-regulated proteins, mainly pro-inflammatory cytokines and transcription regulators including NFκB. In differentiated human adipocytes, the release of the anti-inflammatory TNFAIP6 might be part of a counterregulatory response to the pro-inflammatory action of omentin. Omentin-regulated proteins were overrepresented in pathways indicating cellular stress, a pro-inflammatory environment and a crosstalk with other organs. Other potential activators of omentin-regulated proteins point towards a central role of NFκB activation in the omentin-induced secretory process.


Clinical pharmacology of moclobemide during chronic administration of high doses to healthy subjects.
The objectives of this study were to assess the tolerability, safety, pharmacodynamics and pharmacokinetics of high-dose moclobemide in healthy subjects. Two sequential groups of six male and six female subjects (eight on active treatment, four on placebo) received for 8 days moclobemide 450 mg b.i.d. and 600 mg b.i.d., respectively. Intravenous tyramine pressor tests were conducted at baseline, at the beginning of treatment and at steady state. Oral tyramine pressor tests with 50, 100 and 150 mg tyramine were conducted under steady-state conditions. Pharmacokinetic parameters of moclobemide and two of its metabolites in plasma and urine were determined after the first and last dose of moclobemide. The incidence and intensity of adverse events was dose-dependent. The most frequently reported adverse events were insomnia, headache, dizziness and dry mouth. The i.v. tyramine pressor sensitivity during both moclobemide dosing regimens was enhanced 3 to 4-fold. Intake of tyramine 50 mg did not result in systolic blood pressure increases greater than 30 mmHg. With regard to blood pressure increases, tyramine 100 mg is still compatible with moclobemide 450 mg b.i.d. but not with 600 mg b.i.d. The clearance of moclobemide decreased by about 60% on multiple dosing, but no differences were found between both dosing regimens. The urinary excretion of the N-oxide metabolite doubled during multiple dosing. In conclusion, the maximum tolerated dose of moclobemide in healthy subjects is 600 mg b.i.d. provided the tyramine content in a meal is not higher than 50 mg.


Is cholesterol a risk factor for breast cancer incidence and outcome?
Cholesterol plays important roles in many physiological processes, including cell membrane structure and function, hormone synthesis, and the regulation of cellular homeostasis. The role of cholesterol in breast cancer is complex, and some studies have suggested that elevated cholesterol levels may be associated with an increased risk of developing breast cancer, while others have found no significant association. On the other hand, other studies have shown that, for total cholesterol and plasma HDL-associated cholesterol levels, there was inverse association with breast cancer risk. One possible mechanism by which cholesterol may contribute to breast cancer risk is as a key precursor of estrogen. Other potential mechanisms by which cholesterol may contribute to breast cancer risk include its role in inflammation and oxidative stress, which have been linked to cancer progression. Cholesterol has also been shown to play a role in signaling pathways regulating the growth and proliferation of cancer cells. In addition, recent studies have shown that cholesterol metabolism can generate tumor promoters such as cholesteryl esters, oncosterone, 27-hydroxycholesterol but also tumor suppressor metabolites such as dendrogenin A. This review summarizes some of the most important clinical studies that have evaluated the role of cholesterol or its derivatives in breast cancer. It also addresses the role of cholesterol and its derivatives at the cellular level.


The bacterial communities of surface soils from desert sites in the eastern Utah (USA) portion of the Colorado Plateau.
Desert-like areas located in the eastern portion of the state of Utah (USA) have geographic features that can resemble the surface of the planet Mars, characterized by red-colored hills, soils and sandstones. We examined the bacterial biodiversity of surface soil samples from several sites from the Colorado Plateau Desert in eastern Utah using pyrosequencing of PCR amplified bacterial 16S rRNA genes from total extracted soil DNA. The sample sites cover the Great Basin, Goblin Valley State Park and nearby regions on the Colorado Plateau. We also examined several physicochemical parameters of the soil samples to investigate any possible correlations between bacterial community structure and environmental drivers. The predominant bacterial phyla present in the samples were found to belong to members of the Proteobacteria, Actinobacteria, Bacteroidetes, and Gemmatimonadetes. The most abundant genera in our samples were found to belong to the Cesiribacter, Lysobacter, Adhaeribacter, Microvirga and Pontibacter genera. We found that the relative abundance of Proteobacteria and Gemmatimonadetes were significantly correlated with soil pH and a low concentration of organic matter, suggesting that, in these relatively high-altitude desert soils, these two parameters may be of primary importance to influence bacterial community composition.


