Quality of life in a German cohort of Parkinson's patients assessed with three different measures.
Parkinson's disease (PD) is characterized by severe motor and non-motor symptoms reducing patients' quality of life (QoL). Instruments have been well established for QoL assessments in PD, including the EuroQol (EQ-5D), the Parkinson's disease questionnaire (PDQ-39), or rather uncommon, like the WHOQOL-100. So far, the impact of variables has been investigated for each of these measures separately in different study populations, limiting the comparability of the results. Thus, this study compared the EQ-5D, PDQ-39, and the WHOQOL-100 (with its short-form WHOQOL-BREF) in the same study population. Seventy-five PD outpatients were assessed in a prospective study, including disease severity according to Hoehn and Yahr stage (HY) and Unified Parkinson Disease Rating Scale (UPDRS). The Geriatric Depression Scale (GDS-15) screened for depression. Decreased QoL was found with all three instruments. In multivariate models, sex and treatment complications had an impact on QoL according to all three measures, while duration of PD and HY was not associated with QoL in any of them. Depression was relevant for the WHOQOL-100/WHOQOL-BREF and the PDQ-39, but not for the EQ-5D. The total variances explained by the WHOQOL-100, WHOQOL-BREF, PDQ-39, and the EQ-5D were 0.27, 0.34, 0.70, and 0.50, respectively. The associations between clinical aspects of PD and QoL vary substantially among all three measures. Importantly, depression as a frequent comorbidity in PD is underestimated by the EQ-5D, but not by the PDQ-39 and the WHOQOL-100/WHOQOL-BREF. In turn, motor impairments are underestimated by the latter and associated strongest with QoL in the EQ-5D.


Niacin skin flushing in schizophrenic and depressed patients and healthy controls.
This study compares the skin reactions to the niacin flushing test of 16 schizophrenic patients with those of 17 depressed patients and 16 healthy controls. Methyl nicotinate (niacin) in a concentration of 0.1 M was applied to the forearm for 5 min. Significant differences could be observed between the group of schizophrenic patients (less flushing) in comparison to the other groups. There were no statistical differences in niacin flushing between patients with depression and healthy controls. Gender, age and the use of antipsychotic agents did not appear to be confounders. The differences in flushing within the group of schizophrenic patients were striking, however. Most patients showed little or no flushing, but some patients reacted strongly. Although the three groups could be differentiated by the niacin flushing test, to develop a reliable clinical application of this test, further research is necessary.


An animal model of stress-induced cardiomyopathy utilizing the social defeat paradigm.
Stress-induced cardiomyopathy (SIC) is a form of acute heart disease triggered by extreme psychological stress. In patients who develop SIC, the outward symptoms are almost indistinguishable from acute myocardial infarction (AMI). However, some important criteria differentiate patients with SIC from those with AMI. Patients with SIC: (1) experience some form of extreme psychological stress from minutes to hours before developing heart disease, (2) do not suffer from atherosclerosis or coronary artery obstruction, and 3) exhibit abnormal ballooning of the left ventricle. In the present study, the resident-intruder (RI) social defeat test was investigated as a potential rat model for stressed-induced cardiomyopathy. Adult Long-Evans rats were implanted with a biotelemetry transmitter for ECG recordings and habituated for two weeks. An intruder rat was placed in the cage of a resident rat behind a wire-mesh partition for 5 min. The partition was then removed for 5 min to allow direct contact between the intruder and resident rats. After this interval, the wire-mesh partition was replaced and the intruder rat remained behind the partition for an additional 50 min. Behavioral responses were noted and ECG recordings were collected during the entire 60-min testing period. Upon completion of the test, the intruder rat was removed from the cage of the resident rat and sacrificed. The heart was examined and blood was collected. Heart weight/body weight ratio, left ventricle/body weight ratio, heart length, plasma corticosterone levels, and plasma troponin I levels of intruder rats were significantly higher as compared to control rats. Intruder rats significantly increased their heart rate during the first 5 min of the RI test. It is concluded that the RI test to induce social defeat is a novel rodent paradigm for modeling stress-induced cardiomyopathy in the human.


