Incidence and clinical relevance of paraneoplastic syndromes in patients with renal cell carcinoma.
Paraneoplastic syndromes (PNS) are defined as the signs and symptoms attributed to cytokines or hormones released from a tumor or a patient's immune system. PNS have been reported with many cancers for decades and data supporting their relevance in renal cell carcinoma (RCC) are largely historical. The widespread use of electronic medical record (EMR) systems provides a more robust method to capture data. The objective of this study was to establish contemporary data regarding the incidence and relevance of PNS in patients undergoing nephrectomy for suspected RCC. In this retrospective single-institution study, 851 patients undergoing nephrectomy for suspected RCC between 2011 and 2018 were assessed for the presence or absence of PNS as defined by laboratory abnormalities. Factors associated with PNS and with all-cause mortality were examined. The incidence of PNS was 33.1% among 851 patients prior to nephrectomy. The most prevalent PNS were anemia (22.4%), thrombocytosis (7.5%), and elevated C-reactive protein (CRP) (7.4%). PNS were more common in women (39.2% vs. 29.4%, p = 0.0032) and higher stage RCC (31.1% of stage I vs. 54.2% of stage IV, p = 0.0036). Factors associated with the presence of PNS in multivariable analysis included female gender, high comorbidity, and stage IV RCC. Prenephrectomy PNS were associated with poorer survival in multivariable analysis (HR: 2.12, p = 0.0002). Resolution of PNS occurred in 52.1% of patients after nephrectomy, including 55.2% with stage I to III and 38.5% with stage IV RCC (p = 0.10). Using EMR data, laboratory evidence of PNS was present in one-third of a contemporary cohort of patients undergoing nephrectomy, with >50% of PNS resolving after surgery. Consistent with prior reports, PNS are more common in higher-stage RCC and are associated with poorer survival in RCC patients.


Mechanistic insights into Candida biofilm eradication potential of eucalyptol.
Candida-associated fungal infections are prevalent in hospitalized and immune-compromised patients. Their biofilm architecture and high rate of antifungal resistance make treatment challenging. Eucalyptol (EPTL), a monoterpene majorly present in the essential oil of eucalyptus is well known for curing respiratory infections. Hence, the present study investigated the anti-biofilm efficacy of EPTL against the laboratory strains and clinical isolates of Candida to delineate its mode of action. The effect of EPTL on the viability, biofilm formation, and mature biofilm of Candida strains was studied. Furthermore, its effect on cell cycle arrest, mitochondrial membrane potential (MMP), ROS generation, germ tube formation, ergosterol content and transcriptional expression of selected genes was also investigated. EPTL exhibited anti-biofilm activity against mature and developing biofilm of Candida albicans and Candida glabrata along with their clinical isolates. The biochemical components and enzyme activity were differentially modulated in EPTL-treated biofilm extracellular matrix. EPTL generated ROS and arrested cell cycle at the G1 /S phase in both the species, while altered MMP was recorded in C. glabrata. Transcriptional analysis evidenced for differential gene expression of selected ABC transporters, secreted hydrolytic enzymes, and cell wall biogenesis in C. albicans/C. glabrata upon treating with EPTL. The current data on anti-biofilm activity of EPTL establish its candidacy for drug development or as an adjuvant with existing antifungal formulations. Present investigation elucidates the mode of action of Eucalyptol as antifungal agent and would stand as a candidate for management of topical fungal infection.


Bacterial sepsis following prostatic biopsy.
Despite the recent innovations, complications of prostate biopsy can occur. The aim of this study was a prospective monitoring of major septic complications occurring after transrectal prostate biopsy, to describe their causing agents, to report the clinical course of these patients, and to give guidelines based on our personal experience. This prospective study was carried out between January 2009 and September 2010. Complications were evaluated by telephone interviews. Between January 2009 and September 2010, 447 (96.5%) completed the telephone interview. Urosepsis occurred in ten patients (2.2%) and in three cases evolved into septic shock. Of these ten patients, nine had a positive blood culture, of whom eight for Escherichia coli and one for Aeromonas hydrophila, Aeromonas caviae, and Aeromonas sobria. In seven cases, the E. coli isolated were resistant to fluoroquinolone and six produced an extended spectrum beta-lactamase. Six E. coli were classified as multidrug-resistant organisms. Of the 10 patients, one died after the onset of multiorgan failure. For the other nine, the mean time spent in the hospital was 9 days (range, 6-15 days). Escherichia coli are developing new drug resistances. Early recognition of patients who harbor MDRO E. coli in their rectum or in the urine could be an important strategy for preventing sepsis. If a patient who has recently undergone transrectal prostate biopsy shows clinical signs of sepsis in the 48 h, a multiresistant E. coli infection must be suspected. The patient must be admitted urgently to the hospital, and carbapenem antibiotic therapy should be started.


Oxidative DNA damage induced by nitrotyrosine, a biomarker of inflammation.
Inflammation has been postulated as a risk factor for several cancers. 3-Nitrotyrosine is a biochemical marker for inflammation. We investigated the ability of nitrotyrosine and nitrotyrosine-containing peptides (nitroY-peptide) to induce DNA damage by the experiments using 32P-labeled DNA fragments obtained from the human p53 tumor suppressor gene and an HPLC-electrochemical detector. Nitrotyrosine and nitroY-peptide caused Cu(II)-dependent DNA damage in the presence of P450 reductase, which is considered to yield nitroreduction. Catalase inhibited DNA damage, suggesting the involvement of H2O2. Nitrotyrosine and nitroY-peptide increased 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) formation, an indicator of oxidative DNA damage. Nitrotyrosine-containing peptides of histone induced 8-oxodG formation more efficiently than free nitrotyrosine. We propose the possibility that nitrotyrosine-induced H2O2 formation and DNA damage contribute to inflammation-associated carcinogenesis.


Indications for the presence of circulating peroxidized low density lipoproteins in WHHL rabbits treated with antioxidants.
Low density apolipoprotein (apo) B-100 in homozygous WHHL rabbits appears heterogeneous on SDS-PAGE. At least four high molecular weight apolipoproteins were identified in contrast to the uniform apo B-100 band in the very low density lipoprotein (VLDL) fraction of WHHL-homozygotes and the apo B containing lipoproteins present in WHHL heterozygotes or New Zealand White rabbits. We studied whether these aberrations in homozygote WHHL-LDL were due to physical changes induced by lipid peroxidation. Therefore we treated WHHL rabbits for 28 days with a standard dose of 1% probucol or with a dose of 0.1% vitamin E and studied the parameters indicating lipid peroxidation in circulating LDL and in vitro in relation to its antioxidant content. The LDL of probucol-fed rabbits appeared completely resistant against oxidation in vitro with Cu2+ ions. LDL fluorescence and serum malondialdehyde concentrations, indicators of lipid peroxidized LDL, were lower than in the control WHHL rabbits. LDL of vitamin E-fed WHHL rabbits showed a twofold increased lag phase in comparison with LDL of control-fed animals; the maximal rate of oxidation was 2- to 3-fold lower while LDL fluorescence was between the values obtained in the two other groups. Malondialdehyde concentration in the vitamin E-treated group was also decreased when compared with controls. Despite these indications of increased lipid peroxidized circulating LDL in WHHL controls which could be reversed, at least partially, by the antioxidant treatments applied, these treatments were without effect on the physical structure of LDL as examined with agarose gel electrophoresis. Neither antioxidant treatment changed the typical apo B-100 pattern in WHHL-LDL.


Systematic distribution of muscle fiber types in the medial gastrocnemius of the laboratory mouse: a morphometric analysis.
Midbelly cross sections of the medial gastrocnemius muscle of young adult male laboratory mice were subjected to ATPase histochemistry with preincubation at pH 4.6. Through the use of a sampling grid and computer-assisted morphometric analysis, 26 to 35% of the total muscle fibers were sampled and classified as type I, IIa, or IIb. Photomicrographs (16 X 20 in.) of five muscles were divided into octants according to a standardized procedure. Total fiber counts and percent of fibers sampled were determined. Variability of sample size per octant was noted, but when averaged across entire muscles, it was in all instances greater than 33%. Fiber type frequency per octant was tested for goodness of fit to a random model by means of a chi-square statistic for equal expected frequencies. Deviation from random fiber type frequency was significant at the P = 0.001 level for every muscle. More importantly, when these data were pooled and again tested using the same method, the probability estimate was less than P = 0.001. This established that the variations in the fiber type proportions found in each mouse followed a common pattern. The systematic fiber type distribution confirmed by these morphometric and statistical methods supports the impression expressed by many muscle biologists that this muscle displays a consistent and complex intramuscular organization.


Formation of an alkaline phosphatase-immunoglobulin G complex in human sera.
An electrophoretically slow-moving band of alkaline phosphatase (ALP) isoenzyme was found in four patients with chronic liver disease and in one with ulcerative colitis. Immunoelectrophoretic studies revealed that the slow band was a complex containing alkaline phosphatase and an immunoglobulin G of the lambda class. Its molecular weight was approximately 280 000. A complex molecule consisting of one molecule of immunoglobulin G and one molecule of alkaline phosphatase was proposed. The complex was similar to the liver and bone alkaline phosphatases in functional properties. Serum containing the complex was capable of binding liver and bone alkaline phosphatase isoenzymes but not the intestine or placenta alkaline phosphatase isoenzymes from normal controls. The presence of an abnormal immunoglobulin which binds liver and bone alkaline phosphatases appears to be responsible for the development of the complex. In one case of chronic liver disease, the complex disappeared after a few months.


[Association of Wilson's disease with non wilsonian extrapyramidal syndrome in the same family].
Movement disorders, mostly dystonia, sometimes occur in heterozygotes for Wilson's disease (WD). A patient with metabolic abnormalities suggestive of heterozygote for WD and dystonia is reported. His niece showed the typical neurological and metabolic abnormalities of WD. This rare coincidence and the etiopathogenic mechanisms involved are discussed.


Structural integrity of the beta beta alpha-Metal finger motif is required for DNA binding and stable protein-DNA complex formation in R.KpnI.
Restriction endonuclease (REase) R.KpnI from Klebsiella pneumoniae is a homodimeric enzyme, which recognizes palindromic sequence GGTAC|C and cleaves generating 4 base 3' end overhangs. R.KpnI belongs to the HNH superfamily of nucleases, which are characterized by the presence of the beta beta alpha-Me finger motif. Structurally, this motif consists of a twisted beta-hairpin followed by an alpha-helix, and serves as a scaffold for side chains of residues involved in co-ordination of a divalent metal ion that is required for catalysis. Homology modeling studies of R.KpnI suggested a crossover structure for the alpha-helix, which could possibly form dimeric interface and/or structural scaffold for the active site. We have evaluated the role of the residues present in this alpha-helix in intersubunit interactions and/or stabilization of the active site. We show here that mutations of residues in the alpha-helix lead to a loss of the enzyme activity, but not dimerization ability. Intrinsic fluorescence and circular dichroism studies revealed that the loss of function phenotype was due to the structural perturbation of the beta beta alpha-Me finger motif. The results of mutational analysis suggest that the alpha-helix of the beta beta alpha-Me finger of R.KpnI plays an important role for the stability of the protein-DNA complex.


