Bone Turnover in Young Adult Men: Cross-Sectional Determinants and Associations With Prospectively Assessed Bone Loss.
Biochemical markers of bone turnover are higher in young adult men than in middle-aged men or young adult women. Nonetheless, little is known about the determinants and clinical significance hereof. The present study examined determinants of serum bone turnover markers in men around peak bone mass age, and explored whether bone turnover at this age predicts subsequent changes in bone mass. We used cross-sectional and longitudinal data from 973 and 428 healthy men, respectively, aged 25 to 45 years at baseline, including baseline procollagen type I amino-terminal propeptide (P1NP), osteocalcin, and C-terminal telopeptide of type I collagen (CTX) from fasting serum samples, baseline questionnaire-assessed physical activity levels, and baseline and follow-up dual-energy X-ray absorptiometry-derived areal bone mineral density (aBMD) and body composition. Mean follow-up time was 12.4 ± 0.4 years. At baseline, all bone turnover markers were inversely associated with total body fat mass (β ≤ -0.20, p < 0.001), and positively with physical activity during sports activities (β ≥ 0.09, p ≤ 0.003), and, albeit not independently from fat mass, total body lean mass (β ≥ 0.20, p ≤ 0.003). Mean annual aBMD changes in the longitudinal cohort were -0.19% ± 0.24% at the total body, -0.14% ± 0.42% at the spine, -0.49% ± 0.47% at the femoral neck, and -0.25% ± 0.37% at the total hip (all p < 0.001). Higher bone turnover markers at baseline were associated with larger decreases in aBMD at all measurement sites (β ≤ -0.08, p ≤ 0.081 for P1NP; β ≤ -0.16, p ≤ 0.002 for osteocalcin; and β ≤ -0.21, p < 0.001 for CTX). In conclusion, our findings show that sports activities and body composition, primarily fat mass, are the main identified determinants of bone turnover in men around peak bone mass age. Further, bone turnover at this age is an important determinant of subsequent changes in bone mass, with higher levels of bone turnover markers being associated with greater decreases in aBMD. © 2017 American Society for Bone and Mineral Research.


A study of oil of bergamot and its importance as a phototoxic agent. I. Characterization and quantification of the photoactive component.
It is important in the technique of photopatch testing, using oil of bergamot, to have determined the concentration of the active psoralen, bergapten, so as to avoid false negative responses in the assessment of phototoxic reactions. Techniques for assessing the phototoxic components of oil of bergamot are described and quantitative analyses of bergapten, the only significant photoactive compound in the samples examined, are reported. The phototoxicity of bergapten was found to be nearly the same as that of xanthotoxin (8-MOP) in tests on human skin.


Disruption of Chromosomal Architecture of cox2 Locus Sensitizes Lung Cancer Cells to Radiotherapy.
Despite treatment of lung cancer with radiotherapy and chemotherapy, the survival rate of lung cancer patients remains poor. Previous studies demonstrated the importance of upregulation of inflammatory factors, such as cyclooxygenase 2 (cox2), in tumor tolerance. In the present study, we investigated the role of cox2 in radiosensitivity of lung cancer. Our results showed that the combination treatment of radiation with aspirin, an anti-inflammatory drug, induced a synergistic reduction of cell survival in A549 and H1299 lung cancer cells. In comparison with normal human lung fibroblasts (NHLFs), the cell viability was significantly decreased and the level of apoptosis was remarkably enhanced in A549 cells. Mechanistic studies revealed that the reduction of cox2 by aspirin in A549 and H1299 was caused by disruption of the chromosomal architecture of the cox2 locus. Moreover, the disruption of chromatin looping was mediated by the inhibition of nuclear translocation of p65 and decreased enrichment of p65 at cox2-regulatory elements. Importantly, disorganization of the chromosomal architecture of cox2 triggered A549 cells sensitive to γ-radiation by the induction of apoptosis. In conclusion, we present evidence of an effective therapeutic treatment targeting the epigenetic regulation of lung cancer and a potential strategy to overcome radiation resistance in cancer cells.


Enhanced CAR-T activity against established tumors by polarizing human T cells to secrete interleukin-9.
CAR-T cell therapy is effective for hematologic malignancies. However, considerable numbers of patients relapse after the treatment, partially due to poor expansion and limited persistence of CAR-T cells in vivo. Here, we demonstrate that human CAR-T cells polarized and expanded under a Th9-culture condition (T9 CAR-T) have an enhanced antitumor activity against established tumors. Compared to IL2-polarized (T1) cells, T9 CAR-T cells secrete IL9 but little IFN-γ, express central memory phenotype and lower levels of exhaustion markers, and display robust proliferative capacity. Consequently, T9 CAR-T cells mediate a greater antitumor activity than T1 CAR-T cells against established hematologic and solid tumors in vivo. After transfer, T9 CAR-T cells migrate effectively to tumors, differentiate to IFN-γ and granzyme-B secreting effector memory T cells but remain as long-lived and hyperproliferative T cells. Our findings are important for the improvement of CAR-T cell-based immunotherapy for human cancers.


An unusual somatotropin and thyreotropin secreting pituitary adenoma efficiently controlled by Octreotide and Pegvisomant.
We describe the first case of a 36 year-old male patient with a somatotropin and thyreotropin secreting pituitary adenoma, co-treated by a long-acting releasing somatostatin analog (Octreotide) and a GH receptor antagonist (Pegvisomant). The patient normalized his biological disease activity reflected by hormone levels but his tumor size remained unchanged as measured by MRI. The co-treatment was well tolerated and induced a synergic effect on IGF1 levels that allowed us to use low doses of both therapies.


Impact of performance and information feedback on medical interns' confidence-accuracy calibration.
Diagnostic errors are a major, largely preventable, patient safety concern. Error interventions cannot feasibly be implemented for every patient that is seen. To identify cases at high risk of error, clinicians should have a good calibration between their perceived and actual accuracy. This experiment studied the impact of feedback on medical interns' calibration and diagnostic process. In a two-phase experiment, 125 medical interns from Dutch University Medical Centers were randomized to receive no feedback (control), feedback on their accuracy (performance feedback), or feedback with additional information on why a certain diagnosis was correct (information feedback) on 20 chest X-rays they diagnosed in a feedback phase. A test phase immediately followed this phase and had all interns diagnose an additional 10 X-rays without feedback. Outcome measures were confidence-accuracy calibration, diagnostic accuracy, confidence, and time to diagnose. Both feedback types improved overall confidence-accuracy calibration (R2No Feedback = 0.05, R2Performance Feedback = 0.12, R2Information Feedback = 0.19), in line with the individual improvements in diagnostic accuracy and confidence. We also report secondary analyses to examine how case difficulty affected calibration. Time to diagnose did not differ between conditions. Feedback improved interns' calibration. However, it is unclear whether this improvement reflects better confidence estimates or an improvement in accuracy. Future research should examine more experienced participants and non-visual specialties. Our results suggest that feedback is an effective intervention that could be beneficial as a tool to improve calibration, especially in cases that are not too difficult for learners.


Benzothiadiazole covalent organic framework photocatalysis with an electron transfer mediator for selective aerobic sulfoxidation.
Covalent organic frameworks (COFs) are promising visible light photocatalysts for aerobic oxidation reactions. However, COFs usually suffer from the assault of reactive oxygen species, leading to hindered electron transfer. This scenario could be addressed by integrating a mediator to promote photocatalysis. Starting with 4,4'-(benzo-2,1,3-thiadiazole-4,7-diyl)dianiline (BTD) and 2,4,6-triformylphloroglucinol (Tp), TpBTD-COF is developed as a photocatalyst for aerobic sulfoxidation. Adding an electron transfer mediator 2,2,6,6-tetramethylpiperidine-1‑oxyl (TEMPO), the conversions are radically accelerated, over 2.5 times of that without TEMPO. Moreover, the robustness of TpBTD-COF is preserved by TEMPO. Remarkably, TpBTD-COF could endure multiple cycles of sulfoxidation, even with higher conversions than the fresh one. TpBTD-COF photocatalysis with TEMPO implements diverse aerobic sulfoxidation by an electron transfer pathway. This work highlights that benzothiadiazole COFs are an avenue for tailor-made photocatalytic transformations.


Swinepox virus as a vaccine vector for swine pathogens.
Several small and large viruses (e.g., adenovirus, poxvirus, and herpesviruses) have been investigated as vaccine vectors. Each viral system has its advantages and disadvantages. One major advantage for viral vector vaccines is their ability to elicit a protective cell-mediated immunity as well as a humoral response to the antigen delivered by the vector. One major problem to using recombinant viruses as vaccines is the pathogenic potential of the parent virus. Therefore, it is important that along with the optimal expression of the foreign genes and ability to provide protection, the pathogenicity of the vector virus must be reduced during genetic manipulation without affecting its multiplication. The requirements to develop a viral vector, for example, swinepox virus, are a cell culture system that will support the growth of the virus, a suitable nonessential region(s) in the virus genome for insertion of foreign DNA so that virus replication is not affected, a foreign gene(s) that encodes for an immunogenic protein of a swine pathogen, strong transcriptional regulatory elements (promoters) necessary for optimal expression of the foreign genes, a procedure for delivering the foreign gene(s) into the nonessential locus, and a convenient method of distinguishing the recombinant viruses from the parent wild-type virus. Using this methodology, recombinant swinepox virus vaccines expressing pseudorabies virus antigens have been developed and shown to provide protection against challenge. These studies and evidence of local infection of the oral tract by swinepox virus indicate its potential as a recombinant vector for providing immunity against various swine pathogens including those that infect the respiratory and gastrointestinal tracts.


The actions of enkephalins are not modified by the "kininase-II" inhibitor captopril.
The "kininase-II" (EC 22.214.171.124) inhibitor captopril in concentrations up to 10(-4) M did not affect the actions of enkephalins on the isolated electrically stimulated guinea-pig ileum. Captopril (100 mg/kg i.p.) in mice did not influence stimulation-produced analgesia and did not show analgesic properties. It is concluded that "kininase-II" is not involved in enkephalin catabolism, since the pharmacological actions of enkephalins were not enhanced after inhibition of the enzyme by captopril.


