A new method for estimating probability of survival in pediatric patients using revised TRISS methodology based on age-adjusted weights.
TRISS methodology estimates probability of survival (P(s)) based on coefficients derived largely from adult data. We developed a novel pediatric age-specific method to estimate P(s). The Pennsylvania Trauma Outcome Study database was queried for pediatric patients injured between 1993 and 1996 (n = 9730). P(s) derived from the Pediatric Age-Adjusted TRISS (PAAT) methodology was generated using our Age-Specific Pediatric Trauma Score and Injury Severity Score with corresponding weights. A test data set of 7138 pediatric patients entered in the Pennsylvania Trauma Outcome Study from 1997 to 1999 was used to compute an expected number of survivors for PAAT, TRISS, and ASCOT (A Severity Characteristic of Trauma). Observed and expected survival were compared for blunt injured patients, for head injured patients, and by age category. PAAT showed no significant difference between observed and expected survival. TRISS and ASCOT significantly underestimated overall survival: across age groups, for blunt injuries, for head injuries, and for patients whose P(s) was less than 91%. PAAT offers a more reliable methodology than TRISS and ASCOT for comparing pediatric trauma outcomes.


[Guideline-adherent inpatient psychiatric psychotherapeutic treatment of borderline personality disorder : Normative definition of personnel requirements].
Borderline personality disorders (BPD) are severe mental diseases which place high pressure on the psychiatric healthcare system. Nowadays, well-tested, disorder-specific treatment concepts are available also for inpatient treatment in Germany. These show very good and long-term improvements in the psychopathology as well as posttreatment social participation; however, prerequisites for the implementation of these evidence-based inpatient psychotherapy programs are well-trained treatment teams and appropriate financing of resource expenditure. The aim was to formulate a definition of normative needs for treatment duration and intensity for a guideline-conform, empirically proven and effective inpatient treatment of borderline personality disorder as well as the derived personnel requirements in comparison to the currently available resources within the framework of the Psychiatry Personnel Act (Psych-PV). The resource requirements were established based on evaluated hospital ward models, the recommendations of the S2 guidelines and the criteria of specialist societies and compared with the personnel stipulations according to the Psych-PV. The results for a normatively established treatment program showed a pronounced deficit in the financing of the evaluated resource requirements, even when the stipulations laid down in the Psych-PV were implemented to 100 %. Disorder-specific inpatient treatment programs for borderline personality disorder have been scientifically proven to be highly effective; however, resource analyses show that the personnel requirements necessary for effective implementation of these programs are much higher than those allocated by the funding according to the Pysch-PV. The current underfunding leads to inadequate treatment outcomes with high readmission rates and as a result high direct and indirect costs of illness.


Cytomegalovirus-specific IFNgamma and IL-4 are produced by antigen expanded human blood lymphocytes from seropositive volunteers.
The cytokine responses to cytomegalovirus (CMV) antigen in seropositive and seronegative individuals were measured using a combination of antigenic expansion and intracellular staining. Intracellular IFNgamma and IL-4 were produced in a dose-dependent manner by T cells in response to CMV only in the seropositive population. The potential for individual cells to produce both Th1 and Th2 cytokines simultaneously was clear, as IL-4 was most often produced in those cells with the highest IFNgamma production. The cytokine-specific nature of this response was demonstrated by fluorescence microscopy, which showed granular cytoplasmic staining, and at the mRNA level by ribonuclease protection assays. These methods expand our ability to evaluate the immune response to CMV, and can now be correlated to a number of clinical conditions.


[Construction and eukaryotic expression of recombinant plasmid encoding fusion protein of goat complement C3d and foot-and-mouth disease virus VP1].
We constructed a recombinant plasmid encoding VP1 gene of O type foot-and-mouth disease virus fused to a molecular adjuvant, goat complement C3d gene. The goat C3d gene was cloned and three copies were tandem-linked with the linker (G4S)2 sequence. VP1 gene of O type foot-and-mouth disease virus was linked to three tandem repeats of C3d through the linker sequence and cloned into pUC19 to obtain the recombinant plasmid pUC19-VP1-C3d3. The VP1-C3d3 fusion gene was then subcloned into the eukaryotic vector pcDNA3.1(+) that had been modified to contain the tissue plasminogen activator (tPA) leader sequence to obtain pcDNA3.1-tPA-VP1-C3d3. HeLa cells were transfected with pcDNA3.1-tPA-VP1-C3d3 by Lipofectamine 2000. Indirect immunofluorescent assay and Western blot assay showed that VP1-C3d3 fusion gene was successfully expressed in HeLa cells. The fusion protein with the expected size 133 kD could be secreted outside the cells. This study laid a good foundation to further research on the novel vaccine against foot-and-mouth disease virus by using goat C3d as a molecular adjuvant to enhance the immunogenicity of VP1.


Effects of COVID-19 pandemic in a breast unit: Is it possible to avoid delays in surgical treatment?
Coronavirus disease 2019 (COVID-19) pandemic has caused fear all around the world. With people avoiding hospitals, there has been a significant decrease in outpatient clinics. In this study, we aimed to compare and explore the first peak of the pandemic period by studying its effects on patient applications, new diagnoses and treatment approaches in a non-infected hospital. We collected data from the first peak of the pandemic period in Turkey, from the pandemic declaration (11 March 2020) to social normalization (1 June 2020), and compared it with the data from a pre-pandemic period with a similar length of time. We analyzed the data of breast cancer patients from application to surgery. The data of 34 577 patients were analyzed for this study. The number of patients who applied to outpatient clinics decreased significantly during the pandemic period. After excluding control patients and benign disorders, a figure was reached for the number of patients who had a new diagnosis of breast cancer (146 vs. 250), were referred to neoadjuvant treatment (18 vs. 34), and were treated with surgery (121 vs. 229). All numbers decreased during the pandemic period, except for surgeries after neoadjuvant treatment (21 vs. 25). Surgical treatment approaches also changed. However, the rate of newly diagnosed breast cancer patients treated with surgery was similar in both periods. None of these patients were diagnosed with COVID-19 or died during the pandemic. This study shows that non-infected hospitals can be useful in avoiding delays in the surgical treatment of cancer patients.


Efficacy of zinc oxide and copper oxide nanoparticles on virulence genes of avian pathogenic E. coli (APEC) in broilers.
Colibacillosis is one of the broilers' most dominant bacterial diseases, either as a primary or a secondary infection. As E. coli antimicrobial drug resistance is rising; there is a need to develop new approaches to its control. In light of this, a comparative study of the in-vitro antibacterial activity of Arabic gum stabilized zinc and copper nanoparticles (AG-ZnNPs and AG-CuNPs) against PCR-identified field avian pathogenic E. coli (APEC) strains and virulence genes (ibeA, hlyA, iss, pap C and ompA) was applied to study the therapeutic effect of zinc and copper nanoparticles to be used as an antibiotic alternative (Nanobiotic). Furthermore, the in-vivo effects of CuNPs were evaluated. Additionally, the CuNPs liver and muscle residues with or without infection were examined. The eighty broilers were divided into four groups; G1: negative control, G2: infected control with E. coli O17, G3: non-infected treated (AG-CuNPs 50 mg/kg body weight), and G4: infected treated (AG-CuNPs 50 mg/kg body weight). AG-CuNPs treatment was given to broilers for five days in drinking water. E. coli was isolated from diseased broilers at an average incidence rate of 20% from intestinal and liver samples. All identified serotypes (O17, O78, O91, O121, and O159) were resistant to AG-ZnNPs and sensitive to AG-CuNPs. AG-CuNPs minimal inhibitory and bactericidal concentrations (MIC and MBC) for O17 were 7.5 and 60 mg/ml, respectively. Conventional uniplex PCR results showed that strain O17 contained virulence genes (ibeA, hlyA, iss, and papC), where AG-CuNPs significantly reduced the expression of all target genes when examined by Real-time quantitative PCR. Additionally, the bactericidal activity of AG-CuNPs on O17 was 100% at 20 minutes and 40 mg/ml and confirmed by transmission electron microscopy. Furthermore, no mortality was recorded in treated groups compared to G2. Subsequently, no E. coli was re-isolated from the liver in the G4 after treatment. The total protein, albumin, globulin, and lysozyme activity were significantly increased in G4 compared to G2, while the activities of liver enzymes (alanine aminotransferase (ALT), Gamma-glutamyl transferase (GGT), and alkaline phosphatase (ALP)) were markedly decreased in G4 compared to G2. Additionally, uric acid, creatinine, and C-reactive protein levels were decreased in G4 compared to G2. However, the liver enzymes, kidney functions, C-reactive protein levels, and Cu residues were non-significantly changed in G4 compared to G1. Green synthesized AG-CuNPs are recommended as an effective antimicrobial alternative against APEC strains.


The antineoplastic drug Paclitaxel has immunosuppressive properties that can effectively promote allograft survival in a rat heart transplant model.
Recurrent and de novo neoplasms are ominous risk factors for transplant patients. In particular, when organ transplantation is attempted to cure isolated cancers, conventional immunosuppression likely promotes cancer reestablishment. Therefore, drugs with both immunosuppressive and antineoplastic activity are needed. We show that the anticancer agent paclitaxel may fulfill these diverse expectations. Heterotopic heart transplantation was performed in the ACI-to-Lewis or Lewis-to-ACI rat-strain combination and paclitaxel was injected i.p. daily (days 0-14) at doses from 0.75-1.5 mg/kg. Serum cytotoxic antidonor antibody levels were measured using a complement-mediated cell cytotoxicity assay. In vitro, the effect of paclitaxel on Lewis lymphocyte viability and apoptosis was determined. Also, Lewis lymphocytes preconditioned with irradiated ACI cells+/-paclitaxel, were restimulated with ACI cells and tested for cytotoxic T cell (CTL) activity and interleukin-2 (IL-2) production. Paclitaxel promoted heart allograft survival in a dose-dependent manner in both high- and low-responder transplant combinations. Furthermore, low-doses of paclitaxel (0.75-1.0 mg/kg) and cyclosporine (1 mg/kg) in combination synergistically increased transplant survival. Immunologically, paclitaxel markedly reduced the antidonor cytotoxic antibody response. In vitro, nearly 90% of prestimulated lymphocytes were killed by paclitaxel and cells became positive for the apoptosis marker, annexin-V. Furthermore, paclitaxel reduced CTL activity and IL-2 production after alloantigen rechallenge. Paclitaxel, a clinically proven antineoplastic agent, also has potent immunosuppressive properties in rodent organ transplantation. This drug could be extremely valuable in transplant situations where de novo cancer develops, or when organ transplantation is performed to treat isolated, but typically recurrent, neoplasms.