The impact of CO2 emissions on economic growth: evidence from selected higher CO2 emissions economies.
The main purpose of this work is to analyze the impact of environmental degradation proxied by CO2 emissions per capita along with some other explanatory variables namely energy use, trade, and human capital on economic growth in selected higher CO2 emissions economies namely China, the USA, India, and Japan. For empirical analysis, annual data over the period spanning between 1971 and 2013 are used. After using relevant and suitable tests for checking data properties, the panel fully modified ordinary least squares (FMOLS) method is employed as an analytical technique for parameter estimation. The panel group FMOLS results reveal that almost all variables are statistically significant, whereby test rejects the null hypotheses of non cointegration, demonstrating that all variables play an important role in affecting the economic growth role across countries. Where two regressors namely CO2 emissions and energy use show significantly negative impacts on economic growth, for trade and human capital, they tend to show the significantly positive impact on economic growth. However, for the individual analysis across countries, the panel estimate suggests that CO2 emissions have a significant positive relationship with economic growth for China, Japan, and the USA, while it is found significantly negative in case of India. The empirical findings of the study suggest that appropriate and prudent policies are required in order to control pollution emerging from areas other than liquefied fuel consumption. The ultimate impact of shrinking pollution will help in supporting sustainable economic growth and maturation as well as largely improve society welfare.


The Polarized Effect of Intracellular Calcium on the Renal Epithelial Sodium Channel Occurs as a Result of Subcellular Calcium Signaling Domains Maintained by Mitochondria.
The renal epithelial sodium channel (ENaC) provides regulated sodium transport in the distal nephron. The effects of intracellular calcium ([Ca(2+)]i) on this channel are only beginning to be elucidated. It appears from previous studies that the [Ca(2+)]i increases downstream of ATP administration may have a polarized effect on ENaC, where apical application of ATP and the subsequent [Ca(2+)]i increase have an inhibitory effect on the channel, whereas basolateral ATP and [Ca(2+)]i have a stimulatory effect. We asked whether this polarized effect of ATP is, in fact, reflective of a polarized effect of increased [Ca(2+)]i on ENaC and what underlying mechanism is responsible. We began by performing patch clamp experiments in which ENaC activity was measured during apical or basolateral application of ionomycin to increase [Ca(2+)]i near the apical or basolateral membrane, respectively. We found that ENaC does indeed respond to increased [Ca(2+)]i in a polarized fashion, with apical increases being inhibitory and basolateral increases stimulating channel activity. In other epithelial cell types, mitochondria sequester [Ca(2+)]i, creating [Ca(2+)]i signaling microdomains within the cell that are dependent on mitochondrial localization. We found that mitochondria localize in bands just beneath the apical and basolateral membranes in two different cortical collecting duct principal cell lines and in cortical collecting duct principal cells in mouse kidney tissue. We found that inhibiting mitochondrial [Ca(2+)]i uptake destroyed the polarized response of ENaC to [Ca(2+)]i. Overall, our data suggest that ENaC is regulated by [Ca(2+)]i in a polarized fashion and that this polarization is maintained by mitochondrial [Ca(2+)]i sequestration.


Challenge and rechallenge: drotrecogin alfa (activated)-induced prolongation of activated partial thromboplastin time in a patient with severe sepsis.
An 81-year-old woman with ischemic bowel underwent laparotomy with small-bowel resection and developed septic shock. She required broadspectrum antibiotics, norepinephrine, and mechanical ventilation. The patient received drotrecogin alfa (activated) 24 microg/kg/hour for a total of 67.5 hours. Coagulation parameters were monitored during her therapy. Significant increases in activated partial thromboplastin time (aPTT) during infusion led to two temporary discontinuations of the drug. Coagulation parameters decreased when the drug was held and increased with each rechallenge. The patient survived the episode and was discharged on postoperative day 27. Medical records of 26 other patients who received drotrecogin alfa (activated) at our institution from November 2001-August 2003 were reviewed retrospectively for coagulation parameters and bleeding rate. Of the 26 patients, nine (35%) were treatment compliant (>90% of the 96-hr course). Coagulopathy and bleeding resulted in early discontinuation in four (15%) and six (23%) patients, respectively. An increase in aPTT from baseline to during infusion of drotrecogin alfa (activated) was noted in 14 patients with complete data (p=0.56). A decrease in median platelet count from baseline to during infusion was noted in the six patients who bled during therapy (p=0.01). Two of these patients had platelet counts less than 30x10(3)/mm3 during administration. Drotrecogin alfa (activated) should be considered an anticoagulant. In postmarketing reports, clinically significant bleeding occurred more frequently than was noted in a large, randomized, multicenter trial. Patients receiving drotrecogin alfa (activated) should be closely monitored for prolongation of coagulation parameters. Temporary discontinuation of the drug should be considered when international normalized ratio is greater than 3.0, platelet count is less than 15x10(3)/mm3, and aPTT is greater than 100 seconds.