Lipid rafts and plasma membrane microorganization: insights from Ras.
The spatial organization of plasma membrane components in discrete microdomains is thought to be a key factor in the generation of distinct signal outputs. A detailed characterization of plasma membrane microdomains, including descriptions of their size, dynamics and abundance, has proved to be a taxing problem for cell biologists and biophysicists. The use of novel techniques is providing exciting new insights into the challenging problem of plasma membrane microstructure and has allowed the visualization of domains with the characteristics expected of lipid rafts - microdomains of the plasma membrane enriched in cholesterol and sphingolipids. This review focuses on some of these recent advances and uses Ras signaling as a paradigm for understanding inner plasma membrane organization and the role of lipid rafts in cellular function.


An auto-adaptive background subtraction method for Raman spectra.
Background subtraction is a crucial step in the preprocessing of Raman spectrum. Usually, parameter manipulating of the background subtraction method is necessary for the efficient removal of the background, which makes the quality of the spectrum empirically dependent. In order to avoid artificial bias, we proposed an auto-adaptive background subtraction method without parameter adjustment. The main procedure is: (1) select the local minima of spectrum while preserving major peaks, (2) apply an interpolation scheme to estimate background, (3) and design an iteration scheme to improve the adaptability of background subtraction. Both simulated data and Raman spectra have been used to evaluate the proposed method. By comparing the backgrounds obtained from three widely applied methods: the polynomial, the Baek's and the airPLS, the auto-adaptive method meets the demand of practical applications in terms of efficiency and accuracy.


Degradative properties of two newly isolated strains of the ascomycetes Fusarium oxysporum and Lecanicillium aphanocladii.
Two ascomycete strains were isolated from creosote-contaminated railway sleeper wood. By using a polyphasic approach combining morpho-physiological observations of colonies with molecular tools, the strains were identified as Fusarium oxysporum Schltdl. (IBPPM 543, MUT 4558; GenBank accession no. MG593980) and Lecanicillium aphanocladii Zare & W. Gams (IBPPM 542, MUT 242; GenBank accession no. MG593981). Both strains degraded hazardous pollutants, including polycyclic aromatic hydrocarbons, anthraquinone-type dyes, and oil. Oil was better degraded by F. oxysporum, but the aromatic compounds were better degraded by L. aphanocladii. With both strains, the degradation products of anthracene, phenanthrene, and fluorene were 9,10-anthraquinone, 9,10-phenanthrenequinone, and 9-fluorenone, respectively. During pollutant degradation, F. oxysporum and L. aphanocladii produced an emulsifying compound(s). Both fungi produced extracellular Mn-peroxidases, enzymes possibly involved in the fungal degradation of the pollutants. This is the first report on the ability of L. aphanocladii to degrade four-ring PAHs, anthraquinone-type dyes, and oil, with the simultaneous production of an extracellular Mn-peroxidase.


Factors related to delayed treatment: A case report of a huge cutaneous horn and review of the literature.
We present a case of a man with a giant cutaneous horn over his frontal region. This case has been presented for the size of the lesion, due to delayed treatment, and to illustrate the reasons why the growth of this lesion has been possible in a western country, in the 21st century. It was a solitary, not painful lesion which caused significant aesthetic problems. The diagnosis was based on an ultrasonographic study and the treatment of choice was a surgical excision. This case is an opportunity to review the literature about the cutaneous horns, to talk about the main causes of delayed diagnosis and treatment of cutaneous lesions and, to define the role of the specialist in the assessment of emotions and patient support.


Dual-energy CT: clinical application in differentiating an adrenal adenoma from a metastasis.
Application of dual-energy CT in characterization of adrenal nodules has not been well evaluated. To evaluate the ability of dual-energy CT scan to differentiate an adrenal adenoma from a metastasis. Fifty-five patients presenting 63 adrenal nodules underwent dual-energy CT scan at tube voltages of 80 kVp and 140 kVp. Mean attenuation values were measured for every nodule at 80/140 kVp and at 40/100 keV. Mean attenuation value changes between 140 kVp and 80 kVp (MAVC140-80kVp) and mean attenuation value changes between 100 keV and 40 keV (MAVC100-40keV) were calculated. Of the 63 adrenal nodules available for analyses, 42 nodules were classified as adenoma (26 lipid-rich and 16 lipid-poor) and 21 were classified as metastases. MAVC140-80kVp and MAVC100-40keV of all adenomas (including lipid-poor and lipid-rich) were significantly higher than metastases (P < 0.001). According to receiver-operating characteristic (ROC) curve analyses, areas under the ROC curve of MAVC140-80kVp and MAVC100-40keV for diagnosing adrenal adenomas were both of 0.964. When the cut-off points were set at 2.42 HU and 6.95 HU for MAVC140-80kVp and MAVC100-40keV, the two parameters both had a sensitivity of 78.6% and a specificity of 100% in adenoma diagnosis. Unique energy spectrum information provided by dual-energy CT scan displays a high capacity to distinguish adrenal adenoma from metastasis.


Testicular seminoma with a progressing pulmonary nodule and mediastinal lymphadenopathy without retroperitoneal metastasis.
Testicular germ cell cancer has a relatively good prognosis even if visceral and/or lymph node metastases are present thanks to chemotherapy. Yet chemotherapy can lead to various adverse events. Therefore, it is crucial to distinguish whether a suspected metastatic disease is metastasis or not. A 33-year-old male visited our hospital to receive subsequent therapy for suspected recurrent seminoma with a progressing pulmonary nodule and mediastinal lymphadenopathy after orchiectomy. The pathological diagnosis of needle aspiration and resected specimen of the several lesions was consistent with epithelioid cell granuloma without caseous necrosis. Based on these findings, the lung and mediastinal lymph node lesions were diagnosed as sarcoidosis. In cases where the simultaneous occurrence of other benign or malignant diseases is suspected, pathological confirmation is necessary for appropriate decision-making.


Health behaviours of forensic mental health service users, in relation to smoking, alcohol consumption, dietary behaviours and physical activity-A mixed methods systematic review.
People with mental disorders have increased risk of dying from diabetes and cardiovascular diseases compared to the general population. Diabetes and cardiovascular diseases are preventable by improved lifestyle regarding smoking, alcohol consumption, physical activity and dietary behaviours. Forensic mental health service users are treated for longer periods of time compared to non-forensic mental health service users, giving the opportunity to affect the lifestyle for a substantial period of time. This review gathers existing research on forensic mental health service users' lifestyle regarding smoking, alcohol consumption, physical activity, and dietary behaviours and factors influencing it. The lifestyle was found to be unfavourable with many patients being smokers, having problematic alcohol consumption, being physically inactive and eating a diet of poor nutritional value and rich in calories. Therefore, it seems likely that an unfavourable lifestyle is one reason for the excess mortality from diabetes and cardiovascular diseases. Smoking cessation and improving dietary habits was perceived difficult, but nicotine replacement and practical advice was suggested to support a change. The treatment period gives an opportunity to improve the lifestyle of forensic mental health service users to prevent diabetes and cardiovascular diseases in this high-risk group. We recommend a holistic approach, when planning the prevention activities, since activities that are perceived fun are more likely to succeed. Introduction People with mental disorders have increased risk of dying from diabetes and cardiovascular diseases, both of which can be prevented by lifestyle. Aim To review existing research, in order to investigate the characteristics of, and factors that influence forensic mental health service users' (FMU) health behaviours. Method We searched PubMed, CINAHL, PsycInfo and Scopus for primary research on FMU's health behaviours regarding smoking, alcohol consumption, physical activity and dietary behaviours, and factors that influence them. Results We found 13 eligible studies. The findings consistently indicated the presence of unfavourable health behaviours in FMU: Smoking, problematic alcohol consumption, physical inactivity and a high-calorie diet of poor nutritional value. Changing smoking and dietary habits was perceived as difficult, but nicotine replacement and practical advice were suggested to support change. Discussion The existing research on FMU's health behaviours is sparse. In particular, there is a lack of research on factors that influence health behaviours. From our findings, it seems likely that FMU's unfavourable health behaviours contribute to their increased risk of dying from diabetes and cardiovascular diseases. Implications for practice FMU's health behaviours should be improved to prevent diabetes and cardiovascular diseases in this high-risk group.


An exploratory study on needs for clinical research training: data from Chinese hospitals.
Through preliminary investigation of needs for clinical research training, to provide some initial evidence for design and operation of clinical research training programs in China. An online questionnaire containing 23 questions about demographics, current practice of clinical research and needs for clinical research training was formulated to collect data from physicians and researchers in hospital. Convenience sampling was adopted. A total of 600 valid questionnaires were collected, including 507 from physicians, 58 from full-time clinical researchers and 35 from full-time basic medical researchers. Results showed that 14 % of the participants never participated in any clinical research, difficulties in data statistics were reported by more than 70 % of participants, and over 50 % reported training needs for cohort and biobank construction, data management and clinical study design. As to the training form, a combined on-line lecture with off-line communication is preferred. As for the content of the training program, strategies for literature reading and grant writing are highly demanded. In China, even physicians in top hospitals tend to encounter various difficulties when conducting clinical research. This study highlights the importance of systematic training for future physician scientists in China, with a particular focus on data statistics, cohort and biobank construction and data management.


Ongoing transmission of hepatitis B virus infection among inmates at a state correctional facility.
We sought to determine hepatitis B virus (HBV) infection prevalence, associated exposures, and incidence among male inmates at a state correctional facility. A cross-sectional serological survey was conducted in June 2000, and susceptible inmates were retested in June 2001. At baseline, 230 inmates (20.5%; 95% confidence interval [CI]=18.2%, 22.9%) exhibited evidence of HBV infection, including 11 acute and 11 chronic infections. Inmates with HBV infection were more likely than susceptible inmates to have injected drugs (38.8% vs 18.0%; adjusted prevalence odds ratio [OR]=3.0; 95% CI=1.9, 4.9), to have had more than 25 female sex partners (27.7% vs 17.5%; adjusted prevalence OR=2.0; 95% CI=1.4, 3.0), and to have been incarcerated for more than 14 years (38.4% vs 17.6%; adjusted prevalence OR=1.7; 95% CI=1.1, 2.6). One year later, 18 (3.6%) showed evidence of new HBV infection. Among 19 individuals with infections, molecular analysis identified 2 clusters involving 10 inmates, each with a unique HBV sequence. We documented ongoing HBV transmission at a state correctional facility. Similar transmission may occur at other US correctional facilities and could be prevented by vaccination of inmates.


