Dietary omega-3 fatty acids (fish oils) have limited effects on boar semen stored at 17 °C or cryopreserved.
To evaluate the influence of dietary supplementation of omega-3 polyunsaturated fatty acids (n-3 PUFA) on storage of boar semen, three experiments were conducted: two involved long-term, fresh semen storage (Exp. 1 and Exp. 2), whereas the other involved cryopreservation (Exp. 3). Boars were allocated randomly to three dietary treatments (for 6-7 mo). In addition to a daily allowance of 2.5 kg of a basal diet, they received: 1) 62 g of hydrogenated animal fat (AF); 2) 60 g of menhaden oil (MO), containing 18% docosahexanoic acid (DHA) and 15% eicosapentanoic acid (EPA); or 3) 60 g of tuna oil (TO), containing 33% DHA and 6.5% EPA. In Experiment 1 (n = 26) and Experiment 2 (n = 18), semen was cooled and stored in vitro for several days at 17 °C before assessment, whereas in Experiment 3 (n = 18), viability, motility, acrosomal integrity, susceptibility to peroxidation (LPO), and DNA fragmentation were determined in fresh and frozen-thawed sperm. In Experiment 1, sperm from boars fed TO had better resistance to fresh storage; even after 7 or 9 d of storage at 17 °C, there were more (P = 0.03) motile sperm in boars fed TO (>60%) than in those fed AF or MO. In Experiment 2, fish oil supplementation did not influence any aspect of sperm quality during semen storage (P > 0.10). In Experiment 3, cryopreservation decreased the proportion of motile and viable frozen-thawed sperm as well as acrosomal integrity and increased DNA fragmentation and LPO (P < 0.01) relative to fresh semen, although sperm quality was unaffected by treatments (P > 0.09). In conclusion, although adding fish oil to the diet failed to significantly improve the quality of cryopreserved boar sperm, inconsistent responses of long-term storage of cooled sperm to dietary n-3 PUFA supplementation warrant further investigation.


Importance of habitat quality and landscape connectivity for the persistence of endangered natterjack toads.
The natterjack toad (Bufo calamita) is endangered in several parts of its distribution, including Belgium, where it occurs mainly in artificial habitats. We parameterized a general model for natterjack population viability analysis (PVA) and tested its sensitivity to changes in the values of basic parameters. Then we assessed the relative efficiency of various conservation measures in 2 situations: a small isolated population and a system of 4 populations connected by rare dispersal movements. We based the population viability analysis on a stage-structured model of natterjack population dynamics. We parameterized the model in the RAMAS GIS platform with vital rates obtained from our own field experience and from published studies. Simulated natterjack populations were highly sensitive to habitat quality (particularly pond drying), to dispersal from surrounding local populations, and to a lesser extent to values of fecundity and survival of terrestrial stages. Population trajectories were nearly insensitive to initial abundances, carrying capacities, and the frequency of extreme climatic conditions. The simulations showed that in habitats with highly ephemeral ponds, where premetamorphosis mortality was high, natterjack populations nearly always had a very high extinction risk. We also illustrated how low dispersal rates (<1 dispersing individual/generation) efficiently rescued declining local populations. Such source-sink dynamics demonstrate that the identification and management of source populations should be a high priority.


The many facets of PEDF in drug discovery and disease: a diamond in the rough or split personality disorder?
Pigment epithelium-derived factor (PEDF) was discovered as a neurotrophic factor secreted by retinal pigment epithelial cells. A decade later, it re-emerged as a powerful angiogenesis inhibitor guarding ocular function. Since then, significant advances were made identifying PEDF's mechanisms, targets and biomedical applications. The authors review several methodologies that have generated significant new information about the potential of PEDF as a drug. Furthermore, the authors review and discuss mechanistic and structure-function analyses combined with the functional mapping of active fragments, which have yielded several short bioactive PEDF peptides. Additionally, the authors present functional studies in knockout animals and human correlates that have provided important information about conditions amenable to PEDF-based therapies. Through its four known receptors, PEDF causes a wide range of cellular events vitally important for the organism, which include survival and differentiation, migration and invasion, lipid metabolism and stem cell maintenance. These processes are deregulated in multiple pathological conditions, including cancer, metabolic and cardiovascular disease. PEDF has been successfully used in countless preclinical models of these conditions and human correlates suggest a wide utility of PEDF-based drugs. The most significant clinical application of PEDF, to date, is its potential therapeutic use for age-related macular degeneration. Moreover, PEDF-based gene therapy has advanced to early stage clinical trials. PEDF active fragments have been mapped and used to design short peptide mimetics conferring distinct functions of PEDF, which may address specific clinical problems and become prototype drugs.


Application of Bioluminescent Methods to Study the Effect of the Membrane-active Antibiotic Colistin on Bacterial Cells.
For the first time, recombinant Escherichia coli cells expressing thermostable Luciola mingrelica firefly luciferase were used to study the effect of the membrane-active antibiotic colistin on live cells. Simple, fast, and highly sensitive bioluminescent methods were developed for measurement of luciferase activity and ATP concentration inside and outside E. coli cells incubated in a nutrient medium, or in saline. Luciferase proved to be an informative protein marker for detecting the irreversible changes in cell membrane permeability. The study of kinetics of intra- and extracellular ATP concentration at different concentrations of colistin showed that the rate of decrease in intracellular ATP concentration significantly exceeded the rate of accumulation of extracellular ATP concentration. This fact could not be explained only by the release of ATP from the cell with an increase in the permeability of the outer cell membrane under the action of colistin. The loss of a significant part of intracellular ATP in presence of the colistin is probably due to a decrease in the activity of the respiratory chain enzymes and ATP synthase which operate in the cytoplasmic cell membrane, which leads to a decrease in the rate of ATP synthesis or even to its halt.


[Principles and technique of magnetic resonance guided focused ultrasound surgery (MRgFUS) in the treatment of uterine fibroids].
Uterine fibroids are a significant source of morbidity for women of reproductive age, and can result in substantial symptoms affecting their quality of life. Definitive treatment has traditionally been a myomectomy, but increasingly women are not prepared to undergo such an invasive procedure for a benign and usually self-limiting condition. Focused ultrasound ablation is one of the least invasive treatment options outside medical therapy and does not require an anesthetic.Magnetic resonance guided focused ultrasound (MRgFUS) ablation combines therapy delivered by an ultrasound transducer with imaging guidance for therapy and thermal feedback provided by magnetic resonance imaging. This paper provides an overview of the MRgFUS technique, including a brief description of the treatment system, guidelines for selection of patients and follow-up, and a comparison with other treatment techniques.


[Analysis of the influence of social status on fertility of women in Bulgaria].
"The author studies the influence [of] the social status of women upon their fertility during first marriages [in Bulgaria]. The study has been made by means of the structural-factor analysis which is based on conventional one-dimensional and two-dimensional moment distributions. The degree of variations is determined by the integral coefficient of structural differences, the mean arithmetic value, the standard deviation, coefficients of asymmetry and excess. The author discusses: 1) the changes in the structure of various categories of women according to social groups, 2) the changes in the separate structures for each of the social groups of women according to the number of live-born children during the 1965-1985 period. The method of filtering variables is used to control the influence of the important demographic factor 'duration of marriage'." Data are from the censuses of 1965, 1975, and 1985. (SUMMARY IN ENG AND RUS)


CHARGE (coloboma, heart defect, atresia choanae, retarded growth and development, genital hypoplasia, ear anomalies/deafness) syndrome and chromosome 22q11.2 deletion syndrome: a comparison of immunologic and nonimmunologic phenotypic features.
CHARGE (coloboma, heart defect, atresia choanae, retarded growth and development, genital hypoplasia, ear anomalies/deafness) syndrome and chromosome 22q11.2 deletion syndrome are known to have significant clinical overlap including cardiac anomalies, ear abnormalities, hearing loss, developmental delay, renal abnormalities, and cleft palate. Immunodeficiency has been well documented in 22q11.2 deletion, but there has been limited recognition of this potentially serious complication in CHARGE syndrome. The goals of our study were to identify clinical features unique to CHARGE syndrome or 22q11.2 deletion and to describe the spectrum of immunodeficiency found in patients with CHARGE syndrome. This study included 25 children diagnosed with CHARGE syndrome with positive CHD7 mutations through the Children's Hospital of Philadelphia genetics program. Clinical features and laboratory findings were reviewed retrospectively. We compared our findings to data available for a large cohort of patients with 22q11.2 deletion syndrome followed in our clinical genetics program. Features found more commonly in CHARGE syndrome included coloboma, choanal atresia, facial nerve palsy, tracheoesophageal fistula, and genital hypoplasia in boys. A high incidence of marked hypocalcemia was observed in our study group (72%). We found a spectrum of cell-mediated immunodeficiency in our study group, which ranged from lymphopenia (60%) to severe combined immunodeficiency (8%). Defects in humoral immunity were documented in 4 patients and included severe hypogammaglobulinemia with decreased T-cell numbers, transient hypogammaglobulinemia during infancy, and immunoglobulin A deficiency. The presence of coloboma, choanal atresia, facial nerve palsy, tracheoesophageal fistula, or genital hypoplasia in boys should alert the clinician to the possibility of CHARGE syndrome rather than the 22q11.2 deletion. Molecular testing for CHD7 mutations may help to confirm the diagnosis. In this study, significant hypocalcemia and lymphopenia occurred more frequently in patients with CHARGE syndrome than in those with 22q11.2 deletion syndrome. Early inclusion of immunologists to the multidisciplinary care team (as with 22q11.2 deletion) may be of great benefit to affected patients.


Synganglial and neurosecretory morphology of the chicken mite Dermanyssus gallinae (DeGeer) (Mesostigmata: Dermanyssidae).
Histological techniques and paraldehyde-fuchsin (PAF) staining were used to study the synganglion and to locate neurosecretory regions and neurosecretion within the synganglion of the chicken mite, Dermanyssus gallinae. The synganglion, which is formed internally by neuropilar ganglia, gives rise to a single esophageal and paired cheliceral, palpal, pedal (I-IV), and opisthosomal nerves. The neuropilar ganglia are interconnected by commissures and connectives within the synganglion. Twelve PAF-positive neurosecretory regions are present in unfed protonymphs, unfed deutonymphs, virgin males and females, and mated males. There are 11 PAF-positive neurosecretory regions in larvae, 24-72 hours post-fed deutonymphs and mated females. Neurosecretory regions in these developmental stadia are described in relation to their positions adjacent to individual neuropilar ganglia.


Metabolic engineering of Saccharomyces cerevisiae for 2,3-butanediol production.
Saccharomyces cerevisiae is a work horse for production of valuable biofuels and biochemicals including 2,3-butanediol (2,3-BDO), a platform chemical with wide industrial applications for synthetic rubber, biosolvents and food additives. Recently, a cutting-edge technology of metabolic engineering has enabled S. cerevisiae to produce 2,3-BDO with high yield and productivity. These include (i) amplification of the 2,3-BDO biosynthetic pathway, (ii) redirection of carbon flux from ethanol or glycerol toward 2,3-BDO, and (iii) 2,3-BDO production from sugars derived from renewable biomass. These breakthroughs enforced S. cerevisiae to become a promising microbial host for production of 2,3-BDO.