Preferences for opt-in and opt-out enrollment and consent models in biobank research: a national survey of Veterans Administration patients.
In 2006, the Department of Veterans Affairs launched the Genomic Medicine Program with the goal of using genomic information to personalize and improve health care for veterans. A step toward this goal is the Million Veteran Program, which aims to enroll a million veterans in a longitudinal cohort study and establish a database with genomic, lifestyle, military-exposure, and health information. Before the launch of the Million Veteran Program, a survey of Department of Veterans Affairs patients was conducted to measure preferences for opt-in and opt-out models of enrollment and consent. An online survey was conducted with a random sample of 451 veterans. The survey described the proposed Million Veteran Program database and asked respondents about the acceptability of opt-in and opt-out models of enrollment. The study examined differences in responses among demographic groups and relationships between beliefs about each model and willingness to participate. Most respondents were willing to participate under both opt-in (80%) and opt-out (69%) models. Nearly 80% said they would be comfortable providing access to residual clinical samples for research. At least half of respondents did not strongly favor one model over the other; of those who expressed a preference, significantly more people said they would participate in a study using opt-in methods. Stronger preferences for the opt-in approach were expressed among younger patients and Hispanic patients. Support for the study and willingness to participate were high for both enrollment models. The use of an opt-out model could impede recruitment of certain demographic groups, including Hispanic patients and patients under the age of 55 years.


Mangiferin is a new potential antimalarial and anticancer drug for targeting serine hydroxymethyltransferase.
Mangiferin, a polyphenolic xanthone glycoside found in various botanical sources, including mango (Mangifera indica L.) leaves, can exhibit a variety of bioactivities. Although mangiferin has been reported to inhibit many targets, none of the studies have investigated the inhibition of serine hydroxymethyltransferase (SHMT), an attractive target for antimalarial and anticancer drugs. SHMT, one of the key enzymes in the deoxythymidylate synthesis cycle, catalyzes the reversible conversion of l-serine and (6S)-tetrahydrofolate (THF) into glycine and 5,10-methylene THF. Here, in vitro and in silico studies were used to probe how mangiferin isolated from mango leaves inhibits Plasmodium falciparum and human cytosolic SHMTs. The inhibition kinetics at pH 7.5 revealed that mangiferin is a competitive inhibitor against THF for enzymes from both organisms. Molecular docking and molecular dynamic (MD) simulations demonstrated the inhibitory effects of the deprotonated forms of mangiferin, specifically the C6-O- species and its resonance C9-O- species appearing at pH 7.5, combined with two docked poses, either a xanthone or glucose moiety, placed inside the THF-binding pocket. The MD analysis revealed that both C6-O- and its resonance-stabilized C9-O- species can favorably bind to SHMT in a similar fashion to THF, supporting the THF competitive inhibition of mangiferin. In addition, characterization of the proton dissociation equilibria of isolated mangiferin revealed that only three hydroxy groups of the xanthone moiety, C6-OH, C3-OH, and C7-OH, underwent varying degrees of deprotonation with pKa values of 6.38 ± 0.11, 8.21 ± 0.35, and 12.37 ± 0.30, respectively, while C1-OH remained protonated. Altogether, our findings demonstrate a new bioactivity of mangiferin and provide the basis for the future development of mangiferin as a potent antimalarial and anticancer drug.


Tickborne encephalitis virus, Norway and Denmark.
Serum from 2 Norwegians with tickborne encephalitis (TBE) (1 of whom was infected in Denmark) and 810 Norwegian ticks were tested for TBE virus (TBEV) RNA by reverse transcription-polymerase chain reaction. Sequencing and phylogenetic analysis were performed. This is the first genome detection of TBEV in serum from Norwegian patients.


[Prerequisites for the physical training of patients who have had a myocardial infarct (substantiation, functional diagnosis, indications, contraindications)].
The substantiation and the indications and contraindications for the physical training of patients who have had myocardial infarction are discussed on the basis of the experience gained at the Clinic of Internal Diseases of the Medical Department of K. Marx University in Leipzig (DDR) and the First Chair of Hospital Therapy of the N.I. Pirogov Second Moscow Medical Institute. On the strength of their own findings and the information in the current literature, the authors name, among other precoditions for training, diminution of capacity for muscular work, psychologic instability and the persisting threat of the progression of ischemic heart disease. The methods of functional diagnosis, which is also a necessary precondition for the physical rehabilitation of the patients are bicycle ergometry, auxiliary tests for the gaseous composition of blood and exhaled air, determination of the heart volume by means of X-ray, catheterization of the pulmonary artery with a floating catheter, ventriculography, and coronarography.