Anti-obesity effect of Lythri herba water extracts in vitro and in vivo.
Lythrum salicaria L., also called purple loosestrife, has traditionally been used as a medicinal plant to treat internal dysfunction, such as gastrointestinal disorders or hemorrhages. It contains numerous phytochemical compounds, including orientin, and has been reported to have anti-diarrheal, anti-inflammatory, antioxidant, and antimicrobial properties. The effects of Lythrum salicaria L. on obesity have not been explored. Therefore, we investigated the anti-obesity effects of Lythri Herba, the aerial part of this plant, in vitro and in vivo. Using distilled water, Lythri Herba water extracts (LHWE) were prepared by extracting Lythri Herba at 100°Ϲ. The contents of orientin in LHWE were identified using High Performance Liquid Chromatography (HPLC) analysis. To evaluate the anti-obesity effect of LHWE, 3T3-L1 adipocytes and a high-fat diet (HFD)-fed mice were used. Oil-red O staining was performed to examine the anti-adipogenic effects of LHWE in vitro. The histological changes in epididymal white adipose tissue (epiWAT) by LHWE were examined using hematoxylin and eosin staining. Serum leptin levels were measured by enzyme-linked immunosorbent assay. Specific quantification kits measured total cholesterol and triglyceride levels in the serum. The relative fold induction of protein and mRNA was determined using western blot and Quantitative real-time Polymerase Chain Reaction analysis, respectively. HPLC analysis demonstrated the presence of orientin in LHWE. LHWE treatment markedly reduced lipid accumulation in differentiated 3T3-L1 adipocytes. LHWE administration also conferred resistance to HFD-induced weight gain in mice and reduced epiWAT mass. Mechanistically, LHWE significantly decreased lipogenesis by downregulating lipoprotein lipase (LPL), glucose-6-phosphate dehydrogenase, ATP-citrate lyase, fatty acid synthase, stearoyl-CoA desaturase 1, sterol regulatory element binding transcription factor 1, and carbohydrate response element binding protein expression and increased the expression of genes involved in fatty acid oxidation (FAO), peroxisome proliferator-activated receptor α and carnitine palmitoyltransferase 1 in 3T3-L1 adipocytes and epiWAT. Furthermore, LHWE significantly up-regulated the phosphorylation of AMP-activated protein kinase in 3T3-L1 adipocytes and epiWAT. LHWE decreases white adipogenesis in vitro and HFD-induced weight gain in vivo, which is associated with reduced lipogenesis and enhanced FAO.


Linear nevus sebaceous syndrome.
The linear nevus sebaceous syndrome is a rare disorder first described in 1962 in two cases by Feuerstein and Mims. As originally described, it consisted of the triad of the characteristic midline facial linear nevus sebaceous of Jadassohn, seizures, and mental retardation. The authors have followed a patient with this syndrome from birth to age 8 and although he does demonstrate several neurologic and ocular abnormalities, he enjoys normal intelligence and has never suffered seizures. The features of this syndrome and several new ocular findings demonstrated in this case are described. Based on our long-term follow-up of this patient and our review of the reported cases to date, the authors suggest that the triad for this disorder should be changed to include the midline facial linear nevus sebaceous of Jadassohn, neurologic abnormalities which may, but not necessarily, include seizures and mental retardation, and ophthalmologic abnormalities.


Sympathetic nervous system hyperactivity results in potent cerebral hypoperfusion in swine.
Cerebral vasospasm is a complex disease resulting in reversible narrowing of blood vessels, stroke, and poor patient outcomes. Sympathetic perivascular nerve fibers originate from the superior cervical ganglion (SCG) to innervate the cerebral vasculature, with activation resulting in vasoconstriction. Sympathetic pathways are thought to be a significant contributor to cerebral vasospasm. We sought to demonstrate that stimulation of SCG in swine can cause ipsilateral cerebral perfusion deficit similar to that of significant human cerebral vasospasm. Furthermore, we aimed to show that inhibition of SCG can block the effects of sympathetic-mediated cerebral hypoperfusion. SCG were surgically identified in 15 swine and were electrically stimulated to achieve sympathetic activation. CT perfusion scans were performed to assess for changes in cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT) and time-to-maximum (TMax). Syngo.via software was used to determine regions of interest and quantify perfusion measures. SCG stimulation resulted in 20-30% reduction in mean ipsilateral CBF compared to its contralateral unaffected side (p < 0.001). Similar results of hypoperfusion were seen with CBV, MTT and TMax with SCG stimulation. Prior injection of lidocaine to SCG inhibited the effects of SCG stimulation and restored perfusion comparable to baseline (p > 0.05). In swine, SCG stimulation resulted in significant cerebral perfusion deficit, and this was inhibited by prior local anesthetic injection into the SCG. Inhibiting sympathetic activation by targeting the SCG may be an effective treatment for sympathetic mediated cerebral hypoperfusion.


Immunogenecity of synthetic peptides representing linear B-cell epitopes of VapA of Rhodococcus equi.
Amino acid 65-78 of membrane protein VapA of the facultative intracellular Rhodococcus equi contained an immunodominant N-terminal B-cell epitope (N15Y peptide). Safety and immunogenecity of a synthetic peptide consisting of the amino acid 65-78 of VapA (peptide N15Y) were evaluated first in mice and in healthy adult horses. A single dose of a peptide-VapA vaccine induced and only in presence of adjuvant, specific IgG antibodies in sera of mice. After challenge with virulent R. equi 3 weeks after immunization, tissue clearance was more delayed in immunized mice than in control mice. An antibody-mediated response (restricted to IgG1 and IgG2b subclasses) predominated in vaccinated mice sera and no specific lymphocytes proliferation was observed. Next, a total of 15 mares were given systemic inoculation of N15Y peptide with IMS3012 ( n = 4 ) or IMS2211 ( n = 4 ) or ISA35 ( n = 4 ) or placebo ( n = 2). Serological responses to the peptide vaccine were found in all but not in placebo group. A significant increase of IgGb subclass in sera of vaccinated mare with N15Y peptide in presence of IMS3012 was observed in comparison to IMS2211 or ISA35 or control group. Moreover, INF-gamma, IL-2 and IL-10 mRNA expression increased more significantly in peripheral blood lymphocytes of IMS3012 group than in IMS2211 or ISA35 group. Interestingly, a significant decrease of IL-4 mRNA expression (undetectable level) was observed with all adjuvants. These results support the use of peptide N15Y in presence of IMS3012 adjuvant in future studies of protection of foals against R. equi.


The fatty liver index (FLI) and incident hypertension: a longitudinal study among Chinese population.
Hypertension and nonalcoholic fatty liver both have been considered as the serious public health problems in recent years. However, the longitudinal association between hypertension and nonalcoholic fatty liver remains unclear in Chinese population. This study was aimed to investigate the longitudinal association between nonalcoholic fatty liver assessed by fatty liver index and the incident hypertension among Chinese population and to evaluate the ability of FLI index, through comparing with the predictive value of other indexes. Four thousand six hundred eighty-six subjects (3177 males and 1509 females) were involved and followed up for 9 years. The subjects were divided into groups according to the fatty liver index. Univariate and multivariate Cox regression models were used to analyze the risk factors of hypertension. After 9 years of follow-up, 2047 subjects developed hypertension. The overall 9-year cumulative incidence of HTN was 43.7%, ranging from 36.0% (FLI < 30) to 75.3% (FLI ≥ 60) (P for trend < 0.001). Cox regression analyses indicated that nonalcoholic fatty liver assessed by fatty liver index was independently and positively associated with the risk of incident hypertension. In receiver operating characteristic (ROC) curve analysis, the ROC curve (AUC) of FLI was 0.701 (95% CI 0.686-0.716), which was larger than that of its components. The nonalcoholic fatty liver assessed by FLI independently predicted the incident hypertension among the Chinese population.


Impact of the shared decision-making process on lung cancer screening decisions.
Professional organizations recommend the use of shared decision-making (SDM) in supporting patients' decisions about lung cancer screening (LCS). The objective of this study was to assess the impact of the SDM process on patient knowledge about LCS, decisional conflict, intentions to adhere to screening recommendations, and its role in how the patient made the final decision. This study surveyed patients screened for lung cancer within 12 months of the survey, recruited from two academic tertiary care centers in the South Central Region of the U.S. (May to July 2018). Two hundred and sixty-four patients completed the survey (87.9% White, 52% male, and mean age of 64.81). Higher SDM process scores (which indicates a better SDM process reported by patients) were significantly associated with greater knowledge of LCS (b = 0.17 p < 0.01). Higher SDM process scores were associated with less decisional conflict about their screening choice (b = 0.45, p < 0.001), greater intentions to make the same decision again (OR = 1.42, 95% CI = [1.06-1.89]), and greater intentions to undergo LCS again (OR = 1.32, 95% CI = [1.08-1.62]). The SDM process score was not associated with patients' report of whether or not they shared the final decision with the healthcare provider (OR = 1.07, 95% CI = [0.85-1.35]). This study found that a better SDM process was associated with better affective-cognitive outcomes among patients screened for lung cancer.


Procedure for determination of trace ions in boric acid by matrix volatilization-ion chromatography.
A method for determination of anions and cations in boric acid is proposed by matrix volatilization. The boric acid matrix was eliminated as trimethyl borate ester in a vapour phase matrix elimination (VPME) system using a mixture of glycerol-methanol. In this VPME system, in situ reagent purification, sample decomposition and digest evaporation were achieved in a single step. Trace anions were separated on anion-exchange column (IonPac AS17) by an isocratic elution with 15 mM sodium hydroxide and the cations on a cation-exchange column (IonPac CS12) by 20 mM hydrochloric acid as eluents. Method detection limits (3sigma) for most ions ranged from 0.3 to 8 ng/g (ppb). Recovery experiments combined with comparison of data obtained by other methods were employed to verify the accuracy of the proposed method. Application of the method to determine trace levels of anions like acetate, oxalate, sulfate, phosphate and cations such as lithium, sodium, potassium, magnesium and calcium in two highly pure grades of boric acid using ion chromatography is demonstrated.