Recognition by restriction endodeoxyribonuclease EcoRI of octadeoxyribonucleotides containing modified sugar and base moieties.
The modified base and sugar moieties, 8-oxo-7,8-dihydroadenine (HO8A),8-methoxyadenine (MeO8A),8-methoxyguanine (MeO8G) and 9-[(2-hydroxy-1-(hydroxymethyl)-ethoxy)-methyl]-adenine (acA), were chemically introduced in place of the adenine or guanine in the octa-deoxyribonucleotides [d(GGAATTCC)] containing recognition sequence of Eco RI. to the regular DNA-fragment.


Pathophysiology, evaluation, and management of sleep disorders in the mucopolysaccharidoses.
The mucopolysaccharidoses (MPS) represent a heterogeneous group of lysosomal storage disorders, each one associated with a deficiency in one of the enzymes involved in glycosaminoglycan degradation. Sleep disorders are a frequent manifestation of all types of MPS. Underlying causes are diverse and comprised of both respiratory and central nervous system (CNS) abnormalities. Sleep disordered breathing such as obstructive sleep apnea and nocturnal hypoventilation can arise in patients with upper airway obstruction and/or with alterations in respiratory mechanics, causing restrictive pulmonary disease. MPS patients with CNS disease can also develop sleep disturbances unrelated to ventilatory impairments, often associated with severe behavioral problems or night-time epileptic seizures. The present review discusses the pathophysiology, evaluation, and management of sleep disorders in MPS based on information from a meeting on the brain in MPS, attended by an international group of experts (April 28-30, 2016, Stockholm, Sweden), and additional literature searches.


Electrospinning polyvinylidene fluoride fibrous membranes containing anti-bacterial drugs used as wound dressing.
The aim of this study was to synthesis drug-loaded fibrous membrane scaffolds for potential applications as wound dressing. Polyvinylidene fluoride (PVDF) fibrous membranes were loaded with enrofloxacin (Enro) drugs by using an electrospinning process, and their mechanical strength, drug release profile and anti-bacterial properties were evaluated. Enro drug-loaded PVDF membranes exhibited good elasticity, flexibility and excellent mechanical strength. The electrospinning Enro/PVDF membranes showed a burst drug release in the initial 12h, followed by sustained release for the next 3 days, which was an essential property for antibiotic drugs applied for wound healing. The drug-loaded PVDF fibrous membranes displayed excellent anti-bacterial activity toward Escherichia coli and Staphylococcus aureus. The results suggest that electrospinning PVDF membrane scaffolds loaded with drugs can be used as wound dressing.


Requirements for in vitro reconstruction of protein synthesis.
Translation of f2am3 RNA and MS2 RNA in a system containing purified ribosomes and precharged aminoacyl-tRNA, does not occur in the presence of the "known" initiation (IF-1, IF-2 and IF-3), elongation (EF-Tu, EF-Ts and EF-G) and termination (RF-1, RF-2) factors. Translation in this system requires at least three additional protein factors. These are EF-P and the rescue protein as well as a previously undescribed factor we call W, which is found in the high-salt ribosomal eluate.


[The Prevention of the Root Accident in the Department of Radiological Examination Room -Analysis of the Results of Questionnaire Survey about Medical Accident to Many Hospital].
The purpose of this paper is to analyze the characteristics of incidents related to routes and drains that occur in the radiological examination room for the prevention of these incidents. We conducted a questionnaire survey on incident cases that occurred in the radiological examination room. There were 373 responses, of which 76 responses were related to routes and drains. The question contents were the number of hospital beds, radiology department of occurrence, time of occurrence, patient's situation, method of visiting, years of experience of the radiological technologists, and countermeasures, and so on. Based on these answers to these questions, we analyzed which factors were involved in the occurrence of the incidents. Incidents related to routes and drains often occur when moving examination table or transferring the patients to the examination table using the slider. On the other hand, the years of experience of the radiological technologists hardly participated in the factor of these incidents. From these answers to questions, 75% of incidents might predictable, and these incidents could be prevented by improvement of human factors accounted for the majority rather than that of physical factors. The number of incidents related to routes and drains may reduce by that all staff involved in the radiological examination recognizing the characteristic of these incidents.


Monopole directional antenna bioinspired in elliptical leaf with golden ratio for WLAN and 4G applications.
In this work, it is proposed the development a new monopole directional antenna, bioinspired in elliptical leaf, with cut by golden ratio, for 4G band application, by the use of the technique of the cut of the radiating element for the increasing of the antenna perimeter, being the first work to use this technique in a bioinspired antenna, promotes resonance frequency turned, and reconfiguring of the antenna parameters as bandwidth, radiation pattern and gain, with the use of the reflector near to the group plane, without the insertion of active devices as the pin diode or change in radiating element. The shape antenna is generated by Gielis formula, built in FR4 substrate, with cuts calculated by golden ratio. To compare the results of the bioinspired monopole on the elliptical sheet, a square-shaped monopole antenna was designed, simulated and measured, the structures were designed in the MATLAB software version 2015(b) and the simulations were performed in the Ansys software version 2016. In the results compared between the square monopole and the bioinspired antenna in the elliptical sheet, it can be seen that the measured bioinspired antenna, compared to the square monopole, presented a bandwidth reduction of 77.27%, a more compact structure, with a reduction of 98%, covering the wireless local area network, and long-time evolution 4G at 2.5 GHz. The proposed technique uses a reflector on the ground plane, to change the parameters of the monopole planar antenna, of omnidirectional radiation pattern to a directional, maintaining the characteristics of the broadband, half-power beamwidth great than 100°, with high current density, and similar gain of a directional antenna. From the results, it has been observed that the elliptical leaf monopole antenna shows broadband characteristics, with a half-power beamwidth of 128°, wideband, the bandwidth of 500 MHz, a gain of 6.28 dBi, a current density of 13.01 A/m2, and circular polarization.


A shift in the virulence potential of Corynebacterium pseudotuberculosis biovar ovis after passage in a murine host demonstrated through comparative proteomics.
Corynebacterium pseudotuberculosis biovar ovis, a facultative intracellular pathogen, is the etiologic agent of caseous lymphadenitis in small ruminants. During the infection process, C. pseudotuberculosis changes its gene expression to resist different types of stresses and to evade the immune system of the host. However, factors contributing to the infectious process of this pathogen are still poorly documented. To better understand the C. pseudotuberculosis infection process and to identify potential factors which could be involved in its virulence, experimental infection was carried out in a murine model using the strain 1002_ovis and followed by a comparative proteomic analysis of the strain before and after passage. The experimental infection assays revealed that strain 1002_ovis exhibits low virulence potential. However, the strain recovered from the spleen of infected mice and used in a new infection challenge showed a dramatic change in its virulence potential. Label-free proteomic analysis of the culture supernatants of strain 1002_ovis before and after passage in mice revealed that 118 proteins were differentially expressed. The proteome exclusive to the recovered strain contained important virulence factors such as CP40 proteinase and phospholipase D exotoxin, the major virulence factor of C. pseudotuberculosis. Also, the proteome from recovered condition revealed different classes of proteins involved in detoxification processes, pathogenesis and export pathways, indicating the presence of distinct mechanisms that could contribute in the infectious process of this pathogen. This study shows that C. pseudotuberculosis modifies its proteomic profile in the laboratory versus infection conditions and adapts to the host context during the infection process. The screening proteomic performed us enable identify known virulence factors, as well as potential proteins that could be related to virulence this pathogen. These results enhance our understanding of the factors that might influence in the virulence of C. pseudotuberculosis.


The role of CD24 in various human epithelial neoplasias.
CD24 is a small, heavily glycosylated glycosylphosphatidylinositol-linked cell surface protein, which is expressed in hematologic malignancies and in a large variety of solid tumors. It appears to function as a ligand of P-selectin, an adhesion molecule present in activated platelets and endothelial cells. The authors aimed at evaluating CD24 protein expression in adenoma and adenocarcinoma of the stomach, colon, gallbladder, ovary, and breast to establish a correlation with clinicopathologic data. Staining was evaluated using four degrees of positivity (negative, weakly, moderately, strongly positive), and the staining patterns (membranous vs. intracytoplasmic) were analyzed for statistical analysis. The present study clearly demonstrates that CD24 is abundantly expressed in adenocarcinoma compared to adenoma of the colon and breast. Moreover, the positivity degree of CD24 expression increases with positive nodal status in advanced gastric carcinoma. Intracytoplasmic CD24 expression was found to be highly associated with adenocarcinoma of the colon, gallbladder, and ovary compared to the adenoma group of those organs, and with the positive nodal status compared to the negative nodal status of the colonic adenocarcinoma. We conclude that the degree of positivity and the staining pattern of CD24 constitute an important molecular marker for various epithelial neoplasms, which could help to define malignant transformation and to predict lymph node metastasis.


Increased sensitivity of antigen-experienced T cells through the enrichment of oligomeric T cell receptor complexes.
Although memory T cells respond more vigorously to stimulation and they are more sensitive to low doses of antigen than naive T cells, the molecular basis of this increased sensitivity remains unclear. We have previously shown that the T cell receptor (TCR) exists as different-sized oligomers on the surface of resting T cells and that large oligomers are preferentially activated in response to low antigen doses. Through biochemistry and electron microscopy, we now showed that previously stimulated and memory T cells have more and larger TCR oligomers at the cell surface than their naive counterparts. Reconstitution of cells and mice with a point mutant of the CD3ζ subunit, which impairs TCR oligomer formation, demonstrated that the increased size of TCR oligomers was directly responsible for the increased sensitivity of antigen-experienced T cells. Thus, we propose that an "avidity maturation" mechanism underlies T cell antigenic memory.


Leishmania-encoded orthologs of macrophage migration inhibitory factor regulate host immunity to promote parasite persistence.
Leishmania major encodes 2 orthologs of the cytokine macrophage migration inhibitory factor (MIF), whose functions in parasite growth or in the host-parasite interaction are unknown. To determine the importance of Leishmania-encoded MIF, both LmMIF genes were removed to produce an mif(-/-) strain of L. major This mutant strain replicated normally in vitro but had a 2-fold increased susceptibility to clearance by macrophages. Mice infected with mif(-/-) L. major, when compared to the wild-type strain, also showed a 3-fold reduction in parasite burden. Microarray and functional analyses revealed a reduced ability of mif(-/-) L. major to activate antigen-presenting cells, resulting in a 2-fold reduction in T-cell priming. In addition, there was a reduction in inflammation and effector CD4 T-cell formation in mif(-/-) L. major-infected mice when compared to mice infected with wild-type L. major Notably, effector CD4 T cells that developed during infection with mif(-/-) L. major demonstrated statistically significant differences in markers of functional exhaustion, including increased expression of IFN-γ and IL-7R, reduced expression of programmed death-1, and decreased apoptosis. These data support a role for LmMIF in promoting parasite persistence by manipulating the host response to increase the exhaustion and depletion of protective CD4 T cells.-Holowka, T., Castilho, T. M., Baeza Garcia, A., Sun, T., McMahon-Pratt, D., Bucala, R. Leishmania-encoded orthologs of macrophage migration inhibitory factor regulate host immunity to promote parasite persistence.