Preoperative serum C-reactive protein levels and early breast cancer by BMI and menopausal status.
Serum C-reactive protein (CRP), a sensitive marker of systemic inflammation, has been reported to be associated with the risk of a number of cancers including breast cancer. However, the results are inconsistent. To investigate the association between serum CRP levels and early breast cancer, we conducted a hospital-based case-control study among 506 newly diagnosed breast cancer patients and 506 controls with benign breast diseases matched by age and menopausal status. Odds ratios (ORs) were computed with unconditional logistic regression models, adjusted for major confounding factors. Relative to women with the lowest quartile of CRP level, women with the highest quartile had 1.65-fold increased breast cancer risk (OR: 1.65, 95% CI: 1.12-2.42) in a significant dose-response manner (p(trend) = .011). Stratification analysis revealed a positive association only for overweight postmenopausal women (highest CRP quartile versus lowest CRP quartile: OR: 2.78, 95% CI: 1.18-6.6). Multinominal logistic regression analysis showed that only hormonal receptor (HR) positive and human epidemiological receptor 2 (HER2) negative breast cancers had elevated serum CRP levels. We observed that elevated serum CRP levels are positively associated with early breast cancer, predominantly among overweight and postmenopausal women. This study provided epidemiological evidence that chronic inflammation might mediate the association between obesity and postmenopausal breast cancer. Although a positive association between serum CRP and HR positive/HER2 negative breast cancer is intriguing, further epidemiological studies are needed to confirm such findings.


Brain lipid peroxidation and changes of trace metals in rats following chronic manganese chloride exposure.
The aim of this study was to investigate the effects of chronic, daily, 30-d administration of manganese chloride (MnCl2) to male Sprague-Dawley rats on lipid peroxidation and changes of trace elements (manganese, iron, copper, zinc) in various brain regions. Rats were intraperitoneally injected with MnCl2 (20 mg/kg) once daily for 30 consecutive days. The Mn accumulated in frontal cortex, corpus callosum, hippocampus, striatum, hypothalamus, medulla, cerebellum, and spinal cord. Malondialdehyde, an end product of lipid peroxidation, was markedly decreased in frontal cortex and cerebellum. An increased level of Cu was observed in frontal cortex, medulla, and a cerebellum. A decreased Fe level was found only in cerebellum, and a decreased Zn level was observed in hippocampus and striatum. In a second group of animals, Mn (20 mg/kg/d) and glutathione (GSH, 15 mg/kg/d) were administered ip for 30 d. In CSH-Mn-treated rats, compared to Mn-treated rats, MDA concentrations were significantly reduced in frontal cortex, medulla and cerebellum. The changes of trace elements in rat brain were similar to the Mn-treated group. We suggest that Mn is an atypical antioxidant, as well as not involved in oxidative damage in rat brain. Fe and Cu may play roles in the protective effect of Mn against lipid peroxidation in rat brain.


Bis{5-[(2-propyn-1-yl-oxy)meth-yl]-1,3-phenyl-ene}-32-crown-10.
The mol-ecule of the title compound {systematic name: 17,35-bis-[(2-propyn-1-yl-oxy)meth-yl]-2,5,8,11,14,20,23,26,29,32-deca-oxatricyclo-[188.8.131.52(15,19)]octa-triaconta-1(37),15,17,19 (38),33,35-hex-a--ene}, C(36)H(48)O(12), has crystallographic inversion symmetry and adopts a chair-like conformation. The polyether bridges of the macrocycle adopt gauche conformations and the cavity of the macrocycle is collapsed. In the crystal structure, there are weak inter-molecular C-H⋯O hydrogen bonds driven in part by the elevated acidity of acetylenyl H atoms.


The Coma Morphology Due to an Extended Active Region and the Implications for the Spin State of Comet Hale-Bopp.
We show that the circular character of continuum structures observed in the coma of comet Hale-Bopp around the perihelion passage is most likely due to a dust jet from a large extended active region on the surface. The coma morphology due to a wide jet is different from that due to a narrow jet. The latter shows foreshortening effects due to observing geometry; a wider jet produces more circular features. This circularization effect provides a self-consistent explanation for the evolution of near-perihelion coma morphology. No changes in the direction of the rotational angular momentum vector are required during this period, in contrast to the models of Schleicher et al. This circularization effect also enables us to produce near-circular coma features in the southeast quadrant in late February of 1997, and therefore it puts into question the basic premise on which Sekanina bases his morphological arguments for a gravitationally bound satellite nucleus.


Associations of Inflammatory Bowel Disease and Subsequent Cancers in a Population-Based Study of Older Adults in the United States.
Cancer risk is elevated in patients with inflammatory bowel disease (IBD). A comprehensive investigation of cancer risk in older patients (≥66 years of age) is needed, because this understudied population is at high risk. We performed a case-control study using Surveillance Epidemiology and End Results-Medicare data including 1 986 735 incident cancer cases (aged 66-99 years; diagnosed 1992-2015) and 200 000 controls matched by sex, age, race and ethnicity, and selection year. IBD was identified by ulcerative colitis (UC) or Crohn's disease (CD) diagnosis codes. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated with logistic regression, adjusting for potential confounders. For colorectal cancers, we further adjusted for screening rates. We assessed confounding by medication exposure among patients with prescription drug coverage. IBD, CD, and UC were present in 0.8%, 0.3%, and 0.5% in both cancer cases and non-cancer controls. Of 51 cancers examined, IBD was statistically significantly associated with cancers of the small intestine (OR = 2.55, 95% CI = 2.15 to 3.01), intrahepatic (OR = 1.92, 95% CI = 1.47 to 2.51) and extrahepatic bile ducts (OR = 1.75, 95% CI = 1.38 to 2.22), rectum (OR = 1.61, 95% CI = 1.36 to 1.90), and colon (OR = 1.21, 95% CI = 1.10 to 1.33). CD was associated with cancers of the small intestine (OR = 4.55, 95% CI = 3.65 to 5.67), and UC was associated with cancers of the intrahepatic bile ducts (OR = 1.87, 95% CI = 1.34 to 2.61), rectum (OR = 1.80, 95% CI = 1.47 to 2.20), and colon (OR = 1.28, 95% CI = 1.14 to 1.43). After adjusting for medication exposure, IBD was not statistically significantly associated with lung cancer, melanoma, diffuse large B-cell lymphoma, and myelodysplastic syndrome. In this large study among older adults (≥66 years of age), IBD was positively associated with gastrointestinal cancers. Associations with extraintestinal cancers may reflect the effect of immunosuppressive medications.


Histopathological evaluation of radical prostatectomy in the treatment of localized prostate cancer.
Incidence of prostate cancer has risen dramatically in the past decade. Radical prostatectomy is indicated in patients who have disease localized to the prostate. The aim of the study is to make histopathological evaluation of radical prostatectomy in the treatment local prostate cancer. Authors analyzed 49 cases of radical prostatectomy due to cancer localized to the prostate in period 1996-2000 in Clinic of Urology in Clinical Center of Serbia, Belgrade. The average age of the patients was 65, 6 years (range 44-76, pick 61-70). The most cases 25 (51%, p < 0.001) we found in pT2a N0M0, in pT2b N1M0 9 (18.36%), in pT3bN0M0 10 (20.4%), in pT3bN1M0 3 (6.12%), in pT4aN0M0 2 (4.08%). Nodal status positive was in 12 cases: 9 (18%) in pT2bN1M0- iliac 3 (right 2, left 1), obturatory 6 (right 1, left 5) and 3 cases in pT3bN1M0-iliac left 1 and obturatory 2 (1 right and 1 left). We found Gleason score 8 in 9 cases (18.36%) in pT2bN1M0 versus 7 cases (14.5%) without nodal metastases. Gleason score 9 we found in 3 cases (6.1%) in pT3bN1M0 versus one case without nodal metastases (difference is not significant). Gleason score 3 was in 6.1%, 4 in 12.2%, 5 in 8.1%, 6 in 16, 3%, 7 in 24.5%. Grade 1 of tumors we found in 9 cases (18%), grade 2 in 11 (22%), grade 3 in 29 (60%). HG PIN was in 18 cases (36.7%), LG PIN in 10 (20.4%). In all cases was elevated PSA: 4-10 mmol/L in 24 pts, 11-20 in 15 pts and > 20 in 10 pts. Radical prostatectomy is most adequate method in surgical treatment cancer localized in the prostate. Pelvic lymphadenectomy is necessary for staging purposes in adenocarcinoma of the prostate. Early detection adenocarcinoma of the prostate is important factor in decreasing rate of death.


Cytokines as a stressor: implications for depressive illness.
Stressful events have been implicated in the provocation of depressive illness. Inasmuch as immunological challenge, and particularly cytokine administration, engender neuroendocrine and central neurochemical changes reminiscent of those provoked by psychogenic stressors, it was suggested that immune activation may also contribute to affective illness. The present report provides a brief overview of the neurochemical sequelae of acute and repeated interleukin-1beta (IL-1beta), tumour necrosis factor-alpha (TNF-alpha) and IL-2 treatment, describes some of the synergisms associated with these treatments, as well as their potential interactions with psychogenic stressors. In addition, a discussion is provided concerning the fact that cytokines, like stressors, may have time-dependent proactive effects, so that re-exposure to the treatments provoke greatly augmented neurochemical changes (sensitization). Given that the effects of cytokines are evident within hypothalamic, as well as extrahypothalamic sites, including various limbic regions, it is suggested that cytokines may impact on emotional changes, including depression.


[Preoperative evaluation of cardiac disease for patients with lung cancer: usefulness of treadmill exercise electrocardiogram].
118 patients with lung cancer who underwent treadmill exercise electrography (ECG) as part of their preoperative evaluation, were investigated for postoperative events. On the treadmill exercise ECG 27 patients were positive and 91 were negative. The more elderly patients tended to reveal ischemic findings in treadmill exercise ECG. Of the 71 patients with normal of result by ECG at rest, 15 patients (21.1%) had postoperative ischemic change on ECG. As a result, it was considered that this examination was insufficient to detect latent ischemic heart disease. The patients who had a discontinued at stage 2 or less of the Bruce protocol and had a negative result by treadmill exercise ECG, were classified as insufficient group and separated from the others. (27/118 patients). This group consisted of advanced age (p < 0.05) who tended to experience postoperative events. In the sufficient group, patients showed ischemic events predominantly on ECG at postoperative period (p < 0.01). We concluded that as preoperative screening of heart disease prior to lung cancer surgery ECG at rest was not adequate while treadmill exercise ECG was useful.