Phylogeny of novel naked Filose and Reticulose Cercozoa: Granofilosea cl. n. and Proteomyxidea revised.
Naked filose and reticulose protozoa were long lumped as proteomyxids or left outside higher groups. We cultivated eight naked filose or reticulose strains, did light microscopy, 18S rDNA sequencing and phylogeny (showing all are Cercozoa), and sequenced 80 environmental 18S-types. Filose species belong in subphylum Filosa and reticulose ones in subphylum Endomyxa, making proteomyxids polyphyletic. We therefore transfer the classically mainly reticulose Proteomyxidea to Endomyxa, removing evident filosans as new class Granofilosea (including Desmothoracida, Acinetactis and new heliomonad family Heliomorphidae (new genus Heliomorpha (=Dimorpha)). Five new species of Limnofila gen. n. (L. mylnikovi; L. anglica; L. longa; L. oxoniensis; L. borokensis, previously misidentified as Biomyxa (=Gymnophrys) cometa) form a large freshwater clade (new order Limnofilida). Mesofila limnetica gen., sp. n. and Nanofila marina gen., sp. n. group separately in Granofilosea (Cryptofilida ord. n.). In Endomyxa, a new genus of reticulose proteomyxids (Filoreta marina, F. japonica, F. turcica spp. n., F. (=Corallomyxa) tenera comb. n.) forms a clade (Reticulosida) related to Gromiidea/Ascetosporea. Platyreta germanica gen., sp. n. and Arachnula impatiens are related vampyrellids (Aconchulinida) within a large clade beside Phytomyxea. Biomyxidae and Rhizoplasmidae fam. n. remain incertae sedis within Proteomyxidea. Gymnophrydium and Borkovia are revised. The reticulose Corallomyxa are unlike Filoreta and possibly Amoebozoa, not Cercozoa.


BoneSource hydroxyapatite cement: a novel biomaterial for craniofacial skeletal tissue engineering and reconstruction.
BoneSource-hydroxyapatite cement is a new self-setting calcium phosphate cement biomaterial. Its unique and innovative physical chemistry coupled with enhanced biocompatibility make it useful for craniofacial skeletal reconstruction. The general properties and clinical use guidelines are reviewed. The biomaterial and surgical applications offer insight into improved outcomes and potential new uses for hydroxyapatite cement systems.


Synthesis and biological activity of stable and potent antitumor agents, aniline nitrogen mustards linked to 9-anilinoacridines via a urea linkage.
To improve the chemical stability and therapeutic efficacy of N-mustard, a series of phenyl N-mustard linked to DNA-affinic 9-anilinoacridines and acridine via a urea linker were synthesized and evaluated for antitumor studies. The new N-mustard derivatives were prepared by the reaction of 4-bis(2-chloroethyl)aminophenyl isocyanate with a variety of 9-anilinoacridines or 9-aminoacridine. The antitumor studies revealed that these agents exhibited potent cytotoxicity in vitro without cross-resistance to taxol or vinblastine and showed potent antitumor therapeutic efficacy in nude mice against human tumor xenografts. It also showed that 24d was capable of inducing marked dose-dependent levels of DNA cross-linking by comet assay and has long half-life in rat plasma.


Active site structure and antigen binding properties of idiotypically cross-reactive anti-fluorescein monoclonal antibodies.
This report includes complete VH and V kappa nucleotide and deduced amino acid sequences of idiotypically cross-reactive monoclonal anti-fluorescein antibodies that differed greater than 10(5)-fold in affinity. High affinity monoclonal antibody 4-4-20 and intermediate affinity antibodies 10-25, 5-14, 9-40, 12-40, and 3-24 utilized greater than or equal to 90% homologous VHIIIC germ-line genes. Extensive D segment length and sequence variability were observed; however, compensatory germ-line JH4 (4-4-20 and 3-24) or JH3 (10-25, 5-14, 9-40, and 12-40) sequence lengths resulted in H chain CDR3 + FR4 to be a constant 18 amino acids. In addition, each antibody and low affinity 3-13 rearranged greater than or equal to 96% homologous V kappa II genes to J kappa 1, except for 10-25 (J kappa 5) and 3-13 (J kappa 4). Resolved crystal structure of complexed fluorescein and 4-4-20 Fab fragments revealed residues HisL27d, TyrL32, ArgL34, SerL91, TrpL96, and TrpH33 acted as hapten contact residues. Antibodies 5-14, 9-40, 12-40, and 3-24 primary structures possessed identical contact residues as 4-4-20 except for the substitution of HisL34 for ArgL34. Thus, ArgL34 was implicated in the increased affinity of monoclonal antibody 4-4-20. Finally, it was difficult to correlate extensive H chain CDR3 residue heterogeneity directly with fluorescein binding and idiotypy.


Craniofacial morphology in untreated shunt-treated hydrocephalic children.
Craniofacial morphology was studied in 45 shunt-treated hydrocephalic children and 7 untreated hydrocephalic patients. A sample of 74 normal children from northern Finland were used as controls. Following shunt treatment the sella turcica became shallow and J-shaped. The cranial base angles changed markedly during shunt treatment. The cranial base angles were more obtuse in untreated patients than in control subjects, whereas the opposite was the case in shunt treated patients. The Nasion-Sella-Basion angle was 143.4 degrees in untreated hydrocephalic patients, 132.6 degrees in normal subjects and 127.9 in shunt-treated hydrocephalics. The changes in cranial base angles appeared to be progressive during a two-year follow-up period.


The proliferative state, graft-site and contact-time of competent chick ectoblast determine the quality and quantity of neural induction by Hensen's node.
We have assessed the type and amount of neural tissue induced in the chick gastrula ectoblast with increasing duration of contact with the Hensen node inducer. At least 4 h contact is necessary to induce the ectoblast in the area pellucida, 9 h in the area opaca and even longer at the margin of overgrowth. In the area pellucida, the inductive response shifts from archencephalic type at 4-6 h contact to deuterencephalic type after 9 h contact. The induced tissue volume and cell number increased as graft-host contact increased from 4-9 h, and then decreased with longer contact. We suggest that in addition to the period of contact and the grafting position on competent ectoblast, the rate of cell proliferation may control the axial specificity and morphological organization of the induced neural tissue.


Transplant Immunobiology: Many Answers Raising Even More Questions.
Immunologic complications following organ, cell, or tissue transplantation still raise significant challenges related to their diagnosis and treatment [...].


Functional upregulation of system xc- by fibroblast growth factor-2.
The cystine/glutamate antiporter (system xc-) is a Na(+)-independent amino acid transport system. Disruption of this system may lead to multiple effects in the CNS including decreased cellular glutathione. Since multiple neurological diseases involve glutathione depletion, and disruption of growth factor signaling has also been implicated in these diseases, it is possible that some growth factors effects are mediated by regulation of system xc-. We tested the growth factors fibroblast growth factor-2 (FGF-2), insulin-like growth factor-1 (IGF-1), neuregulin-1 (NRG), neurotrophin-4 (NT-4), and brain derived neurotrophic factor (BDNF) on system xc- mediated 14C-cystine uptake in mixed neuronal and glial cortical cultures. Only FGF-2 significantly increased cystine uptake. The effect was observed in astrocyte-enriched cultures, but not in cultures of neurons or microglia. The increase was blocked by the system xc- inhibitor (s)-4-carboxyphenylglycine, required at least 12 h FGF-2 treatment, and was prevented by the protein synthesis inhibitor cycloheximide. Kinetic analysis indicated FGF-2 treatment increased the V(max) for cystine uptake while the K(m) remained the same. Quantitative PCR showed an increase in mRNA for xCT, the functional subunit of system xc-, beginning at 3 h of FGF-2 treatment, with a dramatic increase after 12 h. Blocking FGFR1 with PD 166866 blocked the FGF-2 effect. Treatment with a PI3-kinase inhibitor (LY-294002) or a MEK/ERK inhibitor (U0126) for 1 h prior to and during the FGF-2 treatment, each partially blocked the increased cystine uptake. The upregulation of system xc- by FGF-2 may be responsible for some of the known physiological actions of FGF-2. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.


Reducing suicides through an alliance against depression?
Since 2003, the Regensburg Alliance Against Depression, the regional partner of the German Alliance Against Depression, has been conducting a four-level intervention program to improve early detection and treatment of patients with depression, which was successfully piloted in the framework of the German Research Network on Depression and Suicidality. After 5 years of campaign, the suicide rates before and after the intervention were evaluated in comparison with two control regions and with the German overall rate. The results show that only the suicide rate in Regensburg fell significantly during the intervention period. The drop in the suicide rate was due to a significant decrease in male suicides. An intensive community-based campaign could be effective in lowering suicide rates. Especially, the combination of continuing medical educations (CMEs) for general practitioners focusing on 'male depression' and low-threshold campaigns for the general public seems to reach male depressive patients.


A novel lectin from the wild mushroom Polyporus adusta.
A lectin with antiproliferative activity toward tumor cell lines and mitogenic activity toward splenocytes was isolated from the mushroom Polyporus adusta. The lectin was composed of two identical subunits each with a molecular weight of 12 kDa. It was adsorbed on both DEAE-cellulose and Q-Sepharose and unadsorbed on CM-Sepharose. The hemagglutinating activity of the lectin was inhibited by turanose and by a large variety of other carbohydrates. It was adversely affected in the presence of NaOH or HCl at a concentration of 7.5mM and above, and when the ambient temperature was raised above 70 degrees C. All divalent and trivalent metallic chlorides tested at 1.25-10mM including CaCl(2), MgCl(2), ZnCl(2), MnCl(2), and AlCl(3), did not alter the hemagglutinating activity of the lectin. FeCl(3) at 10mM caused the hemagglutinating activity to increase by 100%, but it did not change the lectin activity when tested at lower concentrations up to 5mM.


New modality of collapse therapy for pulmonary tuberculosis sequels: tissue expander.
Classical collapse therapy with extrapleural Lucite balls placement used for tuberculosis sequelae is associated with long term complications, such as migration of the foreign body. We report a new modality of collapse therapy for tuberculosis cavitation which may avoid this complication and which uses percutaneous tissue expanders. Postoperative course was uneventful and mid term follow-up confirmed the functional improvement without recurrence of the infection. This new modality of post-tuberculosis collapse therapy may allow treatment with fewer physical and physiologic sequelae of the residual cavities, and should reduce long term complications such as migration.


Combination of WFDC2, CHI3L1, and KRT19 in Plasma Defines a Clinically Useful Molecular Phenotype Associated with Prognosis in Critically Ill COVID-19 Patients.
COVID-19 is now a common disease, but its pathogenesis remains unknown. Blood circulating proteins reflect host defenses against COVID-19. We investigated whether evaluation of longitudinal blood proteomics for COVID-19 and merging with clinical information would allow elucidation of its pathogenesis and develop a useful clinical phenotype. To achieve the first goal (determining key proteins), we derived plasma proteins related to disease severity by using a first discovery cohort. We then assessed the association of the derived proteins with clinical outcome in a second discovery cohort. Finally, the candidates were validated by enzyme-linked immunosorbent assay in a validation cohort to determine key proteins. For the second goal (understanding the associations of the clinical phenotypes with 28-day mortality and clinical outcome), we assessed the associations between clinical phenotypes derived by latent cluster analysis with the key proteins and 28-day mortality and clinical outcome. We identified four key proteins (WFDC2, GDF15, CHI3L1, and KRT19) involved in critical pathogenesis from the three different cohorts. These key proteins were related to the function of cell adhesion and not immune response. Considering the multicollinearity, three clinical phenotypes based on WFDC2, CHI3L1, and KRT19 were identified that were associated with mortality and clinical outcome. The use of these easily measured key proteins offered new insight into the pathogenesis of COVID-19 and could be useful in a potential clinical application.