Risk stratification of survival by lymphovascular invasion, pathological stage, and surgical margin in patients with bladder cancer treated with radical cystectomy.
The aim of this study was to investigate prognostic factors and develop a prognostic factor-based risk stratification model for disease-specific survival (DSS) in a radical cystectomy (RC) series. The patient cohort comprised 194 consecutive patients with bladder cancer treated with RC. Univariate and multivariate Cox proportional hazard model analyses were performed to identify significant prognostic factors for DSS. A risk stratification model was developed based on the relative risks (RRs) of DSS. Median follow-up period was 26.8 months. The 1-, 3-, and 5-year DSS were 88.0, 74.0, and 64.9%, respectively. In the univariate analysis, pathological T (pT) (≥ pT2), lymphovascular invasion (LVI), non-urothelial carcinoma component, surgical margin (SM), and lymph node metastases (pN) were significantly associated with poor prognosis. In the multivariate analysis, pT (≥ pT2), LVI, and SM were independent factors for predicting poor prognosis. Based on these results, patients were stratified into three risk groups: low (RR = 1.00-3.626), intermediate (5.860-9.826), and high (21.24). The 1-, 3-, and 5-year survival rates were 96.9, 85.1, and 85.1% in the low-risk group, 83.0, 63.4, and 43.8% in the intermediate group, and 51.0, 19.4, and 19.4% in the high-risk group, respectively. The differences among these groups were significant. In our RC series, pT (≥ pT2), LVI, and SM were independent prognostic factors. This information may be useful to identify patients with poor prognosis, who might be good candidates for innovative treatment.


Blockade of early and late retinal biochemical alterations associated with diabetes development by the selective bradykinin B1 receptor antagonist R-954.
The chronic hyperglycemia measured alongside diabetes development is associated with significant long-term damage and failure of various organs. In the present study it was shown that hyperglycemia induced early and long term increases in nitric oxide (NO) levels, kallikrein activity and vascular capillary permeability measured as plasma extravasation, and decreases of Na/K ATPase activity in diabetic rat retina 4 and 12 weeks after streptozotocin (STZ) injection. Treatment of the animals for 5 consecutive days with a novel selective bradykinin B(1) receptor (BKB(1)-R) antagonist R-954 (2mg/kg s.c) at the end of the 4 and 12 week periods highly reduced NO, kallikrein and capillary permeability and increased Na/K ATPase activity in the retina. These results suggest that the BKB(1)-R receptor subtype is over-expressed during the streptozotocin-induced development of diabetes in rat retina as evidenced by the inhibitory effects of the BKB(1)-R antagonist R-954 on NO, kallikrein and vascular permeability increases as well as Na/K ATPase decreases. The beneficial role of the BKB(1)-R antagonist R-954 for the treatment of the diabetic retinopathy is also suggested.


Quantification of renal perfusion and function on a voxel-by-voxel basis: a feasibility study.
The feasibility of a voxel-by-voxel deconvolution analysis of T(1)-weighted DCE data in the human kidney and its potential for obtaining quantification of perfusion and filtration was investigated. Measurements were performed on 14 normal humans and 1 transplant at 1.5 T using a Turboflash sequence. Signal time-courses were converted to tracer concentrations and deconvolved with an aorta AIF. Parametric maps of relative renal blood flow (rRBF), relative renal volume of distribution (rRVD), relative mean transit time (rMTT), and whole cortex extraction fraction (E) were obtained from the impulse response functions. For the normals average cortical rRBF, rRVD, rMTT, and E were 1.6 mL/min/mL (SD 0.8), 0.4 mL/mL (SD 0.1), 17s (SD 7), and 22.6% (SD 6.1), respectively. A gradual voxelwise rRBF increase is found from the center of two infarction zones toward the edges. Voxel IRFs showed more detail on the nefron substructure than ROI IRFs. In conclusion, quantitative voxelwise perfusion mapping based on deconvolved T(1)-DCE renal data is feasible, but absolute quantification requires inflow correction. rRBF maps and quantitative values are sufficiently sensitive to detect perfusion abnormality in pathologic areas, but further research is necessary to separate perfusion from extraction and to characterize the different compartments of the nephron on the (sub)voxel level.


Prevalence, demographics, and clinical correlates of antisocial personality disorder in Chinese methamphetamine patients.
Antisocial personality disorder (ASPD) is very common among methamphetamine (MA) patients, but very few studies have been conducted in China. This study aimed to investigate the prevalence and clinical correlates of ASPD among Chinese MA patients. We recruited 627 MA patients and collected demographic and MA use data through one-on-one semi-structured interviews. ASPD was measured by the Mini International Neuropsychiatric Interview (M.I.N.I.). The Desires for Drug Questionnaire (DDQ) and visual analog scale (VAS) were used to assess drug cravings. The prevalence rate of ASPD among MA patients was 27.59% (173/627). Patients with ASPD had greater age at the first onset, duration of MA use, length of abstinence, VAS, DDQ desire and intention, negative reinforcement, and total DDQ scores than patients without ASPD. Stepwise binary logistic regression analysis revealed that age, age at the first onset, length of abstinence, and DDQ-negative reinforcement were independently associated with ASPD in MA patients. Our findings suggest that the prevalence of ASPD is high among Chinese MA patients. Furthermore, some demographic and clinical variables are associated with ASPD in MA patients. We focused our study on the clinical profile of ASPD and the reasons for its high prevalence in Chinese methamphetamine patients. We identified several demographic and clinical variables as correlates of the occurrence of ASPD in methamphetamine patients, which provides evidence for ASPD comorbidity in methamphetamine patients.


Long-Term Use of Proton Pump Inhibitors Disrupts Intestinal Tight Junction Barrier and Exaggerates Experimental Colitis.
Proton pump inhibitors [PPIs] are widely used to treat a number of gastro-oesophageal disorders. PPI-induced elevation in intragastric pH may alter gastrointestinal physiology. The tight junctions [TJs] residing at the apical intercellular contacts act as a paracellular barrier. TJ barrier dysfunction is an important pathogenic factor in inflammatory bowel disease [IBD]. Recent studies suggest that PPIs may promote disease flares in IBD patients. The role of PPIs in intestinal permeability is not clear. The aim of the present study was to study the effect of PPIs on the intestinal TJ barrier function. Human intestinal epithelial cell culture and organoid models and mouse IBD models of dextran sodium sulphate [DSS] and spontaneous enterocolitis in IL-10-/- mice were used to study the role of PPIs in intestinal permeability. PPIs increased TJ barrier permeability via an increase in a principal TJ regulator, myosin light chain kinase [MLCK] activity and expression, in a p38 MAPK-dependent manner. The PPI-induced increase in extracellular pH caused MLCK activation via p38 MAPK. Long-term PPI administration in mice exaggerated the increase in intestinal TJ permeability and disease severity in two independent models of DSS colitis and IL-10-/- enterocolitis. The TJ barrier disruption by PPIs was prevented in MLCK-/- mice. Human database studies revealed increased hospitalizations associated with PPI use in IBD patients. Our results suggest that long-term use of PPIs increases intestinal TJ permeability and exaggerates experimental colitis via an increase in MLCK expression and activity.


Metabolic acidosis is undertreated and underdiagnosed: a retrospective cohort study.
Guidelines recommend treatment of metabolic acidosis (MA) in patients with chronic kidney disease (CKD), but the diagnosis and treatment rates in real-world settings are unknown. We investigated the frequency of MA treatment and diagnosis in patients with CKD. In this retrospective cohort study, we examined administrative health data from two US databases [Optum's de-identified Integrated Claims + Clinical Electronic Health Record Database (US EMR cohort; 1 January 2007 to 30 June 2019) and Symphony Health Solutions IDV® (US claims cohort; 1 May 2016 to 30 April 2019)] and population-level databases from Manitoba, Canada (1 April 2006 to 31 March 2018). Patients who met laboratory criteria indicative of CKD and chronic MA were included: two consecutive estimated glomerular filtration results <60 mL/min/1.73 m2 and two serum bicarbonate results 12 to <22 mEq/L over 28-365 days. Outcomes included treatment of MA (defined as a prescription for oral sodium bicarbonate) and a diagnosis of MA (defined using administrative records). Outcomes were assessed over a 3-year period (1 year pre-index, 2 years post-index). A total of 96 184 patients were included: US EMR, 6179; Manitoba, 3223; US Claims, 86 782. Sodium bicarbonate treatment was prescribed for 17.6%, 8.7% and 15.3% of patients, and a diagnosis was found for 44.7%, 20.9% and 20.9% of patients, for the US EMR, Manitoba and US Claims cohorts, respectively. This analysis of 96 184 patients with laboratory-confirmed MA from three independent cohorts of patients with CKD and MA highlights an important diagnosis and treatment gap for this disease-modifying complication.


Improving the microbiological diagnosis of tuberculous meningitis: A prospective, international, multicentre comparison of conventional and modified Ziehl-Neelsen stain, GeneXpert, and culture of cerebrospinal fluid.
Tuberculous meningitis (TBM) is the severest form of tuberculosis, but current diagnostic tests are insensitive. Recent reports suggest simple modifications to conventional cerebrospinal fluid (CSF) Ziehl-Neelsen (ZN) staining may greatly improve sensitivity. We sought to define the performance of modified and conventional ZN stain for TBM diagnosis. In hospitals in Vietnam, South Africa and Indonesia we conducted a prospective study of modified ZN with or without cytospin, conventional ZN smear, GeneXpert, and culture on CSF in adults with suspected TBM. A total of 618 individuals were enrolled across 3 sites. Compared with the TBM clinical diagnostic gold standard for research (definite probable or possible TBM), sensitivity of conventional ZN and modified ZN with cytospin were 33.9% and 34.5% respectively (p = 1.0 for the difference between tests), compared with culture 31.8% and Xpert 25.1%. Using culture as a reference, sensitivities of conventional ZN, modified ZN with cytospin, and Xpert were 66.4%, 67.5%, and 72.3%, respectively. Higher CSF volume and lactate, and lower CSF:blood glucose ratio were independently associated with microbiologically confirmed TBM. Modified ZN stain does not improve diagnosis of TBM. Currently available tests are insensitive, but testing large CSF volumes improves performance. New diagnostic tests for TBM are urgently required.