Development of an Artificial Intelligence Model to Guide the Management of Blood Pressure, Fluid Volume, and Dialysis Dose in End-Stage Kidney Disease Patients: Proof of Concept and First Clinical Assessment.
Fluid volume and blood pressure (BP) management are crucial endpoints for end-stage kidney disease patients. BP control in clinical practice mainly relies on reducing extracellular fluid volume overload by diminishing targeted postdialysis weight. This approach exposes dialysis patients to intradialytic hypotensive episodes. Both chronic hypertension and intradialytic hypotension lead to adverse long-term outcomes. Achieving the optimal trade-off between adequate fluid removal and the risk of intradialytic adverse events is a complex task in clinical practice given the multiple patient-related and dialysis-related factors affecting the hemodynamic response to treatment. State-of-the-art artificial intelligence has been adopted in other complex decision-making tasks for dialysis patients and may help personalize the multiple dialysis-related prescriptions affecting patients' intradialytic hemodynamics. As a proof of concept, we developed a multiple-endpoint model predicting session-specific Kt/V, fluid volume removal, heart rate, and BP based on patient characteristics, historic hemodynamic responses, and dialysis-related prescriptions. The accuracy and precision of this preliminary model is extremely encouraging. Such analytic tools may be used to anticipate patients' reactions through simulation so that the best strategy can be chosen based on clinical judgment or formal utility functions.


Systemic Inflammation but not Oxidative Stress Is Associated with Physical Performance in Moderate Chronic Obstructive Pulmonary Disease.
Chronic obstructive pulmonary disease (COPD) patients manifest muscle dysfunction and impaired muscle oxidative capacity, which result in reduced exercise capacity and poor health status. The aim of this study was to compare the physical performance, systemic inflammation, and oxidative stress of patients with moderate COPD, and to associate physical performance with inflammatory and oxidative stress plasma markers. Twenty CONTROL (n = 10) and moderate COPD (n = 10) patients participated in this study. Systematic inflammation and oxidative stress plasma markers, maximal aerobic capacity (VO2peak), and maximal isometric strength (MVIC) of the knee extensor (KE) muscles were measured. VO2peak was 31.3% greater in CONTROL compared to COPD (P = 0.006). The MVIC strength of the KE was 43.9% greater in CONTROL compared to COPD (P = 0.002). Tumor necrosis factor-alpha (TNF-α) was 79.6% greater in COPD compared to CONTROL (P < 0.001). Glutathione peroxidase activity (GPx) activity was 27.5% lesser in COPD compared to CONTROL (P = 0.05). TNF-α concentration was correlated with KE MVC strength (R = -0.48; P = 0.045) and VO2peak (R = -0.58; P = 0.01). Meanwhile, malondialdehyde (MDA) and GPx activity were not associated with KE strength or VO2peak (P = 0.74 and P = 0.14, respectively). COPD patients showed lesser muscle strength and aerobic capacity than healthy control individuals. Furthermore, patients with COPD showed greater systemic inflammation and lesser antioxidant capacity than healthy counterparts. A moderate association was evident between levels of systemic inflammation and physical performance variables.


Survey of stigma across healthcare workers in an urban, academic medical center regarding perinatal patients using opioids.
To examine healthcare workers' attitudes towards pregnant woman using opioids across provider type, specialty, and years of service. Cross-sectional, anonymous survey of healthcare workers at an urban, academic medical center regarding attitudes towards pregnant women using opioids. One hundred and nineteen surveys were completed. Nurses were less likely to feel sympathetic towards pregnant women that use opioids (p = .016). Differences in attitudes towards pregnant women using opioids were found between clinicians and nurses. Training and experience may contribute to attitude differences towards pregnant women using opioids.


Baroreflex control of renin release in spontaneously hypertensive rats after administration of felodipine.
The baroreflex control of heart rate will be rapidly reset to operate at a lower pressure level after blood pressure reduction by felodipine. The present study investigates whether the baroreflex control of renin release in spontaneously hypertensive rats (SHR) will also be reset after prolonged felodipine administration. Conscious SHR, fitted with catheters in the tail artery and vein, were given felodipine intravenously for 5 hours. The initial reflexogenic elevation in plasma renin activity and heart rate caused by felodipine-induced blood pressure reduction were successively normalised with time. Heart rate returned to pre-drug values after 3 hours and plasma renin activity after 5 hours of stable blood pressure reduction. This indicates rapid resetting of baroreflex control of both cardiac and renal function after blood pressure reduction by felodipine.


High-throughput screen identifies disulfiram as a potential therapeutic for triple-negative breast cancer cells: interaction with IQ motif-containing factors.
Triple-negative breast cancer (TNBC) represents an aggressive subtype, for which radiation and chemotherapy are the only options. Here we describe the identification of disulfiram, an FDA-approved drug used to treat alcoholism, as well as the related compound thiram, as the most potent growth inhibitors following high-throughput screens of 3185 compounds against multiple TNBC cell lines. The average IC50 for disulfiram was ~300 nM. Drug affinity responsive target stability (DARTS) analysis identified IQ motif-containing factors IQGAP1 and MYH9 as direct binding targets of disulfiram. Indeed, knockdown of these factors reduced, though did not completely abolish, cell growth. Combination treatment with 4 different drugs commonly used to treat TNBC revealed that disulfiram synergizes most effectively with doxorubicin to inhibit cell growth of TNBC cells. Disulfiram and doxorubicin cooperated to induce cell death as well as cellular senescence, and targeted the ESA(+)/CD24(-/low)/CD44(+) cancer stem cell population. Our results suggest that disulfiram may be repurposed to treat TNBC in combination with doxorubicin.


MiR-802 alleviates lipopolysaccharide-induced acute lung injury by targeting Peli2.
Acute respiratory distress syndrome (ARDS) is a life-threatening medical condition. It is characterized by serious lung inflammation or injury. Characterizing novel miRNAs implicated in ARDS pathogenesis may provide new therapeutic strategy for managing ARDS. We employed LPS-induced lung injury model to profile miRNAs associated with ARDS. We isolated one miRNA candidate and characterized its role in lipopolysaccharide (LPS)-induced proinflammatory cytokine production in lung macrophages. We further evaluated its functional role in ARDS model by assessing histological change, neutrophil activation, tissue permeability and tumor necrosis factor alpha (TNFα) production. We also characterized its downstream target using luciferase assay, Western blotting, enzyme-linked immunosorbent assay and cell inflammation assay. Microarray profiling revealed miR-802 was significantly downregulated in ARDS mouse model. LPS-induced miR-802 downregulation was confirmed in lung macrophages. Overexpression of miR-802 significantly suppressed LPS-induced inflammatory cytokine production in vitro and alleviates LPS-induced acute lung injury in vivo. Peli2 was identified as a downstream target of miR-802 and found upregulated in ARDS model. Overexpressing Peli2 abolished the antagonizing effect of miR-802 on LPS-mediated inflammatory response. MiR-802 carried a protective role against LPS-induced acute lung injury by downregulating Peli2. MiR-802/Peli2 axis may act as intervening targets to manage ARDS.


Rapid Freezing of Skeletal and Cardiac Muscles Using Isopentane Cooled with Liquid Nitrogen and Tragacanth Gum for Histological, Genetic, and Protein Expression Studies.
Histological and molecular genetic evaluation of skeletal and cardiac muscles is an indispensable part of understanding muscle biology and the pathology of muscle disorders. Proper processing of the muscle tissue is a prerequisite for optimal evaluation. However, the processing of skeletal muscle samples often comes with many challenges. One of the commonly used methods of frozen tissue preparation involves optimal cutting temperature compound (OCT compound) embedding. This method is considered optimal for the processing of most of the routinely studied tissue samples. However, the processing of skeletal muscle samples using this method is often unsuitable as it causes artifacts and low DNA, RNA, and protein yield and quality due to the slow freezing of skeletal muscle tissues that allows ice crystals to form. One of the most suitable methods for skeletal muscle tissue processing for histological, genetic, and molecular studies is rapid freezing of freshly collected tissue samples using isopentane cooled with liquid nitrogen and tragacanth gum, which provides distinct advantages in consuming less time, preserving the cell morphology, and helping higher nucleic acids and protein yields. This chapter describes a protocol for rapid freezing of freshly collected skeletal muscle tissues using isopentane pre-chilled with liquid nitrogen and tragacanth gum. Skeletal muscle tissue samples processed using this protocol can be used for histological and immunological staining investigations and studies requiring DNA, RNA, and proteins from these tissues.


A silver nanorod resonance rayleigh scattering-energy transfer analytical platform for trace tea polyphenols.
The stable silver nanorod (AgNR) sol in red was prepared by the two-step procedure of NaBH4-H2O2 and citrate heating reduction, and it exhibited a strong resonance Rayleigh scattering (RRS) peak at 346 nm. In pH 3.8 HAc-NaAc buffer solution, tea polyphenols (TP) reacted with ammonium molybdate (AM) to form yellow organic molybdate (OM) as receptor that was closed to the donor of AgNR, the RRS energy transfer (RRS-ET) takes place, owing to the overlapping between the AgNR RRS spectra and OM absorption spectra. When TP concentration increased, the RRS intensity decreased due to the RRS-ET increasing. So, a simple and sensitive AgNR surface plasmon RRS-ET analytical platform was fabricated to detect trace TP in the range of 0.05-0.85 μg/mL, with a detection limit of 0.03 μg/mL TP. The TP in tea samples was analyzed by this RRS-ET analysis platform, with satisfactory results.


Prognostic value of vocal cord fixation with respect to treatment in cancers of the supraglottis and pyriform sinus.
Vocal cord fixation in supraglottic and pyriform sinus cancers has, in the past, precluded management by radiotherapy alone. Ninety-eight patients were reviewed to determine the prognostic effect of vocal cord fixation. The predictive value of cord mobility status after 50 Gy was evaluated with respect to treatment modality. For patients treated with radiotherapy alone, cord mobility status was predictive of recurrence, yielding 3 year recurrence rates of 33.3% (mobile) versus 80% (fixed) [p = 0.04]. Mobile cords after 50 Gy had similar recurrence rates (33.3% vs. 40.0%, p = 0.60) whether treated by radiotherapy or radiotherapy/surgery. Radiotherapy alone may be used in cases when fixed cords become mobile after 50 Gy without compromising cure rates or laryngeal function. Combined modality provides the best results when cords remain fixed.