Dopamine mediates ipsi- and contraversive circling elicited from the substantia nigra.
It was found that ipsiversive and contraversive circling could be induced by imposed stimulation of the lateral and median portions of the substantia nigra pars compacta (SNC), respectively. Stimulation of more ventral sites in the substantia nigra (SN) did not elicit circling. Pimozide, a dopamine (DA) antagonist, dose dependently blocked both ipsiversive and contraversive circling induced by imposed stimulation of the SN, but did not alter circling elicited from the non-dopaminergic cerebral peduncle. However, amphetamine, a catecholamine agonist, did not facilitate stimulation-induced circling elicited from the SN possibly because it releases DA on both sides of the brain and thus fails to exaggerate the imbalance of activity produced by stimulation. Taken together these results suggest that DA is involved in SN mechanisms mediating both ipsiversive and contraversive stimulation induced circling and provide further evidence that the lateral SN may be functionally antagonistic to the medial SN.


Altered expression of Raet1e, a major histocompatibility complex class 1-like molecule, underlies the atherosclerosis modifier locus Ath11 10b.
Quantitative trait locus mapping of an intercross between C57.Apoe⁻/⁻ and FVB.Apoe⁻/⁻ mice revealed an atherosclerosis locus controlling aortic root lesion area on proximal chromosome 10, Ath11. In a previous work, subcongenic analysis showed Ath11 to be complex with proximal (10a) and distal (10b) regions. To identify the causative genetic variation underlying the atherosclerosis modifier locus Ath11 10b. We now report subcongenic J, which narrows the 10b region to 5 genes, Myb, Hbs1L, Aldh8a1, Sgk1, and Raet1e. Sequence analysis of these genes revealed no amino acid coding differences between the parental strains. However, comparing aortic expression of these genes between F1.Apoe⁻/⁻ Chr10SubJ((B/F)) and F1.Apoe⁻/⁻ Chr10SubJ((F/F)) uncovered a consistent difference only for Raet1e, with decreased, virtually background, expression associated with increased atherosclerosis in the latter. The key role of Raet1e was confirmed by showing that transgene-induced aortic overexpression of Raet1e in F1.Apoe⁻/⁻ Chr10SubJ((F/F)) mice decreased atherosclerosis. Promoter reporter constructs comparing C57 and FVB sequences identified an FVB mutation in the core of the major aortic transcription start site abrogating activity. This nonbiased approach has revealed Raet1e, a major histocompatibility complex class 1-like molecule expressed in lesional aortic endothelial cells and macrophage-rich regions, as a novel atherosclerosis gene and represents one of the few successes of the quantitative trait locus strategy in complex diseases.


Reliability of the posterior condylar offset.
The posterior condylar offset (PCO) has been proposed as a determinant of a postoperative range of motion after total knee arthroplasty, although there is no consensus. This study aimed to demonstrate the error introduced by forcing the femoral rotation to overlap both condyles for the "true" lateral X-ray projection for the PCO measurement. We hypothesize that the angular discrepancy between the posterior femoral cortical reference plane and the posterior condylar axis plane due to rotation invalidates the acquisition of reliable measurements on X-rays. We have measured the PCO in 50 "true" lateral X-rays and compared it with the medial and lateral condyles PCO's assessed on a computed tomography-scan-based three-dimensional (3D) model of each knee. PCO based on the 3D imaging differed significantly between the medial (25.8 ± 3.67 mm) and lateral (16.59 ± 2.92 mm) condyle. Three-dimensional PCO values differ significantly from those determined in the radiographic studies. Also, the mean values of the medial and lateral condyle PCO measurements differed significantly (p < 0.001) with all PCO measurements on radiographs. We have identified a difference between the posterior cortical plane and the posterior condylar axis projections, both on the axial plane with a mean value of 11.23° ± 3.64°. Our data show an interplane discrepancy angle between the posterior femoral diaphyseal cortical and the posterior condylar axis plane (due to the femur's necessary rotation to overlap both condyles) may invalidate the 2D X-ray PCO assessment as a reliable measurement.