Differential urinary glycoproteome analysis of type 2 diabetic nephropathy using 2D-LC-MS/MS and iTRAQ quantification.
Diabetic nephropathy (DN) is the leading cause of chronic kidney failure and end-stage kidney disease. More accurate and non-invasive test for the diagnosis and monitoring the progression of DN is urgently needed for the better care of such patients. In this study we utilized urinary glycoproteome to discover the differential proteins during the course of type 2 DN. The urinary glycoproteins from normal controls, normalbuminuira, microalbuminura, and macroalbuminuria patients were enriched by concanavalin A (ConA) and analyzed by 2DLC/MS/MS and isobaric tags for relative and absolute quantitation quantification. A total of 478 proteins were identified and 408 were annotated as N-linked glycoproteins. A total of 72, 107 and 123 differential proteins were identified in normalbuminuria, microalbuminuria and macroalbuminuria, respectively. By bioinformatics analysis, in normalbuminruia state, cell proliferation and cell movement were activated, which might reflect the compensatory phase during the disease development. In micro- and macro-albuminuria, cell death and apoptosis was activated, which might reflect the de-compensatory phase. Pathway analysis showed acute phase proteins, the member of high density lipoprotein and low density lipoprotein proteins were changed, indicating the role of the inflammatory response and lipid metabolism abnormality in the pathogenesis of DN. Six selected differential proteins were validated by Western Blot. Alpha-1-antitrypsin (SERPINA1) and Ceruloplasmin are the two markers with excellent area under curve values (0.929 and 1.000 respectively) to distinguish the microalbuminuria and normalbuminuria. For the first time, we found pro-epidermal growth factor and prolactin-inducible protein were decreased in macroalbuminuria stage, which might reflect the inhibition of cell viability and the activation of cell death in kidney. Above data indicated that urinary glycoproteome could be useful to distinguish the differences in protein profiles in different stages in DN, which will help better individualized care of patients in DN.


Identification of biomarkers, immune infiltration landscape, and treatment targets of ischemia-reperfusion acute kidney injury at an early stage by bioinformatics methods.
Mechanisms underlying ischemia/reperfusion injury-acute kidney injury (IRI-AKI) are not fully elucidated. We conducted an integrative analysis of IRI-AKI by bioinformatics methods. We screened gene expression profiles of the IRI-AKI at early phase from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified and enrichment pathways were conducted based on gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) database, and Gene set enrichment analysis (GSEA). Immune cell infiltration analysis was performed to reveal the change of the microenvironment cell types. We constructed protein-protein interaction (PPI), and Cytoscape with plug-ins to find hub genes and modules. We performed robust rank aggregation (RRA) to combine DEGs and analyzed the target genes for miRNA/transcription factor (TF) and drug-gene interaction networks. A total of 239 and 384 DEGs were identified in GSE87024 and GSE34351 separately, with the 73 common DEGs. Enrichment analysis revealed that the significant pathways involve mitogen-activated protein kinase (MAPK) signaling, interleukin-17, and tumor necrosis factor (TNF) signaling pathway, etc. RRA analysis detected a total of 27 common DEGs. Immune cell infiltration analysis showed the plasma cells reduced and T cells increased in IRI-AKI. We identified JUN, ATF3, FOS, EGR1, HMOX1, DDIT3, JUNB, NFKBIZ, PPP1R15A, CXCL1, ATF4, and HSPA1B as hub genes. The target genes interacted with 23 miRNAs and 116 drugs or molecular compounds such as curcumin, staurosporine, and deferoxamine. Our study first focused on the early IRI-AKI adopting RRA analysis to combine DEGs in different datasets. We identified significant biomarkers and crucial pathways involved in IRI-AKI and first construct the immune landscape and detected the potential therapeutic targets of the IRI-AKI by drug-gene network.


Development of multiplex cross displacement amplification combined with lateral flow biosensor assay for detection of virulent shigella sonnei.
Shigella sonnei is the most common Shigella spp. in developed areas and the second most common in undeveloped regions. In this study, a multiple cross displacement amplification (MCDA) assay was used in combination with a lateral flow biosensor (LFB) assay to detect virulent S. sonnei strains containing the ipaH and wbgX genes. The multiplex MCDA-LFB assay detected wbgX at ≥1 pg/μL and ipaH at ≥10 fg/μL within 30 min in pure cultures maintained at 63°C. This assay was sensitive for ~37 CFU of virulent S. sonnei and ~3.7 CFU of Shigella spp. and enteroinvasive E. coli in stimulated fecal samples and had 100% specificity among 59 reference strains. The MCDA-LFB assay was also able to differentiate between virulent S. sonnei and other Shigella spp. and enteroinvasive E. coli among 99 clinical isolates. In summary, a multiplex MCDA-LFB assay was developed for rapid, convenient, point-of-care, and accurate identification of virulent S. sonnei within 30 min and at a constant temperature without the need for expensive lab equipment.


MET Gene Amplification and Overexpression in Chinese Non-Small-Cell Lung Cancer Patients Without EGFR Mutations.
The prevalence and clinical pathologic characteristics of MET amplification and overexpression in Chinese patients with non-small-cell lung cancer (NSCLC) remain unknown. In this multicenter study, we sought to reveal the frequency and clinical pathologic characteristics of MET amplification and to explore the predictive value of MET amplification and overexpression status in relation to survival in Chinese NSCLC patients. MET amplification was detected by fluorescence in-situ hybridization in 791 patients with EGFR wild-type samples. MET protein expression was detected by immunohistochemistry. In total, 8 of 791 NSCLC patients with EGFR wild type patients were identified as harboring MET amplification. Among these 8 patients, 1 had adenosquamous carcinoma histology and 7 adenocarcinoma. There was no statistically significant difference among age, sex, smoking status, and histologic type between patients with and without MET amplification. MET amplification was more frequent in advanced-stage disease and in the solid predominant subtype of adenocarcinoma. MET protein expression was performed in 395 patients, and 138 were positive. Patients positive for MET protein expression had worse overall survival (OS) compared to those without MET protein expression (45.0 vs. 65.8 months; P = .001). Multivariate analysis revealed that MET expression was an independent prognostic factor for poor OS (R = 1.497, P = .017), while MET amplification had weak relevance for OS (hazard ratio = 1.974, P = .251). MET amplification was rare in Chinese NSCLC patients without EGFR mutation, with a prevalence of about 1%. MET expression but not amplification could be an independent prognostic factor for shorter OS among these EGFR wild-type NSCLC patients.


Recombinant expression of twelve evolutionarily diverse subfamily Ialpha aminotransferases.
Aminotransferases are essential enzymes involved in the central metabolism of all organisms. The Ialpha subfamily of aspartate and tyrosine aminotransferases (AATases and TATases) is the best-characterized grouping, but only eight enzymes from this subfamily, representing relatively little sequence diversity, have been experimentally characterized for substrate specificity (i.e., AATase vs. TATase). Genome annotation, based on this limited dataset, provides tentative assignments for all sequenced members of this subfamily. This procedure is, however, subject to error, particularly when the experimental basis set is limited. To address this problem we cloned twelve additional subfamily Ialpha enzymes from an evolutionarily divergent set of organisms. Nine were purified to homogeneity after heterologous expression in Escherichia coli in native, intein-tagged or His(6)-tagged forms. The two Saccharomyces cerevisiae isoforms were recombinantly produced in yeast. The effects of the C-terminal tags on expression, purification and enzyme activity are discussed.


Thoracoscopic treatment of mediastinal cysts in children.
The development of thoracoscopic surgery has made many procedures possible, including the treatment of mediastinal cysts in children. The authors report their experience with this procedure between 1992 and 1997. Surgery was performed on 22 children aged from 1 month to 9 years (median, 27 months), weighing 5 to 49 kg (median, 12.5 kg). Diagnosis was made by antenatal ultrasound scan in six cases (27%), with a chest x-ray performed for respiratory symptoms in 14 cases, and with a chest x-ray performed for positive tuberculin intradermoreaction in two cases. Decision to resect the cyst was determined by thoracoscopy in 21 of the 22 cases, and by open surgery in one case only (subcarinal compressive cyst with left lung distension and a mediastinal shift). Eighteen of the 21 (86%) cases were treated successfully by thoracoscopy. In three cases of bronchogenic cysts, we performed an associated thoracotomy because the dissection was too difficult and dangerous. In three cases, a small part of a common wall between the cyst and the bronchus was not removed. The pathological diagnosis was bronchogenic cysts in 15 cases (71%), pleuropericardiat cysts in three cases (14%), esophageal duplication in two cases (10%), and cystic hygroma in one case (5%). Two postoperative complications were observed: one esophageal wound and a case of recurrent pneumothorax after chest tube removal. Patients were discharged after 2 to 11 days (median, 3 days). Follow-up was uneventful. Treatment of mediastinal cyst by thoracoscopy is feasible in most cases. Compressive cysts with lung distension and mediastinal shift remain a contraindication. If the cysts have a common wall with the bronchus or esophagus, or if they are subcarinal, the dissection may be difficult and dangerous, and thoracotomy may be preferable.


Heart murmurs and valvular regurgitation in thoroughbred racehorses: epidemiology and associations with athletic performance.
Cardiac murmurs associated with valvular regurgitation occur commonly in conditioned performance horses, but their association with athletic performance is unknown. Cardiac valvular regurgitation has a negative association with race performance. Five hundred and twenty-six "race fit" Thoroughbred racehorses engaged in either flat (race distance 1,000-2,500 m) or jump racing (race distance 3,200-6,400 m). Cardiac auscultation and color flow Doppler (CFD) echocardiography were performed on 777 occasions. The associations between the presence and severity of either an audible cardiac murmur or valvular regurgitation assessed by CFD, and published, objective measures of race performance were determined using a standard regression approach. The prevalence of murmurs and of regurgitation varied significantly between racetypes (P<.02), generally increasing from 2-year olds to chasers. There were no consistent associations between racing performance and either grade of murmur or regurgitation, whether the presence or absence of regurgitation or murmur, or only murmurs > or =3/6 or regurgitation > or =6/9, were considered. There were differences in prevalence and severity of murmurs of atrioventricular and aortic valve regurgitation between racehorses in different disciplines. Data also showed that neither regurgitation nor murmurs were negatively associated with Timeform rating, an index of UK racehorse quality, in any of the groups of racehorses studied.


Molecular gene mapping of human aldolase A (ALDOA) gene to chromosome 16.
Mapping of human aldolase A (ALDOA) gene was performed by molecular hybridization techniques using a panel of human-mouse cell hybrids and sorted fractions of human metaphase chromosomes besides in situ hybridization. For the purpose, three kinds of DNA probes derived from the coding region (probe-1), the 3' noncoding region (probe-2), and the coding and 3' noncoding regions (probe-3) of human aldolase A cDNA clone, pHAAL116-3, were selectively employed. The results of RNA and DNA blot analyses indicated that the human ALDOA gene is located on chromosome 16. The in situ hybridization experiment also indicated that the ALDOA gene was localized to 16q22-q24.