Ammonium, bicarbonate and calcium effects on tomato plants grown under saline conditions.
Tomato plants (70 days old) were grown in hydroponic culture into a greenhouse, where supply of inorganic carbon, ammonium and calcium to saline nutrient solution, was investigated in order to reduce the negative effect of salinity. After 70 days, an ameliorating effect upon the decrease in growth observed under salinity was only observed with the treatments NaCl+Ca(2+) and NaCl+HCO(3)(-)+NH(4)(+)+Ca(2+). A large reduction of hydraulic conductance (L(0)) and stomatal conductance (G(s)) was observed with all treatments, compared with the control. However, the reductions were less when NaCl and Ca(2+) were added together. Organic acids (mainly malic acid) in the xylem were decreased with all treatments except with NaCl+NH(4)(+) and with all single treatments added together (NaCl+HCO(3)(-)+NH(4)(+)+Ca(2+)). Amino acid concentrations in the xylem (mainly asparagine and glutamine) decreased when plants were treated with NaCl and NaCl+Ca(2+), but there was a large increase in the plants treated with NaCl+NH(4)(+) or with all treatments together. As HCO(3)(-) is an important source of carbon for NH(4)(+) assimilation, the increase in the concentration of amino acids and organic acids caused by the treatments that contained NH(4)(+), support the idea that fixation of dissolved inorganic carbon was occurring and that the products were transported via the xylem to the shoot. The ameliorating effect of Ca(2+) on root hydraulic conductivity plus the increase of NH(4)(+) incorporation into the amino acid synthesis pathway possibly due to dissolved inorganic carbon fixation, could reduce the negative effect of salinity on tomato plants.


Role of nitric oxide and cGMP in human septic serum-induced depression of cardiac myocyte contractility.
Previous studies have demonstrated the existence of a circulating myocardial depressant substance during human septic shock. We have recently identified this substance as a synergistic combination of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta). This study utilized an in vitro cardiac myocyte assay to evaluate the potential mechanistic role of nitric oxide (NO) and cGMP in depression of myocyte contractility induced by TNF-alpha, IL-1beta, TNF-alpha + IL-1beta (at low concentrations), and human septic shock serum (HSS). TNF-alpha, IL-1beta, TNF-alpha + IL-1beta, and each of 5 sera from patients with acute septic shock caused depression of both maximum extent and peak velocity of cardiac myocyte shortening and an increase in intracellular cGMP concentration during 30 min of exposure (minimum P < 0.01). NO synthetase (NOS) and guanylate cyclase inhibitors such as N-methyl-L-arginine (L-NMA) and methylene blue prevented these effects; an excess of L-arginine with L-NMA restored them (minimum P < 0.01). In contrast, D-arginine failed to reestablish cytokine-induced myocyte depression and cGMP accumulation prevented by L-NMA. Exposure of myocytes to TNF-alpha, IL-1beta, or TNF-alpha + IL-1beta produced a concentration-dependent increase in intracellular cGMP that paralleled the depression of cardiac myocyte contractility (minimum P < 0.001). In addition, TNF-alpha, IL-1beta, TNF-alpha + IL-1beta, or HSS application to cardiac myocytes resulted in increased NO gas generation, which was inhibited by L-NMA (minimum P < 0.01). Furthermore, unstimulated cardiac myocytes were shown to harbor constitutive but not inducible NOS activity. These data suggest that the sequential generation of NO by a constitutive NOS and cGMP by guanylate cyclase represents an important mechanism of cardiac myocyte depression by TNF-alpha, IL-1beta, TNF-alpha + IL-1beta, and the myocardial depressant substance(s) of septic shock.


Urethral pressure profilometry in Scott artificial urinary sphincter.
The Scott sphincter models AS 791 and AS 800 were implanted in 22 men with urinary incontinence. Urethral pressure profilometry was used intraoperatively and postoperatively to measure the urethral closure pressure (UCP) and to improve the rate of continence and reduce the risk of erosion. Success was achieved in 20 of 24 patients. The utility of urethral profilometry in these cases is described.


Prevalence of canine Lyme disease from an endemic area as determined by serosurvey.
From August 1984 through February 1985, 423 dogs from 43 municipalities in 7 New Jersey counties were evaluated for the presence of antibodies to the Lyme disease spirochete (Borrelia burgdorferi). Of these dogs, 34.7% with no apparent clinical symptoms were serologically reactive (IFA greater than or equal to 1:64); titers in this study ranged from non-reactive to 1:2048. Ninety percent of the dogs surveyed had a current vaccination status to Leptospira interrogans serovars canicola and icterohaemorhagiae. Dogs vaccinated to leptospirosis elicited homologous antibody titers of less than or equal to 1:16 and, therefore, did not interfere with interpretation of antibody levels to B. burgdorferi. Effects of age, degree of outdoor activity, travel history, and location of residence were evaluated. The use of serosurveys of dogs as a tool for Lyme disease surveillance is discussed.


Adiponectin protects against myocardial ischemia-reperfusion injury through AMPK- and COX-2-dependent mechanisms.
Obesity-related disorders are associated with the development of ischemic heart disease. Adiponectin is a circulating adipose-derived cytokine that is downregulated in obese individuals and after myocardial infarction. Here, we examine the role of adiponectin in myocardial remodeling in response to acute injury. Ischemia-reperfusion in adiponectin-deficient (APN-KO) mice resulted in increased myocardial infarct size, myocardial apoptosis and tumor necrosis factor (TNF)-alpha expression compared with wild-type mice. Administration of adiponectin diminished infarct size, apoptosis and TNF-alpha production in both APN-KO and wild-type mice. In cultured cardiac cells, adiponectin inhibited apoptosis and TNF-alpha production. Dominant negative AMP-activated protein kinase (AMPK) reversed the inhibitory effects of adiponectin on apoptosis but had no effect on the suppressive effect of adiponectin on TNF-alpha production. Adiponectin induced cyclooxygenase (COX)-2-dependent synthesis of prostaglandin E(2) in cardiac cells, and COX-2 inhibition reversed the inhibitory effects of adiponectin on TNF-alpha production and infarct size. These data suggest that adiponectin protects the heart from ischemia-reperfusion injury through both AMPK- and COX-2-dependent mechanisms.


Is there a common control mechanism for anti-saccades and reading eye movements? Evidence from distributional analyses.
In the saccadic literature, the voluntary control of eye movement involves inhibiting automatic saccadic plans. In contrast, the dominant view in reading is that linguistic processes trigger saccade planning. The present study explores the possibility of a common control mechanism, in which cognitively driven responses compete to inhibit automatic, perceptually driven saccade plans. A probabilistic model is developed to account for empirical distributions of saccadic response time in anti-saccade tasks (Studies 1 and 2) and fixation duration in reading and reading-like tasks (Studies 3 and 4). In all cases the distributions can be decomposed into a perceptually based component and a component sensitive to cognitive demands. Parametric similarities among the models strongly suggest a shared cognitive control mechanism between reading and other voluntary saccadic tasks.


Screening for fear of cancer recurrence: Instrument validation and current status in early stage lung cancer patients.
Fear of cancer recurrence (FCR) is one of the most distressing concerns for cancer patients. A psychometrically validated brief scale is urgently needed for use in busy clinical oncology settings. This study aimed to (1) develop and validate the 7-item fear of cancer recurrence scale Chinese version (FCR7-C), and (2) explore the severity of FCR in post-operative early-stage lung cancer patients in Taiwan. Early-stage lung cancer patients were recruited from a medical center in Taiwan. The FCR7-C was evaluated for content and construct validity and internal consistency reliability. Construct validity of FCR7-C was determined by the empirically supported correlation and confirmatory factor analysis (CFA). A total of 160 subjects were recruited. The FCR7-C was shown to have satisfactory content validity and internal consistency reliability (Cronbach's α = 0.9). The uni-dimensional structure was confirmed by CFA that showed a good fit for the model. The FCR7-C score correlates positively with the degree of most of the physical symptoms, anxiety, and depression, but correlates negatively with patient age, performance status, and quality of life. We found that 81.9% of patients reported at least some FCR, with a mean FCR severity of 15.18 (SD = 7.78). FCR7-C is a brief screening tool with good psychometrics. Patients with early-stage lung cancer still revealed mild to moderate level of FCR. Applying the FCR7-C for to screen cancer patients' distress and further develop personalized psychological interventions would be strongly suggested.


The impact of domestication on fearfulness: a comparison of tonic immobility reactions in wild and domesticated finches.
We examined differences in the fear response between Bengalese finches and their wild ancestor, the white-backed munia, to explore the evolutionary mechanisms of behavioural changes due to domestication. The Bengalese finch (Lonchura striata var. domestica) was domesticated from the wild-living white-backed munia (L. striata) approximately 250 years ago. A previous study indicated that Bengalese finches sing much more complex songs than white-backed munias. We hypothesised that Bengalese finches are likely able to allocate more resources to reproduction in exchange for reduced survival effort. We measured tonic immobility (TI) reactions as a response to physical restraint to evaluate fearfulness related to coping with predation. The results showed that Bengalese finches exhibited decreased TI responses compared with white-backed munias. TI responses were unaffected by sex, body weight or growth conditions. These differences suggest that the fearfulness in Bengalese finches has been reduced by selective pressure during domestication. Bengalese finches may have been able to increase the investment of energy in reproduction in exchange for reduced costs of predation and coping necessary to survive in the wild; these behavioural changes may have been a major target of domestication effects in this species.


An Epidemic Supplanted by a Pandemic: Vaping-Related Illness and COVID-19.
Before the coronavirus disease 2019 (COVID-19) pandemic, vaping-related illness was the prevailing public health concern. The incidence of vaping-related illnesses-mainly e-cigarette, or vaping, product use-associated lung injury (EVALI)-went from a peak in September 2019 to a low in February 2020, and the Centers for Disease Control and Prevention decided to discontinue the collection of EVALI case reports. Despite the decrease in EVALI with the arrival of COVID-19, EVALI should still be considered a differential diagnosis for people with COVID-19 for reasons outlined in this review. This narrative review describes vaping devices, summarizes the adverse health effects of vaping on the lungs and other systems, considers the potential interplay between vaping and COVID-19, and highlights gaps in knowledge about vaping that warrant further research.


Expression and function of alternative splice variants of the mouse TGF-beta type I receptor.
Mouse TGF-beta type I receptor, Alk5, encodes two types of mRNA generated by alternative splicing of four amino acids in the extracellular region. In the present study, the expression and function of alternative splice variants of Alk5, i.e., Alk5-L (Alk5 with the four amino acids) and Alk5-S (Alk5 without the four amino acids), were examined. Expression of Alk5 was detected in all examined tissues, and no significant differences in the ratio of Alk5-S to Alk5-L were detected between tissues. Expression of Alk5 was also detected in various cells, with Alk5-L being especially abundant in A-6 ES cells when it was examined by RT-PCR and subsequent image analyses. No clear difference in Smad2 phosphorylation in response to treatment with TGF-beta(1) was detected between L17 cells expressing Alk5-S and those expressing Alk5-L. Consistent with these results, transcription mediated by Alk5-S in L17 cells treated with TGF-beta(1) was comparable to that mediated by Alk5-L. In addition, alternative splicing had no effect on transcriptional activation induced by GDF-8, a member of the TGF-beta family. The present results indicate ubiquitous expression of Alk5 isoforms in mouse tissues and cells, and insignificant effects of alternative splicing on signaling induced by TGF-beta(1) and GDF-8.