Gas chromatography-mass spectrometry-based untargeted metabolomics analysis reveals circulating biomarkers related to wooden breast myopathy in broilers: a preliminary study.
Approaches for the diagnosis of wooden breast (WB) myopathy in live birds are urgently required before applying intervention strategies to reduce occurrence and severity for the poultry industry. The objective of this study was to characterize the serum metabolic profiles in male broilers affected by WB and to identify biomarkers related to this myopathy. Broilers were categorized into normal (CON) and WB groups based on gross scoring and histological evaluation. Gas chromatography-mass spectrometry-based metabolomics, multivariate analysis, and orthogonal partial least squares discriminant analysis revealed a clear separation between CON and WB. A total of 73 significantly different (P < 0.05) metabolites with 17 upregulated and 56 downregulated were identified, which were mainly involved in pathways of alanine, aspartate, and glutamate metabolism, carbohydrate metabolism, and taurine and hypotaurine metabolism. By using the nested cross-validation function of random forest analysis, 9 significantly altered (P < 0.05) metabolites (cerotinic acid, arabitol, phosphoenolpyruvate, terephthalic acid, cis-gondoic acid, N-acetyl-d-glucosamine, 4-hydroxymandelic acid, caffeine, and xanthurenic acid) were identified as biomarkers with an excellent discriminant performance for WB myopathy. Collectively, this study provides new insights for a deeper understanding of the pathogenesis and provides metabolites as biomarkers for diagnostic utilization of WB myopathy.


Impact of an outpatient palliative care consultation and symptom clusters in terminal patients at a tertiary care center in Pakistan.
Patients with terminal diseases may benefit physically and psychosocially from an outpatient palliative care visit. Palliative care services are limited in Pakistan. An improved understanding of the symptom clusters present in our population is needed. The first outpatient palliative care center in Karachi, Pakistan, was established at our tertiary care institution. The primary aim of this study was to evaluate the impact of a palliative care outpatient consultation on symptom burden in patients with a terminal diagnosis. The secondary aim was to analyze the symptom clusters present in our population. Patients with a terminal diagnosis referred to our outpatient palliative department between August 2020-August 2022 were enrolled. The Edmonton Symptom Assessment Scale (ESAS) questionnaire was administered at the initial visit and the first follow-up visit at one month. Change in symptom burden was assessed using a Wilcoxon signed ranks test. A principal component analysis with varimax rotation was performed on the symptoms reported at the initial visit to evaluate symptom clusters. The palliative performance scale (PPS) was used to measure the performance status of palliative care patients. Among the 78 patients included in this study, the average age was 59 ± 16.6 years, 52.6% were males, 99% patients had an oncological diagnosis, and the median duration between two visits was 14 (Q1-Q3: (7.0, 21.0) days. The median PPS level was 60% (Q1-Q3: 50-70). Overall, ESAS scores decreased between the two visits (6.0 (2.8, 11.0), p < 0.001) with statistically significant improvement in pain (5.0 vs. 2.5, p < 0.001), loss of appetite (5.0 vs. 4.0, p = 0.004), depression (2.0 vs. 0.0, p < 0.001), and anxiety (1.5 vs. 0.0, p = 0.032). Based on symptoms at the initial visit, 3 clusters were present in our population. Cluster 1 included anxiety, depression, and wellbeing; cluster 2 included nausea, loss of appetite, tiredness, and shortness of breath; and cluster 3 included drowsiness. An outpatient palliative care visit significantly improved symptom burden in patients with a terminal diagnosis. Patients may benefit from further development of outpatient palliative care facilities to improve the quality of life in terminally ill patients.


Embolization of a superior sagittal sinus dural arteriovenous fistula under intrasinus balloon protection: A case report.
Endovascular embolization has evolved to become the primary therapeutic option for dural arteriovenous fistulas (DAVFs). While guaranteeing complete occlusion of the fistula orifice, the goal of DAVF embolization is also to ensure the patency of normal cerebral venous drainage. This paper describes a case of successful embolization of a complex DAVF in the superior sagittal sinus with a multistaged approach using a combination of transvenous and transarterial tactics. The strategies and techniques are discussed.