Nerve growth factor induces a gene homologous to the glucocorticoid receptor gene.
Nerve growth factor (NGF) is required for the development and survival of sympathetic and neural crest-derived sensory neurons. The mechanism of action of NGF has been extensively studied in the NGF-responsive rat pheochromocytoma cell line, PC12. When treated with NGF, PC12 cells initiate neurite outgrowth and differentiate into cells with a neuronal phenotype. This process is prevented by RNA synthesis inhibitors. NGFI-B is a gene, identified by differential hybridization, that is rapidly, but transiently induced in PC12 cells by NGF. The nucleotide sequence of the NGFI-B gene was determined, and it encodes a 61 kd protein with strong homologies to members of the glucocorticoid receptor gene family. The two regions of homology between NGFI-B and this family of ligand-dependent transcriptional activators are the region corresponding to the DNA-binding domain and the region comprising the ligand-binding domain near the COOH-terminus. NGFI-B, as a possible ligand-dependent transcriptional activator induced by NGF, may play a role in initiating NGF-induced differentiation.


Why does the bud-galling sawfly, Euura mucronata, attack long shoots?
The bud-galling sawfly, Euura mucronata, attacked longer shoot length classes on its host, Salix cinerea, more frequently than shorter shoots. Shoot length accounted for 76 to 93 percent of the variance in number of galls per 100 shoots in three habitats: forest, watermeadow, and lakeside. The reasons for this pattern were addressed with studies on shoot length in relation to: 1. Number of resources (buds) per shoot; 2. Success in establishment of larvae in galls; 3. Gall size and resources per gall; and 4. Survival of larvae after establishment as influenced by plant resistance and natural enemy attack. The most important factors proved to be success in establishment of larvae, with percent of variance accounted for ranging from 57 to 77 percent in three of four sites where relationships were significant, and survival after establishment of larvae, with variance accounted for ranging from 40 to 54 percent in the same three sites. The pattern of survival was dictated by plant resistance and not by natural enemies. These two additive factors resulted in a general relationship across all sites of increasing emergence of fully developed larvae per cohort as shoot length increased, accounting for 78 percent of the variance. These adaptive advantages to attacking longer shoots are sufficient to account for the pattern of increased probability of shoots being attacked as they increase in length.


pBFK, a new thermosensitive shuttle vector for Streptococcus pyogenes gene deletion by homologous recombination.
Streptococcus pyogenes, or Group A Streptococcus (GAS), is a major human pathogen for which genetic manipulation remains an ongoing challenge. We created a new temperature-sensitive plasmid pBFK expressing spectinomycin resistance adapted to homologous recombination procedure to perform a complete gene deletion in GAS. Herein the mutagenesis strategy with pBFK was performed in a highly virulent GAS emm3 genotype.


Selective removal of aqueous Hg2+ by magnetic composites sulfur-containing on the hyper-branched surface: Characterization, performance and mechanism.
The adsorbents with recyclable, large adsorption capacity and selective adsorption can effectively remove the pollution and harm of heavy metal ions in water. Therefore, two magnetic composites containing sulfur (MCP-S4 and MCP-S8) on the hyper-branched surface were prepared, furthermore, their structures were characterized and adsorption performance was analyzed by FTIR, XRD, TGA, BET, SEM, TEM, VSM and ICP. The results showed that both MCP-S4 and MCP-S8 had superparamagnetism with saturation susceptibility of 22.10 and 22.26 emu/g, and owned a specific surface area of 11.394 and 11.235 m2/g, respectively. MCP-S4 and MCP-S8 could selectively adsorb Hg2+ with the exist of Fe3+, Cu2+, Co2+, Ni2+, Mn2+, and Al3+ in solution. The adsorption kinetics accorded with pseudo-second-order model and Boyd film diffusion model, and the adsorption isotherm was fitted better with Langmuir isotherm model and D-R model, furthermore, the adsorption was an entropic-increasing and endothermic process. The removal rate of Hg2+ from simulated sewage by the two materials was more than 91%, and the adsorption retention rate was more than 85% after five adsorption-desorption cycles. The adsorption mechanism was analyzed by comparing the changes of FTIR, EDS and XPS spectra before and after adsorption. It was found that functional groups (C-N, CONH, CS, SH) could form stable chelates with Hg2+, which was the main reason why MCP-S4 and MCP-S8 could adsorb Hg2+ selectively, furthermore, S atoms of CS and -SH played a leading role in the process of adsorption. In addition, DFT calculation was also used as an auxiliary means to verify the adsorption mechanism.


BIAS: A Regional Management of Underwater Sound in the Baltic Sea.
Management of the impact of underwater sound is an emerging concern worldwide. Several countries are in the process of implementing regulatory legislations. In Europe, the Marine Strategy Framework Directive was launched in 2008. This framework addresses noise impacts and the recommendation is to deal with it on a regional level. The Baltic Sea is a semienclosed area with nine states bordering the sea. The number of ships is one of the highest in Europe. Furthermore, the number of ships is estimated to double by 2030. Undoubtedly, due to the unbound character of noise, an efficient management of sound in the Baltic Sea must be done on a regional scale. In line with the European Union directive, the Baltic Sea Information on the Acoustic Soundscape (BIAS) project was established to implement Descriptor 11 of the Marine Strategy Framework Directive in the Baltic Sea region. BIAS will develop tools, standards, and methodologies that will allow for cross-border handling of data and results, measure sound in 40 locations for 1 year, establish a seasonal soundscape map by combining measured sound with advanced three-dimensional modeling, and, finally, establish standards for measuring continuous sound. Results from the first phase of BIAS are presented here, with an emphasis on standards and soundscape mapping as well as the challenges related to regional handling.


Clinical and Prognostic Significance of Baseline Serum Vitamin D Levels in Hospitalized Egyptian Covid-19 Patients.
Vitamin D is a hormone with essential roles in both cellular metabolism and immunity. It controls calcium homeostasis and modulates innate and adaptive immune system responses. Many studies suggested an association between vitamin D deficiency and clinical outcomes of covid-19 infection, while others failed to document such a relation. The present study aimed to evaluate the clinical and prognostic significance of baseline vitamin D levels in hospitalized Egyptian covid-19 patients. The present retrospective study included 300 hospitalized covid-19 patients. Patients were submitted to standard clinical, laboratory, and radiological assessment. According to vitamin D levels, patients were classified to have normal levels (≥30), insufficient levels (20-29) or deficient levels (<20). According to their vitamin D levels, patients were classified into those with normal vitamin D (n=135), others with vitamin D insufficiency (n=114), and a third group with vitamin D deficiency (n=51). Patients with normal vitamin D levels and vitamin D insufficiency are significantly younger [median (IQR): 49.0 (39.0-57.0) versus 51.0 (40.0-61.0) and 55.0 (43.0-62.0) years, respectively, p=0.012] and had less frequency of severe disease (24.4% versus 40.4% and 51.0%, respectively) when compared with those with vitamin D deficiency. Moreover, they had significantly lower levels of D dimer [median (IQR): 1.5 (0.9-2.5) versus 1.8 (0.9-3.1) and 2.0 (1.0-3.2)], CRP [median (IQR): 58.0 (30.0-120.0) versus 76.0 (42.5-160.0) and 105.0 (74.0-208.0), respectively, p<0.001], ferritin [median (IQR): 458.0 (240.0-759.0) versus 606.0 (433.8-897.8) and 820.0 (552.0-1087.0), respectively, p<0.001], and procalcitonin [median (IQR): 290.0 (152.0-394.0) versus 372.5 (227.0-530.5) and 443.0 (272.0-575.0), respectively, p<0.001]. Only lower vitamin D levels were significant predictors of mortality in multivariate analysis [OR (95% CI): 0.88 (0.84-0.92), p<0.001]. Low vitamin D levels are related to exaggerated inflammatory response, disease severity, and poor clinical outcome in hospitalized covid-19 patients.


Introducing Braining-physical exercise as adjunctive therapy in psychiatric care: a retrospective cohort study of a new method.
Patients with severe mental disorders suffer from higher rates of poor somatic health and have shorter life expectancy than the average population. Physical activity can treat and prevent several diseases, e.g. cardiovascular and metabolic disorders as well as psychiatric symptoms. It is therefore of utmost importance to develop effective methods to integrate physical activity into psychiatric care. To meet this need, the physical activity intervention Braining was developed. This study aims to describe Braining, to assess the number of patients reached during the first years of pilot testing, to analyze clinical data in the group of patients participating in Braining 2017-2020 and to assess the intervention. In this descriptive retrospective study we analyzed data from all patients participating in Braining training sessions ≥ 3 times (n = 239), the Braining Participants. Regular patients at the clinic served as a comparison. Furthermore, medical records were studied for a smaller cohort (n = 51), the Braining Pilot Cohort. Data was analyzed using Chi-square and Fisher's tests. During the introduction period of Braining, 580 patients attended an information meeting about Braining, or at least one training session. 239 patients participated in ≥ 3 training sessions, considered to be participants of Braining. These Braining Participants (n = 239), ages 19 to 82, males 23.4%, attended between 3 and 308 training sessions (median 9). The main diagnoses were affective and anxiety disorders. Number of diagnoses ranged from 0 to 10 (median = 2). For the subsample, the Braining Pilot Cohort (n = 51), participants attended between 3 and 208 training sessions (median = 20). Twelve percent were working full-time, and symptom severity of depression and general anxiety was moderate. Two thirds had ≥ 3 different classes of medication. Regarding metabolic morbidity, 28 had been diagnosed with hypertension, though blood lipids, blood glucose as well as blood pressure were within the normal range. Thirty-seven percent were prescribed Physical Activity on Prescription during 2017-2020. One severe adverse event was reported. The Braining intervention reached all age-groups and patients with a wide and representative diagnostic panorama, suggesting that Braining could be a promising and safe method for implementing physical activity in a psychiatric patient population.


Arachidonic acid epoxygenase: detection of epoxyeicosatrienoic acids in human urine.
Epoxyeicosatrienoic acids, metabolites of the cytochrome P-450-mediated epoxygenase reaction, were detected in human urine by gas chromatographic-mass spectroscopic techniques after conversion to their hydrogenated and non-hydrogenated methyl and pentafluorobenzyl esters. Initial analysis of the regioisomeric composition utilizing the corresponding hydrogenated pentafluorobenzyl esters revealed the presence of the 8,9- and 14,15-isomers.