Pediatric Adrenocortical Neoplasms: A Study Comparing Three Histopathological Scoring Systems.
Adrenocortical neoplasms are rare in childhood. Their histopathological categorization into benign and malignant is often challenging, impacting further management. While the AFIP/Wieneke scoring system is widely used for the prognostic classification of these tumors, it has limitations. Few other tumor scoring systems have evolved over the past few years. These have been validated in adults but not yet in pediatric patients. We evaluated a cohort of pediatric adrenocortical neoplasms to assess the applicability of AFIP/Wieneke criteria and the recently introduced Helsinki score and reticulin algorithm in predicting clinical outcomes. A tumor was considered 'clinically aggressive' in the presence of any of the following: metastases, recurrence, progressive disease, or death due to disease. Cases without any such event were considered 'clinically good'. Event-free survival time was the duration from the date of clinical presentation to any post-operative adverse event. For overall survival analysis, the endpoint was either the last follow-up or death due to disease.Using ROC curve analysis, the obtained cut-off Helsinki score of 24 could stratify the cases into two prognostically relevant groups. Survival analysis showed significant differences in the event-free and overall survival of these two groups of patients, validating the proposed cut-off. None of the three histopathological scoring systems could predict an unfavorable outcome with 100% accuracy. All showed a sensitivity of ≥ 80%, with the reticulin algorithm achieving 100% sensitivity. The specificity and accuracy of the AFIP/Wieneke criteria were the lowest (62.5% and 73.08%, respectively). While the Helsinki score (at the cut-off score of 24) and the reticulin algorithm had similar accuracy rates (80.77%, and 80%, respectively), the specificity of the former was higher (81.25%) than the latter (68.75%). A separate analysis revealed that the Ki-67 index at a cut-off of 18% had a sensitivity of 80% and a specificity of 81.25% for predicting an unfavorable outcome.


The effects of aerobic training on children's creativity, self-perception, and aerobic power.
The article examines whether participation in an aerobic exercise program (AE), as compared with a traditional physical education class (PE), significantly increased children's perceived athletic competence, physical appearance, social acceptance, behavioral conduct, and global self-worth; increased their figural creativity; and improved aerobic power as measured by an 800-meter run around a track. Further research on the effects of different types of AE is discussed, as well as the need for aerobic conditioning in the elementary school.


Genetic and Environmental Influences on Rumination, Distraction, and Depressed Mood in Adolescence.
Rumination is an established cognitive vulnerability for depression. Despite substantial work on the environmental origins of rumination, the heritability of rumination has not been examined and it is not known whether rumination accounts for some of the genetic vulnerability associated with depression. 756 adolescent twins ages 12-14 years completed the Response Styles Questionnaire and multiple measures of depressive symptoms. Brooding correlated positively and distraction correlated negatively with concurrent depressive symptoms. Estimated heritabilites were 54% for depression, 21% for brooding, 37% for reflection, and 30% for distraction. Bivariate genetic analyses suggested that (1) individual differences in distraction share both genetic and environmental sources of variation with depression; and (2) although the heritable influences on brooding are small, these heritable influences account for the majority of the relationship between brooding and depression (h2 = .62).


Non-blinking single-photon generation with anisotropic colloidal nanocrystals: towards room-temperature, efficient, colloidal quantum sources.
Blinking and single-photon emission can be tailored in CdSe/CdS core/shell colloidal dot-in-rods. By increasing the shell thickness it is possible to obtain almost non-blinking nanocrystals, while the shell length can be used to control single-photon emission probability.


Association between the adiponectin +45T>G genotype and risk of cardiovascular disease: a meta-analysis.
Numerous studies have investigated the association between adiponectin +45 nucleotide T/G (+45T>G) polymorphisms and cardiovascular disease (CVD). However, these studies have been inconclusive because of obvious inconsistencies among results. The present study aims to quantify the strength of the association between +45T>G (rs2241766) in the adiponectin gene and the risk of CVD. We searched the PubMed, Embase, and Wangfang databases for studies related to the association between the adiponectin +45T>G genotype and the risk of CVD. We estimated the summary odds ratio (OR) with 95% confidence interval (CI) to assess the association. A total of 28 case-control studies, with 12,378 CVD cases and 19,368 controls, were included in the meta-analysis. The meta-analysis of the 28 studies showed that the single-nucleotide polymorphism (SNP) +45T>G genotype was associated with an increased risk of CVD (random-effects OR = 1.22, 95% CI 1.08-1.39, p = 0.002). After adjusting for heterogeneity, the meta-analysis showed that the SNP +45T>G genotype was associated with the risk of CVD in the analyses of the total population and the Caucasian population (for the total population, fixed-effects OR = 1.11, 95% CI 1.01-1.23, p = 0.012; for the Caucasian population, fixed-effects OR = 1.16, 95% CI 1.01-1.34, p = 0.039). No significant association was found in other populations. Evidence of publication bias was observed in the meta-analysis. A significant association between rs2241766 in the adiponectin gene and CVD was established by the meta-analysis.


Laboratory validation of an ELISA method to measure circulating immune complexes levels in canine visceral leishmaniasis.
Susceptible dogs suffering from canine leishmaniasis (CanL) develop an ineffective humoral immune response that leads to the formation of circulating immune complexes (CIC). These CIC are aggregates of Leishmania proteins and anti-Leishmania immunoglobulins. Their deposition in different tissues is considered the main cause of mortality. For this reason, CIC have been suggested as an excellent CanL biomarker for measuring the progression of the disease and the effectiveness of specific treatments. The present study aims to perform a laboratory validation of a Leishmania-specific method to isolate and quantify CIC in dog serum samples. CIC isolated from serum samples of infected dogs, grouped according to the LeishVet classification, were quantified following a PEG-ELISA procedure. The validation established a cut-off of 0.274 OD. All the parameters analyzed (including linearity, specificity, precision, and robustness) fulfilled the defined criteria, confirmed by statistical analyses. The results also proved the reproducibility and reliability of the method when samples were tested under the same conditions, and the consistency and usefulness of the method for an optimal staging of infected dogs. In conclusion, the laboratory validated method offers a potent tool to clinicians for a proper CanL management and to measure the progression of the disease.


Missing links in multiple sclerosis etiology. A working connecting hypothesis.
The etiology of multiple sclerosis is still elusive despite an extended patchwork of mechanistic events has been accumulated. In this article, are tentatively identified from scattered literature sources new factors that may link well known characteristic of MS such as the central alteration of BBR selectivity, its association with EBV status and its biased distribution of the globe more comprehensively. The hypothesis proposes that the concomitant important rise in some heterophilic antibodies (anti Neu5Gc) which activate BBB endothelial cells and in the frequency of anti EBV committed T cells and of memory B infected cells with EBV contemporary to EBV infection play a major role in MS etiology. In addition, the hypothesis proposes new possible explanations for the elevated risk of MS in specific geographical area.


Structure and function of the water-soluble carotenoid-binding proteins of cyanobacteria.
The orange carotenoid protein (OCP) and its derivative, the red carotenoid protein (RCP), appear to play important photoprotective roles in cyanobacteria. Structural and functional characterization is gradually elucidating the specific details of how carotenoid-protein interactions, including the role of six methionine residues oriented toward the pigment, contribute to the spectral and functional properties of these proteins.


Adsorption behavior of Cr(VI) by biomass-based adsorbent functionalized with deep eutectic solvents (DESs).
This study was aimed to evaluate the performance of DESs functionalized peanut shell (PSD) as biosorbent for removing Cr(VI) from water. The effects of pretreatment, initial concentration, adsorption temperature, kinetics, adsorption isotherm, and thermodynamics were investigated. Scanning electron microscopy (SEM) and Point of Zero charge (pHpzc) techniques were used for characterization of the adsorbents. The results showed that the rigid structure of peanut shell was broken down after DESs modification and the point of zero charge was 6.02 for peanut shell and 6.84 for PSD, which exhibited a slightly acid character. Based on the comparisons of linear and nonlinear analysis of four kinetic models and four isotherms, the pseudo-second-order kinetic model was found to be suitable for describing the adsorption process. The presence of a boundary effect was observed within the range of research, indicating that internal diffusion was not the only rate-controlling step. The equilibrium data were well represented by the Langmuir model rather than the Freundlich, Temkin, and Dubinin-Radushkevich models. The maximum capacity derived was 5.36 mg g-1. Changes in Gibb's free energy, enthalpy, and entropy revealed that Cr(VI) adsorption onto modified peanut-shell powders was a spontaneous and endothermic process. However, the highest desorption efficiency was only 8.77% by using NaOH as a desorbing agent.


Biochemical stability during parenteral nutrition in children.
The aim of this study was to assess the frequency and importance of biochemical abnormality related to parenteral nutrition (PN) in a group of infants, and to devise an appropriate policy for routine biochemical surveillance. A standard monitoring protocol based on widely published guidelines was applied to 30 consecutive patients (age 3 days-3 years) referred to a children's hospital nutritional care team for PN. No serious biochemical abnormalities were observed to arise simply as a consequence of PN. Electrolyte disturbance most commonly occurred before starting PN. Biochemical abnormality was most likely to be found in patients with abnormal fluid and electrolyte losses. Protocols for biochemical surveillance during PN err on the side of caution and often suggest frequent and comprehensive testing. In stable patients such as the surgical newborn, this is both expensive and unnecessary, and simpler monitoring regimes may be used with safety.


The protein phosphatase activity of PTEN is essential for regulating neural stem cell differentiation.
The tumor suppressor gene Phosphatase and tensin homolog (PTEN) is highly expressed in neural progenitor cells (NPCs) and plays an important role in development of the central nervous system. As a dual-specificity phosphatase, the loss of PTEN phosphatase activity has been linked to various diseases. Here we report that the protein phosphatase activity of Pten is critical for regulating differentiation of neural progenitor cells. First we found that deletion of Pten promotes neuronal differentiation. To determine whether the protein or lipid phosphatase activity is required for regulating neuronal differentiation, we generated phosphatase domain-specific Pten mutations. Interestingly, only expression of protein phosphatase-deficient mutant Y138L could mimic the effect of knocking down Pten, suggesting the protein phosphatase of Pten is critical for regulating NPC differentiation. Importantly, we showed that the wild-type and lipid phosphatase mutant (G129E) forms of Pten are able to rescue neuronal differentiation in Pten knockout NPCs, but mutants containing protein phosphatase mutant cannot. We further found that Pten-dependent dephosphorylation of CREB is critical for neuronal differentiation. Our data indicate that the protein phosphatase activity of PTEN is critical for regulating differentiation of NSCs during cortical development.