Effect of hypothyroidism on the lipid composition of rat plasma and erythrocyte membranes.
The effect of hypothyroidism on plasma and erythrocyte membrane lipid components has been investigated. This pathological state is accompanied by a) a cholesterol increase of about 60% in plasma, and at the same time a 22% reduction in erythrocyte membranes; b) 44% and 30% phospholipid level decreases in both plasma and red cell membranes, respectively; and c) almost unaffected phospholipid and fatty acid compositions of both plasma and erythrocyte membranes. All changes were corrected by treatment of the hypothyroid rats with triiodothyronine for two days. These findings suggest that in hypothyroid rats a reduced transfer of cholesterol from plasma to erythrocyte membrane probably takes place. This could explain, at least in part, the increased hematic cholesterol level observed in hypothyroid animals. In red cell membranes, the simultaneous decrease in cholesterol and phospholipid levels does not alter the cholesterol/phospholipid molar ratio, thus avoiding their abnormal function.


In vivo studies of whole ricin monoclonal antibody immunoconjugates for the treatment of murine tumours.
Ricin is a highly potent toxin which binds to cells via galactose binding sites on the B chain; the toxicity is manifest by the A chain and most studies with immunotoxins have used ricin A chain-antibody conjugates. We have previously described a method for the coupling of whole ricin to monoclonal antibody (MoAb) so that the galactose binding sites on the B chain are blocked; these conjugates are not non-specifically toxic. Whole ricin-MoAb conjugates were examined in vivo for their stability, clearance rates and toxicity, and these were compared with modified ricin-MoAb conjugates produced by periodate treatment of ricin. First, the biological half-life of whole ricin or modified ricin was determined and indicated that while ricin was rapidly cleared from the circulation (t 1/2 = 4.5 +/- 0.5 min) compared with modified ricin (t 1/2 = 17 +/- 1 min), covalent linkage of native ricin to MoAb increased the blood circulation time of the toxin (t 1/2 = 22 +/- 1 min). Immunotoxins synthesized with the Ly-2.1 MoAb using native or modified (deglycosylated) ricin were compared in vivo. In two different models anti-Ly-2.1 immunotoxins could be shown to be effective in vivo: (i) intraperitoneal tumours, thymomas grown in the peritoneal cavity could be completely eradicated by ricin-MoAb; (ii) subcutaneous tumours, mice with tumours approximately 0.75 cm in diameter received intravenous doses of the whole ricin-MoAb and a substantial reduction in tumour size was achieved. Thus whole ricin-antibody conjugates made with the galactose binding site blocked combine the advantage of high potency with high specificity (which was previously lacking in intact ricin conjugates) and can be successfully used in vivo to treat tumours.


Expression of human beta defensin (HBD-1 and HBD-2) mRNA in nasal epithelia of adult cystic fibrosis patients, healthy individuals, and individuals with acute cold.
Lack or inactivation of defensins may facilitate chronic bacterial colonization in the cystic fibrosis (CF) lung. CF nasal epithelium exhibits typical biochemical abnormalities and can be used to study defensin expression in CF. To evaluate the expression of beta defensin (HBD-1 and HBD-2) mRNA and the presence of inflammatory markers (percentage of neutrophils and IL-8 mRNA expression) in CF and non-CF nasal mucosa. Case-control study. Nasal brushing samples were obtained from 22 stable adult CF patients and 32 non-CF controls (25 healthy individuals and 7 individuals with acute cold). Samples were subjected to analysis involving mRNA expression (semiquantitative RT-PCR) and differential cell counting. Defensins and inflammatory markers were expressed at low levels in healthy individuals and at high levels in subjects with acute cold. In non-CF controls, defensin expression correlated significantly with inflammatory parameters (p < 0.001). In CF, defensin mRNA expression was comparable to healthy individuals (p = 0.2). In contrast to non-CF controls, in CF patients high levels of inflammatory markers did not correlate with defensin mRNA levels. Defensin expression is not upregulated in CF epithelium in response to inflammatory stimuli. Further studies are necessary to elucidate whether this is a consequence of the CF gene mutation.