Children with Down syndrome and sleep disordered breathing have altered cardiovascular control.
Sleep disordered breathing (SDB) in typically developing (TD) children is associated with adverse cardiovascular effects. As children with Down syndrome (DS) are at increased risk for SDB, we aimed to compare the cardiovascular effects of SDB in children with DS to those of TD children with and without SDB. Forty-four children with DS (3-19 years) were age and sex matched with 44 TD children without SDB (TD-) and with 44 TD children with matched severity of SDB (TD+). Power spectral density was calculated from ECG recordings, for low frequency (LF), high frequency (HF), total power and the LF/HF ratio. Children with DS had lower HF power, and higher LF/HF during sleep and when awake. There were no differences between groups for LF power. SpO2 nadir, average SpO2 drop and SpO2 > 4% drop were larger in the DS group compared to the TD+ group (p < 0.05 for all). Our findings demonstrate significantly reduced parasympathetic activity (reduced HF power) and increased LF/HF (a measure of sympathovagal balance) in children with DS, together with greater exposure to hypoxia, suggesting SDB has a greater effect in these children that may contribute to an increased risk of adverse cardiovascular outcomes. Sleep disordered breathing in children with Down syndrome exacerbates impaired autonomic control and increases exposure to hypoxia, compared to typically developing children. In typically developing children sleep disordered breathing has adverse effects on autonomic cardiovascular control. The prevalence of sleep disordered breathing is very high in children with Down syndrome; however, studies on the effects on cardiovascular control are limited in this population. This study supports screening and early treatment of sleep disordered breathing in children with Down syndrome.


A cross-sectional survey of adrenal steroid hormones among overweight/obese boys according to puberty stage.
Obesity is associated with many chronic diseases including cortisol rhythm disorder and low testosterone. Furthermore, studies on obese children are quite limited and no concordance results have been obtained, especially for boys in puberty. Moreover, the sample sizes of previous studies were small, and were not representative. We conducted a cross-sectional survey including 1148 boys aged 6-14 years, they were divided into overweight/obesity (OW/OB) group and normal weight (NW) group. Puberty status was assessed according to Tanner scale and testicular volume. Serum levels of pregnenolone, 17-OH progesterone, corticosterone, dehydroepiandrosterone (DHEA), and androstenedione were detected by LC-MS. Serum free testosterone and sex hormone-binding globulin (SHBG) levels were measured by chemiluminescence immunoassay. The 17-OH progesterone, DHEA, androstenedione and free testosterone levels of OW/OB boys at prepubertal stage or at the age 6 = < 10 years group were higher than those of the NW boys (all the P values were < 0.01). Furthermore, androstenedione and free testosterone levels were lower in OW/OB boys at late puberty, and the trend continued at the post pubertal stage for FT (P < 0.01-0.05). DHEA, androstenedione, and FT levels persisted to be higher at the 10~ < 12 years in OW/OB boys but not for 17-OH progesterone. FT level was lower in the OW/OB group at the 12~ < 15 years group. The SHBG levels in the OW/OB boys were lower than those in the NW ones at the 6~12 years group, and prepubertal to early pubertal stage. Premature adrenarche is more likely in OW/OB boys. More attention should be given to the lower androgen levels of OW/OB boys at late pubertal and post pubertal stages.


Carbohydrate metabolism and transport in apple roots under nitrogen deficiency.
Soluble sugars play important roles in plant development and stress response, and the nitrogen supply level can affect the among-organ distribution and metabolism of sugar in plants and, in turn, plant growth. To explore the adaptive response of apple root growth to nitrogen supply and its relationship with sugar metabolism, we used a hydroponic culture system to study how the nitrogen supply affects soluble sugar concentrations and sugar metabolism in apple roots. In hydroponic seedlings of Malus hupehensis, low nitrogen application caused rapid and vigorous proliferation of lateral roots, and the transcript levels of MdSOT1 and MdSUT3, which are involved in photoassimilate unloading in roots, were upregulated. The accumulation of sorbitol and sucrose in the fine roots was higher, and the activities of sucrose synthase, invertase and sorbitol dehydrogenase, which are involved in the degradation of sucrose and sorbitol, were significantly increased under a low nitrogen supply. Genes involved in sugar degradation, such as MdSDH1, MdSuSy5, and MdNINV3, play important roles in the efficient use of sorbitol and sucrose under nitrogen deficiency. Additionally, the activity of fructokinase and hexokinase, which are involved in hexose phosphorylation, and transcript levels of MdFRK2 and MdHK3 were significantly upregulated under nitrogen deficiency, and the hexose phosphate products F6P and G6P accumulated greatly in the roots. These results showed that the sugar metabolism capability and sink strength of the roots increased under low nitrogen, indicating that low nitrogen promotes the utilization of sugar in the roots to meet the demand for sugar under rapid root growth.