Treatment of post-menopausal hypercholesterolaemia with estradiol.
Replacement therapy with estradiol valerate in 29 post-menopausal women reduced low-density lipoprotein (LDL) cholesterol concentrations by 22% and increased high-density lipoprotein (HDL) cholesterol by 21% after 12 months. Apart from a 67% increase of HDL-triglyceride estradiol had only a slight effect on the levels of lipoprotein triglycerides. Post-heparin plasma lipoprotein lipase (LPL) activity was significantly decreased in subjects with normal pre-treatment very-low-density lipoprotein (VLDL) triglyceride levels, and hepatic lipase (HL) activity was significantly decreased in the group as a whole. It is suggested that estradiol replacement therapy should be considered in climacteric women with high LDL-cholesterol or low HDL-cholesterol levels, or both.


Quantitative Diffusion and Spectroscopic Neuroimaging Combined with a Novel Early-Developmental Assessment Improves Models for 1-Year Developmental Outcomes.
Preterm infants are at risk for overt and silent CNS injury, with developmental consequences that are difficult to predict. The novel Specific Test of Early Infant Motor Performance, administered in preterm infants at term age, is indicative of later developmental gross motor and cognitive scores at 12 months. Here, we assessed whether functional performance on this early assessment correlates with CNS integrity via MR spectroscopy or diffusional kurtosis imaging and whether these quantitative neuroimaging methods improve predictions for future 12-month developmental scores. MR spectroscopy and quantitative diffusion MR imaging data were acquired in preterm infants (n = 16) at term. Testing was performed at term and 3 months using the Specific Test of Early Infant Motor Performance and the Bayley Scales of Infant and Toddler Development, Third Edition, at 12 months. We modeled the relationship of MR spectroscopy and diffusion MR imaging data with both test scores via multiple linear regression. MR spectroscopy NAA ratios at a TE of 270 ms in the frontal WM and basal ganglia and kurtosis metrics in major WM tracts correlated strongly with total Specific Test of Early Infant Motor Performance scores. The addition of MR spectroscopy and diffusion separately improved the functional predictions of 12-month outcomes. Microstructural integrity of the major WM tracts and metabolism in the basal ganglia and frontal WM strongly correlate with early developmental performance, suggesting that the Specific Test of Early Infant Motor Performance reflects CNS integrity after preterm birth. This study demonstrates that combining quantitative neuroimaging and early functional movement improves the prediction of 12-month outcomes in premature infants.


[Management of cancer-related fatigue].
Cancer-related fatigue is very common but its management remains frustrating. We thus sought to review current knowledge in this field: epidemiologic data, pathophysiological mechanisms, assessment, and treatment. We queried the Medline database for all articles on this topic published between 1997 and 2007 and analyzed the articles published in English and French, as well as some of the essential earlier work. Approximately 60 to 96% of patients treated for cancer report fatigue. The prevalence of fatigue that persists after the disease is considered to be in remission is substantial. Fatigue is a multidimensional problem with biological, psychological, social, and personal aspects. Physical causes must be systematically considered (comorbidities, anemia, and endocrine disorders), but most cases remain unresolved. Many may be attributed to deconditioning. There is not now any pharmacological therapy that treats this symptom effectively. Some psychostimulants are being tested, but the initial results of the studies are contradictory. Exercise is the intervention for which there is the most evidence of effectiveness. Cancer-related fatigue is a very common symptom for which no specific cause can usually be identified. In this situation, rest may be more harmful than exercise.


Occurrence of ACTH- and enkephalin-like peptides in the developing gut of Dicentrarchus labrax L.
We carried out immunohistochemical tests in the developing gut of the sea bass Dicentrarchus labrax to follow the appearance and distribution of the immunoreactivity (IR) to antibodies against POMC-derived, adrenocorticotropic hormone (ACTH), alpha-melanocyte stimulating hormone (alpha-MSH) and beta-endorphin (beta-End), and against two enkephalins, with the aim to study a possible involvement of these molecules in the early neuro-immune-endocrine integration. Our data show that IR to antibodies against some molecules involved in the stress response, such as ACTH and enkephalins, are present in the sea bass gut from an early larval stage (4 days after hatching), before transition to the exotrophic feeding. Moreover, the present study demonstrates for the first time the presence of ACTH-like immunoreactive material in developing gut of a fish. The possible roles of tested molecules are discussed.


What do losses in selenium and arsenic bioavailability signify for health?
Levels of As and Se in human foods and animal feeds respectively have decreased in recent years as a result of official limits and other factors. The reduction of SeO2 by SO2 to Se0 results in less bioavailability in the food cycle. Acid rain further reduces the pH of Se-depleted soils and soluble forms of Se are bound by metal ions in fallout from burning of fossil fuels. However, there is evidence that Se and As act as essential nutrients with anticancer value. The need for As in nutrition was shown by three laboratories in four mammalian species. Selenium inadequacies among people, as well as animals, are being recognized worldwide in the form of Se-responsive diseases. Reported data indicate that we have yet to learn the optimal intake levels for Se or As and how their decreased bioavailabilities affect human health.


The influence of authentic leadership on nurses' turnover intentions and satisfaction with quality of care in Saudi Arabia: A structural equation modelling study.
The study aimed to test a model that examined the relationships between authentic leadership, psychological safety, work engagement and team effectiveness and subsequent effects of team effectiveness on job turnover intentions and nurse satisfaction with quality of care. Nurse leaders who exhibit authentic leadership have been shown to contribute to the development of healthy work environments. In workplaces with demonstrated authentic leadership, nurses are more engaged and have lower job turnover intentions. A non-experimental, cross-sectional design was used to test the hypothesized model via structural equation modelling. A total of 456 nurses were included. Structural equation modelling analysis indicated a good fit for the hypothesized model. Authentic leadership had a positive, significant and direct relationship with team effectiveness, nurses' work engagement and psychological safety. Team effectiveness was found to be negatively related to job turnover intentions but positively related to nurse satisfaction with quality of care. Results of this study may help nursing leaders have a better understanding of the essential role of leadership style in increasing healthy work environments. Applying authentic leadership style in nursing practice could help to reduce the shortage of nurses stemming from the high turnover intentions of nurses.


Acute stress of the typical disinfectant glutaraldehyde-didecyldimethylammonium bromide (GD) on sludge microecology in livestock wastewater treatment plants: Effect and its mechanisms.
Glutaraldehyde and didecyldimethylammonium bromide (GD) is a disinfectant widely used to prevent African swine fever (ASF) in livestock farms. However, the effect of residual GD on the activated sludge microbial ecology of receiving wastewater treatment plants (WWTPs) remains largely unknown. In this study, seven simulated systems were established to research the effects of GD on WWTPs and reveal the underlying mechanisms of microecological responses to GD at different concentrations. Both the nitrogen and carbon removal rates decreased with increasing GD concentrations, and nitrogen metabolism was inhibited more obviously, but the inhibition weakened with increasing stress duration. Microorganisms activated their SoxRS systems to promote ATP synthesis and electron transfer to support the hydrolysis and efflux of GD by producing a small number of ROS when exposed to GD at less than 1 mg/L. The overproduction of ROS led to a decrease of antioxidant and nitrogen removal enzyme activities, and upregulation of the porin gene increased the risk of GD entering the intracellular space upon exposure to GD at concentrations higher than 1 mg/L. Some denitrifiers survived via resistance and their basic capabilities of sugar metabolism and nitrogen assimilation. Notably, low concentrations of disinfectants could promote vertical and horizontal transfer of multiple resistance genes, especially aminoglycosides, among microorganisms, which might increase not only the adaptation capability of denitrifiers but also the risk to ecological systems. Therefore, the risks of disinfectants targeting ASF on ecology and health as well as the effects of disinfectant residuals from the COVID-19 epidemic should receive more attention.


The importance of defining 'data' in data management policies: Commentary on: "Issues in data management".
What comprises 'data' varies from one institution to another based on the information which is deemed important by individual institutions. To effectively and efficiently produce, collect, and retain data, an organization develops specific defining characteristics of data to meet its informational needs. Procedures to maintain and retain knowledge among laboratory members and principal investigators will allow for improved efficiency of data collection. Optimization of communication, maintenance of inventories, record keeping, and updating relevant training programs are all critical to supporting the quality and integrity of a particular organization's data. Concurrent revisions to such procedures will ensure that the definition of data as well as the means by which it is collected and maintained remain appropriate to the needs of the individual organization.


Strategy for the Analysis and Visualization of Electronic Medical Record Data for Public Hospitals in the City of Buenos Aires.
Through the development of a dashboard with participative methodology we present a centralized strategy to analyze and visualize EMRs data for the management of 15 public hospitals from Buenos Aires City. This approach could constitute an efficient option for public health systems from developing countries.


Almost invisible: A review of inclusion of LGBTQI people with cancer in online patient information resources.
This review assessed the inclusion of lesbian, gay, bisexual, trans, queer and/or intersex (LGBTQI) people in online cancer information. The websites of Australian cancer organizations were reviewed to identify if they included LGBTQI people and the extent and nature of this inclusion. Websites that did not include LGBTQI people were then reviewed to identify if information was implicitly LGBTQI inclusive. International LGBTQI cancer information resources were reviewed to identify key content. Of sixty-one Australian cancer organization websites reviewed, eight (13%) mentioned LGBTQI people, including 13 information resources targeted to LGBTQI people and 19 general cancer information resources that mentioned LGBTQI people. For Australian cancer websites that did not mention LGBTQI people, 88% used gender neutral language to refer to partners, 69% included a range of sexual behaviours, 13% used gender neutral language when referring to hormones or reproductive anatomy but none acknowledged diverse relationship types. Internationally, 38 LGBTQI-specific cancer information resources were identified. Cancer patient information resources need to be LGBTQI inclusive. LGBTQI-targeted resources are required to address this population's unique needs and improve cultural safety and cancer outcomes. Recommendations are provided for LGBTQI inclusive cancer patient information resources.