Accumulation and distribution of neurotoxin BMAA in aquatic animals and effect on the behavior of zebrafish in a T-maze test.
Neurotoxin β-N-methylamino-L-alanine (BMAA) has been widely detected in diverse aquatic organisms within different ecosystem trophic levels in recent years. It was the goal of this study to investigate the accumulation and tissue distribution of BMAA in marine opossum shrimp (Neomysis awatschensis) and freshwater zebrafish (Danio rerio) in exposure experiments. A T-maze test was tentatively adopted to assess the effects of BMAA on the learning and memory ability of zebrafish. Interestingly, N. awatschensis was testified to be capable of accumulating free soluble BMAA from bathing seawater through a biological filtration pathway (max. 110.6 μg g-1 wet weight). BMAA was transferred quickly from viscus to muscle and head tissues of zebrafish after intraperitoneal administration of 16.3 μg BMAA per individual twice in two weeks. BMAA accumulated mainly as the total soluble form in both experimental organisms. Results do not support the hypothesis that free BMAA molecules can be largely incorporated into protein in aquatic animals. Behavior of zebrafish in the T-maze test demonstrated that the short-term learning and memory ability was negatively impacted to some degree after three-days exposure to BMAA. Moreover, on Day 3, certain individual zebrafish exhibited freezing and loitering behavior. However, further investigation will be required to discern the long-term effects of BMAA on animals in order to evaluate the risk of BMAA exposure to human health.


A new subspecies and a new synonym of the genus Coladenia (Hesperiidae, Pyrginae) from China.
The second subspecies of Coladenia buchananii (de Nicéville, 1889), viz. Coladenia buchananii separafasciata Xue, Inayoshi & Hu, ssp. n., is discovered from south Jiangxi Province and west Fujian Province, southeast China. External and genital characters of both male and female of this new subspecies are illustrated and described. Coladenia neomaeniata Fan & Wang, 2006, syn. n. is proposed to be a junior synonym of Coladenia maeniata Oberthür, 1896, and the distribution of this species is briefly discussed.


Memory load, critical features and retrieval processes in facial recognition.
A Sternberg-type varied set procedure was used in which the set of stimuli associated with the "different" response was, in some cases, large and unspecified. A 3-factor design was used with repeated measures on list length (1, 2, or 4 faces), decision ("same" or "different"), and number of critical features varied between memory and target faces (0, 2, 4, or 7). Reaction times of college students for recognition of faces were analyzed to determine the nature of the retrieval processes employed. Reaction times were faster as the number of feature changes increased, and both parallel and serial processes were indicated for both "same" and "different" responses.


Legitimate suffering: a case of belonging and sickle cell trait in Brazil.
Patient activism organizations are formed around and seek legitimacy via both biological and biographical identities (Fassin, in: Theory Cult Soc 26(5):44-60, 2009). In the case of sickle cell disease (SCD) in Brazil, two different modes of suffering authenticate the lived experience-one is based on the disease state, the other is based on the ways in which racial inequalities and disadvantage contribute to its own suffering while also entangled with disease-based suffering. SCD is a rare genetic disorder that affects red blood cells and whose hallmark symptom is pain. This paper places an ethnographic focus on the failed mobilization of suffering by an organization leader in attempts to make claims for inclusion. The leader's social and biological identities of mother, sickle cell trait carrier, middle class, and mulata disrupted biosocial cohesion. This disruption reveals a hierarchy of suffering, where some indices of suffering are delegitimized. This hierarchy illuminates how exclusion and representation work within a patient organization whose membership embody both physical and social distress.


Cytoskeletal features of rat aortic cells during development. An electron microscopic, immunohistochemical, and biochemical study.
Actin, vimentin, desmin, and tropomyosin distribution in rat aortic endothelial and smooth muscle cells has been studied during development using fetal (18 to 20 days of gestation), and 5- and 14-day-, and 5-, and 12-week-old rats. Endothelial cells of newborn animals actively replicate and contain many actin stress fibers, whereas, in adult animals, replication is minimal and actin stress fibers are rare. The actin, vimentin, desmin, and tropomyosin content of smooth muscle cells increases gradually from fetal to adult animals. The number of desmin-containing cells also increases from 13% in fetal rats to 51% in adult rats. The beta-actin isoform is predominant in fetal and newborn animals, but gradually the alpha-isoform becomes quantitatively the most important, as seen by bidimensional polyacrylamide gels. Several analogies exist between the features of developing smooth muscle and what is known for developing striated muscle cells. The evolution of cytoskeletal features from fetal to adult animals is remarkably the opposite of what takes place in: (1) rat aortic smooth muscle cells proliferating after an endothelial injury, (2) human arterial smooth muscle cells present in atheromas, and (3) actively growing rat aortic smooth muscle cells in vitro. Thus, the assumption that pathological or cultured smooth muscle cells are "dedifferentiated" is supported by our biochemical observations.


Streptomyces chromofuscus phospholipase D interaction with lipidic activators at the air-water interface.
The phospholipase D from Streptomyces chromofuscus (PLDSc) is a soluble enzyme that interacts with membranes to catalyse phosphatidylcholine (PC) transformation. In this work, we focused on the interaction between PLDSc and two lipid activators: a neutral lipid, diacylglycerol (DAG), and an anionic one, phosphatidic acid (PA). DAG is a naturally occurring alcohol, so it is a potent nucleophile for the transphosphatidylation reaction catalysed by PLD. Concerning PA, it is a widely described activator of PLDSc-catalysed hydrolysis of PC. The monolayer technique allowed us to define PLDSc interaction with DAG and PA. In the case of DAG, the results suggest an insertion of PLDSc within the acyl chains of the lipid with an exclusion pressure of approximately 45 mN/m. PLDSc-DAG interaction seemed to occur preferentially with the lipid in the liquid-expanded (LE) phase. PLDSc interaction with PA was found to be more effective at high surface pressures. The overall results obtained with PA show a preferential interaction of the protein with condensed PA domains. No exclusion pressure could be found for PLDSc-PA interaction indicating only superficial interaction with the polar head of this lipid. Brewster angle microscopy (BAM) images were acquired in order to confirm these results and to visualise the patterns induced by PLDSc adsorption.


Application of immunohistochemistry to breast lesions.
Immunohistochemistry has an expanding role in mammary pathology that has been facilitated by a growing list of available antibodies and a better understanding of biology. To explore the key role of immunohistochemistry in guiding adjuvant therapy decisions and sentinel node staging in breast cancer, as well as the role of immunohistochemistry as an aid to distinguishing usual ductal hyperplasia from atypical ductal hyperplasia/low-grade carcinoma in situ; subtyping a carcinoma as ductal or lobular, basal or luminal; ruling out microinvasion in extensive intraductal carcinoma; distinguishing invasive carcinoma from mimics; and establishing that a metastatic carcinoma of unknown primary site has originated in the breast. Current literature is reviewed, including clinical and pathologic journals. As new, targeted treatments for breast cancer are developed, pathologists can expect additional immunohistochemistry applications in the future.


[Detoxifying action of various plasma substitute solutions in acute intestinal obstruction (experimental study)].
Animal experiments have established that infusions of plasma substituting solution from milk serum in combination with sodium succinate produce detoxifying effect in ileus. The use of the solution allows one to correct water electrolyte metabolism and to enhance detoxifying processes.


Core outcome domains of pediatric palliative care for children with severe neurological impairment and their families: A qualitative interview study.
The interest in outcome measurement in pediatric palliative care is rising. To date, the majority of studies investigating relevant outcomes of pediatric palliative care focus on children with cancer. Insight is lacking, however, about relevant outcome domains for children with severe neurological impairment and their families. The aim of this study was to identify meaningful outcome domains of pediatric palliative care for children with severe neurological impairment and their families. A qualitative research design following a constructivist research paradigm was employed. Guided interviews were conducted with parents of children with life-limiting conditions and severe neurological impairment and professional caregivers. The data were analyzed using qualitative content analysis. Overall, 10 cooperating pediatric palliative care institutions across Germany (outpatient and inpatient settings) aided in the recruitment of eligible parents and professional caregivers. A total of 11 interviews with 14 parents and 17 interviews with 20 professional caregivers were conducted. Six core outcome domains of pediatric palliative care for children with severe neurological impairment and their families were identified, namely (1) symptom control, (2) respite and support, (3) normalcy, (4) security, (5) empowerment, and (6) coping with the disease, each consisting of 1 to 13 individual aspects. As for other diagnostic groups, symptom control is a relevant outcome domain for children with severe neurological impairment. However, other outcome domains which focus on the whole family and take into account the long disease trajectory, such as respite and support, security, empowerment, and coping with the disease, are also crucial.


Locoregional therapy of hepatocellular carcinoma.
Hepatocellular carcinoma can be treated using minimally invasive, image-guided, catheter-based or percutaneous techniques. Such procedures offer compelling clinical outcomes with a favorable side-effect profile in a population of patients who are poor candidates for surgical or systemic treatment. This article discusses key data regarding the effectiveness of locoregional therapies in treating these patients. Disease-specific treatment is discussed in the context of hepatocellular carcinoma, with additional data discussed in the context of transplantation. As rapid innovation occurs in the realm of oncology, interventional oncology represents a safe, effective alternative that continues to generate impressive data that could potentially change treatment paradigms.


Strong but flexible: How fundamental social motives support but sometimes also thwart favorable attractiveness biases.
Research corroborates the notion that fundamental social motives play an important role in biases that favor attractive people. Although an adaptationist framework expects favorable social effects of good looks in most situations and contexts, it simultaneously allows for potential negative social reactions and outcomes that may be elicited by physical attractiveness in other contexts. These effects of attractiveness reflect the reproductive opportunities and threats posed by potential mates and rivals.


The antibiofilm activity of selected substances used in oral health prophylaxis.
Oral health is a window to a patient's general well-being. Balance in oral microbiome functions is crucial for health maintenance. A state of oral dysbiosis may lead to a variety of local and systemic pathological conditions. The presence of dental plaque is related to the majority of oral infections. Proper oral hygiene is crucial and the most economic practice contributing to oral health prophylaxis. Aside from prophylactic treatments provided by dental practitioners, mouth rinses, containing antimicrobial agents, are one of the possible tools used for oral care. Our study was to determine whether available mouth rinses and selected products dedicated for professional use are efficient to eradicate biofilm formed by reference and clinical strains of Streptococcus mutans, Streptococcus sanguinis, Streptococcus oralis, Streptococcus mitis, Staphylococcus aureus, Enterococcus faecalis, Lactobacillus rhamnosus and Candida albicans on the surface of hydroxyapatite - major mineral component of a tooth. Therefore, such antimicrobials as chlorhexidine, cetylpyridine chloride, polyhexanide, silver nanoparticles, sulphonated phenolics, and natural antiplaque essential oils and coconut oil were analyzed. Applied experimental settings in in vitro models were designed to reflect accurately the recommended use of the tested substances, therefore four types of eradication procedure were conducted. Sialorrhea simulation was also performed to evaluate antibiofilm potential of diluted mouth rinses. Biofilm was investigated with quantitative method where absorbance values were measured. Statistical differences were assessed using the Kruskal-Wallis test with a post-hoc Dunnett's analysis. Results have shown that biofilms displayed a diversified sensitivity to the tested antimicrobials. The highest antibiofilm activity was detected for cetylpyridine chloride while the lowest for chlorhexidine. However the differences in E. faecalis biofilm reduction observed after the use of these two compounds were not statistically significant (p > 0.05), whereas all observed differences in S. aureus survival after exposure to the examined antimicrobial agents were statistically significant (p < 0.5). The PHMB, both in standard and in sialorrhea simulated conditions had the highest potential against streptococci. The coconut oil reduced C. albicans fungus biofilm by 65.48% but low eradication level was observed in case of bacterial biofilms. The dehydrating mechanism of action of sulfonated phenolics turned out to be ineffective against streptococcal biofilm which in turn was effectively eradicated by silver nanoparticles. The implementation of Antibiofilm Dressing's Activity Measurement method allowed to observe strain-related differences in terms of antimicrobial sensitivity. The obtained results may be introduced in everyday out-patient dental plaque prophylaxis as well as clinical environment.