Immunocytochemical differential diagnosis of adrenocortical neoplasms using the monoclonal antibody D11.
The monoclonal antibody D11 is a valuable aid in the accurate typing of adrenal tumours as, in formalin-fixed, paraffin-embedding material, strong nuclear D11 positivity was observed only in adrenocortical cells in 190 neoplasms (including 100 adrenal tumours). This pattern was demonstrated for all zona glomerulosa cells in 27 normal adrenals and for the neoplastic cells of 15 adrenocortical adenomas derived from that zone, as judged from clinically evident hyperaldosteronism. Normal cells of zona fasciculata and reticularis also showed strong diffuse D11 immunostaining and the same nuclear plus cytoplasmic D11 reactivity was evident in 15 benign and malignant adrenocortical neoplasms derived from these zones, documented by hypercortisolism. Cytoplasmic and/or nuclear D11 staining made topohistogenetic typing possible in 15 non-functioning cortical tumours. D11 immunostaining gave negative results in 50 specimens containing normal, hyperplastic and neoplastic adrenomedullary cells. In addition, absence of D11 reactivity was recorded in 4 adrenal metastases of extra-adrenal carcinomas, 5 paragangliomas, 25 primary renal carcinomas and 59 of 60 primary thyroid carcinomas. D11 immunocytochemistry allows the accurate typing of benign and malignant adrenocortical neoplasms, irrespective of histology and function. With this method, primary adrenocortical tumours can be separated from carcinomas metastatic to the adrenal gland, including secondary tumours of similar phenotype (such as renal carcinomas). By exclusion, D11 negativity provides evidence of the medullary origin of primary adrenal tumours even in the absence of clinical, structural, histochemical and conventional immunohistochemical indicators of phaeochromocytoma.


Treatment of vulvar intraepithelial neoplasia with CO(2) laser vaporization and excision surgery.
To evaluate the recurrence rate after a single treatment of vulvar intraepithelial neoplasia (VIN) with CO(2) laser vaporization. Fifty women with usual-type or differentiated VIN (grades 2 and 3) treated with CO(2) laser vaporization or surgery excision (cold knife or CO(2) laser) were retrospectively evaluated. Of the 50 patients, 41 (82.0%) had usual-type VIN and 9 (18.0%) had differentiated VIN. Moreover, 24 (48.0%) were treated with surgery excision and 26 (52.0%) underwent CO(2) laser vaporization. Laser-treated patients were significantly younger (p < .01) with more multifocal (p < .05) and multicentric lesions (p < .01) than in the surgery group. Recurrence-free survival (RFS) rates at 1 year were 91.0% for the surgery and 65.2% for the laser vaporization groups (p < .01). At 5 years, RFS rates were unchanged for the surgery group and dropped to 51.3% (p < .01) for the laser group. On the univariate analysis, current smoker (p = .03), multicentric VIN (p = .02), and laser vaporization treatment (p < .01) had a statistically significant impact on RFS. One patient progressed to invasive cancer (2%). The recurrence rate after CO(2) laser vaporization requires regular, close, and extended monitoring.


Pharmacological use of a novel scaffold, anomeric N,N-diarylamino tetrahydropyran: molecular similarity search, chemocentric target profiling, and experimental evidence.
Rational drug design against a determined target (disease, pathway, or protein) is the main strategy in drug discovery. However, regardless of the main strategy, chemists really wonder how to maximize the utility of their new compounds by drug repositioning them as clinical drug candidates in drug discovery. In this study, we started our drug discovery "from curiosity in the chemical structure of a drug scaffold itself" rather than "for a specific target". As a new drug scaffold, anomeric diarylamino cyclic aminal scaffold 1, was designed by combining two known drug scaffolds (diphenylamine and the most popular cyclic ether, tetrahydropyran/tetrahydrofuran) and synthesized through conventional Brønsted acid catalysis and metal-free α-C(sp3)-H functionalized oxidative cyclization. To identify the utility of the new scaffold 1, it was investigated through 2D and 3D similarity screening and chemocentric target prediction. The predicted proteins were investigated by an experimental assay. The scaffold 1 was reported to have an antineuroinflammatory agent to reduce NO production, and compound 10 concentration-dependently regulated the expression level of IL-6, PGE-2, TNF-α, ER-β, VDR, CTSD, and iNOS, thus exhibiting neuroprotective activity.