Central nervous system side-effects with hydrophilic and lipophilic beta-blockers.
Previous investigations have suggested that hydrophilic beta-blockers, which appear at low concentrations in brain tissue, are less likely to produce CNS-related side-effects than are lipophilic beta-blockers, which occur at higher concentrations in the brain. The validity of this hypothesis was tested in a double-blind crossover study in which the hydrophilic beta-blocker atenolol was compared with the lipophilic agents metoprolol and propranolol, in 14 patients with a previous history of nightmares or hallucinations when treated with lipophilic beta-blockers. Nightmares or hallucinations were reported by all patients receiving lipophilic beta-blockers but by only three patients receiving atenolol. The total number of episodes was significantly lower (p less than 0.01) for patients receiving atenolol (8) than for those receiving lipophilic beta-blockers (54). It is concluded that atenolol is significantly less likely to provoke nightmares and hallucinations than are the lipophilic beta-blockers, metoprolol and propranolol. It seems likely that this finding is due to the differences in hydrophilicity amongst these drugs.


Characterization of [125I]AR-M100613, a high-affinity radioligand for delta opioid receptors.
AR-M100613 ([I]-Dmt-c[-D-Orn-2-Nal-D-Pro-D-Ala-]) is the iodinated analog of a cyclic casomorphin previously shown to be a potent antagonist at the delta opioid receptor. Specific [125I]AR-M100613 binding to rat whole brain membranes was saturable, reversible, and best fit to a one-site model (Kd = 0.080 +/- 0.008 nM, Bmax = 45.2 +/- 4.4 fmol/mg protein). [125I]AR-M100613 binding was displaced with high affinity by the delta opioid receptor ligands SNC-80, Deltorphin II and DPDPE but not the mu or kappa-selective receptor ligands DAMGO and U69593. Residual non-selective binding of [125I]AR-M 100613 to mu opioid receptors is blocked by the addition of CTOP to the assay buffer. [35S]GTPgammaS binding assays indicate that AR-M100613 is a potent, selective, and reversible antagonist for delta opioid receptors in rat brain membranes. The high-affinity, high specific activity, low nonspecific binding and antagonist profile of [125I]AR-M100613 favor its use as a radiochemical probe for delta opioid receptors.


Persistence of airborne tree pollen from the Cupressaceae family during the last decade in the city of Bahia Blanca.
Airborne pollen is a major contributor to allergic respiratory diseases. However, the literature on patterns and seasonality of specific pollen types mainly comes from northern hemisphere and developed regions, limiting our ability to extrapolate these findings to other geographical locations. With this research letter, our aim is to contribute to the current knowledge of aerobiology by analyzing the decade-long patterns of airborne tree pollen in the city of Bahia Blanca, Argentina. In general, we found late winter to early spring as the period with the highest Cupressaceae pollen counts. In 2020, the average pollen count during July through September was 78.81 (SD 79.70), the highest recorded during the last 10 years. These months had varying pollen concentrations from moderate (15-89 grains/m3 of air) to high (90-1499 grains/m3 of air). Regardless of such variation, August had consistently been the month with the highest peak concentrations from 2010 to 2020 (61.2, SD 57.3), followed by September (27.1, SD 20.3). We did not find any month with very high (˃1500 grains/m3 of air) peak concentration. Further studies need to be done to expand our knowledge on aerobiology to characterize specific pollen sub-types and determine the exact allergenic potential of airborne pollen in different regions.


The huntingtin inclusion is a dynamic phase-separated compartment.
Inclusions of disordered protein are a characteristic feature of most neurodegenerative diseases, including Huntington's disease. Huntington's disease is caused by expansion of a polyglutamine tract in the huntingtin protein; mutant huntingtin protein (mHtt) is unstable and accumulates in large intracellular inclusions both in affected individuals and when expressed in eukaryotic cells. Using mHtt-GFP expressed in Saccharomyces cerevisiae, we find that mHtt-GFP inclusions are dynamic, mobile, gel-like structures that concentrate mHtt together with the disaggregase Hsp104. Although inclusions may associate with the vacuolar membrane, the association is reversible and we find that inclusions of mHtt in S. cerevisiae are not taken up by the vacuole or other organelles. Instead, a pulse-chase study using photoconverted mHtt-mEos2 revealed that mHtt is directly and continuously removed from the inclusion body. In addition to mobile inclusions, we also imaged and tracked the movements of small particles of mHtt-GFP and determine that they move randomly. These observations suggest that inclusions may grow through the collision and coalescence of small aggregative particles.


Integration of Friend murine leukemia virus into both alleles of the p53 oncogene in an erythroleukemic cell line.
The Friend virus-transformed erythroleukemic cell line DP16-9B4 has undergone a complex rearrangement of the p53 oncogene and lacks any detectable expression of the p53 protein. We report here characterization of both p53 alleles in this cell line and identify independent integrations of Friend murine leukemia virus sequences into the coding region of both alleles.


Mycobacterium abscessus Lung Disease in a Patient with Kartagener Syndrome.
Primary ciliary dyskinesia (PCD) is characterized by the congenital impairment of mucociliary clearance. When accompanied by situs inversus, chronic sinusitis and bronchiectasis, PCD is known as Kartagener syndrome. The main consequence of impaired ciliary function is a reduced mucus clearance from the lungs, and susceptibility to chronic respiratory infections due to opportunistic pathogens, including nontuberculous mycobacteria (NTM). There has been no report of NTM lung disease combined with Kartagener syndrome in Korea. Here, we report an adult patient with Kartagener syndrome complicated with Mycobacterium abscessus lung disease. A 37-year-old female presented to our hospital with chronic cough and sputum. She was ultimately diagnosed with M. abscessus lung disease and Kartagener syndrome. M. abscessus was repeatedly isolated from sputum specimens collected from the patient, despite prolonged antibiotic treatment. The patient's condition improved and negative sputum culture conversion was achieved after sequential bilateral pulmonary resection.


Expansion microscopy of Plasmodium gametocytes reveals the molecular architecture of a bipartite microtubule organisation centre coordinating mitosis with axoneme assembly.
Transmission of malaria-causing parasites to mosquitoes relies on the production of gametocyte stages and their development into gametes. These stages display various microtubule cytoskeletons and the architecture of the corresponding microtubule organisation centres (MTOC) remains elusive. Combining ultrastructure expansion microscopy (U-ExM) with bulk proteome labelling, we first reconstructed in 3D the subpellicular microtubule network which confers cell rigidity to Plasmodium falciparum gametocytes. Upon activation, as the microgametocyte undergoes three rounds of endomitosis, it also assembles axonemes to form eight flagellated microgametes. U-ExM combined with Pan-ExM further revealed the molecular architecture of the bipartite MTOC coordinating mitosis with axoneme formation. This MTOC spans the nuclear membrane linking cytoplasmic basal bodies to intranuclear bodies by proteinaceous filaments. In P. berghei, the eight basal bodies are concomitantly de novo assembled in a SAS6- and SAS4-dependent manner from a deuterosome-like structure, where centrin, γ-tubulin, SAS4 and SAS6 form distinct subdomains. Basal bodies display a fusion of the proximal and central cores where centrin and SAS6 are surrounded by a SAS4-toroid in the lumen of the microtubule wall. Sequential nucleation of axonemes and mitotic spindles is associated with a dynamic movement of γ-tubulin from the basal bodies to the intranuclear bodies. This dynamic architecture relies on two non-canonical regulators, the calcium-dependent protein kinase 4 and the serine/arginine-protein kinase 1. Altogether, these results provide insights into the molecular organisation of a bipartite MTOC that may reflect a functional transition of a basal body to coordinate axoneme assembly with mitosis.


On a new species of the spider genus Attacobius Mello-Leitão (Araneae: Corinnidae) from Brazilian Cerrado.
At the time the genus Attacobius Mello-Leitão, 1925 was first acknowledged as a member of the subfamily Corinninae, Corinnidae, by Platnick Baptista (1995), only three species were recognized. Since then, that number has increased to 15 currently valid species (Bonaldo Brescovit 1998; 2005; Pereira-Filho et al. 2018). Recently we had the opportunity to discover an additional species of Attacobius, collected in association with fire ants of the genus Solenopsis Westwood in the State of Goiás, Midwest Brazil, a region that harbors a large portion of the Brazilian Cerrado, one of the most threatened savannas in the planet. Attacobius lavape n. sp., described below, appears to belong to the same group of species as A. verhaaghi Bonaldo Brescovit, 1998 and A. lamellatus Bonaldo Brescovit, 2005, since these three species share, in the male palp, the presence of an unsclerotized median lobe on the retrolateral tibial apophysis (Figs 9, 11).


Fertility projection based on birth order data--a Swedish approach.
"The decreasing fertility rates in Sweden during the 1970s can be explained as postponement of childbearing. An increasingly larger part of each generation has chosen to bear children at a late age, after education and some years of occupational work. As a consequence, the yearly age-specific rates will, in years to come, change systematically towards relatively high rates for women in the second half of the fertile period; changes which are important in population projections. To predict the future rates a model based on birth order data and assumptions about the final family size is used. The model and its application in the 1989 projection of the Swedish population is discussed in the paper. Alternative projections and the assumptions behind the alternatives are specified."


Variable-temperature study of hydrogen-bond symmetry in cyclohexene-1,2-dicarboxylate monoanion in chloroform-d.
The symmetry of the hydrogen bond in hydrogen cyclohexene-1,2-dicarboxylate monoanion was determined in chloroform using the NMR method of isotopic perturbation. As the temperature decreases, the (18)O-induced (13)C chemical-shift separations increase not only at carboxyl carbons but also at ipso (alkene) carbons. The magnitude of the ipso increase is consistent with an (18)O isotope effect on carboxylic acid acidity. Therefore it is concluded that this monoanion is a mixture of tautomers in rapid equilibrium, rather than a single symmetric structure in which a chemical-shift separation arises from coupling between a desymmetrizing vibration and anharmonic isotope-dependent vibrations, which is expected to show the opposite temperature dependence.


A purple patch for evidence-based health policy?
The global focus on nation states' responses to the COVID-19 pandemic has rightly highlighted the importance of science and evidence as the basis for policy action. Those with a lifelong passion for evidence-based policy (EBP) have lauded Australia's and other nations' policy responses to COVID-19 as a breakthrough moment for the cause. This article reflects on the complexity of the public policy process, the perspectives of its various actors, and draws on Alford's work on the Blue, Red and Purple zones to propose a more nuanced approach to advocacy for EBP in health. We contend that the pathway for translation of research evidence into routine clinical practice is relatively linear, in contrast to the more complex course for translation of evidence to public policy - much to the frustration of health researchers and EBP advocates. Cairney's description of the characteristics of successful policy entrepreneurs offers useful guidance to advance EBP and we conclude with proposing some practical mechanisms to support it. Finally, we recommend that researchers and policy makers spend more time in the Purple zone to enable a deeper understanding of, and mutual respect for, the unique contributions made by research, policy and political actors to sound public policy.