Challenging the motor control of walking: Gait variability during slower and faster pace walking conditions in younger and older adults.
Gait variability is a measure of motor control of gait. Little is known about age-related changes in the motor control of gait (gait variability) during challenging walking conditions, such as slower and faster pace walking. The purpose of this study was to examine the impact of challenging walking conditions (slower and faster speeds) on gait variability in younger and older adults. This study was a cross-sectional, observational design. Forty younger (mean age=26.6±6.0years) and 111 community-dwelling older adults (mean age=77.3±6.0years), independent in ambulation, were studied. Gait characteristics were collected using a computerized walkway (GaitMat II™). Step length, step width, step time, swing time, stance time and double support time variability were derived as the standard deviation of all steps across the 4 passes. Compared to younger, older adults had a significant change in their gait variability from usual to slower in step width (-0.006±0.003), step time (0.028±0.006), swing time (0.023±0.004), stance time (0.042±0.008), and double support time (0.024±0.005). Changes in gait variability from usual to faster were not significantly different between younger and older adults. Gait variability was examined during self-selected over-ground walking, where subjects directed to walk "slower", "usual" and "faster". Walking slowly is more challenging to the motor control of gait and may be more sensitive to age-related declines in gait than usual and faster speed walks.


Increased sympathetic nervous system activity and its therapeutic reduction in arterial hypertension, portal hypertension and heart failure.
Although the underlying mechanisms no doubt differ, activation of the sympathetic nervous system is an important pathophysiological feature in primary arterial hypertension, in portal hypertension accompanying hepatic cirrhosis, and in heart failure, and is a logical therapeutic target for centrally acting sympathetic nervous system suppressant drugs. Portal hypertension: The sympathetic outflows to skeletal muscle vasculature, the heart, the kidneys and to the hepatomesenteric circulation are stimulated in patients with alcoholic cirrhosis of the liver, perhaps as a reflex response to the vasodilatation and vascular shunting present. Acute dosing with clonidine produces dose dependent reduction in noradrenaline spillover from visceral organs and reduction in hepatic vein wedge pressure, with preservation of hepatic blood flow and negligible fall in arterial pressure. These findings indicate the clinical potential of drugs such as clonidine, moxonidine and rilmenidine for chronically lowering portal venous pressure in cirrhosis. Arterial hypertension: Activation of the sympathetic outflow to the heart, kidneys and skeletal muscle vasculature is commonly present in younger (< 45 years) patients with essential hypertension. The sympathetic stimulation appears to have adverse consequences in hypertensive patients beyond blood pressure elevation. Neural vasoconstriction in skeletal muscle has metabolic effects by impairing glucose delivery, which is a basis for insulin resistance and hyperinsulinemia. Within the heart a trophic effect of sympathetic activation on cardiac growth, contributing to the development of left ventricular hypertrophy, and an arrhythmogenic effect are also likely. Cardiac failure: The cardiac sympathetic nerves are preferentially stimulated in severe heart failure, with norepinephrine release from the failing heart at rest being increased as much as 50-fold, similar to the level seen in healthy people during near maximum exercise. This preferential activation of the cardiac sympathetic outflow contributes to arrhythmogenesis and possibly to progression of the heart failure, and has been directly linked to mortality; a high rate of spillover of noradrenaline from the heart is a strong, independent predictor of poor prognosis in severe cardiac failure. The mechanisms underlying sympathetic nervous stimulation are not entirely clear. Increased intracardiac diastolic pressure seems to be one peripheral signal, and increased forebrain norepinephrine turnover an important central mechanism. Following the demonstration of the beneficial effect of the beta-adrenergic blocker, carvedilol, and with second generation centrally acting sympathetic suppressants now under clinical investigation, elucidation of the abnormalities in central nervous control of sympathetic outflow in heart failure has become clinically relevant.


A demographic survey of unwanted horses in Ireland 2005-2010.
The Irish Horse Industry expanded during the Celtic Tiger boom years, then contracted in the current economic recession. High value horses were traditionally controlled through sale at public auction, private sales and sales to dealers; these are now also being reduced by decreases in production (> 40%), and increases in retirement, re-homing, euthanasia and disposal through Category 2 plants and abattoirs. The absence or banning of horse abattoirs has been shown to have very significant welfare social and economic consequences in the USA. This study described the currently available data on the demographics of unwanted horses in Ireland from 2005 to 2010. The majority of horses euthanised by practicing veterinarians are destroyed on medical grounds but the number euthanised at the request of welfare groups and the state, as well as welfare related calls and the number of horses involved in these calls and subsequent visits is increasing reflecting the increasing involvement of the veterinary profession in equine welfare. Welfare groups have limited resources and do not have a tradition of recording data, but they too have reported increasing calls, visits and numbers of horses per visit. Welfare groups provide significant service to equine welfare and the community. Local Authorities report similar trends. Over 300 horses were found dead or required immediate or subsequent euthanasia following welfare group and local authority visits in 2010, which is of national concern. The majority of local authority interfaces with unwanted horses are with urban (60%) rather than rural (40%) horses. Mortality figures are poor indicators of non-fatal neglect. More horses were admitted into the care of local authorities than welfare groups, reflecting significant state and taxpayer investment in the control of low value horses. Category 2 plants and abattoirs represent a significant state investment in licensing and control in the national interest. Abattoirs provide an increasingly important and essential service for the disposal of unwanted horses. Despite the increase in unwanted horses, Ireland is a minority contributor to the EU slaughter total. There is a need for annual demographic data compilation and review of the numbers of unwanted horses and ponies within the horse industry to assist policy makers and legislators.


The impact of O(2) on the Fe-S cluster biogenesis requirements of Escherichia coli FNR.
In this study, the functions of two established Fe-S cluster biogenesis pathways, Isc (iron-sulfur cluster) and Suf (sulfur mobilization), under aerobic and anaerobic growth conditions were compared by measuring the activity of the Escherichia coli global anaerobic regulator FNR. A [4Fe-4S] cluster is required for FNR activity under anaerobic conditions. An assay of the expression of FNR-dependent promoters in strains containing various deletions of the iscSUAhscBAfdx operon revealed that, under anaerobic conditions, FNR activity was reduced by 60% in the absence of the Isc pathway. In contrast, a mutant lacking the entire Suf pathway had normal FNR activity, although overexpression of the suf operon fully rescued the anaerobic defect in FNR activity in strains lacking the Isc pathway. Expression of the sufA promoter and levels of SufD protein were upregulated by twofold to threefold in Isc(-) strains under anaerobic conditions, suggesting that increased expression of the Suf pathway may be partially responsible for the FNR activity remaining in strains lacking the Isc pathway. In contrast, use of the O(2)-stable [4Fe-4S] cluster FNR variant FNR-L28H showed that overexpression of the suf operon did not restore FNR activity to strains lacking the Isc pathway under aerobic conditions. In addition, FNR-L28H activity was more impaired under aerobic conditions than under anaerobic conditions. The greater requirement for the Isc pathway under aerobic conditions was not due to a change in the rate of Fe-S cluster acquisition by FNR-L28H under aerobic and anaerobic conditions, as shown by (55)Fe-labeling experiments. Using [(35)S]methionine pulse-chase assays, we observed that the Isc pathway, but not the Suf pathway, is the major pathway required for conversion of O(2)-inactivated apo-FNR into [4Fe-4S]FNR upon the onset of anaerobic growth conditions. Taken together, these findings indicate a major role for the Isc pathway in FNR Fe-S cluster biogenesis under both aerobic and anaerobic conditions.


The foraging ecology of sympatric marine fish in the genus Embiotoca (Embiotocidae): Importance of foraging behavior in prey size selection.
Two locally sympatric temperate marine reef fishes, Embiotoca jacksoni and E. lateralis (Embiotocidae), have high taxonomic similarity in diets. Subdivision of gammarid amphipods, their principal prey, was found. E. jacksoni took more tubicolous gammarid amphipods whereas E. lateralis consumed mostly free-living individuals. The species differed considerably with respect to between-individual variability in taxonomic compositions of their diets. Each E. jacksoni closely resembled other conspecifics in this regard while individual E. lateralis displayed very high between-fish variation. The principal interspecific difference in fish diets concerned the sizes of prey items taken. E. jacksoni ate small but very common items and the mean prey weight in their guts did not differ from random collections of available prey. E. lateralis concentrated on large, rarer sizes such that the average prey weight in their guts was much heavier than available or in the diet of E. jacksoni of the same length. Disparate foraging behaviors was a much better indicator of the relative differences in diets of these two fishes than was external fish morphology. E. jacksoni, which can winnow prey items from unwanted debris, was a relatively indiscriminant forager. E. lateralis did not winnow but actively searched for prey. This species was a much more discriminating forager, but displayed much variability in foraging behavior.


[dFOXO Transcription Factor Regulates Juvenile Hormone Metabolism in Drosophila melanogaster Females].
dFOXO transcription factor is a component of the insulin/insulin-like growth factor signaling pathway in Drosophila. Juvenile hormone negatively regulates dFOXO gene expression. In the present work, the effect of hypomorphic dFOXO mutation on juvenile hormone metabolism under normal and stressing conditions and on D. melanogaster female resistance to thermal stress was studied. It was demonstrated that dFOXO mutation in D. melanogaster females induces (1) an increase in the level of juvenile hormone degradation and in the intensity of the response of the juvenile hormone metabolism system to thermal stress and (2) a decrease in thermal stress resistance. These parameters are indicators of the level of juvenile hormone synthesis and indicate its decrease in females with decreased dFOXO expression. Thus, the presence of feedback in the regulation of dFOXO gene expression by juvenile hormone was established for the first time.


[RESEARCH PROGRESS OF ANGIOGENESIS IN VASCULARIZED TISSUE ENGINEERED BONE].
To review the research progress of the role of seed cells and related cytokines in angiogenesis of the vascularized tissue engineered bone. The latest literature of tissue engineered bone angiogenesis was reviewed, including the common source of seed cells, biological characteristics, transformation mechanism, related cytokines, and signaling pathways in re-vascularization. Microsurgery technique, genetic technique, and co-culture system of vascularized tissue engineered bone have developed to a new level. Moreover, both the induction of introduced pluripotent stem cells and vascular endothelial growth factor-angiopoietins 1 transfected mesenchymal stem cells and endothelial progenitor cells have some advantages for bone regeneration and vascularization. However, all the techniques were not used in clinical practice. Using techniques of genetically modified seed cells, related cytokines, and scaffolds may have bright prospects for building vascularized tissue engineered bone.