A pilot trial of consolidation bevacizumab after hypo-fractionated concurrent chemoradiotherapy in patients with unresectable locally advanced non-squamous non-small-cell lung cancer.
To determine the feasibility of incorporating bevacizumab consolidation into hypo-fractionated concurrent chemoradiotherapy (hypo-CCRT) for patients with unresectable locally advanced non-squamous non-small-cell lung cancer (LA-NS-NSCLC). Eligible patients were treated with hypo-RT (40Gy in 10 fractions) followed by hypo-boost (24-28Gy in 6-7 fractions), along with concurrent weekly chemotherapy. Patients who completed the hypo-CCRT without experiencing ≥G2 toxicities received consolidation bevacizumab every 3 weeks for up to 1 year, until disease progression or unacceptable treatment-related toxicities. The primary endpoint was the risk of G4 or higher hemorrhage. Secondary endpoints included progression-free survival (PFS), overall survival (OS), locoregional failure-free survival (LRFS), distant metastasis-free survival (DMFS), and objective response rate (ORR). All time-to-event endpoints (OS, PFS, LRFS, and DMFS) were measured from the start of radiotherapy. Between December 2017 and July 2020, a total of 27 patients were included in the analysis, with a median follow-up duration of 28.0 months. One patient (3.7%) developed G5 hemorrhage during bevacizumab consolidation. Additionally, seven patients (25.9%) had G3 cough and three patients (11.1%) experienced G3 pneumonitis. The ORR for the entire cohort was 92.6%. The median OS was 37.0 months (95% confidence interval, 8.9-65.1 months), the median PFS was 16.0 months (95% confidence interval, 14.0-18.0 months), the median LRFS was not reached, and the median DMFS was 18.0 months. This pilot study met its goal of demonstrating the tolerability of consolidation bevacizumab after hypo-CCRT. Further investigation of antiangiogenic and immunotherapy combinations in LA-NSCLC is warranted, while the potential for grade 3 respiratory toxicities should be taken into consideration.


Fluvastatin synergistically enhances the antiproliferative effect of gemcitabine in human pancreatic cancer MIAPaCa-2 cells.
The new combination between the nucleoside analogue gemcitabine and the cholesterol-lowering drug fluvastatin was investigated in vitro and in vivo on the human pancreatic tumour cell line MIAPaCa-2. The present study demonstrates that fluvastatin inhibits proliferation, induces apoptosis in pancreatic cancer cells harbouring a p21ras mutation at codon 12 and synergistically potentiates the cytotoxic effect of gemcitabine. The pharmacologic activities of fluvastatin are prevented by administration of mevalonic acid, suggesting that the shown inhibition of geranyl-geranylation and farnesylation of cellular proteins, including p21rhoA and p21ras, plays a major role in its anticancer effect. Fluvastatin treatment also indirectly inhibits the phosphorylation of p42ERK2/mitogen-activated protein kinase, the cellular effector of ras and other signal transduction peptides. Moreover, fluvastatin administration significantly increases the expression of the deoxycytidine kinase, the enzyme required for the activation of gemcitabine, and simultaneously reduces the 5'-nucleotidase, responsible for deactivation of gemcitabine, suggesting a possible additional role of these enzymes in the enhanced cytotoxic activity of gemcitabine. Finally, a significant in vivo antitumour effect on MIAPaCa-2 xenografts was observed with the simultaneous combination of fluvastatin and gemcitabine, resulting in an almost complete suppression and a marked delay in relapse of tumour growth. In conclusion, the combination of fluvastatin and gemcitabine is an effective cytotoxic, proapoptotic treatment in vitro and in vivo against MIAPaCa-2 cells by a mechanism of action mediated, at least in part, by the inhibition of p21ras and rhoA prenylation. The obtained experimental findings might constitute the basis for a novel translational research in humans.


Tuning Anion-Binding Properties of 22-Membered Unclosed Cryptands by Structural Modification of the Lariat Arm.
A series of 22-membered unclosed cryptands end-capped with intra-annular methyl (1), phenyl (2), p-tert-butylphenyl (3), and p-nitrophenyl (4) amide substituents (lariat arm) were synthesized to elucidate the effect of steric and electronic factors on their anion recognition behavior. The 1H NMR titrations in DMSO-d 6 with 0.5% water reveal enhanced selectivity for H2PO4 - vs Cl- and PhCO2 -. The para-attachment of the electron-withdrawing nitro group (-NO2 vs -H and -t-Bu) was found to increase anion-binding affinity, whereas the steric bulkiness of lariat arm (methyl vs aryl) has a marginal effect. DFT calculations reveal that binding of H2PO4 - is associated with minimal conformational change in the lariat arm moiety and involve four hydrogen bond acceptor and one donor sites of host.