A new Pseudophoxinus (Teleostei, Cyprinidae) species from Southwestern Anatolia, with remarks on the distribution of the genus in western Anatolia.
Pseudophoxinus burduricus sp. n. is described from drainages of Salda and Burdur lakes, southwestern Turkey. It is distinguished from other Anatolian Pseudophoxinus by a combination of characters: lateral line incomplete, with 21-39 (commonly 26-37) perforated scales and 47-57+1-2 scales in lateral series; 10½-12½ scale rows between lateral line and dorsal fin origin, 3-4(5) scale rows between lateral line and the pelvic fin origin; dorsal fin commonly with 7½ branched rays; anal fin commonly with 6½ branched rays; 7-8(9) gill rakers on the first branchial arch; a faint and diffuse epidermal black stripe from eye to caudal fin base in alive and preserved individuals; mouth slightly subterminal, tip of mouth cleft on about level of lower margin of eye; snout rounded, its length greater than eye diameter. Comparison is given with all Pseudophoxinus species from western Anatolia.


Active pulmonary tuberculosis in a patient with secukinumab treatment.
Numerous investigations have documented active tuberculosis (TB) infection following biologic treatment. One of the most secure biologic medications for infections is secukinumab. Additionally, no cases of active TB while receiving secukinumab therapy were recorded. Secukinumab 150 mg per month has been administered for a 19-year-old man with spondyloarthritis since May 2020. A diagnosis of pulmonary TB was made when the patient complained of a moderate fever, a productive cough, and weight loss after 2 years. His fever and respiratory symptoms were relieved after 6 weeks of treatment by stopping secukinumab and utilizing 4 antibiotics: isoniazid, rifampicin, pyrazinamide, and ethambutol, while non-steroidal anti-inflammatory drugs reduced his joint and back discomfort. During biological therapy, even with secukinumab, annual screening for latent and active TB is crucial. We require additional study on secukinumab-treated patients with active TB in nations with high TB burdens, including Vietnam.


[On 14C-nicotinate penetration into cellular and subcellular structures of animals following adrenalectomy and hormone administration].
The experiments on the Wistar line rats and mongrel dogs showed that gravitational overloading, surgical and chemical adrenalectomy, injections of certain hormones and actinomycin D affect essentially the permeability of blood cells and liver mitochondria to 14C nicotinic acid. An assumption is advanced that the transport of 14C nicotinic acid to biological structures occurs with participation of complex mechanisms, the function of which is regulated by hormones and is coupled with the processes of protein synthesis.


Educational differences in mortality associated with central obesity: Decomposing the contribution of risk and prevalence.
Thousands of preventable deaths are attributed to obesity in the United States. However, the harmfulness of obesity varies across the population; individuals' education determines access to healthful resources and exposure to competing risks, dampening/amplifying obesity-associated mortality risk. Using restricted U.S. National Health and Nutrition Examination Survey data (N = 40,058; 1988-2015), this study estimates educational differences in mortality attributable to central obesity (waist-to-height ratio ≥0.5) - a dangerous form of abdominal adiposity. Over 30% of excess deaths are attributable to central obesity among college-educated adults, compared to 1-10% among their less-educated counterparts. This difference is larger for cardiometabolic-related mortality, as central obesity may explain 60-70% of excess deaths among college-educated adults. Decomposition analyses show differences are driven by greater obesity-associated risk among college-educated adults, rather than prevalence. Policies targeting health disparities should recognize central obesity as a key risk among highly-educated adults, but only one of many encountered by those with less education.


Topological Alterations of the Structural Brain Connectivity Network in Children with Juvenile Neuronal Ceroid Lipofuscinosis.
We used diffusion MR imaging to investigate the structural brain connectivity networks in juvenile neuronal ceroid lipofuscinosis, a neurodegenerative lysosomal storage disease of childhood. Although changes in conventional MR imaging are typically not visually apparent in children aged <10 years, we previously found significant microstructural abnormalities by using diffusion MR imaging. Therefore, we hypothesized that the structural connectivity networks would also be affected in the disease. We acquired diffusion MR imaging data from 14 children with juvenile neuronal ceroid lipofuscinosis (mean ± SD age, 9.6 ± 3.4 years; 10 boys) and 14 control subjects (mean ± SD age, 11.2 ± 2.3 years; 7 boys). A follow-up MR imaging was performed for 12 of the patients (mean ± SD age, 11.4 ± 3.2 years; 8 boys). We used graph theoretical analysis to investigate the global and local properties of the structural brain connectivity networks reconstructed with constrained spherical deconvolution-based whole-brain probabilistic tractography. We found significantly increased characteristic path length (P = .003) and decreased degree (P = .003), which indicated decreased network integration and centrality in children with juvenile neuronal ceroid lipofuscinosis. The findings were similar for the follow-up MR imaging, and there were no significant differences between the two acquisitions of the patients. In addition, we found that the disease severity correlated negatively (P < .007) with integration, segregation, centrality, and small-worldness of the networks. Moreover, we found significantly (P < .0003) decreased local efficiency in the left supramarginal gyrus and temporal plane, and decreased strength in the right lingual gyrus. We found significant global and local network alterations in juvenile neuronal ceroid lipofuscinosis that correlated with the disease severity and in areas related to the symptomatology.