Exploring Donotion-related Knowledge Attitudes, Beliefs and Distrust Among African Americans.
Within the field of organ donation, multiple studies have shown differences in patterns of trust, however, it is unclear which elements are significantly related to donation decision making among African Americans. This study sought to disentangle the construct of trust by parceling out measures related to the healthcare system, the donation/allocation system, and the physician; and determine the relationship of these dimensions to attitudes toward organ and tissue donation. Cross-sectional survey data were gathered from 585 African American adults residing in the Atlanta metropolitan area. Results indicate that varying dimensions of trust function differently in their influence on attitudes toward donation. Our findings suggest that trust is critical to donation decision-making and should be measured with a multidimensional approach, particularly among racial/ethnic groups with complex histories with the healthcare system. This study underlines the need for a more tailored, individualized approach to promoting organ and tissue donation among African Americans. We also thank Rianot Amzat, Mohua Basu and Rhonda DeLaremore for their assistance with data collection, cleaning, entry, and analysis.


Unexplained syncope--a diagnostic pacemaker?
We describe our initial experience with a pacemaker which performs the dual function of registering episodes of cardiac arrest and pacing the heart when necessary. The apparatus has a prolonged escape interval (2.30-2.65 seconds) and is capable of counting up to 128 "events." Twenty-five patients complaining of infrequent episodes of loss of consciousness have been studied. Blackouts ceased and episodes of ventricular standstill were recorded in 14 cases; the unit helped to establish a non-cardiac etiology for the attacks in two cases. It is suggested that a bradycardia-recording facility incorporated into a programmable pacemaker would provide a much needed tool in the diagnosis and management of patients with infrequent episodes of loss of consciousness in whom a cardiac mechanism is suspected but unproven.


MicroED characterization of a robust cationic σ-alkane complex stabilized by the [B(3,5-(SF5)2C6H3)4]- anion, via on-grid solid/gas single-crystal to single-crystal reactivity.
Microcrystalline (∼1 μm) [Rh(Cy2PCH2CH2PCy2)(norbornadiene)][S-BArF4], [S-BArF4] = [B(3,5-(SF5)2C6H3)4]-, reacts with H2 in a single-crystal to single-crystal transformation to form the σ-alkane complex [Rh(Cy2PCH2CH2PCy2)(norbornane)][S-BArF4], for which the structure was determined by microcrystal Electron Diffraction (microED), to 0.95 Å resolution, via an on-grid hydrogenation, and a complementary single-crystal X-ray diffraction study on larger, but challenging to isolate, crystals. Comparison with the [BArF4]- analogue [ArF = 3,5-(CF3)2(C6H3)] shows that the [S-BArF4]- anion makes the σ-alkane complex robust towards decomposition both thermally and when suspended in pentane. Subsequent reactivity with dissolved ethene in a pentane slurry, forms [Rh(Cy2PCH2CH2PCy2)(ethene)2][S-BArF4], and the catalytic dimerisation/isomerisation of ethene to 2-butenes. The increased stability of [S-BArF4]- salts is identified as being due to increased non-covalent interactions in the lattice, resulting in a solid-state molecular organometallic material with desirable stability characteristics.


Phenotypic characterization with somatic genome editing and gene transfer reveals the diverse oncogenicity of ependymoma fusion genes.
Recurrent RELA and YAP1 fusions are intimately associated with tumorigenesis in supratentorial ependymomas. Chromothripsis and focal copy number alterations involving 11q are hallmarks of these tumors. However, it is unknown whether the chromosomal alterations are a direct causal event resulting in fusion transcripts. In addition, the biological significance of the RELA fusion variants and YAP1 fusions is not yet fully characterized. In this study, we generated gene rearrangements on 11q with the CRISPR/Cas9 system and investigated the formation of oncogenic ependymoma fusion genes. Further, we examined the oncogenic potential of RELA fusion variants and YAP1 fusions in a lentiviral gene transfer model. We observed that endogenous RELA fusion events were successfully induced by CRISPR/Cas9-mediated genome rearrangement in cultured cells. In vivo genome editing in mouse brain resulted in the development of ependymoma-like brain tumors that harbored the Rela fusion gene. All RELA fusion variants tested, except a variant lacking the Rel homology domain, were able to induce tumor formation, albeit with different efficacy. Furthermore, expression of YAP1-FAM118B and YAP1-MAMLD1 fusions induced the formation of spindle-cell-like tumors at varying efficacy. Our results indicate that chromosomal rearrangements involving the Rela locus are the causal event for the formation of Rela fusion-driven ependymomas in mice. Furthermore, the type of RELA. fusion might affect the aggressiveness of tumors and that the Rel homology domain is essential for the oncogenic functions of RELA. fusions. The YAP1 fusion genes are also oncogenic when expressed in mice.


Use of an otolith-deficient mutant in studies of fish behavior in microgravity.
The mutant strain (ha) of medaka (Oryzias latipes) lack utricular otoliths as fry, and some never form otoliths for life. The cross (F1 generation) between the strain having good eyesight and another strain having ordinary eyesight augmented visual acuity of the F1 generation. Crossing the good eyesight strain and ha mutant produced fish having good eyesight and less sensitivity to gravity in the F2 population. Their tolerance to microgravity was tested by parabolic flight using an airplane. The fish exhibited less looping and no differences in degree of looping between light and dark conditions, suggesting that loss of eyesight (in darkness) is not a direct cause for looping behavior in microgravity. The ha embryos could not form utricular otoliths. They did form saccular otoliths, but with a delay. Fry of the mutant fish lacking the utricular otoliths are highly dependent on light upon hatching and exhibit a perfect dorsal-light response (DLR). As they grow, they eventually shift from being light-dependent to being gravity-dependent. Continuous treatment of the fry with altered light direction suppressed this shift to gravity dependence. Being less dependent on gravity, these fish can serve as models in studying the differences expected for the vestibular system of fish reared in microgravity. When these fish were exposed to microgravity (parabolic flights) of an airplane, they spent far less time looping than fish reared in an ordinary light regimen.


Computed tomography in diagnosis of abdominal masses in infancy and childhood. Comparison with excretory urography.
Computed tomography (CT) of the abdomen and pelvis was performed in 26 instances of suspected mass in 24 infants and children. The information obtained was compared to that of standard abdominal radiography and excretory urography (IVP). Results were analyzed prospectively. CT was able to detect and define masses more precisely than abdominal radiography and IVP. The information obtained by CT, in a single noninvasive examination emitting minimal ionising radiation, seems comparable to that offered by a combination of multiple radiological and other imaging procedures. It is conceivable that with accumulating experience and further technological improvement CT may become an excellent screening procedure in the investigation of abdominal and pelvic masses. The high cost of CT scanning may be offset by the benefits cited.


Biphasic insulin Aspart 30 vs. NPH plus regular human insulin in type 2 diabetes patients; a cost-effectiveness study.
The aim of this study was to compare the efficacy, safety, costs, and cost-effectiveness of biphasic insulin aspart 30 (BIAsp 30) with NPH plus regular human insulin (NPH/Reg) in patients with type 2 diabetes mellitus (T2DM). It was a Single-center, parallel-group, randomized, clinical trial (Trial Registration: NCT01889095). One hundred and seventy four T2DM patients with poorly controlled diabetes (HbA1c ≥ 8 % (63.9 mmol/mol)) were randomly assigned to trial arms (BIAsp 30 and NPH/Reg) and were followed up for 48 weeks. BIAsp 30 was started at an initial dose of 0.2-0.6 IU/Kg in two divided doses and was titrated according to the glycemic status of the patient. Similarly, NPH/Reg insulin was initiated at a dose of 0.2-0.6 IU/Kg with a 2:1 ratio and was subsequently titrated. Level of glycemic control, hypoglycemic events, direct and indirect costs, quality adjusted life year (QALY) and incremental cost-effectiveness ratio have been assessed. HbA1c, Fasting plasma glucose (FPG), and two-hour post-prandial glucose (PPG) were improved in both groups during the study (P < 0.05 for all analyses). Lower frequencies of minor, major, and nocturnal hypoglycemic episodes were observed with BIAsp 30 (P < 0.05). Additionally, BIAsp 30 was associated with less weight gain and also higher QALYs (P < 0.05). Total medical and non-medical costs were significantly lower with BIAsp 30 as compared with NPH/Reg (930.55 ± 81.43 USD vs. 1101.24 ± 165.49 USD, P = 0.004). Moreover, BIAsp 30 showed lower ICER as a dominant alternative. Despite being more expensive, BIAsp 30 offers the same glycemic control as to NPH/Reg dose-dependently and also appears to cause fewer hypoglycemic events and to be more cost-effective in Iranian patients with type 2 diabetes.


Potential risks in using midodrine for persistent hypotension after cardiac surgery: a comparative cohort study.
Persistent hypotension is a frequent complication after cardiac surgery with cardiopulmonary bypass (CPB). Midodrine, an orally administered alpha agonist, could potentially reduce intravenous vasopressor use and accelerate ICU discharge of otherwise stable patients. The main objective of this study was to explore the clinical impacts of administering midodrine in patients with persistent hypotension after CPB. Our hypothesis was that midodrine would safely accelerate ICU discharge and be associated with more days free from ICU at 30 days. We performed a retrospective cohort study that included all consecutive patients having received midodrine while being on vasopressor support in the ICU within the first week after cardiac surgery with CPB, between January 2014 and January 2018 at the Montreal Heart Institute. A contemporary propensity score matched control group that included patients who presented similarly prolonged hypotension after cardiac surgery was formed. After matching, 74 pairs of patients (1:1) fulfilled inclusion criteria for the study and control groups. Midodrine use was associated with fewer days free from ICU (25.8 [23.7-27.1] vs 27.2 [25.9-28] days, p = 0.002), higher mortality (10 (13.5%) vs 1 (1.4%), p = 0.036) and longer ICU length of stay (99 [68-146] vs 68 [48-99] hours, p = 0.001). There was no difference in length of intravenous vasopressors (63 [40-87] vs 44 [26-66] hours, p = 0.052), rate of ICU readmission (6 (8.1%) vs 2 (2.7%), p = 0.092) and occurrence of severe kidney injury (11 (14.9%) vs 10 (13.5%) patients, p = 0.462) between groups. The administration of midodrine for sustained hypotension after cardiac surgery with CPB was associated with fewer days free from ICU and higher mortality. Routine prescription of midodrine to hasten ICU discharge after cardiac surgery should be used with caution until further prospective studies are conducted.