Analysis of intention tremor.
A marked effect of stereotaxic thalamotomy on intention tremor is described and a neurophysiological interpretation is offered. Tremor-generating activity seems to start in the ventral intermediate nucleus (VIM) of the thalamus, as revealed by recording of the unitary activity through a microelectrode at the tip of the insertion needle, after diminution of facilitatory input due to pathology of the cerebellum or its efferent pathway to the cerebrum. This secondary change within the VIM and the loss of facilitatory input leads to an intention tremor as one of the cerebellar symptoms seen in various neurological diseases.


Enhancement of photo-bactericidal effect of tetrasulfonated hydroxyaluminum phthalocyanine on Pseudomonas aeruginosa.
At the present time, photodynamic inactivation (PDI) is receiving considerable interest for its potential as an antimicrobial therapy. The results of our study indicate that enhancement of the phototoxic effect on Pseudomonas aeruginosa can be achieved by combination of tetrasulfonated hydroxyaluminum phthalocyanine (AlPcS4) and bimetallic gold/silver nanoparticles (Au/Ag-NPs) synthesized by the cell-free filtrate of Aureobasidium pullulans. The bimetallic nanoparticles were characterized by a number of techniques including UV-vis, XPS, TEM, and SEM-EDS to be 14 ± 3 nm spherical particles coated with proteins. The effect of diode lasers with the peak-power wavelength ʎ = 650 nm (output power of 10 and 40 mW; radiation intensity of 26 and 105 mW/cm2) in combination with the AlPcS4 and the bimetallic nanoparticles mixture on the viability of P. aeruginosa rods was shown. Particularly high efficiency of killing bacterial cells was obtained for the light intensity of 105 mW/cm2, after 20, 30, and 40 min of irradiation corresponding to 126, 189, and 252 J/cm2 energy fluences. For AlPcS4+Au/Ag-NPs treatment, the viable count reduction were equal to 99.90, 99.96, and 99.975%, respectively. These results were significantly better than those accomplished for irradiated separated assays of AlPcS4 and Au/Ag-NPs.


Safety and effectiveness of sorafenib in Japanese patients with hepatocellular carcinoma in daily medical practice: interim analysis of a prospective postmarketing all-patient surveillance study.
Sorafenib was approved for treatment of unresectable hepatocellular carcinoma (HCC) in Japan in 2009. A prospective postmarketing all-patient surveillance (PMS) study was requested by Japanese authorities to confirm safety and effectiveness of sorafenib in Japanese HCC population. Patients with unresectable HCC treated with sorafenib were followed up for 12 months. Data on patient demographic characteristics, treatment status, clinical outcome, and adverse events (AEs) were collected. This interim analysis included 1109 and 1065 patients evaluable for safety and effectiveness, respectively. Most patients (83.4 %) received the recommended initial dose of 400 mg twice daily. After a follow-up of 12-months, 89.8 % had discontinued treatment, most because of AEs (44.5 %) or progression (33.8 %). The most common drug-related adverse events (DRAE) were hand-foot skin reaction (51.4 %), liver dysfunction (26.4 %), diarrhea (25.1 %), and hypertension (21.6 %). The median overall survival (OS) was 348 days [95 % confidence interval (CI) 299-389 days], and the median duration of treatment was 87 days (95 % CI 78-98 days). Multivariate analyses identified baseline prognostic factors for longer OS, including female sex, low Child-Pugh score, Eastern Cooperative Oncology Group performance status 0, tumor stage I/II/III, low aspartate aminotransferase level, high hemoglobin level, hepatitis C and history of surgical resection. In general, the safety and effectiveness findings in this PMS were consistent with findings from previous clinical studies. Sorafenib was well tolerated and clinically useful for Japanese patients. NCT01411436.