Different types of nutritional deficiencies affect different domains of spatial memory function checked in a radial arm maze.
Several studies using animal models have suggested that the effects of nutritional insult on the developing brain are long-lasting and lead to permanent deficits in learning and behavior. Malnutrition can refer to the availability of all the nutrients but in insufficient quantities or it may imply that one or more of essential nutrients is either missing or is present, but in the wrong proportions in the diet. The hypothesis addressed in this study is that different domains of cognitive functioning can be affected by malnutrition and this can be related to the type of nutritional deficiency that the brain has been exposed to during development. To study the effect of nutritional deprivation during brain development, a paradigm of maternal malnutrition during the period of gestation and lactation was used and its effects were studied on the F1 offspring using Swiss albino mice. Three different types of malnutrition were used, that involve, caloric restriction, inadequate amount of protein in the diet and condition of low iron content. Our results show that the domain of spatial memory affected in the F1 generation depended on the kind of malnutrition that the mother was subjected to. Further our study shows that although hippocampal volume was reduced in all F1 pups, hippocampal subregions of the F1 animals were differentially vulnerable depending on type of malnutrition that the mother was subjected to. These results highlight the importance of qualifying the kind of malnutrition that is suffered by the mother during the period of gestation and lactation as it has consequences for the cognitive domain affected in the offspring. Awareness of this should inform prevention strategies in trying to reverse the effects of adverse maternal nutrition during critical periods in brain development.


Cardiorespiratory Responses to Pool Floor Walking in People Poststroke.
To compare cardiorespiratory responses between pool floor walking and overground walking (OW) in people poststroke. Cross-sectional study. University-based therapeutic exercise facility. Participants (N=28) were comprised of 14 community-dwelling individuals poststroke (5.57±3.57y poststroke) and 14 age- and sex-matched healthy adults (mean age, 58.00±15.51y; male/female ratio, 9:5). Not applicable. A telemetric metabolic system was used to collect cardiorespiratory variables, including oxygen consumption (V˙o2), energy expenditure (EE), and expired volume per unit time (V˙e), during 6-minute walking sessions in chest-depth water and on land at a matched speed, determined by average of maximum walking speed in water. Individuals poststroke elicited no significant differences in cardiorespiratory responses between pool floor walking and OW. However, healthy controls showed significant increases in mean V˙o2 values by 94%, EE values by 109%, and V˙e values by 94% (all P<.05) during pool floor walking compared with OW. A 2×2 mixed model analysis of variance revealed a significant group × condition interaction in V˙o2, in which the control group increased V˙o2 from OW to pool floor walking, whereas the stroke group did not. Our results indicate that people poststroke, unlike healthy adults, do not increase EE while walking in water compared with on land. Unlike stationary walking on an aquatic treadmill, forward locomotion during pool floor walking at faster speeds may have increased drag force, which requires greater EE from healthy adults. Without demanding excessive EE, walking in water may offer a naturally supportive environment for gait training in the early stages of rehabilitation.


Teleguidance for Patient Self-Imaging of Hemophilic Joints Using Mobile Ultrasound Devices: A Pilot Study.
Teleguidance on portable devices opens the possibility of joint self-imaging in persons with hemophilia (PWH). Determine the feasibility of patient self-imaging with/without teleguidance. Adult PWH received ultrasound teaching including 11 views for hemarthrosis detection in ankles, elbows, and knees. The patients acquired five randomly selected views with the Butterfly/IQ probe without assistance at 2, 6-8 weeks, and 3-4 months later, followed by teleguidance. Image acquisition was timed, patients identified anatomic landmarks, and image quality was graded. Questionnaires assessed the imaging experience. Hemophilia Joint Health Score (HJHS) indicated arthropathy status. Of 132 PWH, 10 (median age 52 years) opted for study inclusion. Most had severe Hemophilia A, were white/non-Hispanic, with at least a high school degree and, overall, similar to the other 122 PWH. At 2 and 6 weeks after training, ~80% images were acquired correctly compared with 53% at 12 weeks. Accuracy of landmark recognition was ~55%. With teleguidance, all images were acquired correctly, with near-perfect image quality (P ≤ .01 compared with the 3-4 month time point). Median HJHS of scanned joints was 11.5 at each time point, demonstrating a similar spectrum of arthropathic changes. Median time of image acquisition was fast, and similar with or without teleguidance (median 01:04 [mm:ss] vs median 01:02), but differed slightly between arthropathic and non-arthropathic joints. Study participants and the imaging facilitator rated that it was easy to navigate mobile technology and acquire images with teleguidance. Mobile ultrasound with teleguidance for joint self-imaging is feasible and warrants further exploration.


Actin microfilaments are involved in the regulation of HVA1 transcript accumulation in drought-treated barley leaves.
Drought is one of the stresses that limit the yield of barley. Despite extensive studies focused on the issue, the molecular mechanism of the response to drought is still not fully understood. In our previous study, we proposed drought-induced signal perception controlled by actin filaments (AFs). To test this hypothesis, we used a chemical inhibitor of AF polarization-latrunculin B. In drought-treated barley leaves, latrunculin B induced AF depolymerization and altered gene expression (mainly those controlling AF formation), notably inhibiting the expression of HVA1, a dehydrin encoding gene whose function in drought tolerance has been widely studied. These results suggest that AFs might be involved in water-deficit signal perception in plant cells.


Effect of turpentine-induced inflammation on the disposition kinetics of propranolol, metoprolol, and antipyrine in the rat.
Plasma concentrations after oral administration of the high extraction drug propranolol are increased in patients and animals with inflammation. This could be due to increased serum propranolol binding, but also to decreased first-pass metabolism. We studied the pharmacokinetics of 3 drugs in control rats and in rats with turpentine-induced inflammation: propranolol, which is bound extensively to alpha 1-acid glycoprotein (alpha 1-AGP); metoprolol, another high extraction drug, but which is negligibly bound to alpha 1-AGP; and antipyrine, a low extraction drug, not bound to serum proteins. After IV administration of propranolol in rats with inflammation, systemic clearance, volume of distribution, and free fraction decreased, and the area under the curve (AUC) increased, whereas the half-life did not change. As the systemic clearance of a high extraction drug such as propranolol depends on hepatic blood flow only, a fall in hepatic blood flow or transition to a low extraction situation should be postulated. After oral administration of propranolol, the AUC was increased 20-fold in rats with inflammation; as the decrease in free fraction was only 4-fold, it can be concluded that a considerable decrease in hepatic intrinsic clearance was present. For metoprolol, in contrast to propranolol, after IV administration, no changes in pharmacokinetic parameters as a result of inflammation were observed. After oral administration, the AUC was increased about 4 times in rats with inflammation; as metoprolol is only negligibly bound to serum proteins, the increase in AUC can be attributed to a decrease in hepatic intrinsic clearance.(ABSTRACT TRUNCATED AT 250 WORDS)


Role of interstitial cell migration in generating position-dependent patterns of nerve cell differentiation in Hydra.
The role of interstitial cell migration in the formation of newly differentiated nerve cells was examined during head regeneration in Hydra magnipapillata. When distal tissue was removed from the body of a wild-type strain (105), nerve cell differentiation occurred at a rapid rate during the first 48 hr of regeneration, slowing after this point. Rapid nerve cell differentiation was due primarily to migration of interstitial cells, some of which appeared to be nerve cell precursors, into the regenerating head. The migration decreased considerably after the first 48 hr of regeneration. In reg-16, a mutant strain deficient in head regeneration, no migration of interstitial cells and hence no new nerve cell differentiation were observed in the regenerating tip. However, the interstitial cells of reg-16 were observed to migrate into regenerating tissue of strain 105. These observations suggest that the migration of nerve cell precursors plays an important role when the new nerve net is being established during head regeneration.


Chemometric studies of lysozyme upon interaction with sodium dodecyl sulfate and beta-cyclodextrin.
The interaction of hen egg-white lysozyme with sodium n-dodecyl sulfate (SDS) as an anionic surfactant was investigated by UV-vis spectrophotometry at different pHs at 25 degrees C using HCl/glycine and NaOH/glycine for acidic and basic pH ranges, respectively. Analysis of the spectral data using chemometric method gave the evidence for the existence of intermediate components during the cited interaction. Results also indicated a connection between turbidity of the protein solution upon interaction with SDS and distribution of our newly found intermediates. As intermediates are important in aggregation of proteins, beta-cyclodextrin was employed as an anti-aggregation agent and the results obtained for the lysozyme-SDS-beta-cyclodextrin ternary system were compared with those obtained in the absence of beta-cyclodextrin on distribution and mole fraction of intermediates with. It is also shown that as the distribution of intermediates broadens in a range of SDS concentrations, the turbidity and aggregation state of solution are reduced.


Molecular characterization of two CuZn-SOD family proteins in the Pacific oyster Crassostrea gigas.
Superoxide dismutases (SOD) are multifamily antioxidant enzymes, playing an important role in the defense against oxidative stress in all organisms. Genomic information indicated the presence of genetic diversification of the copper and zinc SOD (CuZn-SOD) family in oysters. In the present research, we characterized two CuZn-SOD family proteins, Cg-CuZn-SOD and Cg-dominin3, in the Pacific oyster Crassostrea gigas using comprehensive sequence analyses, recombinant proteins and site-directed mutagenesis, and observations of gene expression in larval and adult oysters. We found that Cg-CuZn-SOD possessed sequence and structural elements conserved in a CuZn-SOD molecule and the recombinant protein was confirmed empirically to have the SOD enzyme activity. In contrast, Cg-dominin3 lacked five of the seven residues essential for the conformation of SOD active center and the recombinant protein did not have the enzyme activity. However, recombinant Cg-dominin3 showed strong binding activities toward zinc and copper ions. Substitutions of five conserved His residues in the active center demolished the SOD activity but enhanced the metal binding capacity in Cg-CuZn-SOD. On the other hand, reinstallation of the five His residues that were assumed to be activity essential and lost in evolution did not restore the SOD enzyme activity in Cg-dominin3. Additionally, the coding genes of the two proteins exhibited different patterns of expression during larval development and in adult oyster in response to zinc challenges. These results have led to the discovery of the first cytoplasmic CuZn-SOD molecule and the confirmation of molecular diversification of extracellular CuZn-SOD homologs in oysters.


Influences of root distribution and growth on predicted water uptake and interspecific competition.
Root distribution and growth measured in the field were incorporated into a water uptake model for the CAM succulent Agave deserti and its nurse plant Hilaria rigida, a common desert bunchgrass. Agave deserti responds to the infrequent rainfalls of the Sonoran Desert by extending its existing established roots and by producing new roots. Most of such root growth was completed within one month after soil rewetting, total root length of A. deserti increasing by 84% for a seedling and by 58% for a mediumsized plant in the summer. Root growth in the winter with its lower soil temperatures was approximately half as much as in the summer. For a 15-year period, predicted annual root growth of A. deserti varied more than 18-fold because of annual variations in rainfall amount and pattern as well as seasonal variation in soil temperature. Predicted annual water uptake varied 47-fold over the same period. The nurse plant, which is crucial for establishment of A. deserti seedlings, reduced seedling water uptake by 38% during an average rainfall year. Lowering the location of the root system of a medium-sized A. deserti by 0.24 m reduced its simulated annual water uptake by about 25%, reflecting the importance of shallow roots for this desert succulent. Lowering the root system of a medium-sized H. rigida by 0.28 m increased the simulated annual water uptake of an associated A. deserti seedling by 17%, further indicating the influence of root overlap on competition for water.