The use of nalbuphine in paediatric anaesthesia.
Nalbuphine is an agonist-antagonist opioid. It causes analgesic and sedative effect and because of ceiling effect it does not cause a respiratory depression. In a perioperative therapy of paediatric patients it may be used for premedication, sedation during diagnostic procedures as well as for postoperative pain treatment. It reverses adverse reactions of other opioids such as itch or urinary retention, not significantly influencing its analgetic properties. After sevoflurane anaesthesia of small children, it reduces the incidences of emergence agitation. Nalbuphine is considered a safe drug, which causes nausea and vomiting less frequently than other opioids. Analgesic effect, the ability to provide moderate sedation and a large margin of safety make that analgesic often used for paediatric patients.


Effect of seminal plasma concentration and various extenders on postthaw motility and glass wool-Sephadex filtration of cryopreserved stallion semen.
To compare the effect of semen extender and seminal plasma on postthaw motility and filtration through a glass wool-Sephadex (GWS) filter for frozen stallion semen. 7 stallions from which we collected > or = 3 ejaculates/stallion. 4 experiments were conducted to evaluate postthaw quality of frozen stallion semen. Kenney extender was compared with glucose-EDTA extender by use of various dilution rates that resulted in differing concentrations of seminal plasma. Stallions known to produce semen with poor postthaw quality were used to investigate whether a particular extender or dilution rate could improve ability of such semen to survive freeze-thaw procedures. Use of Kenney extender as the centrifugation extender significantly improved postthaw motility and GWS filtration, compared with glucose-EDTA. Extending semen at a dilution of 1:3 was significantly better than 1:1 for both motility and GWS filtration. In addition, including seminal plasma at a concentration of 5% in the cryopreserved semen resulted in significantly higher yield of spermatozoa after GWS filtration, compared with complete removal of SP or use of seminal plasma at 25%. Lastly, semen with poor postthaw quality had significantly improved postthaw quality in regard to motility and GWS filtration when semen was frozen with seminal plasma at a concentration of 5%, compared with semen frozen with seminal plasma at a concentration of 25%. Use of Kenney extender at a high dilution (> or = 1:3) immediately after collection of semen can improve postthaw quality of frozen stallion semen.


Corneal manifestations and in vivo confocal microscopy of Gaucher disease.
To report corneal abnormalities and confocal microscopy findings in a patient with a variant of Gaucher disease (GD). Case report with slit-lamp photography, confocal microscopy, and molecular analysis of the glucocerebrosidase gene. Ophthalmic evaluation in a 57-year-old white patient demonstrated corneal opacities scattered throughout the cornea. Confocal microscopy revealed a completely distorted stromal architecture. The anterior part showed keratocytes with an abnormal morphology intermingled with minute white dots. In the posterior part, normal keratocytes were virtually absent and replaced by hyperreflective rod-like structures. Analysis of the glucocerebrosidase gene disclosed a heterozygous F216Y/L444P mutation. The patient's old records revealed that these corneal abnormalities were already present at the age of 16 years, almost 15 years before the diagnosis of GD was made. His 2 siblings known with the same disorder and mutations also showed abnormal visual acuity and increased central corneal thickness. The confocal microscopy demonstrated some subclinical abnormalities, but otherwise normal corneas. Our patient had an unusual mutation responsible for his GD. Although corneal opacities are virtually unknown in GD, except in the D409H homozygous cardiovascular subtype, this patient had marked corneal stromal abnormalities.


The role of casein kinase II in flowering time regulation has diversified during evolution.
Casein kinase II (CK2) is a protein kinase with an evolutionarily conserved function as a circadian clock component in several organisms, including the long-day plant Arabidopsis (Arabidopsis thaliana). The circadian clock component CIRCADIAN CLOCK ASSOCIATED1 (CCA1) is a CK2 target in Arabidopsis, where it influences photoperiodic flowering. In rice (Oryza sativa), a short-day plant, Heading date6 (Hd6) encodes a CK2alpha subunit that delays flowering time under long-day conditions. Here, we demonstrate that control of flowering time in rice by the Hd6 CK2alpha subunit requires a functional Hd1 gene (an Arabidopsis CONSTANS ortholog) and is independent of the circadian clock mechanism. Our findings from overexpressing the dominant-negative CK2 allele in rice support the independence of CK2 function from the circadian clock. This lack of control of the circadian clock by Hd6 CK2alpha might be due to the presence of glutamate in OsLHY (a CCA1 ortholog in rice) instead of the serine at the corresponding CK2 target site in CCA1. However, this glutamate is critical for the control of the OsPRR1 gene (a rice ortholog of the Arabidopsis TOC1/PRR1 gene) by OsLHY for regulation of the circadian clock. We also demonstrated that the other conserved CK2 target sites in OsLHY conferred robust rhythmic expression of OsLHY-LUC under diurnal conditions. These findings imply that the role of CK2 in flowering-time regulation in higher plants has diversified during evolution.


Inhibition of the early circulatory effects of triiodothyronine in rats by propranolol.
In two identical experiments, A and B, we studied the effect of the simultaneous l.v. injection of propranolol (Inderal, 0.5 mg/kg) on the circulatory effects of triiodothyronine (T3 500 microgram/kg i.v. 3 hours before measuring). The two substances act at different rates and so the blocking effect of propranolol preceded the development of the circulatory effects of T3. Cardiac output was measured by the Evans blue dilution method, the heart rate was calculated from the ECG recording and blood pressure was measured with a mercury manometer; stroke volume and total peripheral vascular resistance were also calculated. The isolated injection of T3 was followed by a significant increase in cardiac output (experiment A: 129%, B: 118%) and stroke volume (A: 125%, B: 118%) and by a drop in total peripheral vascular resistance (A: 82%, B: 85%). There was no change, in this early phase, in the heart rate or blood pressure. No changes were found 3 hours after the isolated administration of Inderal (the maximum effect of propranolol is attained in 30-60 min). During the same period, the above initial effects of T3 were completely suppressed by the simultaneous injection of Inderal. These results were probably related to the experimental conditions (early and not very marked changes after T3), but they demonstrate that the initial effects of T3 on cardiac performance and on the peripheral blood vessels can be completely suppressed by a block of beta receptors. From this it can be concluded that beta-adrenergic regulation is an important part of the mechanism of the early haemodynamic action of T3.


Differential production of interleukin-1 family cytokines (IL-1β, IL-18, IL-33 and IL-37) in patients with paracoccidioidomycosis: correlation with clinical form and antifungal therapy.
Besides interleukin (IL)-1β and IL-18, the newly described cytokines of IL-1 family IL-33 and IL-37 can contribute to the differentiation and maintenance of different population of T cells. IL-33 acts as an allarmin and promotes a predominant Th2 inflammatory response, whereas IL-37 plays an important role as an antagonist of inflammation. In paracoccidioidomycosis (PCM), caused by the dimorphic fungi Paracoccidioides brasiliensis and P. lutzii, it has been shown that the acquired immune responses are associated with the diverse clinical manifestations. The severe and disseminated forms (acute form [AF] and multifocal chronic form [CF-MF]) are characterized by high Th2 cytokines and antibody production, impaired cellular immune response, and eosinophilia. In contrast, in the localized form (unifocal chronic form [CF-UF]), the cellular immune response is preserved, with high production of Th1 and Th17 cytokines, and low antibody titers. This study aimed to quantify interleukin-1 family cytokines (IL-1β, IL-18, IL-37, IL-33, and the soluble IL-33 receptor sST2) in sera of patients presenting different clinical forms of PCM before, during, and after antifungal treatment, as well as to analyze the expression of these cytokines in lesions of PCM patients. We found that AF patients presented high serum levels of IL-1β, IL-18, IL-33, sST2, and IL-37, and that these cytokines are strongly expressed in lymph nodes lesions. Furthermore, antifungal therapy resulted in the diminution of circulating cytokines and sST2 levels in all groups of patients. These results indicate that, besides IL-1β and IL-18, IL-33, IL-37, and sST2 can be associated with the disease activity and severity.


The new polio eradication end game: rationale and supporting evidence.
Polio eradication requires the removal of all polioviruses from human populations, whether wild poliovirus or those emanating from the oral poliovirus vaccine (OPV). The Polio Eradication & Endgame Strategic Plan 2013-2018 provides a framework for interruption of wild poliovirus transmission in remaining endemic foci and lays out a plan for the new polio end game, which includes the withdrawal of Sabin strains, starting with type 2, and the introduction of inactivated poliovirus vaccine, for risk mitigation purposes. This report summarizes the rationale and evidence that supports the policy decision to switch from trivalent OPV to bivalent OPV and to introduce 1 dose of inactivated poliovirus vaccine into routine immunization schedules, and it describes the proposed implementation of this policy in countries using trivalent OPV.


Transforming Growth Factor-β Signaling Regulates Tooth Root Dentinogenesis by Cooperation With Wnt Signaling.
Proper differentiation of odontoblasts is crucial for the development of tooth roots. Previous studies have reported the osteogenic/odontogenic potential of pre-odontoblasts during root odontoblast differentiation. However, the underlying molecular pathway that orchestrates these processes remains largely unclear. In this study, ablation of transforming growth factor-β receptor type 2 (Tgfbr2) in root pre-odontoblasts resulted in abnormal formation of root osteodentin, which was associated with ectopic osteogenic differentiation of root odontoblasts. Disrupting TGF-β signaling caused upregulation of Wnt signaling characterized by increased Wnt6, Wnt10a, Tcf-1, and Axin2 expression. Interestingly, inhibiting Wnt signaling by deleting Wntless (wls) in Osteocalcin (Ocn)-Cre; Tgfbr2 fl/fl ; Wls fl/fl mice or overexpressing the Wnt antagonist Dkk1 in Ocn-Cre; Tgfbr2 fl/fl ; ROSA26 Dkk1 mice decreased ectopic osteogenic differentiation and arrested odontoblast differentiation. Our results suggest that TGF-β signaling acts with Wnt signaling to regulate root odontogenic differentiation.


The wise baby as the voice of the true self.
Sandor Ferenczi wrote about a typical dream of the "Wise Baby" and later used this figure to represent the child who is traumatized into precocious wisdom, who becomes "the family psychiatrist." We discuss Ferenczi's theory of traumatization and the "split self," noting how it was taken up in D. W. Winnicott's "True Self/False Self" conceptualization. We then present three patients' wise baby dreams to show how these trauma theories can be used in dream interpretation and how dream interpretation can support them.