Identifying the barriers and enablers to palliative care nurses' recognition and assessment of delirium symptoms: a qualitative study.
Delirium is underrecognized by nurses, including those working in palliative care settings where the syndrome occurs frequently. Identifying contextual factors that support and/or hinder palliative care nurses' delirium recognition and assessment capabilities is crucial, to inform development of clinical practice and systems aimed at improving patients' delirium outcomes. The aim of the study was to identify nurses' perceptions of the barriers and enablers to recognizing and assessing delirium symptoms in palliative care inpatient settings. A series of semistructured interviews, guided by critical incident technique, were conducted with nurses working in Australian palliative care inpatient settings. A hypoactive delirium vignette prompted participants' recall of delirium and identification of the perceived factors (barriers and enablers) that impacted on their delirium recognition and assessment capabilities. Thematic content analysis was used to analyze the qualitative data. Thirty participants from nine palliative care services provided insights into the barriers and enablers of delirium recognition and assessment in the inpatient setting that were categorized as patient and family, health professional, and system level factors. Analysis revealed five themes, each reflecting both identified barriers and current and/or potential enablers: 1) value in listening to patients and engaging families, 2) assessment is integrated with care delivery, 3) respecting and integrating nurses' observations, 4) addressing nurses' delirium knowledge needs, and 5) integrating delirium recognition and assessment processes. Supporting the development of palliative care nursing delirium recognition and assessment practice requires attending to a range of barriers and enablers at the patient and family, health professional, and system levels.


Complete sequence of a subgroup 3.4 strain of classical swine fever virus from Taiwan.
Classical swine fever viruses from Taiwan have been classified into two subgroups (3.4 and 2.1). Outbreaks caused by 3.4 viruses were reported in Taiwan prior to 1996 and which mainly distributed in the geographic range from southern Japan to Taiwan. We have determined the complete sequence of a reference strain, 94.4/IL/94/TWN. The genome contains 12,296 nucleotides, encoding 3,898 amino acids flanked by a 372-nt region at the 5' untranslated region (UTR) and a 227-nt region at the 3'-UTR. Similarities of nucleotides among 3.4 viruses isolated from Taiwan and Japan (Kanagawa/74; Okinawa/86) maintained in 94.2-97.5%; however, comparing to subgroup 1.1 (ALD/64/Jap) and 2.1 (TD/96/TWN) only showed about 72.5-80.8%, respectively. Phylogenetic analysis based on positioning from 11,157 to 11,565 nt (NS5B region) revealed that CSFVs were divided into three major lineages and their sublineages. Strain 94.4/IL/94/TWN is the first completely genomic sequence of subgroup 3.4 viruses.


Anxiety and depression in the first year of medical residency training.
To perform a screening, follow-up and comparative evaluation of depression and anxiety symptoms in a group of 59 first-year internal medicine residents of a teaching hospital and evaluate the influence of their rotation, nature of rotation, subgroup, sex and the time of year on these symptoms. We used the Spielberger State-Trait Anxiety Inventory (STAI) and the Beck Depression Inventory (BDI), applied seven times, in the last week of every rotation. We obtained two identical averages (P=0.98) of trait-anxiety, six months apart one from the other. There was a significant correlation (R=0.65, P < 0.001) between the indexes of state-anxiety and depression. Women had higher levels of symptoms of both anxiety and depression (P < 0.001) compared to men. A cluster of three subgroups of residents with higher trait-anxiety levels (P=0.001) also showed significantly higher levels of symptoms of state-anxiety and depression (P < 0.001). The time of the year and the nature of the rotation (emergency or not) did not interfere with the levels of depression (P=0.47). We detected rotations where there was greater frequency of residents with symptoms compatible with moderate and severe depression. There were 2.1% of residents with symptoms compatible with severe, 4.2% with moderate and 27% with mild depression. It was possible to graduate symptoms of anxiety and depression in residents, evaluate factors involved in their genesis and locate residents with moderate and severe depression.