Preparation, drug release and cellular uptake of doxorubicin-loaded dextran-b-poly(ɛ-caprolactone) nanoparticles.
Amphiphilic dextran-b-poly(ɛ-caprolactone) diblock copolymers were synthesized with the purpose of preparing nanocarriers for doxorubicin (DOX), an anticancer drug. The Dex-b-PCL diblock copolymers were synthesized by end-to-end coupling of amino-terminated dextran and aldehyde-terminated poly(ɛ-caprolactone) and characterized by (1)H NMR spectra and gel permeation chromatography. The DOX-loaded Dex-b-PCL nanoparticles were prepared by a modified nanoprecipitation method and characterized by transmission electron microscopy and dynamic light scattering. In vitro release of DOX from DOX-Dex-b-PCL nanoparticles showed a sustained release manner with certain amount of burst release in the first 9h. In vitro cytotoxicity test of DOX-Dex-b-PCL nanoparticles against SH-SY5Y cells showed that DOX is still pharmacologically active after drug loading. The fluorescence imaging results showed that DOX-Dex-b-PCL nanoparticles could be easily uptaken by SH-SY5Y cells. These results indicate that DOX-Dex-b-PCL nanoparticles may be a promising nanocarrier for DOX.


Catalase and glutathione peroxidase mimics.
Overproduction of the reactive oxygen species (ROS) superoxide (O(2)(-)) and hydrogen peroxide (H(2)O(2)) are increasingly implicated in human disease and aging. ROS are also being explored as important modulating agents in a number of cell signaling pathways. Earlier work has focused on development of small catalytic scavengers of O(2)(-), commonly referred to as superoxide dismutase (SOD) mimetics. Many of these compounds also have substantial abilities to catalytically scavenge H(2)O(2) and peroxynitrite (ONOO(-)). Peroxides have been increasingly shown to disrupt cell signaling cascades associated with excessive inflammation associated with a wide variety of human diseases. Early studies with enzymatic scavengers like SOD frequently reported little or no beneficial effect in biologic models unless SOD was combined with catalase or a peroxidase. Increasing attention has been devoted to developing catalase or peroxidase mimetics as a way to treat overt inflammation associated with the pathophysiology of many human disorders. This review will focus on recent development of catalytic scavengers of peroxides and their potential use as therapeutic agents for pulmonary, cardiovascular, neurodegenerative and inflammatory disorders.


Asthma History, Current Situation, an Overview of Its Control History, Challenges, and Ongoing Management Programs: An Updated Review.
Asthma is a disease of the airways that is characterized by chronic inflammation and disordered airway function. The purpose of writing the current review paper is to review the history, current situation, control history, challenges, and ongoing management programs of asthma. Some official websites of known respiratory professional bodies were consulted for asthma guidelines, and information from Google Scholar® and PubMed® was also consulted. We reviewed around two hundred eight papers, and then, inclusion and exclusion criteria were applied to prepare this manuscript. Out of these papers, thirty papers, factsheets, and some official websites were used to prepare this manuscript. Physicians should follow already existing asthma guidelines in order to manage asthma. All prescribed medications should be continued. The government should make and adopt more strategies to promote the rational use of anti-asthmatic drugs and healthcare facilities and also make plans to disseminate more awareness among people about the schemes and programs made for safeguarding people against this life-threatening disease. We have done so much advancement to fight against this deadly disease, and we still need time to make the globe asthma-free. The number of people suffering from asthma is more than the number of people suffering from HIV infection and tuberculosis. Understanding the recommendations of professional bodies will assist in medical decision-making in asthma management. The individual needs of patients should be considered by healthcare professionals.


Management of esophageal foreign bodies: experience in a developing country.
The outcome of esophagoscopy for removal of suspected esophageal foreign bodies (EFBs) is dependent on the FB characteristics and the surgeon's experience. This study was conducted to review our experience and highlight challenges in the management of EFBs in a developing country. The value of radiologic signs in FB detection was also evaluated. We conducted a retrospective chart review of 131 patients: 58.8% males and 41.9% females aged 8 months to 64 years, treated for suspected EFBs in our institution over a 13-year period. Statistics were derived by univariate analysis Foreign bodies were found and retrieved in 118 cases. Coins were the predominant FB in children (35%), and bones (25%) and dentures (17%) were predominant in adults. Plain radiography was highly useful in detecting FBs in children (coins/metals 100%) but less so in adults (bones 25%, dentures 11%). Repeated esophagoscopy attempts were encountered more in patients with impacted sharp objects (85%) and were recorded significantly among trainee surgeons (p = 0.004). Open esophagotomy was carried out in 13 (10%) difficult cases. Major complications including two iatrogenic esophageal perforations and one death occurred following esophagoscopy by trainee surgeons. Rigid esophagoscopy is relatively safe and useful procedure in trained hands for removal of EFBs. Management of long-standing EFBs, dentures, and other sharp objects requires the skills of the most experienced members of the surgical team for a successful outcome. Open surgical treatment is unavoidable in cases of irretrievable esophageal FBs or in the presence of esophageal perforation.


Phosphorus-31 magnetic resonance spectroscopy of the human liver using chemical shift imaging techniques.
Phosphorus-31 magnetic resonance spectroscopy of the human liver was undertaken in 28 healthy adult individuals and in 49 patients with liver disease of varying aetiology. Data localised to the liver were obtained using chemical shift imaging techniques. The mean (+/- 1 S.D.) of the peak area ratio phosphomonoesters (PME)/phosphodiesters (PDE) in healthy adult individuals, from spectra obtained with pulse angle 45 degrees and repetition time 1 s, was 0.24 +/- 0.07. The intra-examination variability of this ratio was 20%, the intra-subject variability 27% and the inter-subject variability 32%. An increase in the PME/PDE was observed in the 31P hepatic MR spectrum from primary or secondary tumours in all 17 patients studied, which invariably represented an increase in PME/ATP and, in some cases, a reduction in PDE/ATP. The spectra did not show aetiological characteristics. A non-specific elevation in PME/PDE was also observed in the 31P hepatic MR spectra of 10 (40%) of 25 patients studied who had diffuse liver diseases, such as cirrhosis and infiltrating malignancies. The spectral pattern did not distinguish between diseases of varying aetiologies, but there was a linear correlation between increasing PME/PDE and a reduction in plasma albumin concentrations (p = 0.03). In three patients with hepatic malignancy and abnormal hepatic 31P-MRS, marked spectral changes were observed after successful treatment to debulk the tumour. Only minor changes were observed in the abnormal spectrum of a fourth patient in whom treatment was unsuccessful. Hepatic 31P-MR spectroscopy may prove useful for monitoring disease processes and treatment effects in well characterised patient populations.


In situ experimental measurement of mercury by combining PGNAA and characteristic X-ray fluorescence.
In our previous research, a new detection method was proposed to measure Hg and Pb simultaneously by combining Prompt Gamma-ray Neutron Activation Analysis (PGNAA) and X-ray Fluorescence (XRF) and proved by the Monte Carlo N-Particle (MCNP) simulation code. For further experimental verification, a combined measurement experimental facility, comprising an 241Am-Be neutron source, SAINT-GOBAIN Bismuth Germanate (BGO) as the γ-ray detector, and an NaI detector with 25 μm Be window as the X-ray detector, was presented. Specifically, the characteristic X-ray fluorescence of the Hg directly induced in this experimental facility was utilized to improve the limits of detection (LOD) of Hg instead of traditional excitation sources. The simulation and experiment results indicated that LOD for Hg by the combined measurement instrument was 19.4 mg kg-1. The empirical formula of the calibration curve in this method was given based on the aforementioned calculations.


Comparative Effectiveness of Angiotensin-Converting Enzyme Inhibitor-Based Treatment on Cardiovascular Outcomes in Hypertensive Blacks Versus Whites.
Clinical trial evidence suggests poorer outcomes in blacks compared with whites when treated with an angiotensin-converting enzyme (ACE) inhibitor-based regimen, but this has not been evaluated in clinical practice. This study evaluated the comparative effectiveness of an ACE inhibitor-based regimen on a composite outcome of all-cause mortality, stroke, and acute myocardial infarction (AMI) in hypertensive blacks compared with whites. We conducted a retrospective cohort study of 434,646 patients in a municipal health care system. Four exposure groups (Black-ACE, Black-NoACE, White-ACE, White-NoACE) were created based on race and treatment exposure (ACE or NoACE). Risk of the composite outcome and its components was compared across treatment groups and race using weighted Cox proportional hazard models. Our analysis included 59,316 new users of ACE inhibitors, 47% of whom were black. Baseline characteristics were comparable for all groups after inverse probability weighting adjustment. For the composite outcome, the race treatment interaction was significant (p = 0.04); ACE use in blacks was associated with poorer cardiovascular outcomes (ACE vs. NoACE: 8.69% vs. 7.74%; p = 0.05) but not in whites (6.40% vs. 6.74%; p = 0.37). Similarly, the Black-ACE group had higher rates of AMI (0.46% vs. 0.26%; p = 0.04), stroke (2.43% vs. 1.93%; p = 0.05), and congestive heart failure (3.75% vs. 2.25%; p < 0.0001) than the Black-NoACE group. However, the Black-ACE group was no more likely to develop adverse effects than the White-ACE group. ACE inhibitor-based therapy was associated with poorer cardiovascular outcomes in hypertensive blacks but not in whites. These findings confirm clinical trial evidence that hypertensive blacks have poorer outcomes than whites when treated with an ACE inhibitor-based regimen.


Gel-to-inverted hexagonal (L beta-HII) phase transitions in phosphatidylethanolamines and fatty acid-phosphatidylcholine mixtures, demonstrated by 31P-NMR spectroscopy and x-ray diffraction.
The phase behaviour of distearoyl- and dihexadecylphosphatidylethanolamine at high salt concentration and of dipalmitoylphosphatidylcholine + 66 mol% palmitic acid at pH 4.0 have been studied by high-field 31P-NMR spectroscopy and X-ray diffraction. In saturated NaCl, dihexadecylphosphatidylethanolamine undergoes a reversible transition at 74 degrees C directly from the lamellar gel phase L beta to the inverted hexagonal HII phase. A similar transition is observed at 78.4 degrees C for distearoylphosphatidylethanolamine in saturated NaCl (cooling scan). The single, sharp calorimetric transition at 61 degrees C observed in dipalmitoylphosphatidylcholine + 66 mol% palmitic acid at pH 4.0 also corresponds to a transformation directly from the lamellar gel to the inverted hexagonal phase, without an intervening fluid lamellar phase.