Combined carotid and transcranial ultrasound findings compared with clinical classification and stroke severity in acute ischemic stroke.
The aim of this study was to assess the association between cerebral hemodynamics and the clinical picture as defined by the Oxfordshire Community Stroke Project (OCSP) classification, as well as the clinical severity as defined by the National Institute of Health Stroke Scale (NIHSS) within the first 6 h of an acute middle cerebral artery (MCA) stroke onset. 70 unselected patients were grouped according to the OCSP classification and NIHSS. All patients immediately had extracranial and transcranial Doppler (TCD) ultrasound examinations. In the study population as a whole, there was a significant association between intracranial vascular pathology and the OCSP classification (p<0.001) as well as the NIHSS score (p<0.001). In patients with severe stroke, however, TCD demonstrated the hypothesized proximal MCA(1) occlusion in only 34% of patients with an OCSP-defined total anterior circulation syndrome and in 42% of patients with an NIHSS score of >or=15. In moderate stroke, the OCSP classification was misleading in almost half of the patients with a partial anterior circulation syndrome, i.e. a hypothesized distal MCA(2) occlusion suitable for thrombolysis. Neither the OCSP classification nor the NIHSS grading provided reliable information about the site or presence of intracranial arterial occlusion in acute stroke within the first 6 h after stroke onset in the individual patient. The results of this study strongly suggest that selection of acute ischemic stroke patients for thrombolysis should also include an assessment of cerebral hemodynamics.


Immunostimulatory Properties of Chemotherapy in Breast Cancer: From Immunogenic Modulation Mechanisms to Clinical Practice.
Breast cancer (BC) is the most common malignancy among females. Chemotherapy drugs remain the cornerstone of treatment of BC and undergo significant shifts over the past 100 years. The advent of immunotherapy presents promising opportunities and constitutes a significant complementary to existing therapeutic strategies for BC. Chemotherapy as a cytotoxic treatment that targets proliferation malignant cells has recently been shown as an effective immune-stimulus in multiple ways. Chemotherapeutic drugs can cause the release of damage-associated molecular patterns (DAMPs) from dying tumor cells, which result in long-lasting antitumor immunity by the key process of immunogenic cell death (ICD). Furthermore, Off-target effects of chemotherapy on immune cell subsets mainly involve activation of immune effector cells including natural killer (NK) cells, dendritic cells (DCs), and cytotoxic T cells, and depletion of immunosuppressive cells including Treg cells, M2 macrophages and myeloid-derived suppressor cells (MDSCs). Current mini-review summarized recent large clinical trials regarding the combination of chemotherapy and immunotherapy in BC and addressed the molecular mechanisms of immunostimulatory properties of chemotherapy in BC. The purpose of our work was to explore the immune-stimulating effects of chemotherapy at the molecular level based on the evidence from clinical trials, which might be a rationale for combinations of chemotherapy and immunotherapy in BC.


Prophylactic effects of an N- and L-type Ca2+ antagonist, cilnidipine, against cardiac hypertrophy and dysfunction in stroke-prone, spontaneously hypertensive rats.
To clarify the beneficial effects of cilnidipine, an L- and N-type calcium channel blocker, which were clinically observed against diastolic dysfunction in hypertrophied hearts of hypertensive patients, we investigated the effects of cilnidipine on cardiac remodeling and enhanced gene expression in stroke-prone, spontaneously hypertensive rats in comparison with that of captopril, a well-known angiotensin-converting enzyme inhibitor, at threshold doses with little blood pressure lowering effect. The expression of type III collagen and beta/alpha-myosin heavy chain as well as transforming growth factor-beta, and basic fibroblast growth factor were suppressed by both treatments, indicating the prevention or amelioration of cardiac dysfunction. Such beneficial effects were much more intense with cilnidipine treatment than in captopril. These results indicate that Ca2+ is a key factor in the pathogenesis of cardiac remodeling in hypertension. One possible beneficial effect of cilnidipine in the prevention of cardiac dysfunction may be due to the decreased amount of growth factors such as transforming growth factor-beta and basic fibroblast growth factor via direct action for Ca2+ influx and also via inhibition of local renin-angiotensin system in the myocardium.


Virtual Reality and Human Consciousness: The Use of Immersive Environments in Delirium Therapy.
Immersive virtual environments can produce a state of behavior referred to as "presence," during which the individual responds to the virtual environment as if it were real. Presence can be arranged to scientifically evaluate and affect our consciousness within a controlled virtual environment. This phenomenon makes the use of virtual environments amenable to existing and in-development forms of therapy for various conditions. Delirium in the intensive care unit is one such condition for which virtual reality technology has not been evaluated to date. We are currently assessing the feasibility and utility of a delirium prevention and treatment system which implements virtual reality to improve quality of sleep, reduce pain, lower usage of sedatives, and stimulate cognition. The proposed system will consist of 3-axis wearable accelerometers, 6-DOF position trackers, a virtual reality system, and apps designed to promote sleep quality and mindfulness. Our a priori hypothesis is that our virtual reality therapy system would lower the occurrence of delirium in patients admitted to intensive care units.


High-efficiency Pd nanoparticles loaded porous organic polymers membrane catalytic reactors.
An innovative tactic to prepare porous organic polymer membranes was developed via interfacial azo-coupling polymerization. The membranes possess plentiful anchoring sites for loading Pd nanoparticles, and served as a membrane reactor, which exhibits high-performance catalytic reduction with a flux of 27.3 t m-2 day-1 and good long-term stability due to almost zero Pd leaching.


Variation on islands: major histocompatibility complex (Mhc) polymorphism in populations of the Australian bush rat.
Loss of genetic variation in small, isolated populations is commonly observed at neutral or nearly neutral loci. In this study, the loss of genetic variation was assessed in island populations for a locus of major histocompatibility complex (Mhc), a locus shown to be under the influence of balancing selection. A total of 36 alleles was found at the second exon of RT1.Ba in 14 island and two mainland populations of Rattus fuscipes greyii. Despite this high overall diversity, a substantial lack of variation was observed in the small island populations, with 13 islands supporting only one to two alleles. Two populations, Waldegrave and Williams Islands, showed moderately high levels of heterozygosity (52-56%) which were greater than expected under neutrality, suggesting the action of balancing selection. However, congruence between the level of variation at this Mhc locus and in previous allozyme electrophoresis and mitochondrial DNA studies highlights the dominant influence of genetic drift and population factors, such as bottlenecks and structuring in the founding population, in the loss of genetic variation in these small, isolated populations.


Cyanobacterial Mn-catalase 'KatB': Molecular link between salinity and oxidative stress resistance.
Catalases are ubiquitous enzymes that detoxify H2O2 in virtually all organisms exposed to oxygen. The filamentous, nitrogen-fixing cyanobacterium, Anabaena PCC 7120, shows the presence of 2 genes (katA and katB) that encode Mn-catalases. We have recently shown that pre-treatment of Anabaena with NaCl causes substantial induction of the KatB protein, which consequently leads to increased oxidative stress resistance in that cyanobacterium. Interestingly, when compared to the wild-type, the katB mutant shows decreased growth and impaired photosynthetic activity in the presence of NaCl. Furthermore, the NaCl-treated katB mutant is extremely sensitive to H2O2. In this study, the ultrastructural changes occurring in the katB mutant and the wild-type Anabaena cells are analyzed to understand the cellular basis of the above-mentioned protective phenomena. Other data show that a wide variety of osmolytes induce katB expression in Anabaena, indicating that katB is a genuine osmo-inducible gene. These results have important biotechnological implications for the development of novel cyanobacterial biofertilzers and transgenic plants with improved resistance to salinity.


Analysis of the mechanism of graft-versus-host-like disease in B6 mice with transferred B6-lpr spleen cells.
Irradiated C57BL/6(B6) mice, when they were injected with spleen cells of C57BL/6J-lpr/lpr(B6-lpr) mice, developed splenomegaly at 2 weeks post-transfer, but afterward displaced by GVH-like disease. At 2 weeks the enlarged spleen in the chimeric mice, designated as [B6-lpr----B6] chimera, contained about 70% of the total cell population as CD8-positive T cells. Spleen cells from [B6-lpr----B6] chimeras were unresponsive to Con A and LPS stimulation and suppressed the mitogenic response of B6, B6-lpr, and C3H spleen cells to Con A. However, they had no cytotoxic activity towards Con A blasts of B6 and B6-lpr spleen cells. The suppressor activity found in the [B6-lpr----B6] spleen cells was removed by pretreatment of them with anti-Thy-1.2 or anti-CD8(Lyt2.2) plus complement. The present experiment showed that enormous proliferation of CD8-positive suppressor T cells was induced in the [B6-lpr----B6] chimeras. These cells were probably responsible for the GVH-like lymphoid atrophy observed in these [B6-lpr----B6] chimeras.


Postpartum return to work: mothering stress, anxiety, and gratification.
Over half of mothers with infants less than 1 year old are employed, yet there is limited research examining the early parenting experiences of these women. The purpose of this study was to examine maternal gratification, stress, and separation anxiety, in relation to employment patterns and selected health-status indicators, of women returning to work during the first postpartum year. Data were gathered from 142 employed, well-educated, partnered, predominantly Caucasian women at 1, 4, and 8 months postpartum, using a mailed questionnaire. Their parenting experiences improved throughout the first postpartum year. While depression and fatigue were associated with greater parenting stress and anxiety, as well as a decreased sense of gratification from parenting, few women experienced these symptoms at clinically significant levels. Employment patterns were unrelated to parenting stress or gratification. These findings can be used by clinicians when counselling women regarding the decision to return to work after childbirth.


Intermolecular insertion of an N,N-heterocyclic carbene into a nonacidic C-H bond: Kinetics, mechanism and catalysis by (K-HMDS)2 (HMDS = Hexamethyldisilazide).
The reaction of 2-[13C]-1-ethyl-3-isopropyl-3,4,5,6-tetrahydropyrimidin-1-ium hexafluorophosphate ([13C1]-1-PF6) with a slight excess (1.03 equiv) of dimeric potassium hexamethyldisilazide ("(K-HMDS)2") in toluene generates 2-[13C]-3-ethyl-1-isopropyl-3,4,5,6-tetrahydropyrimid-2-ylidene ([13C1]-2). The hindered meta-stable N,N-heterocyclic carbene [13C1]-2 thus generated undergoes a slow but quantitative reaction with toluene (the solvent) to generate the aminal 2-[13C]-2-benzyl-3-ethyl-1-isopropylhexahydropyrimidine ([13C1]-14) through formal C-H insertion of C2 (the "carbene carbon") at the toluene methyl group. Despite a significant pKa mismatch (Delta pKa 1+ and toluene estimated to be ca. 16 in DMSO) the reaction shows all the characteristics of a deprotonation mechanism, the reaction rate being strongly dependent on the toluene para substituent (rho = 4.8(+/-0.3)), and displaying substantial and rate-limiting primary (k(H)/k(D) = 4.2(+/-0.6)) and secondary (k(H)/k(D) = 1.18(+/-0.08)) kinetic isotope effects on the deuteration of the toluene methyl group. The reaction is catalysed by K-HMDS, but proceeds without cross over between toluene methyl protons and does not involve an HMDS anion acting as base to generate a benzyl anion. Detailed analysis of the reaction kinetics/kinetic isotope effects demonstrates that a pseudo-first-order decay in 2 arises from a first-order dependence on 2, a first-order dependence on toluene (in large excess) and, in the catalytic manifold, a complex noninteger dependence on the K-HMDS dimer. The rate is not satisfactorily predicted by equations based on the Brønsted salt-effect catalysis law. However, the rate can be satisfactorily predicted by a mole-fraction-weighted net rate constant: -d[2]/dt = ({x2 k(uncat)} + {(1-x2) k(cat)})[2]1[toluene]1, in which x2 is determined by a standard bimolecular complexation equilibrium term. The association constant (Ka) for rapid equilibrium-complexation of 2 with (K-HMDS)2 to form [2(K-HMDS)2] is extracted by nonlinear regression of the 13C NMR shift of C2 in [13C1]-2 versus [(K-HMDS)2] yielding: Ka = 62(+/-7) M(-1); delta(C(2)) in 2=237.0 ppm; delta(C(2)) in [2(K-HMDS)2] = 226.8 ppm. It is thus concluded that there is discrete, albeit inefficient, molecular catalysis through the 1:1 carbene/(K-HMDS)2 complex [2(K-HMDS)2], which is found to react with toluene more rapidly than free 2 by a factor of 3.4 (=k(cat)/k(uncat)). The greater reactivity of the complex [2(K-HMDS)2] over the free carbene (2) may arise from local Brønsted salt-effect catalysis by the (K-HMDS)2 liberated in the solvent cage upon reaction with toluene.