Further evidence for a cell surface proteinase essential to the growth of cultured fibroblasts.
Specific antibodies and protein proteinase inhibitors will inhibit cell-surface proteinase activity on human fibroblasts and cause a concomitant inhibition of DNA synthesis and of cell multiplication. An insolubilized proteinase inhibitor also inhibits cell multiplication. The same reagents partially inhibit the multiplication of mouse L cells, both in monolayer and suspension culture, and inhibit the mitogenic effect of epidermal growth factor (EGF) on both types of cell.


Dancing Participation and Cardiovascular Disease Mortality: A Pooled Analysis of 11 Population-Based British Cohorts.
Little is known about whether cardiovascular benefits vary by activity type. Dance is a multidimensional physical activity of psychosocial nature. The study aimed to examine the association between dancing and cardiovascular disease mortality. A cohort study pooled 11 independent population surveys in the United Kingdom from 1995 to 2007, analyzed in 2014. Participants were 48,390 adults aged ≥40 years who were free of cardiovascular disease at baseline and consented to be linked to the National Death Registry. Respondents reported participation in light- or moderate-intensity dancing and walking in the past 4 weeks. Physical activity amount was calculated based on frequency, duration, and intensity of participation in various types of exercise. The main outcome was cardiovascular disease mortality based on ICD-9 codes 390-459 or ICD-10 codes I01-I99. During 444,045 person-years, 1,714 deaths caused by cardiovascular disease were documented. Moderate-intensity, but not light-intensity, dancing and walking were both inversely associated with cardiovascular disease mortality. In Cox regression models, the hazard ratios for cardiovascular disease mortality, adjusted for age, sex, SES, smoking, alcohol, BMI, chronic illness, psychosocial distress, and total physical activity amount, were 0.54 (95% CI=0.34, 0.87) for moderate-intensity dancing and 0.67 (95% CI=0.52, 0.87) for moderate-intensity walking. Moderate-intensity dancing was associated with a reduced risk for cardiovascular disease mortality to a greater extent than walking. The association between dance and cardiovascular disease mortality may be explained by high-intensity bouts during dancing, lifelong adherence, or psychosocial benefits.


Regulation of gluconeogenesis in swine kidney proximal tubule cells.
Proximal tubule cells were isolated from swine kidney and cultured for periods of more than 30 days. The cells formed confluent monolayers after plating on a collagen surface and they were passaged more than 5 times on this matrix. The cells maintain several metabolic functions of proximal tubule cells, including gluconeogenesis and the ability to respond to epinephrine and parathyroid hormone. Gluconeogenesis, a principal metabolic pathway in proximal tubule cells, was examined as a function of days in culture. The isolated cells showed a nearly constant rate of gluconeogenesis from 14C-lactate, 14C-alanine and 14C-glycerol with no significant loss of activity for at least 30 days in culture. Likewise, the activities of several cytosolic and membrane associated enzymes including, alkaline phosphatase, delta-glutamyltransferase, fructose-1,6-bisphosphatase and phosphofructokinase were nearly constant over the same time period. The cells responded to treatment with epinephrine and parathyroid hormone, and the rate of gluconeogenesis from 14C-lactate doubled in the presence of these hormones. The morphological and biochemical evidence obtained in these studies show that the proximal tubule cells isolated from swine kidney provide an excellent well defined system for studying the hormonal regulation of carbohydrate metabolism in this tissue.


A Combination of Contrast-Enhanced Ultrasound and Thyroglobulin Level in Fine-Needle Aspirates Improves Diagnostic Accuracy for Metastatic Lymph Nodes of Papillary Thyroid Carcinoma.
To evaluate the diagnostic performance of contrast-enhanced ultrasound (CEUS) combined with thyroglobulin (Tg) levels in fine-needle aspirates (FNA) washout fluid (FNA-Tg) in diagnosing cervical lymph node (LN) metastasis in papillary thyroid cancer (PTC) patients. Data from 190 LNs in 167 patients suspected of metastasis from the US between November 2018 and September 2020 were included. All subjects underwent FNA, CEUS, and FNA-Tg examinations. The final outcomes were confirmed by histopathological or cytological examination or follow-up imaging. Data were analyzed using the Wilcoxon rank-sum or chi-squared test. The diagnostic efficacy of FNA, CEUS, and FNA-Tg in diagnosing LNs was compared. A cutoff value of 6.15 ng/ml (AUC 0.925, 95% confidence interval (CI) 0.885-0.966) successfully identified metastatic LNs. FNA missed 58 LN metastases, of these, 94.8% (55/58) were correctly diagnosed using the combination of CEUS and FNA-Tg. FNA-Tg showed higher sensitivity (90.2%), NPV (86.1%) and accuracy (88.9%) than either FNA (48.2, 57.4 and 69.5%, respectively) or CEUS (82.1, 67.7 and 70.5%, respectively) alone. The combination of CEUS, FNA and FNA-Tg resulted in maximal sensitivity (100%) and NPV (100%) but reduced specificity (51.3%) and overall diagnostic accuracy (80.0%). After adding FNA-Tg to discordant samples between CEUS and FNA, 81.9% of LNs (77/94) were correctly diagnosed. The combination of FNA, FNA-Tg and CEUS was found to be a promising imaging tool in detecting metastatic LNs in PTC patients.


Gene therapy for new bone formation using adeno-associated viral bone morphogenetic protein-2 vectors.
Previous reports have suggested that bone morphogenetic protein (BMP) gene therapy could be applied for in vivo bone regeneration. However, these studies were conducted either using immunodeficient animals because of immunogenicity of adenovirus vectors, or using ex vivo gene transfer technique, which is much more difficult to handle. Adeno-associated virus (AAV) is a replication-defective virus without any association with immunogenicity and human disease. This study was conducted to investigate whether orthotopic new bone formation could be induced by in vivo gene therapy using AAV-based BMP2 vectors. To test the feasibility of this approach, we constructed an AAV vector carrying human BMP2 gene. Mouse myoblast cells (C2C12) transduced with this vector could produce and secrete biologically active BMP2 protein and induce osteogenic activity, which was confirmed by ELISA and alkaline phosphatase activity assay. For in vivo study, AAV-BMP2 vectors were directly injected into the hindlimb muscle of immunocompetent Sprague-Dawley rats. Significant new bone under X-ray films could be detected as early as 3 weeks postinjection. The ossification tissue was further examined by histological and immunohistochemical analysis. This study is, to our knowledge, the first to establish the feasibility of AAV-based BMP2 gene therapy for endochondral ossification in immunocompetent animals.


Structure-based de novo design of ligands using a three-dimensional model of the insulin receptor.
For the first time, a three-dimensional model of the insulin receptor is used in the de novo design of novel ligands that potentially mimic interactions of insulin at its receptor. Compound 4 competed with insulin as seen in autophosphorylation assays and inhibited up to 68% of IR autophosphorylation at 300 microM of 4 in 3T3IR cells induced by 1 nM insulin. This model provides a basis for the design of potent insulin receptor ligands.


K-value and low insulin secretion in a non-obese white population: predicted glucose tolerance after 25 years.
Insulin resistance and insulin deficiency are proposed as risk factors for IGT and type 2 diabetes. We assessed the predictive value of initial parameters for the outcome of an OGTT performed 24.3+/-2.9 years later in an unselected healthy non-obese population. The K-value of an IVGTT was determined in 267 healthy subjects (mean+/-SD: age 31.0+/-12.0 years, BMI 21.8+/-2.8 kg/m(2)). First-phase insulin response to a glucose infusion test was estimated as an incremental 5- or 10-min (DeltaI5 or DeltaI10) value, and as insulinogenic indices (DeltaI5/DeltaG5 or DeltaI10/DeltaG10) adjusted for insulin sensitivity determined by homeostasis model assessment for insulin resistance ([DeltaI5/DeltaG5]/HOMA-IR). At follow-up, six subjects had type 2 diabetes and 47 had IGT; 214 retained normal glucose tolerance. Insulin sensitivity and early (30 min) insulin response decreased with decreasing outcome OGTT. Blood glucose (2 h) at OGTT correlated positively with initial age and BMI, and negatively with DeltaI5/DeltaG5, (DeltaI5/DeltaG5)/HOMA-IR and K-value. In multiple linear regression analysis, (DeltaI5/DeltaG5)/HOMA-IR, DeltaI10, K-value, age, HOMA estimate of insulin secretion, and fasting plasma glucose were significantly associated with 2-h OGTT blood glucose. Similar results were obtained on comparing differences between subjects with normal and decreased (IGT+diabetes) glucose tolerance. In 267 non-obese healthy subjects, initial K-value and first-phase insulin response to glucose adjusted for insulin sensitivity, but not insulin sensitivity itself, were strong predictors of the outcome of an OGTT performed 25 years later. Thus, in contrast to obese or other high-risk populations, in lean subjects, decreased beta cell function, but not insulin resistance itself, determines future glucose tolerance.