Cardiovascular effects of noradrenaline in hypovolemic haemorrhage: role of inducible nitric oxide synthase.
Hypovolemia has been associated with the induction of nitric oxide synthase which is believed to result in an over-production of nitric oxide. In the present study, we have examined the effects of noradrenaline following haemorrhage on cardiac output, blood pressure, mean circulatory filling pressure and vascular resistance in anaesthetized rats after pre-treatment with nitric oxide synthase inhibitor, L-N6-(1-iminoethyl)lysine or dexamethasone. Hypovolemic haemorrhage resulted in induction of nitric oxide synthase, as measured in lungs, and both dexamethasone and L-N6-(1-iminoethyl)lysine inhibited the activity of the inducible form of nitric oxide synthase. An infusion of noradrenaline significantly increased cardiac output, blood pressure and mean circulatory filling pressure in animals pre-treated with L-N6-(1-iminoethyl)lysine and dexamethasone when compared with saline pre-treatment. In addition, the administration of noradrenaline significantly reduced venous resistance in animals pre-treated with L-N6-(1-iminoethyl)lysine when compared with saline pre-treatment. The results of this investigation indicated that the impact of noradrenaline on cardiac output, blood pressure and mean circulatory filling pressure was greater in hypovolemic rats treated with L-N6-(1-iminoethyl)lysine or dexamethasone. In addition, we found that in the hypovolemic state, the greater increase in cardiac output during the infusion of noradrenaline after inhibition of nitric oxide synthase was predominantly due to reduced resistance to venous return.


Nierembergia rivularis poisoning in cattle.
Nierembergia rivularis causes enzootic calcinosis (EC) in sheep. In this work, we describe EC caused by N. rivularis in cattle. For 3 years cattle grazing in 7 paddocks were evaluated. Cows with clinical signs compatible with EC were detected in only one paddock with a morbidity of 9.4%, 24.5%, and 34.5% during the summer of 2019, 2020, and 2021, respectively. Affected cows weighed 55 kg less (p < 0.01) than cows without signs of the same paddock, and 19.6% of these cows had hypercalcemia and/or hyperphosphatemia. Typical soft tissue calcification was observed in 3 autopsied cows. Additionally to the arterial calcification, 2 cows had multiple mineralized foci in several veins. In the Paddock A where EC occurred, the pasture contained 7-12% N. rivularis. In the other 6 paddocks (Paddocks B-G) where EC had not occurred, the pasture had 0.2-3.5% N. rivularis. Cows grazing in Paddock A had ∼30% lower pregnancy rates than cows from Paddocks B-G. At the slaughterhouse, the carcasses of 45 cows from Paddock A weighed 17.6% (p < 0.01) less than 93 carcasses of cows from Paddocks B-G. Furthermore, the carcasses of cows from Paddock A were classified as low quality. Eight cows with EC signs from Paddock A and 10 cows without EC signs from Paddocks B-G were removed to a Lolium multiflorum pasture. After 120 days of grazing, the cows from Paddock A gained 45.2% less (p < 0.01) live weight than cows from Paddocks B-G. Poisoning with N. rivularis may cause significant economic losses in Uruguay due to low fertility rates and weight gain of affected cattle.


Enhancement of human muscle growth in diffusion chambers by bone marrow cells.
Samples of minced human muscle were cultured in millipore diffusion chambers incubated in the peritoneal cavities of mice. In about half the chambers the minced muscle samples were mixed with autogenous bone marrow cells which lead to improved myogenic growth. A similar but less marked effect was produced by mononuclear cells from the patients' blood. No growth enhancement occurred when the muscle and marrow cells were separated by a filter in double chambers. In addition to accelerated myogenesis, the chambers with added bone marrow cells had a much lower incidence of infection. This work may have practical clinical implications for the treatment of muscle injuries. Local implantation of autogenous marrow cells (+/- minced muscle) may prove useful in improving myogenic regeneration.


Methylation of desmethyl analogue of Y nucleosides. Wyosine from guanosine.
Wyosine la, one of the fluorescent hypermodified Y nucleosides found in tRNAsPhe, was synthesized chemically from its biogenetic precursor guanosine 2. The route involved transformation of 2 into the tricyclic structure 3a and subsequent methylation at N-4. The major products of various methylation procedures were isomers of wyosine, methylated at N-5 (3b) or at N-1 (4). Mesoionic compound 4 is a new analogue of 7-methylguanosine 5, modified nucleoside occurring in the unique positions in transfer, messenger and ribosomal RNAs. The chromatographic and spectral characteristics of wyosine and its isomers is given.


Platelet monoamine oxidase activity in panic disorder.
Platelet monoamine oxidase (MAO) activity was studied in 21 patients meeting Research Diagnostic Criteria for panic disorder and in 12 healthy controls. Platelet MAO activity in females in both patient and control groups tended to be higher than that in males, but the results did not reach statistical significance. Platelet MAO activity was significantly decreased in panic disorder patients compared to controls.


Chronic False Aneurysm after a Healed Rupture of the Aortic Isthmus: TEVAR, Hybrid Surgery, or Open Arch Repair?
We report a case of post-traumatic chronic false aneurysm of the aortic isthmus in a 34-year-old man who had been involved in a car accident 10 years earlier. An initial chest X-ray demonstrated a calcified mass in the upper mediastinum and computed tomography scan revealed a false aneurysm of the aortic isthmus arising above the left subclavian artery. Partial covered rupture of the aorta is not always easy to diagnose and can remain clinically silent in a polytrauma patient. The duration from rupture to false aneurysm formation may extend over many years. This chronic lesion can be managed by surgery, by an endovascular procedure, or by a combined procedure. This case report highlights the current therapeutic approach. A debranching procedure was done in view of a secondary exclusion of the huge false aneurysm by a stent graft. Unfortunately, the false aneurysm ruptured during the procedure and a replacement of the aortic arch and the isthmus under total circulatory arrest was successfully done. The patient was doing well at 9-month follow-up.


Comparative outcome analysis of home-initiated non-medical interventions among toddlers with orally ingested substances.
Poison management guidelines recommend contacting or visiting poison centers directly after exposure. However, some parents initiated non-medical interventions on their children before visiting these centers. Aim was to evaluate the clinical and hospital outcomes of such practices among toddlers with orally ingested medication or chemical substances at a tertiary care facility. Retrospective cohort, based on four-arm outcome analysis. Exposures were gender, age, body mass index, arrival time to facility (hours) presented in Median [Interquartile range]. Clinical outcomes were vital signs, physical examination, diagnostic tests; Hospital outcomes were in-hospital admission, length of hospital stay (hours) presented in Median [Interquartile range], hospital cost ($US). Bivariate analysis (nonparametric tests), binary logistic/linear regression were conducted. Significance at p < 0.05. Between 2009-2011, 165 (all previously healthy) toddlers were (Males = 58 %, females = 42 %) and had normal weights in 70 %. Witnessed incidents were in 85 %. Two control groups [Medication (control) = 72, Chemical (control) = 48] directly visited the facility after incident, while two intervention groups [Medication (intervention) = 27, Chemical (intervention) = 18] received orally administered water, salt/sugar solutes, milk/yogurt, lemon juice and/or manually induced vomiting before the visit. Abnormal clinical outcomes in total were in vital signs = 15 %, physical examination = 42 % and diagnostic tests = 26 %; hospital outcomes were admission = 16 %, length of stay range (2 hours-7.5 days), cost range (667-11,500). Bivariate analysis: Length of stay in Medication (intervention) = 9[5.4-12.0] hours significantly higher than Medication (control) = 5[2.7-7.5] hours, p = 0.003; abnormal physical examination in Chemical (intervention) = 77.8 % significantly higher than Chemical (control) = 37.5 %, p = 0.004. In regression: intervention significantly increased length of stay (t = 0.213, adj. P = 0.035); lower weight toddlers were at higher risk of admission (Beta = -0.51, adj. P = 0.018); delayed arrival time significantly increased abnormal physical examination (Beta = 0.29, adj. P = 0.003). No significant control/intervention group differences regarding abnormal vital signs (adj. P = 0.148), physical examination (adj. P = 0.781), diagnostic tests (adj. P = 0.285), admission (adj. P = 0.499), and cost (adj. P = 0.102). Home-initiated non-medical interventions didn't improve the clinical and hospital outcomes. It has delayed the arrival time to emergency department, which added the risk of encountering abnormal physical examination, and in return increased the average length of hospital stay.


In vitro reconstitution of hnRNP particles.
The assembly of hnRNP-like particles was studied by in vitro reconstitution, UV-crosslinking and CsCl-equilibrium centrifugation. Using total nuclear protein and RNA extracts from HeLa cells for RNP reconstitution, RNP particles sedimenting with the same buoyant density of p = 1.4 g/cm3 as 'native' 40 S core hnRNPs were obtained. Under the stringent reconstitution conditions used, hnRNP complexes containing only the Cl-core hnRNP protein could be identified.


Bone Development in Transgender Adolescents Treated With GnRH Analogues and Subsequent Gender-Affirming Hormones.
Hormonal interventions in adolescents with gender dysphoria may have adverse effects, such as reduced bone mineral accrual. To describe bone mass development in adolescents with gender dysphoria treated with gonadotropin-releasing hormone analogues (GnRHa), subsequently combined with gender-affirming hormones. Observational prospective study. 51 transgirls and 70 transboys receiving GnRHa and 36 transgirls and 42 transboys receiving GnRHa and gender-affirming hormones, subdivided into early- and late-pubertal groups. Bone mineral apparent density (BMAD), age- and sex-specific BMAD z-scores, and serum bone markers. At the start of GnRHa treatment, mean areal bone mineral density (aBMD) and BMAD values were within the normal range in all groups. In transgirls, the mean z-scores were well below the population mean. During 2 years of GnRHa treatment, BMAD stabilized or showed a small decrease, whereas z-scores decreased in all groups. During 3 years of combined administration of GnRHa and gender-affirming hormones, a significant increase of BMAD was found. Z-scores normalized in transboys but remained below zero in transgirls. In transgirls and early pubertal transboys, all bone markers decreased during GnRHa treatment. BMAD z-scores decreased during GnRHa treatment and increased during gender-affirming hormone treatment. Transboys had normal z-scores at baseline and at the end of the study. However, transgirls had relatively low z-scores, both at baseline and after 3 years of estrogen treatment. It is currently unclear whether this results in adverse outcomes, such as increased fracture risk, in transgirls as they grow older.