Bridge to transplantation with the CardioWest total artificial heart: the international experience 1993 to 1995.
After reapproval by the Food and Drug Administration of the CardioWest total artificial heart for clinical investigation, an international study was started in January 1993 to ascertain the safety and efficacy of this device for bridging to heart transplantation. To date, 40 devices have been implanted in five centers. Retrospective data collection from participating centers provided enough material for analysis of patient selection, patient survival, adverse events, and comparison with contemporary devices used for bridge to transplantation. Twelve patients (30%) died after implantation and before transplantation after an average of 10.6 +/- 10 days of support. The major cause of death in this group was multiorgan failure. Twenty-eight patients (70%) were supported 36 +/- 36 days before transplantation. There were two deaths after transplantation (1 rejection, 1 multiorgan failure) leaving 26 patients (65% of the total patients and 93% of those who were transplanted) who survived to discharge from the hospital. There was one late death from rejection at one month post discharge. The mean survival time of the 25 surviving patients is 12 months. These results compare favorably with those of other contemporary devices used for bridge to transplantation.


An unusual case with a missing parotid gland: A case report.
Unilateral or bilateral agenesis of the parotid gland is an uncommon condition with unclear aetiology. Only 22 cases of unilateral salivary agenesis have been reported excluding the present case. We present a case of a 4-year-old female child who presented with complaints of slight discoloration of her tongue and was referred for MRI to rule out any vascular malformation. Imaging revealed a complete absence of the right parotid gland. Hypertrophy of the sublingual gland and hypoplasia of the parotid gland on the opposite side was also noted, an unusual finding as the contralateral parotid showed compensatory hypertrophy in the other reported cases.


Cardiac resynchronization therapy-heart failure (CRT-HF) clinic: A novel model of care.
Post-implant care of patients with heart failure (HF) undergoing cardiac resynchronization therapy (CRT) is not addressed in current HF or CRT guidelines and is often fragmented with poor communication between specialties. We sought to develop a new model of post-CRT care which could be implemented in busy clinical settings. We designed a novel, multidisciplinary approach to standardizing post CRT care. All patients receiving a CRT device at the Cleveland Clinic between March 2017 and August 2018 were invited to be seen in the clinic 6 months post implant. A one-time collaborative visit encompassing cardiac imaging, heart failure, and electrophysiology care was performed. We recorded the operational feasibility of the clinic in terms of patient throughput as well as patient characteristics, interventions, and new diagnoses made. Between September 2017 and February 2019, 150 patients were seen in the clinic. Of these, 125 patients had their index CRT implanted for standard indications and were included in the current analysis. Approximately 45 minutes were dedicated for each patient visit. Interventions in care were made in 95% of patients, with CRT non-responders offered a higher number of interventions as compared to responders (median 3 versus 2 interventions). Types of interventions were device-related (26% of population), medication-related (74%), and referral for alternate medical services (80%). Multidisciplinary post-implant care of patients with HF receiving CRT devices, regardless of CRT response status, is feasible and results in frequent medical interventions.


A Simple Method to Optimize the Effectiveness of Chemotherapy: Modulation of Glucose Intake During Chemotherapy.
Cancer cells consume high amounts of glucose to produce ATP and molecules entering biosynthesis. Numerous experimental studies have demonstrated that glucose deprivation and/or glycolysis inhibition arrest cancer cell growth and may increase the efficiency of cytotoxic drugs. In contrast, increasing glycolysis in tumor-infiltrating lymphocytes (TILs) activates these cells that destroy cancer cells. We propose to increase the efficiency of chemotherapy by modulating glucose intake during the course of chemotherapy. Glucose and caloric intake should be drastically reduced the day before and during chemotherapy administration to deprive cancer cells of ATP and molecules required to repair cytotoxic lesions. Few hours after chemotherapy, glucose and caloric intake should be drastically increased for few days to promote the activation of TILs that reinforce the destruction of cancer cells. This strategy could improve the results of chemotherapy by first enhancing cytotoxic stress against tumor cells and then promoting activation of the anti-cancer immune response. The modulation of glucose intake during chemotherapy should be tested clinically. The proposed scheme is simple, surely easier to follow than a strict chronic diet, and should avoid weight loss.


Circulation of mumps virus genotypes in Spain from 1996 to 2007.
Although the WHO recommends the use of genotyping as a tool for epidemiological surveillance for mumps, limited data on mumps virus (MV) genotype circulation that may be used to trace the patterns of virus spread are available. We describe the first complete series of data from Spain. The small hydrophobic region was sequenced from 237 MV-positive samples from several regions of Spain collected between 1996 and 2007. Six different genotypes were identified: A, C, D (D1), G (G1, G2), H (H1, H2), and J. Genotype H1 was predominant during the epidemic that occurred from 1999 to 2003 but was replaced by genotype G1 as the dominant genotype in the epidemic that occurred from 2005 to 2007. The same genotype G1 strain caused concomitant outbreaks in different parts of the world (the United States, Canada, and the United Kingdom). The remaining genotypes (genotypes A, C, D, and J) appeared in sporadic cases or small limited outbreaks. This pattern of circulation seems to reflect continuous viral circulation at the national level, despite the high rates of vaccine coverage.


The Association of Cardio-Ankle Vascular Index and Ankle-Brachial Index with Macroangiopathy in Patients with Type 2 Diabetes Mellitus.
This study elucidates the association of macroangiopathy development in type 2 diabetes patients with various arteriosclerosis risk factors (ARFs) and results of cardio-ankle vascular index (CAVI) and ankle-brachial pressure index (ABI). The correlation between current and past macroangiopathy development, with ARFs or CAVI/ABI data, was retrospectively analyzed using multivariate logistic regression in 816 patients with type 2 diabetes at a single center. C-statistics combining some independent variables selected using the stepwise method were evaluated. CAVI was significantly correlated with macroangiopathies, including coronary artery disease (CAD), arteriosclerosis obliterans (ASO), and stroke with odds ratios (OR) of 1.20, 1.22, and 1.19, respectively. ABI significantly correlated with ASO and stroke with respective OR of 13.6 and 2.47, but not with CAD. Areas under the receiver operating characteristic curves (ROCs) revealed the accuracy of detecting ASO and stroke was increased by the combination of CAVI+ABI (0.94 and 0.74, respectively). However, areas under the ROC for the presence of CAD can be increased by the combination of CAVI and ARFs especially including dyslipidemia. CAVI/ABI and some ARFs are useful tools in daily clinical care units to identify the current and past existence of macroangiopathy in patients with type 2 diabetes, but the prediction weights using these factors were different among CAD, ASO, and stroke.


CORM-3, a water soluble CO-releasing molecule, uncouples mitochondrial respiration via interaction with the phosphate carrier.
Carbon monoxide is continuously produced in small quantities in tissues and is an important signaling mediator in mammalian cells. We previously demonstrated that CO delivered to isolated rat heart mitochondria using a water-soluble CO-releasing molecule (CORM-3) is able to uncouple mitochondrial respiration. The aim of this study was to explore more in depth the mechanism(s) of this uncoupling effect. We found that acceleration of mitochondrial O2 consumption and decrease in membrane potential induced by CORM-3 were associated with an increase in mitochondrial swelling. This effect was independent of the opening of the mitochondrial transition pore as cyclosporine A was unable to prevent it. Interestingly, removal of phosphate from the incubation medium suppressed the effects mediated by CORM-3. Blockade of the dicarboxylate carrier, which exchanges dicarboxylate for phosphate, decreased the effects induced by CORM-3 while direct inhibition of the phosphate carrier with N-ethylmaleimide completely abolished the effects of CORM-3. In addition, CORM-3 was able to enhance the transport of phosphate into mitochondria as evidenced by changes in mitochondrial phosphate concentration and mitochondrial swelling that evaluates the activity of the phosphate carrier in de-energized conditions. These results indicate that CORM-3 activates the phosphate carrier leading to an increase in phosphate and proton transport inside mitochondria, both of which could contribute to the non-classical uncoupling effect mediated by CORM-3. The dicarboxylate carrier amplifies this effect by increasing intra-mitochondrial phosphate concentration.


Antigenotoxic Effect of Curcumin and Carvacrol against Parathion Induced DNA Damage in Cultured Human Peripheral Blood Lymphocytes and Its Relation to GSTM1 and GSTT1 Polymorphism.
In recent years, the use of organophosphorus pesticides has been extensively increased and these compounds signify a major class of agricultural pesticides today. We studied antigenotoxic potential of curcumin and carvacrol against the parathion induced DNA damage in cultured peripheral blood lymphocytes using sister chromatid exchanges as a biomarker of genotoxicity. Heparinised fresh blood from healthy individuals was treated with 2.5 μg/mL concentration of parathion in presence of curcumin and carvacrol in order to observe the antigenotoxic potential of both curcumin and carvacrol. Significant reduction (P < 0.05) was observed in the frequencies of SCEs in presence of 10 μg/mL and 15 μg/mL concentrations of curcumin as compared to parathion exposed sample. Similarly carvacrol had significant (P < 0.05) antigenotoxic effect at the concentrations of 2.5 μg/mL and 5.0 μg/mL against the parathion. We also studied the effect of GSTT1 and GSTM1 on genotoxicity of parathion and antigenotoxic potential of curcumin and carvacrol. We did not observe any significant effect (P > 0.05) of GSTT1 and GSTM1 polymorphism on genotoxicity of parathion and antigenotoxic potential of curcumin and carvacrol.