Bacterial and fungal pneumonias after lung transplantation.
The aim of this study was to evaluate the epidemiology of bacterial and fungal pneumonia in lung transplant (LT) recipients and to assess donor-to-host transmission of these microorganisms. We retrospectively studied all positive cultures from bronchoalveolar lavage (BAL) of 49 lung transplant recipients and their donors from August 2003 to April 2007. There were 108 episodes of pneumonia during a medium follow-up of 412 days (range, 1-1328 days). The most frequent microorganisms were: Pseudomonas aeruginosa (n = 36; 33.3%), Staphylococcus aureus (n = 29; 26.8%), and Aspergillus spp. (n = 18; 16%). Other fungal infections were due to Fusarium spp., Cryptococcus neoformans, and Paracoccidioides brasiliensis. Of the 31 donors with positive BAL, 15 had S. aureus. There were 21 pretransplant colonized recipients (43%) and 16 of them had suppurative underlying lung disease. P. aeruginosa was the most frequent colonizing organism (59% of pretransplant positive cultures). There were 11 episodes of bacteremia and lungs were the source in 5 cases. Sixteen deaths occurred and 6 (37.5%) were due to infection. Statistical analyses showed association between pretransplant colonizing microorganisms from suppurative lung disease patients and pneumonias after lung transplantation (RR = 4.76; P = .04; 95% CI = 1.02-22.10). No other analyzed factor was significant. Bacterial and fungal infections are frequent and contribute to higher mortality in lung transplant recipients. P. aeruginosa is the most frequent agent of respiratory infections. This study did not observe any impact of donor lung organisms on pneumonia after lung transplantation. Nevertheless, we demonstrated an association between pretransplant colonizing microorganisms and early pneumonias in suppurative lung transplant recipients.


Scanning electron microscopic study of erythrocyte shapes artificially jetted through tubes at different pressures by 'in vitro cryotechnique for erythrocytes'.
A new cryotechnique for examining morphological changes of human erythrocytes at different jet pressures was developed in the present study. Human fresh or stored erythrocytes passing through a tube were jetted into precooled isopentane-propane mixture (-193 degrees C), which was named as 'in vitro cryotechnique for erythrocytes'. After the cryotechnique procedure, the routine freeze-substitution method and subsequent t-butyl alcohol freeze-drying method were used for preparing the scanning electron microscopic specimens. At 100 mmHg or higher pressures of jetting, lamellar-arranged erythrocytes were observed to have elongated shapes. The more the jetting pressure increased, the fewer discoid shapes of erythrocytes were observed. This cryofixation technique could preserve the morphology of erythrocytes jetting from tubes, and provide the three-dimensional image of erythrocyte surfaces, as followed by scanning electron microscopy.


A case of splenosis: diagnosis with contrast-enhanced ultrasonography.
We performed contrast-enhanced ultrasonography (CEUS) for a patient with known splenosis. One mass was clearly enhanced while another mass showed moderate enhancement. The right kidney showed similar enhancement and was a little confusing. We concluded that CEUS is useful for diagnosing this entity, although it has some limitations. CEUS could be a better diagnostic option than scintigraphic studies.


CEN plasmid segregation is destabilized by tethered determinants of Ty 5 integration specificity: a role for double-strand breaks in CEN antagonism.
The yeast retrotransposon Ty 5 integrates preferentially into heterochromatin at the telomeres and HM loci. Target specificity is mediated by a six amino acid sequence motif (the targeting domain, TD) of integrase that interacts with Sir4p, a structural component of heterochromatin. When tethered to CEN plasmids as part of a Gal4p DNA binding domain (GBD) fusion protein, TD destabilizes plasmid segregation in a manner similar to that observed for CEN + HM or CEN +TEL antagonism. This instability is caused by the ability of TD to nucleate components of heterochromatin on the CEN plasmid, because CEN +TD antagonism is abrogated by sir2, sir3 and sir4 mutations and by TD mutations that prevent interaction with Sir4p. In strains that acquire resistance to CEN +TD antagonism, the CEN plasmid has either recombined with a 2 mu plasmid or sustained deletions in sequences required to bind GBD-TD. CEN +TD and CEN + HM antagonism is exacerbated by mutations in components of the Ku-mediated non-homologous end-joining pathway. These observations suggest that CEN antagonism is caused by DNA breaks that result from competition between CEN - and Sir-specific segregation pathways.