Eye tracking to evaluate evidence recognition in crime scene investigations.
Crime scene analysts are the core of criminal investigations; decisions made at the scene greatly affect the speed of analysis and the quality of conclusions, thereby directly impacting the successful resolution of a case. If an examiner fails to recognize the pertinence of an item on scene, the analyst's theory regarding the crime will be limited. Conversely, unselective evidence collection will most likely include irrelevant material, thus increasing a forensic laboratory's backlog and potentially sending the investigation into an unproductive and costly direction. Therefore, it is critical that analysts recognize and properly evaluate forensic evidence that can assess the relative support of differing hypotheses related to event reconstruction. With this in mind, the aim of this study was to determine if quantitative eye tracking data and qualitative reconstruction accuracy could be used to distinguish investigator expertise. In order to assess this, 32 participants were successfully recruited and categorized as experts or trained novices based on their practical experiences and educational backgrounds. Each volunteer then processed a mock crime scene while wearing a mobile eye tracker, wherein visual fixations, durations, search patterns, and reconstruction accuracy were evaluated. The eye tracking data (dwell time and task percentage on areas of interest or AOIs) were compared using Earth Mover's Distance (EMD) and the Needleman-Wunsch (N-W) algorithm, revealing significant group differences for both search duration (EMD), as well as search sequence (N-W). More specifically, experts exhibited greater dissimilarity in search duration, but greater similarity in search sequences than their novice counterparts. In addition to the quantitative visual assessment of examiner variability, each participant's reconstruction skill was assessed using a 22-point binary scoring system, in which significant group differences were detected as a function of total reconstruction accuracy. This result, coupled with the fact that the study failed to detect a significant difference between the groups when evaluating the total time needed to complete the investigation, indicates that experts are more efficient and effective. Finally, the results presented here provide a basis for continued research in the use of eye trackers to assess expertise in complex and distributed environments, including suggestions for future work, and cautions regarding the degree to which visual attention can infer cognitive understanding.


Counterregulation in type 2 (non-insulin-dependent) diabetes mellitus. Normal endocrine and glycaemic responses, up to ten years after diagnosis.
We have examined hormonal and metabolic responses to insulin-induced hypoglycaemia in 10 Type 2 (non-insulin-dependent) diabetic patients treated with tablets and 10 age, sex and weight matched control subjects. Diabetic patients were under 110% ideal body weight, had no autonomic neuropathy and were well controlled (HbA1, 7.1 +/- 0.2%). After the diabetic patients were kept euglycaemic by an overnight insulin infusion, hypoglycaemia was induced in both groups by intravenous insulin at 30 mU.m-2.min-1 for 60 min and counterregulatory responses measured for 150 min. There were no significant differences between diabetic patients and control subjects in the rate of fall (3.3 +/- 0.3 vs 4.0 +/- 0.3 mmol.l-1.h-1), nadir (2.4 +/- 0.2 vs 2.3 +/- 0.1 mmol/l) and rate of recovery (0.027 +/- 0.002 vs 0.030 +/- 0.003 mmol.l-1.min-1) of blood glucose. Increments of glucagon (60.5 +/- 5.7 vs 70 +/- 9.2 ng/l) and adrenaline (1.22 +/- 0.31 vs 1.45 +/- 0.31 nmol/l) were similar in both groups. When tested using this model, patients with Type 2 diabetes, without microvascular complications and taking oral hypoglycaemic agents show no impairment of the endocrine response and blood glucose recovery following hypoglycaemia.


Practice guidelines and standards: an overview.
Organized medicine, insurance companies, regulators, and the peer review organizations are all interested in practice guidelines. Recently, the U.S. Congress established the Agency for Health Care Policy and Research, which is charged with overseeing the development of practice guidelines. If properly developed, disseminated, and used, practice guidelines should reduce the incidence of inappropriate care and help control costs. Although guidelines have been used by physicians for years, guidelines now being developed should be more comprehensive, specific, exhaustive, and--on the basis of the best scientific evidence of effectiveness and expert opinion--more effectively discriminate between useful and useless care. Practice guidelines can improve the quality of care when used voluntarily by physicians in practice, when used as standards for quality monitoring and assurance programs, and when used as the basis for reimbursement for services. All interested parties should share responsibilities for the research, development, and production of appropriateness criteria, their translation into guidelines and standards, and the dissemination and maintenance of the guidelines, including evaluation, revision, and updating.


Poor scar formation after ablation is associated with atrial fibrillation recurrence.
Patients routinely undergo ablation for atrial fibrillation (AF) but the recurrence rate remains high. We explored in this study whether poor scar formation as seen on late-gadolinium enhancement magnetic resonance imaging (LGE-MRI) correlates with AF recurrence following ablation. We retrospectively identified 94 consecutive patients who underwent their initial ablation for AF at our institution and had pre-procedural magnetic resonance angiography (MRA) merged with left atrial (LA) anatomy in an electroanatomic mapping (EAM) system, ablated areas marked intraprocedurally in EAM, 3-month post-ablation LGE-MRI for assessment of scar, and minimum of 3-months of clinical follow-up. Ablated area was quantified retrospectively in EAM and scarred area was quantified in the 3-month post-ablation LGE-MRI. With the mean follow-up of 336 days, 26 out of 94 patients had AF recurrence. Age, hypertension, and heart failure were not associated with AF recurrence, but LA size and difference between EAM ablated area and LGE-MRI scar area was associated with higher AF recurrence. For each percent higher difference between EAM ablated area and LGE-MRI scar area, there was a 7-9% higher AF recurrence (p values 0.001-0.003) depending on the multivariate analysis. In AF ablation, poor scar formation as seen on LGE-MRI was associated with AF recurrence. Improved mapping and ablation techniques are necessary to achieve the desired LA scar and reduce AF recurrence.


Antimalarial activity of tetrahydro-β-carbolines targeting the ATP binding pocket of the Plasmodium falciparum heat shock 90 protein.
A series of tetrahydro-β-carboline derivatives of a lead compound known to target the heat shock 90 protein of Plasmodium falciparum were synthesized and assayed for both potency against the parasite and toxicity against a human cell line. Using a rationalized structure based design strategy, a new lead compound with a potency two orders of magnitude greater than the original lead compound was found. Additional modeling of this new lead compound suggests multiple avenues to further increase potency against this target, potentially paving the path for a therapeutic with a mode of action different than any current clinical treatment.


Facial flushing response to alcohol and the risk of esophageal squamous cell carcinoma: A comprehensive systematic review and meta-analysis.
The alcohol flushing response is common among ethnic East Asian populations, and has been associated with an increased risk in developing esophageal cancer, especially squamous cell esophageal cancer (ESCC). We aimed to quantify the relationship between the facial flushing response to alcohol consumption and ESCC. We conducted a meta-analysis of studies reporting on the association between the facial flushing response to alcohol consumption and ESCC. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated using a random effects model for the risk of ESCC associated with the facial flushing response in general, as well for different levels of alcohol consumption. Four databases, Medline, PubMed, Embase, and Current Contents Connect, were searched to 31 August 2015. Seven studies, with 1014 ESCC cases, met the inclusion criteria. There was a positive relationship between the flushing response and ESCC (OR 1.97; 95% CI 1.25-3.13). Heterogeneity was observed (I(2)= 80%, P<0.001). Publication bias was not present. An increased risk of ESCC was present in the moderate and heavy drinkers who experienced flushing, compared with moderate and heavy drinkers who did not (OR 2.54; 95% CI 1.64-3.91, and OR 2.90; 95% CI 1.82-4.82, respectively). Individuals who experience a facial flushing response to alcohol intake may be at increased risk of developing ESCC, particularly if they are moderate to heavy drinkers.


Effect of A-Site Cation Ordering on Chemical Stability, Oxygen Stoichiometry and Electrical Conductivity in Layered LaBaCo₂O5+δ Double Perovskite.
The effect of the A-site cation ordering on the chemical stability, oxygen stoichiometry and electrical conductivity in layered LaBaCo₂O5+δ double perovskite was studied as a function of temperature and partial pressure of oxygen. Tetragonal A-site cation ordered layered LaBaCo₂O5+δ double perovskite was obtained by annealing cubic A-site cation disordered La0.5Ba0.5CoO3-δ perovskite at 1100 °C in N₂. High temperature X-ray diffraction between room temperature (RT) and 800 °C revealed that LaBaCo₂O5+δ remains tetragonal during heating in oxidizing atmosphere, but goes through two phase transitions in N₂ and between 450 °C and 675 °C from tetragonal P4/mmm to orthorhombic Pmmm and back to P4/mmm due to oxygen vacancy ordering followed by disordering of the oxygen vacancies. An anisotropic chemical and thermal expansion of LaBaCo₂O5+δ was demonstrated. La0.5Ba0.5CoO3-δ remained cubic at the studied temperature irrespective of partial pressure of oxygen. LaBaCo₂O5+δ is metastable with respect to La0.5Ba0.5CoO3-δ at oxidizing conditions inferred from the thermal evolution of the oxygen deficiency and oxidation state of Co in the two materials. The oxidation state of Co is higher in La0.5Ba0.5CoO3-δ resulting in a higher electrical conductivity relative to LaBaCo₂O5+δ. The conductivity in both materials was reduced with decreasing partial pressure of oxygen pointing to a p-type semiconducting behavior.


Acute phase response following intravenous zoledronate in postmenopausal women with low bone mass.
An acute phase response (APR) is frequently observed in patients treated with intravenous (i.v.) zoledronate (ZOL). We aimed to define clinical and laboratory parameters that may predict ZOL-induced APR in women with low bone mass. Fifty-one postmenopausal women with low bone mass were given a single i.v. infusion of ZOL 5mg. APR was clinically defined by the visual analog pain scale (VAS) for the musculoskeletal symptoms and body temperature. White blood cell count (WBC), leucocyte subpopulations, C-reactive protein (CRP), parathyroid hormone (PTH), 25-hydroxyvitamin D [25(OH)D], interleukins (IL)-1b and -6, tumor necrosis factor (TNF)α and interferon (IFN)γ were measured before and 48 h following the infusion. Subsequently, patients were divided into those experiencing APR (APR+) or not (APR-). WBC, granulocytes, CRP, IL-1b and IL-6 were significantly increased, whereas lymphocytes, eosinophils, calcium, phosphate and 25(OH)D decreased 48h after ZOL infusion. Twenty-eight of the 51 patients (54.9%) experienced an APR. APR+ patients were younger and had higher baseline lymphocytes compared to APR- patients. There was no difference (p=0.405) in the development of APR between treatment-naive patients (19/32, 59.4%) and patients previously treated with another oral nitrogen-containing bisphosphonate (9/19, 47.4%). In conclusion, our data suggest that pre-treatment higher lymphocyte number increases the risk of APR while previous treatment with another nitrogen-containing bisphosphonate does not significantly reduce the risk. Serum 25(OH)D concentrations decrease significantly after the infusion, possibly as part of the inflammatory response to ZOL.


Phase-I-II study of high-dose melphalan and autologous marrow transplantation in adult patients with poor-risk non-Hodgkin's lymphomas.
Eleven adult patients with poor-risk non-Hodgkin's lymphoma were treated with high-dose melphalan (140 mg/m2) or high-dose combination chemotherapy (BCNU, Ara-C, vindesine and melphalan) followed by autologous bone marrow transplantation. Six of the eight patients evaluable for response achieved complete remission and one achieved partial remission. Response duration ranged from 1.5 to 12 months (median 2 months). Prompt hematological recovery occurred in all patients. The duration of aplasia and the extrahematological toxicity were similar in both groups. High-dose melphalan alone or associated with other drugs followed by marrow infusion appears to produce a high response rate and demonstrates the potential for salvaging patients with refractory lymphoma.