Assistive technology to improve PC interaction for people with intention tremor.
Many patients with upper limb intention tremor encounter difficulties in mouse-driven interaction with the personal computer (PC). An assistive technology system ("the Tremor Control System"), consisting of a motion-filtering software program that supports multiple interfaces, was developed and validated with 36 persons with Multiple Sclerosis in a multi-center trial. PC-tests, requiring basic functions such as cursor placement and click and drag function, were able to differentiate between patients and control subjects (ANOVA: p<0.05). A significant time improvement on the PC-tests was found when using an optimal alternative interface instead of the standard PC-mouse (paired t-tests: p<0.01 for Point & Click test, p<0.05 for Drag & Drop test and p<0.1 for Double Click test). A significant time improvement was found for the Double Click test (paired t-tests: p<0.05) when the motion-filtering program was implemented. The number of patients able to perform fully the PC-tests increased with the Tremor Control System. Patients with marked intention tremor seemed to profit especially from this assistive technology. These users reported that working with the Tremor Control System was less fatiguing and more comfortable compared to the use of the standard PC-mouse.


Defensive Armor of Potato Tubers: Nonpolar Metabolite Profiling, Antioxidant Assessment, and Solid-State NMR Compositional Analysis of Suberin-Enriched Wound-Healing Tissues.
The cultivation, storage, and distribution of potato tubers are compromised by mechanical damage and suboptimal healing. To investigate wound-healing progress in cultivars with contrasting russeting patterns, metabolite profiles reported previously for polar tissue extracts were complemented by GC/MS measurements for nonpolar extracts and quantitative (13)C NMR of interfacial solid suspensions. Potential marker compounds that distinguish cultivar type and wound-healing time point included fatty acids, fatty alcohols, alkanes, glyceryl esters, α,ω-fatty diacids, and hydroxyfatty acids. The abundant long-chain fatty acids in nonpolar extracts and solids from the smooth-skinned Yukon Gold cultivar suggested extensive suberin biopolymer formation; this hypothesis was supported by high proportions of arenes, alkenes, and carbonyl groups in the solid and among the polar markers. The absence of many potential marker classes in nonpolar Atlantic extracts and interfacial solids suggested a limited extent of suberization. Modest scavenging activities of all nonpolar extracts indicate that the majority of antioxidants produced in response to wounding are polar.


Development of high-grade B-cell lymphoma concurrent with T-cell chronic lymphocytic leukemia in a dog.
Second malignancies are frequent complications in human patients with chronic lymphocytic leukemia (CLL). However, the clinical details and outcome of this phenomenon were unclear in their canine counterparts. Here, we report a dog with high-grade lymphoma concurrent with T-cell CLL. A 10-year-old male golden retriever presented with lymphadenopathies. The lymph nodes contained large-sized lymphocytes, raising suspicion of high-grade lymphoma. Meanwhile, small lymphocytic lymphocytosis in the peripheral blood was consistent with CLL. Interestingly, molecular biological analyses revealed that CLL cells were of the T-cell type, whereas lymphoma cells were of the B-cell type. Chemotherapy using the L-VCA short protocol was effective for 155 days, but the dog died on day 194 after diagnosis, despite rescue therapies.


Pharmacological studies of cisplatin encapsulated in long-circulating liposomes in mouse tumor models.
We investigated the pharmacokinetics and therapeutic efficacy of cisplatin encapsulated in polyethyleneglycol-coated long-circulating liposomes in a formulation referred to as SPI-077, in three mouse tumor models (M-109 lung carcinoma inoculated s.c., J-6456 lymphoma inoculated i.p. and A-375 melanoma inoculated s.c.). Tumor-bearing mice were injected i.v. with single doses of SPI-077 and cisplatin. For pharmacokinetic experiments, mice were sacrificed at different timepoints post-treatment. Platinum levels were determined in plasma, spleen, liver, kidneys and tumors using flameless atomic absorption spectrophotometry. Survival times and/or tumor size were recorded for therapeutic studies. The pharmacokinetic studies revealed a prolonged circulation time and enhanced tumor uptake for SPI-077. In contrast to these results, no superior antitumor activity of SPI-077 over cisplatin could be observed in all tumor models. In vitro release experiments showed a negligible release (below 10%) of platinum from the liposomes. An in vitro cytotoxicity assay indicated a reduced cytotoxic activity of SPI-077 in comparison to cisplatin. We concluded that SPI-077 is being delivered to the tumor sites in a low bioavailability form, with extremely slow release kinetics. This explains the discrepant results of high platinum concentrations in tumors and reduced therapeutic activity after administration of SPI-077.


Second-trimester levels of maternal urinary gonadotropin peptide in Down syndrome pregnancy.
Urinary gonadotropin peptide (UGP; beta-core fragment), a major metabolite of human chorionic gonadotropin (hCG), was shown recently to be markedly elevated in Down syndrome pregnancy between 19 and 22 weeks of gestation. To confirm and extend this finding, we obtained maternal urine and matching maternal serum samples from 14 cases of Down syndrome and six other aneuploidies between 17 and 21 weeks of gestation. UGP was measured in all these samples and in 91 singleton control urines. Results were corrected for urinary creatinine level and expressed as multiples of the control median (MOM). hCG levels were assayed in all serum samples from the cases and compared with previously established reference values. The median UGP level in Down syndrome cases was 5.34 MOM (range 2.71-12.57); 88 per cent of the values were above the 95th centile of control levels after modelling. The median maternal serum hCG level for the same cases was 2.20 MOM (range 0.84-3.40); 36 per cent of the values were above the 95th centile. The level of UGP in every case including all other aneuploidies was higher than the comparable maternal serum hCG level. Elevated UGP measurements are strongly associated with fetal Down syndrome during the second trimester and could contribute to improved Down syndrome screening protocols that are more accessible and less expensive than are currently available.


[Case report of malignant sertoli cell tumor].
Malignant sertoli cell tumor is a rare disease and only a few cases have been described previously. We report a terminal case of malignant sertoli cell tumor. A 38-year-old male visited a hospital with a complaint of swelling his left testis. He underwent high left orchiectomy. His pathologic diagnosis was suspected seminoma, and all tumor markers (LDH, HCG, AFP) were negative, and CT imaging confirmed clinical stage 1 (pT1N0M0S0). One year later, a CT scan showed a small retroperitoneum lymph node swelling. Four months later, these lesions increased to 55 x 45 x 70 mm in diameter. He received 3 courses of chemotherapy with BEP (bleomycine, etoposide, cisplatin), but, lymph node size did not change. After he underwent a CT guided lymph node biopsy, his pathologic diagnosis was viable embryonal carcinoma. He then came to our hospital. We selected CPT-11 and nedaplatin for his salvage chemotherapy, but lymph node lesions did not change. After he received 3 courses of chemotherapy, we performed retroperitoneal lymphadenectomy. His pathologic diagnosis was viable sertoli cell tumor, malignant type. After 30 days, he had multiple liver metastases ane died 27 months after orchiectomy. All tumor markers were negative in his all clinical courses.


Management of Locally Advanced and Unresectable Small Bowel Neuroendocrine Tumours.
Three subtypes of small bowel neuroendocrine tumours (SBNETs) have been described: Type A: SBNET with resectable mesenteric disease that does not involve the mesenteric root; Type B: "Borderline resectable" SBNET presenting with mesenteric nodal metastases and fibrosis adjacent but not encasing the main trunk of the superior mesenteric artery (SMA) and superior mesenteric vein (SMV); and Type C: "Locally advanced or irresectable" SBNET where tumour deposits and fibrosis encase the SMA and SMV. Type C SBNETs are rare and constitute around 5% of patients in reported series, although this may underestimate the prevalence. In these patients, almost all will present with symptoms of intestinal ischemia or obstruction and symptom management should be a primary main focus of treatment. All patients should be carefully staged with cross-sectional imaging and 68 Ga-dotate positron emission tomography, and discussed at a dedicated neuroendocrine tumour multidisciplinary meeting. Expert surgical review should always be sought as experienced centers have a high rate of successful resection of primary tumours and mesenteric disease. If resection is not feasible, surgical bypass should be considered in patients with a discrete and symptomatic point of obstruction. Non-operative management should emphasize symptomatic treatment with somatostatin analogs, nutritional advice and support and palliative care. Successful neoadjuvant approaches utilizing peptide radionucleide receptor therapy and systemic chemotherapy with everolimus or temazolamide/capecitabine have not been reported.


Changing Provider Behavior in the Context of Chronic Disease Management: Focus on Clinical Inertia.
Widespread acceptance of evidence-based medicine has led to the proliferation of clinical practice guidelines as the primary mode of communicating current best practices across a range of chronic diseases. Despite overwhelming evidence supporting the benefits of their use, there is a long history of poor uptake by providers. Nonadherence to clinical practice guidelines is referred to as clinical inertia and represents provider failure to initiate or intensify treatment despite a clear indication to do so. Here we review evidence for the ubiquity of clinical inertia across a variety of chronic health conditions, as well as the organizational and system, patient, and provider factors that serve to maintain it. Limitations are highlighted in the emerging literature examining interventions to reduce clinical inertia. An evidence-based framework to address these limitations is proposed that uses behavior change theory and advocates for shared decision making and enhanced guideline development and dissemination.


Electrospun Enzymatic Hydrolysis Lignin-Based Carbon Nanofibers as Binder-Free Supercapacitor Electrodes with High Performance.
Carbon nanofibers consisting of Poly(acrylonitrile) (PAN) and enzymatic hydrolysis lignin (EHL) were prepared in the present study by electrospinning followed by stabilization in air and carbonization in N₂ environment. The morphology and structure of the electrospun carbon nanofibers were characterized by Scanning Electron Microscopy (SEM), Brunauer-Emmett-Teller (BET), Roman, and the electrochemical performances were then evaluated by cyclic voltammetry (CV), galvanostatic charge-discharge (GCD), and electrochemical impedance spectroscopy (EIS)methods. When the amount of EHL was 60 wt. %, the as-prepared nanofibers have the smallest average diameter of 172 nm and the largest BET specific surface area of 675 m²/g without activating treatment. The carbon nanofiber electrode showed excellent specific capacitance of 216.8 F/g at the current density of 1 A/g, maintaining 88.8% capacitance retention after 2000 cycles. Moreover, the carbon nanofiber electrode containing 60 wt. % exhibited a smaller time constant (0.5 s) in comparison to that of carbon nanofibers in literatures. These findings suggest the potential use of EHL could be a practical as a sustainable alternative for PAN in carbon electrode manufacturing.