SP500263, a novel SERM, blocks osteoclastogenesis in a human bone cell model: role of IL-6 and GM-CSF.
Bone metabolism requires tightly coupled activities exhibited by two unique cell populations, the bone-resorbing osteoclasts and the bone-forming osteoblasts. Imbalance in the function of these two cell types can result in osteoporosis, a condition characterized by loss in bone integrity and of bone mass. We developed a human bone cell culture model that allows the in vitro study of bone formation and osteoclastogenesis and employed this bone model for the screening and pharmacological analyses of protein and small molecule therapeutics. The cytokines, interleukin-6 (IL-6) and granulocyte macrophage colony stimulating factor (GM-CSF), play an intricate role in osteoclastogenesis in this system. Neutralizing antibodies to IL-6 and GM-CSF decreased the formation of osteoclast-like cells. SP500263, an early lead compound from a novel class of selective estrogen receptor modulators (SERMs), was more efficacious than estrogen and comparable to raloxifene in blocking cytokine production and formation of osteoclast-like cells. Our research demonstrates the usefulness of the in vitro co-culture model in the dissection of molecular events relevant to bone metabolism and provides greater insight into a potential novel role for cytokines in bone resorption. Furthermore, representatives of the SP500263 family of SERMs may be effective as therapeutics for the treatment of osteoporosis.


Cholesterol gallstone formation and prevention by chenodeoxycholic and ursodeoxycholic acids. A new hamster model.
Prior animal models of cholesterol gallstone formation have been criticized for their dissimilarity to the conditions of humans with gallstones. We present a new hamster model of cholesterol cholelithiasis that more closely approximates the human situation. Sixty female Golden Syrian hamsters (average weight 83.2 +/- 3.4 g) were allocated to six groups of 10 animals each. Groups were fed standard diet (containing 0.8 gm cholesterol/g of food) or increased cholesterol diet (containing 2.4 mg cholesterol/g of food), with or without ethinyl estradiol, 15 micrograms/kg/d. Two groups receiving both increased cholesterol and ethinyl estradiol also received either chenodeoxycholic acid or ursodeoxycholic acid, 20 mg/kg/d. The animsl were sacrificed at 12 wk. Cholesterol gallstones (78.3 +/- 5.0% cholesterol by weight) formed in 30% of the animals fed ethinyl estradiol, 50% of those fed increased cholesterol, and 90% of those fed the combination of both. Bile was saturated in all three groups, with the saturation index of the combination group (2.08 +/- 0.17) being the highest. In both groups receiving bile acid therapy, no gallstones were found, and the bile remained unsaturated. For the bile acid-fed groups, both hepatic HMG-CoAR and hepatic cholesterol 7 alpha-hydroxylase activities were reduced (P less than 0.01) when compared to the group fed standard diet and to the grou fed the combination. Thus, a new animal model of cholesterol gallstone formation has been developed in which chenodeoxycholic acid and ursodeoxycholic acid therapy prevented gallstone formation through mechanisms similar to those reported in cholesterol gallstone patients.


Communicating uncertainty using words and numbers.
Life in an increasingly information-rich but highly uncertain world calls for an effective means of communicating uncertainty to a range of audiences. Senders prefer to convey uncertainty using verbal (e.g., likely) rather than numeric (e.g., 75% chance) probabilities, even in consequential domains, such as climate science. However, verbal probabilities can convey something other than uncertainty, and senders may exploit this. For instance, senders can maintain credibility after making erroneous predictions. While verbal probabilities afford ease of expression, they can be easily misunderstood, and the potential for miscommunication is not effectively mitigated by assigning (imprecise) numeric probabilities to words. When making consequential decisions, recipients prefer (precise) numeric probabilities.


Modeling the COVID-19 Outbreak in China through Multi-source Information Fusion.
Modeling the outbreak of a novel epidemic, such as coronavirus disease 2019 (COVID-19), is crucial for estimating its dynamics, predicting future spread and evaluating the effects of different interventions. However, there are three issues that make this modeling a challenging task: uncertainty in data, roughness in models, and complexity in programming. We addressed these issues by presenting an interactive individual-based simulator, which is capable of modeling an epidemic through multi-source information fusion.