Late adverse events to iodinated contrast media in patients treated with IL-2: a safety report from the Danish Renal Carcinoma Group (DaRenCa) study - 1.
A higher incidence of late adverse events (LAEs) to iodinated contrast media in interleukin-2 (IL-2)-treated patients has been reported. To assess the incidence of LAEs after administration of iodinated contrast media in patients with metastatic renal cell carcinoma (mRCC) treated with IL-2. Patients were randomized to treatment with IL-2 and interferon-α with/without bevacizumab in the Danish Renal Carcinoma Group study - 1. Patients underwent a computed tomography (CT) scan at baseline, at one month, at three months, and every third month until RECIST 1.1 defined progression. LAEs due to iodinated contrast media were systematically registered according to the Common Terminology Criteria for Adverse Events classification. In total, 89 patients were included and underwent a total of 507 contrast-enhanced CT scans. An overall incidence of 46 (9.1%) LAEs was observed in 38 of 89 (42.7%) patients; 3 LAEs at baseline (3.4% of all baseline scans), 39 (13.9%) LAEs during IL-2-based therapies, and 4 (2.9%) LAEs after termination of IL-based therapies. There was no difference in progression-free survival, overall survival, and treatment response in patients experiencing LAEs compared to patients without LAEs (P = 0.2, P = 0.5, and P = 0.6, respectively). Patients with mRCC demonstrated a higher incidence of LAEs after administration of iodinated contrast during ongoing IL-2 therapy, indicating that iodinated contrast media may cause a recall phenomenon of IL-2 toxicities in patients with mRCC. Treatment with IL-2 should not be a contraindication for contrast-enhanced scans in patients with mRCC but expertise and vigilance are required.


Left ventricular systolic function in primary aldosteronism and hypertension.
This study was designed to investigate whether the excess aldosterone found in primary aldosteronism (PA) influences left-ventricular systolic function (LVSF), through a positive inotropic effect M-mode and two-dimensional echocardiography and transmitral Doppler flow velocity measurements were performed in 82 patients: 44 with confirmed PA (23 male; 21 female; aged 51.8+/-13 years) and 38 essential hypertension patients (16 male; 22 female; aged 48.5+/-12 years) matched for demography and blood pressure (BP) values. We measured left-ventricular (LV) midwall fractional shortening (MwFSho) and LV circumferential end-systolic stress (cESS, calculated according to Reichek's equation) and analysed the relationship between MwFSho and cESS. These are given as the mean +/- standard deviation. PA patients had significantly higher cardiac index (CI) (3.55+/-0.94 l/m2 vs 2.98+/-0.58, P < 0.005) and lower E wave/A wave time-velocity integral ratio (0.93+/-0.27 vs 1.26+/-0.41, P < 0.001) than EH, whereas mean BP (126+/-12 mmHg vs 128+/-12), MwFSho (17.1+/-2.4% vs 16.3+/-1.9), cESS (118+/-19 Kdynes/cm2 vs 121+/-18) and the relationship between LV MwFSho and LV cESS did not differ between groups. These findings confirm that PA patients exhibit: (1) a modest increase of CI; (2) an LV diastolic filling mainly occurring with the atrial kick. However, they do not lend support to the contention that the excess of plasma aldosterone seen in PA is associated with enhanced LV inotropism under resting conditions.


A history of juvenile mild malaria exacerbates chronic stress-evoked anxiety-like behavior, neuroinflammation, and decline of adult hippocampal neurogenesis in mice.
Children residing in high malaria transmission regions are particularly susceptible to malaria. This early-life window is also a critical period for development and maturation of the nervous system, and inflammatory insults during this period may evoke a persistent increase in vulnerability for psychopathology. We employed a two-hit model of juvenile mild malaria and a two-week chronic unpredictable mild stress (CUMS) regime, commencing 60 days post-parasite clearance, to assess whether a history of juvenile infection predisposed the mice towards mood-related behavioral alterations and neurocognitive deficits. We showed that adult mice with a history of juvenile malaria (A-H/JMAL) exhibited heightened CUMS-associated anxiety-like behavior, with no observable change in cognitive behavior. In contrast, mice with a history of adult malaria did not exhibit such enhanced stress vulnerability. At baseline, A-H/JMAL mice showed increased activated microglia within the hippocampal dentate gyrus subfield. This was accompanied by a decrease in proliferating neuronal progenitors, with total number of immature hippocampal neurons unaltered. This neuroinflammatory and neurogenic decline was further exacerbated by CUMS. At day-14 post-CUMS, hippocampi of A-H/JMAL mice showed significantly higher microglial activation, and a concomitant decrease in progenitor proliferation and number of immature neurons. Taken together, these results suggest that a history of juvenile mild malaria leaves a neuroinflammatory mark within the hippocampal niche, and this may contribute to a heightened stress response in adulthood. Our findings lend credence to the idea that the burden of malaria in early-life results in sustained CNS changes that could contribute to increased vulnerability to adult-onset neuronal insults.


Identification of lactic acid bacteria from spoiled, vacuum-packaged 'gravad' rainbow trout using ribotyping.
A total of 296 lactic acid bacteria (LAB) isolated from spoiled, vacuum-packaged 'gravad' rainbow trout stored at 3 and 8 degrees C were characterised and identified using a molecular approach. The isolates were initially grouped according to their HindIII restriction endonuclease profiles and further identified to species level using an rRNA gene restriction pattern (ribotype) identification database. Lactobacillus sakei, L. curvatus and Carnobacterium piscicola were the three main species detected. Only one isolate was identified as C. divergens. Most of the carnobacteria were found in the samples stored at 3 degrees C. The relative proportion of L. sakei was higher in the samples stored at 8 degrees C.


Effects of stress on neural processing of combat-related stimuli in deployed soldiers: an fMRI study.
Severe trauma exposure may lead to symptoms of both posttraumatic stress disorder and depression. Neuroanatomical theories suggest that both disorders may share imbalances in fronto-limbic circuits. Longitudinal studies are necessary to better understand the impact of a stressful life situation on potential long-term fronto-limbic imbalances. Here we investigated soldiers neural processing of combat-related stimuli versus negative affective stimuli before and after the deployment in different war zones. In the final analysis we included 104 deployed soldiers (combat group) and 36 soldiers that were not deployed (control group). Behaviorally, we found a significant group by time interaction regarding depression symptom scores with an increase in the combat group. Depressive symptoms were subclinical. On the neural level, neither the whole brain analysis nor the region of interest (ROI) analyses including frontal and limbic ROIs revealed any significant results in the group by time interaction. However, extracted ROI values of the group by time interaction of amygdala and hippocampus were positively associated with the change in depression symptom scores in the combat group, but not in the control group. These results highlight the role of depression in individuals that experience stressful life situations. Future studies may need to investigate the role of depressive symptoms after trauma exposure with different tasks that may be particularly sensitive to changes due to depressive symptoms.


Mouse interferons enhance the accumulation of a human HLA RNA and protein in transfected mouse and hamster cells.
A recombinant clone (pJY150R1.1) encoding the human major histocompatibility antigen (HLA-B7) was introduced into mouse cells and hamster cells by cotransformation with selectable genes. The exposure to mouse interferon of the cells transformed to HLA-B7+ resulted in a severalfold increase in the level of HLA antigen and RNA. The HLA-B7 clone used for the transfection includes a 670-base pair DNA sequence upstream from the coding segment. It remains to be established if the 670-base pair segment is necessary and/or sufficient to make the transcription of the HLA gene responsive to interferon.


Endothelin rapidly stimulates tyrosine phosphorylation in osteoblast-like cells.
The mitogenic activity of endothelin (ET) was studied in osteoblast-like cells, MC3T3-E1. [3H] Thymidine incorporation induced by ET was markedly lower than that of platelet-derived growth factor (PDGF). ET synergistically stimulated [3H] thymidine incorporation induced by PDGF with an apparent ED50 value of 2.5 nM. Treatment of MC3T3-E1 cells with ET and subsequent immunoblotting of the cell extracts with antiphosphotyrosine antibodies followed by labeling with [125I] protein A resulted in the identification of several phosphotyrosine-containing proteins. The intensity of these labeled phosphoproteins significantly increased when the cells were treated with a combination of ET and PDGF. Genistein, an inhibitor of tyrosine kinases, blocked [3H] thymidine incorporation as well as protein tyrosine phosphorylation stimulated by either ET, PDGF or the combination of ET and PDGF. These findings suggest that tyrosine phosphorylation could play a role in the comitogenic activity of ET in osteoblast-like cells.


Prognostic value of metabolic tumour volume and total lesion glycolysis in 18F-FDG PET/CT scans in locally advanced breast cancer staging.
To determine whether metabolic tumour volume (MTV) and total lesion glycolysis (TLG) are able to predict recurrence risk in locally advanced breast cancer (LABC) patients. Retrospective study of LABC patients who undertook neoadjuvant, local and adjuvant treatment and follow up. A 18F-FDG PET/CT study for initial staging was performed analysing in this study different metabolic parameters (MTV, TLG, SUVmax and SUVmed) both in the primary tumour (T) as well as in axillary nodes (N) and whole-body (WB). Forty females were included between January 2010-2011; follow up until January 2015 was completed. The average follow-up was 46 months. Twenty percent presented recurrence: local disease (n=2) and distant metastasis (n=6); 3 patients died (38% of the patients which recurred and 7.5% from the total). SUVmax, MTV and TLG, in T, N and WB, were higher in those patients with recurrence. The MTV and TLG parameters in the tumour (T) were related to the recurrence rate (P=.020 and P=.028, respectively); whereas SUVmax in the lymph nodes (N) was significantly related (P=.008) to the recurrence rate. The best cut-off points to predict recurrence where: MTV T ≥19.3cm3, TLG T≥74.4g and SUVmax N≥13.8, being 10-12 times more likely to recidivate when these thresholds where exceeded. Tumour grade was the only clinical-pathological variable which was related to recurrence probability (p=.035). In this study of LABC patients the metabolic parameters which have a better relationship with recurrence rate are: MTV and TLG in the primary tumour, SUVmax in the regional lymph node disease and whole-body PET data.


A systematic review and meta-analytical synthesis of the relationship between work engagement and job satisfaction in nurses.
This study aimed to clarify the mixed conclusions regarding work engagement and job satisfaction in the nursing research literature by conducting a systematic review and meta-analysis. This meta-analytic review synthesized 15 independent studies published between 2007 and 2021. An overall effect size of random-effect model was calculated as r = 0.47 (k = 15, N = 3,818, 95% confidence interval [0.43;0.51]). Data collection method and presence of control variable, as significant moderators, accounted for 43.6% and 43.8%, respectively, of the effect size heterogeneity. While the positive relationship between work engagement and job satisfaction was higher in studies using the face-to-face data collection method, it was lower in studies using the control variable in their research models.


[Stage-dependent expression of androgen binding protein mRNA in sertoli cell of rat testis].
To investigate the variation of rat androgen binding protein (ABP) mRNA in sertoli cell of rat testis during spermatogenesis. In situ hybridization was performed with digoxin-labeled rat ABP cDNA probe on frozen testis tissue sections from SD rats. The expression of ABP mRNA was quantified by using laser density scanning system. It was shown that ABP mRNA levels were low from stage I to stage VI, increased to the peak level at the stages VII-VIII, and then declined rapidly at stages IX-XI. Thereafter, ABP mRNA levels increased again at stages XII-XIV, and then decreased to the lowest level at stages I-VI. ABP mRNA level was stage-dependent during the spermatogenic cycle.