Extended soft X-ray emission spectroscopy: quantitative assessment of emission intensities.
Soft X-ray emission spectroscopy (SXES) in the energy range between 150 eV and 1500 eV has typical attenuation lengths between tens and a few hundred nanometres. In this work the transmission of soft X-rays in synchrotron-based SXES has been quantitatively analysed using specially prepared layer samples. The possibility of extending the standard qualitative analysis of SXES by exploiting the information underlying the emission intensity was examined for thin layer structures. Three different experiment series were accomplished with model layer systems based on different sulfur-containing substrates: (i) MoS(2), (ii) CuInS(2), (iii) Cu(In,Ga)(S,Se)(2). The absorption of the S L(2,3) emission line by ZnO cover layers of up to 80 nm thickness was monitored and compared with theoretical expectations. By comparison with a reference intensity recorded from a bare substrate, the attenuation of the S L(2,3) emission could be used to accurately determine the ZnO overlayer thickness up to a critical thickness, depending on the set-up and the net S L(2,3) emission intensity. The results from these local energy-resolved spot measurements were compared with spatially resolved scans of the integral S L(2,3) emission intensity over areas of several mm(2). In the scan images the attenuation of the S L(2,3) emission intensity clearly reflects the local ZnO layer thickness. From the attenuation the ZnO layer thicknesses were calculated and compared with ellipsometric measurements and were found to be in excellent agreement. These results demonstrate the benefits of a quantitative analysis of SXES, making it an even more powerful tool for examining buried interfaces and for monitoring lateral inhomogeneities.


[Effects of some chemical and physical agents on the metacestode Taenia solium in spicy meat and sausage].
To assess the effect of different cooking times and temperatures, as well as of some seasonings, on the viability of Taenia solium metacestodes in spicy meat and hot sausage. This study was conducted by the Universidad Autónoma de Guerrero (Guerrero State Autonomous University), Mexico in 1999. Infected pork meat was bought in the community of Azacoaloya, in the municipality of Chilapa de Alvarez, Guerrero State. It was used to prepare spicy meat (adobada) and hot sausage (chorizo). Only the meat in which metacestode viability was proven was used. The products obtained underwent a) room temperature for 12 to 100 hours; b) temperatures of -10 to 37 degrees C for 24 hours; c) boiling (97 degrees C) from 1 to 15 minutes. To determine the effect of the seasonings, batches were prepared using twice the amount of a specific seasoning. Trials were done and assessed three times. Proportion differences were established using the chi-squared test. At room temperature the lowest evagination occurred after 100 hours for both products (p<0.05). After 24 hours, the lowest evagination occurred at -10 degrees C in spicy meat and at 37 degrees C in hot sausage (p<0.05). At boiling temperature there was no evagination after 10 minutes (p<0.05). In spicy meat, adding salt caused the most significant reduction; in hot sausage, thyme caused the most significant reduction (p<0.05). Meat with metacestodes should not be eaten, yet, it is being sold and used to prepare spicy meats. Adding spices can hide the metacestode, thus, adequate cooking of these meat products is necessary. These meats may be consumed at least four days after its preparation and spicy meat after a minimum of four days of refrigeration. The English version of this paper is available at: http://www.insp.mx/salud/index.html.


Virus load during primary Human Immunodeficiency Virus (HIV) type 1 infection is related to the severity of acute HIV illness in Kenyan women.
We evaluated the association between the severity of primary human immunodeficiency virus type 1 (HIV-1) illness and HIV-1 plasma virus load before seroconversion using stored plasma samples obtained from 74 prostitutes in Mombasa, Kenya. Fever, vomiting, headache, fatigue, arthralgia, myalgia, sore throat, skin rash, or being too sick to work were each associated with significantly higher virus loads before HIV-1 seroconversion, and each additional symptom or sign was associated with an increase in virus load of 0.4 log(10) copies/mL.


Clinical presentations of suicidality in relation to medical assistance in dying.
This study explores the assessments of mental health clinicians working with suicidal patients who requested access to medical assistance in dying (MAiD). A sample of convenience completed an online questionnaire about their experiences with suicidal patients. Respondents described their encounters with 227 suicidal patients: 44 requested access to MAiD, and 183 did not. Data were analyzed using chi-squared and simple t-test to identify differences between the respondents' descriptions of the two groups. Results noted differences between patients who experience suicide ideation and request MAiD (SPM), and those who experience suicide ideation and do not (SP). Overall, the SPM group was older, more physical health concerns, chronic pain, existential distress, and less hope. Many had experienced several episodes of mental health care and medication trials, though unlike the SP group, they had a split between accessing a little care and a lot of care. They also engaged in less suicide planning, and some had no history of suicide attempts. It is important that mental health clinicians learn to differentiate between MAiD requests due to an ongoing and irremediable mental disorder, and MAiD requests in response to circumscribed psychological suffering that could be relieved via a change in circumstances and/or access to different treatment options amenable to the patient.


Block to the production of full-length B19 virus transcripts by internal polyadenylation is overcome by replication of the viral genome.
The pre-mRNA processing strategy of the B19 virus is unique among parvoviruses. B19 virus-generated pre-mRNAs are transcribed from a single promoter and are extensively processed by alternative splicing and alternative polyadenylation to generate 12 transcripts. Blockage of the production of full-length B19 virus transcripts at the internal polyadenylation site [(pA)p] was previously reported to be a limiting step in B19 virus permissiveness. We show here that in the absence of genome replication, internal polyadenylation of B19 virus RNAs at (pA)p is favored in cells which are both permissive and nonpermissive for B19 viral replication. Replication of the B19 virus genome, however, introduced either by viral infection or by transfection of an infectious clone into permissive cells or forced by heterologous replication systems in nonpermissive cells, enhanced readthrough of (pA)p and the polyadenylation of B19 virus transcripts at the distal site [(pA)d]. Therefore, replication of the genome facilitates the generation of sufficient full-length transcripts that encode the viral capsid proteins and the essential 11-kDa nonstructural protein. Furthermore, we show that polyadenylation of B19 viral RNA at (pA)p likely competes with splicing at the second intron. Thus, we conclude that replication of the B19 virus genome is the primary limiting step governing B19 virus tropism.


Successful anticoagulation with fresh frozen plasma for cardiopulmonary bypass in a patient with heparin resistance: a cautionary tale.
Heparin resistance (HR) is an increasingly common occurrence due to a greater awareness of the benefits of antithrombosis prophylaxis in hospitalised patients with low molecular weight and unfractionated heparin. Furthermore as more high-risk patients with prior heparin exposure undergo cardiac surgery we can expect to encounter more such cases. Adequate anticoagulation is essential for the safe conduct of any operation requiring cardiopulmonary bypass and is usually achieved with systemic heparinisation. We report a case of successful anticoagulation with the intraoperative administration of fresh frozen plasma in a high-risk coronary patient with HR and highlight the perils of unwitting overheparinisation in such cases. This case highlights the importance of clinical awareness of this phenomenon and the available alternative anticoagulants.


Antitumor efficacy of vaccinia virus-modified tumor cell vaccine.
The antitumor efficacies of vaccinia virus-modified tumor cell vaccines were examined in murine syngeneic MH134 and X5563 tumor cells. UV-inactivated vaccinia virus was inoculated i.p. into C3H/HeN mice that had received whole body X-irradiation at 150 rads. After 3 weeks, the vaccines were administered i.p. 3 times at weekly intervals. One week after the last injection, mice were challenged i.p. with various doses of syngeneic MH134 or X5563 viable tumor cells. Four methods were used for preparing tumor cell vaccines: X-ray irradiation; fixation with paraformaldehyde for 1 h or 3 months; and purification of the membrane fraction. All four vaccines were effective, but the former two vaccines were the most effective. A mixture of the membrane fraction of untreated tumor cells and UV-inactivated vaccinia virus also had an antitumor effect. These results indicate that vaccine with the complete cell structure is the most effective. The membrane fraction of UV-inactivated vaccinia virus-absorbed tumor cells was also effective. UV-inactivated vaccinia virus can react with not only intact tumor cells but also the purified membrane fraction of tumor cells and augment antitumor activity.


[Long-term outcome of acute massive pulmonary thromboembolism following thrombolysis].
To evaluate in-hospital course and long-term outcome of acute massive pulmonary thromboembolism after thrombolysis and to determine its prognostic factors. A total of 260 patients was retrospectively reviewed and followed up for 3.9 - 8.4 years. Close attention was paid to the clinical events, including death, recurrent thromboembolic events, chronic thromboembolic pulmonary hypertension, bleeding complications attributed to anticoagulant therapy, and requirement of oxygen therapy at home. Kaplan-Meier event-free survival curves were generated. The in hospital mortality rate was 8.5%, in which 68.2% were due to pulmonary thromboembolism itself, and the follow-up mortality rate was 31.7%, in which 29.2% were due to recurrent embolism. Univariate analysis showed that six variables were associated with the occurrence of clinical events: (1) Prior thromboembolic diseases; (2) Duration of anticoagulant therapy less than 6 months; (3) Inferior vena cava filter placement; (4) Remaining right ventricular dysfunction/dilatation after thrombolysis detected by echocardiography; (5) Systolic pulmonary pressure > 50 mm Hg after thrombolysis by echocardiography; (6) Greater than 30% residual obstruction of pulmonary vasculature identified by lung ventilation/perfusion scintigraphy before hospital discharge. Multivariate analysis identified three independent risk factors for long-term mortality of acute massive pulmonary thromboembolism after thrombolysis: (1) Systolic pulmonary artery pressure > 50 mm Hg (RR: 3.78, 95% CI = 2.70 - 4.86); (2) Right ventricular dysfunction/dilatation (RR: 2.18, 95% CI = 1.48 - 2.88); (3) Greater than 30% obstruction of pulmonary vasculature (RR: 1.99, 95% CI = 1.25 - 2.70). Doppler echocardiographic assessment after thrombolysis and ventilation/perfusion scintigraphy prior to hospital discharge are valuable to establish a new baseline condition, which is informative for risk stratification and prognostication of long-term outcome.


REO1 and ROX1 are alleles of the same gene which encodes a transcriptional repressor of hypoxic genes in Saccharomyces cerevisiae.
Both the REO1 and ROX1 genes are thought to encode heme-dependent, transcriptional repressors of hypoxic genes in Saccharomyces cerevisiae. However, genetic complementation studies have yielded conflicting results about whether these are the same or different genes. Because of the central importance of these repressors, which control the expression of nearly all known hypoxic genes in yeast, we have sought to resolve this confusion by comparing the phenotypes of reo1 and rox1 mutants using Northern-blot analyses, performing additional complementation studies, and sequencing the ROX1 gene in reo1 strains. Northern-blot analyses of a reo1 strain show wild-type expression of the aerobic genes examined, but de-repression of the Rox1-regulated, hypoxic genes. Aerobic transcript levels of these hypoxic genes were also de-repressed in a diploid strain created by mating a rox1 disrupted strain with a reo1 strain, indicating that genetic complementation did not occur between these two strains. Sequence analyses of ROX1 in reo1 strains reveal a frame-shift mutation in the 5'-end of its coding region, resulting in a nonsense codon in the sixth position. Taken together, these results provide compelling evidence that reo1 is an allele of ROX1.