Modification by genetic polymorphism of lead-induced IQ alteration: a systematic review.
As well as a lead-related environmental factor, genetic factors could also corroborate important changes in intelligence quotient (IQ) through single-nucleotide polymorphisms. Thus, a systematic review was carried out to evaluate the possible influence of polymorphism on blood Pb levels and IQ points in pediatric patients (0-19 years old). Following the PRISMA guideline, the studies were systematically collected on PubMed, Scopus, and Embase databases. Six genes (transferrin (TF); glutamate ionotropic receptor NMDA type subunit 2A (GRIN2A); glutamate ionotropic receptor NMDA type subunit 2B (GRIN2B); dopamine receptor D2/ankyrin repeat and kinase domain containing 1 ankyrin repeat and kinase domain containing 1 (DRD2/ANKK1); aminolevulinate dehydratase (ALAD); vitamin D receptor (VDR)) were found in six selected articles. In these genes, 11 single-nucleotide polymorphisms were searched and six different types of variations (missense variant, intron variant, synonymous variant, stop, stop gained) were observed. Due to the few studies in the literature, there is no conclusive data to point out that there is a direct relationship between polymorphisms, Pb levels, and reduction of IQ points.


The effect of driven exercise on treatment outcomes for adolescents with anorexia and bulimia nervosa.
This study investigated the prevalence of driven exercise (DE) and its role in treatment outcome for adolescents with bulimia nervosa (BN) and anorexia nervosa (AN). Participants were 201 adolescents with an eating disorder (ED) (80 with BN and 121 with AN) presenting for outpatient treatment at two specialist clinics. All adolescents participated in one of two randomized controlled trials. Descriptive statistics were conducted to evaluate the presence and frequency of baseline DE. Exploratory hierarchical regressions were used to evaluate the effect of baseline DE on treatment outcomes. About 66.3% of adolescents with BN and 23.1% of adolescents with AN presented with baseline DE. The presence of baseline DE predicted significantly worse outcomes for adolescents with AN in terms of ED symptom severity (ps < .004); however, baseline DE did not significantly predict any of the evaluated outcomes for adolescents with BN (ps < .05). The results of this secondary exploratory data suggest that DE is prevalent for adolescents with BN and AN. However, DE may be related to different constructs for adolescents with AN than those with BN, suggesting differences in treatment needs.


Automated gastric lavage and a comparison of 0.9% normal saline solution and tap water irrigant.
Gastric lavage is used frequently in the emergency treatment of upper gastrointestinal hemorrhage, toxin ingestion, drug overdose, and other cases requiring repetitive gastric irrigation. An effective automatic method of gastric lavage is described and evaluated. The use of tap water versus 0.9% normal saline solution also is compared. There is no difference in prelavage and postlavage blood cell concentrations or electrolyte profile with either irrigant. The advantages of tap water lavage fluid are discussed.


Abnormal correlation of circulating endothelial progenitor cells and endothelin-1 concentration may contribute to the development of arterial hypertension in childhood acute lymphoblastic leukemia survivors.
It is well known that the rate of arterial hypertension (AH) in childhood acute lymphoblastic leukemia (ALL) survivors is significantly higher than that in the healthy pediatric population; however, the mechanism of this phenomenon is not fully understood. The developing cardiovascular system in children is thought to be highly susceptible to the toxic effects of chemotherapy, which causes damage to the blood vessel wall, including the endothelium. Endothelin-1 (ET-1) is a marker of endothelial damage, and it contributes to AH. Endothelial progenitor cells (EPCs) are derived from the bone marrow and participate in the process of blood vessel repair. The aim of this study was to determine the relationship between the rate of circulating EPCs and plasma levels of ET-1 with respect to hypertension in childhood ALL survivors. The study included 88 childhood ALL survivors and 44 healthy children as controls. All patients and controls had 24-h blood pressure monitoring with a HolCARD CR-07 device. The number of EPCs and the ET-1 serum concentration were measured in the peripheral blood of patients and controls using flow cytometry and enzyme-linked immunosorbent assay, respectively. A correlation was found between the number of EPCs and the ET-1 concentration in the peripheral blood of healthy children and normotensive ALL survivors. However, such a correlation was not found in hypertensive childhood ALL survivors. We conclude that dysregulation of the 'ET-1 and EPC axis' may contribute to the development of AH in some childhood ALL survivors.


[Various problems of surgical treatment of volvulus of the sigmoid].
Some aspects of surgical tactics in 57 patients with sigmoid ileus are discussed. In 42 patients palliative operations were performed, 7 patients (16.7%) died. In 15 cases radical operations were performed. Palliative operations are recommended only for aged patients, but in most cases sigmoidectomy seems to be warranted.


Contribution of Ca2+-activated K+ channels and non-selective cation channels to membrane potential of pulmonary arterial smooth muscle cells of the rabbit.
1. Using the perforated patch-clamp or whole-cell clamp technique, we investigated the contribution of Ca2+-activated K+ current (IK(Ca)) and non-selective cation currents (INSC) to the membrane potential in small pulmonary arterial smooth muscle cells of the rabbit. 2. The resting membrane potential (Vm) was -39.2 +/- 0.9 mV (n = 72). It did not stay at a constant level, but hyperpolarized irregularly, showing spontaneous transient hyperpolarizations (STHPs). The mean frequency and amplitude of the STHPs was 5.6 +/- 1. 1 Hz and -7.7 +/- 0.7 mV (n = 12), respectively. In the voltage-clamp mode, spontaneous transient outward currents (STOCs) were recorded with similar frequency and irregularity. 3. Intracellular application of BAPTA or extracellular application of TEA or charybdotoxin suppressed both the STHPs and STOCs. The depletion of intracellular Ca2+ stores by caffeine or ryanodine, and the removal of extracellular Ca2+ also abolished STHPs and STOCs. 4. Replacement of extracellular Na+ with NMDG+ caused hyperpolarization Vm of without affecting STHPs. Removal of extracellular Ca2+ induced a marked depolarization of Vm along with the disappearance of STHPs. 5. The ionic nature of the background inward current was identified. The permeability ratio of K+ : Cs+ : Na+ : Li+ was 1.7 : 1.3 : 1 : 0. 9, indicating that it is a non-selective cation current (INSC). The reversal potential of this current in control conditions was calculated to be -13.9 mV. The current was blocked by millimolar concentrations of extracellular Ca2+ and Mg2+. 6. From these results, it was concluded that (i) hyperpolarizing currents are mainly contributed by Ca2+-activated K+ (KCa) channels, and thus STOCs result in transient membrane hyperpolarization, and (ii) depolarizing currents are carried through NSC channels.


Effects of oral aspartame on plasma phenylalanine in humans and experimental rodents. Short note.
All aspartame does given to humans cause greater elevations in plasma (and, presumably, brain) phenylalanine than in plasma tyrosine. In contrast, doses of aspartame usually used in experiments on rodents preferentially elevate tyrosine. Since phenylalanine can inhibit brain catecholamine synthesis while tyrosine is the antidote for this effect, we determined the aspartame dose that would be needed to elevate phenylalanine more than tyrosine in rodents, using published data. In general rodents need 60 times as much aspartame, on a mg/kg basis, as humans to obtain comparable elevations in phenylalanine with respect to tyrosine.


[Cardiac rehabilitation in heart failure].
Heart failure is a malignant disorder with increasing prevalence and a high socioeconomic impact. Sceletal muscle myopathy seems to play a key role in the development of exercise intolerance. Cardiac rehabilitation for heart failure mainly adresses training, namely moderate continuous endurance training or interval training in combination with resistance training, and is highly recommended in the current ESC-guidelines. Following a multimodal concept cardiac rehabilitation also implements optimisation of neurohumoral therapy, education and counselling to empower self-care as well as psychosocial support.


Resveratrol mitigates miR-212-3p mediated progression of diesel exhaust-induced pulmonary fibrosis by regulating SIRT1/FoxO3.
Diesel exhaust (DE) exposure contributes to the progression of chronic respiratory diseases and is associated with dysregulation of microRNA expression. The present study aims to investigate the involvement of miRNAs and target genes in DE-induced lung fibrosis. C57BL/6 mice were divided into three groups. Group 1 mice were exposed to filtered air (Control). Group 2 mice were exposed to DE for 30 min per day, 5 days per week, for 8 weeks (DE). Group 3 mice received DE exposure along with resveratrol on alternate days for the last 2 weeks (DE + RES). Mice were sacrificed to isolate RNA from lung tissue for miRNA microarray profiling. Bronchoalveolar lavage fluid and lung tissues were collected for cell count and biochemical analysis. DE exposure resulted in differential expression of 28 miRNAs with fold change >2 (p < 0.05). The upregulated miR-212-3p was selected for further analysis. Consensus analysis revealed enrichment of SIRT1 in the FoxO pathway, along with a co-annotation of reduced body weight (p < 0.05). A549 cells transfected with a miR-212-3p inhibitor showed a dose-dependent increase in SIRT1 expression, indicating SIRT1 as a direct target. Treatment with resveratrol restored SIRT1 and miR-212-3p expression and led to a reduction in inflammatory cytokines (p < 0.05). The modulation of SIRT1 correlated negatively with macrophage infiltration, confirming its role in regulating cellular infiltration and lung inflammation. Fibronectin, alpha-SMA, and collagen levels were significantly decreased in DE + RES compared to DE group suggesting modulation of cellular functions and resolution of lung fibrosis. Furthermore, a significant decrease in FoxO3a and TGF-β gene expressions was observed upon resveratrol administration thereby downregulating pro-fibrotic pathway. The present study demonstrates resveratrol treatment stabilizes SIRT1 gene expression by attenuating miR-212-3p in DE-exposed mice, leading to downregulation of TGF-β and FoxO3a expressions. The study highlights the therapeutic role of resveratrol in the treatment of DE-induced pulmonary fibrosis.


The framework of polysaccharide monooxygenase structure and chemistry.
Polysaccharide monooxygenases, or PMOs (also known as lytic PMOs or LPMOs), are a group of enzymes discovered in recent years to catalyze the oxidative degradation of carbohydrate polymers. The PMO catalytic domain has a β-sandwich fold that bears a strong resemblance to both immunoglobulin (Ig) and fibronectin type III (FnIII) domains. PMOs are secreted by fungi and bacteria, and there is recent evidence for their roles in pathogenesis, in addition to biomass processing. This review addresses the biological origins and functions of emerging PMO families, as well as describes the aspects of PMO structure that support the chemistry of copper-catalyzed, oxidative polysaccharide degradation.