Annealing of thin B/Nb2N bilayers, B/Nb bilayers and Nb/B/Nb trilayers via rapid thermal processing (RTP).
B/Nb and B/Nb(2)N bilayers and Nb/B/Nb trilayers of about 550 nm total thickness have been deposited on Si(100) wafers with 100 nm thermally grown oxide. Nb and B layers were deposited by magnetron sputtering. Nb(2)N layers were prepared by nitridation of Nb films via rapid thermal processing (RTP). The samples were annealed subsequently at temperatures between 600 and 1,200 degrees C in an RTP system under Ar or NH(3) gas flow to study interdiffusion and reactivity of niobium, boron and nitrogen. Formation of phases was investigated by X-ray diffraction (XRD); surface morphology and roughness were studied via scanning electron microscopy (SEM) and atomic force microscopy (AFM), respectively. Elemental depth profiles of selected samples were recorded by secondary ion mass spectrometry (SIMS). Annealing of the B/Nb bilayers and Nb/B/Nb trilayers under Ar leads to the formation of Nb(3)B(2) at 1,200 degrees C at the B/Nb interface. At lower temperatures the high oxygen content in the boron layer is supposed to hinder the formation of borides due to formation of glass-like boron oxides. In NH(3) several niobium nitrides are formed but no boride phases. Here again the reactivity of boron with niobium is suppressed by the high oxygen content and boron oxide formation. During annealing of the B/Nb(2)N bilayers no borides were formed indicating that well-formed Nb(2)N is an effective diffusion barrier for B.


Structure-activity relationship of ETH during ecdysis in the tobacco hornworm, Manduca sexta.
In insects, ecdysis or shedding of the old cuticle, consists of a series of behaviors that are regulated by the coordinated actions of a number of neuropeptides, one of which is ecdysis triggering hormone (ETH). ETH acts directly on central pattern generators of the abdominal ganglia to trigger onset of pre-ecdysis behaviors, as well as indirectly to activate release of eclosion hormone, thereby inducing onset of ecdysis behaviors through a cGMP-mediated mechanism. We assessed the minimal C-terminal amino acids required for biological activity of ETH, by assessing: (i) onset of pre-ecdysis and ecdysis behaviors in vivo, after injection of peptide analogs, (ii) onset of fictive pre-ecdysis and ecdysis motor patterns in vitro, as recorded extracellularly, after incubation of the CNS with the peptide analogs, and (iii) accumulation of cGMP within cells of the abdominal ganglia, as assessed immunohistochemically. Amidation of ETH at the C-terminus was required to elicit a biological response in vivo and in vitro, as well as an accumulation of cGMP within the CNS. The five amino acid amidated C-terminus of ETH (NIPRMamide) was the minimal moiety able to induce a robust pre-ecdysis response in vivo and in vitro, while a seven amino acid core (NKNIPRMa) was required for induction of ecdysis, including accumulation of cGMP immunoreactivity within the CNS. Analogs smaller than 12 amino acids in length were only active at very high concentrations in vivo, suggesting that smaller fragments might be susceptible to hemolymph degradation. Some alanine substitutions or removal of internal amino acids altered the activity of ETH, as well as the time of onset of ecdysis behaviors, suggesting that internal amino acids play a role in maintaining proper folding of the peptide for successful binding or activity at the ETH receptor.


Neoadjuvant therapy in non-small cell lung cancer.
Non-small cell lung cancer (NSCLC) stages I-III were previously predominantly treated with surgery and chemotherapy. With the advent of Checkmate-816, neoadjuvant nivolumab and chemotherapy was FDA approved for the treatment of resectable NSCLC. There are several ongoing trials evaluating other neoadjuvant combinations of chemotherapy and immunotherapy as well as targeted therapies towards driver mutations. Here, we review previous clinical trials and discuss current ongoing trials' potential benefits and challenges.


Rewiring the dyslexic brain.
Overcoming learning disorders is now becoming a realistic goal for neuroscientists and therapists. Seven years after their twin papers in Science suggesting the efficacy of intensive auditory training in children with language learning impairment, the Tallal-Merzenich team now report convincing evidence of just what such training programs can change in these children's brain. With the help of functional imaging, they demonstrate significant reorganization in both hemispheres after only eight weeks of daily training.


Professionals' perspectives on existing practice and conditions for nurse-led gout care based on treatment recommendations: a qualitative study in primary healthcare.
Gout affects nearly 2 % of the population and is associated with repeated painful flares of arthritis. Preventive urate-lowering therapy is widely available, but only one third of patients receive adequate treatment. Lack of knowledge among healthcare professionals and patients within primary healthcare are implicated as partial explanations for this undertreatment. Nurse-led care has proved to be an effective model when treating patients with gout, but there is a need for more knowledge about factors that can be expected to influence the future implementation of such care. The aim of this study was to describe factors influencing existing gout care in primary healthcare and the conditions for a future implementation of nurse-led gout care based on national treatment recommendations. In this qualitative study, focus group discussions with 56 nurses and physicians and individual interviews with eight managers were conducted at nine primary healthcare units in central Sweden. A deductive qualitative content analysis based on the main constructs of the framework Integrated Promoting Action on Research Implementation in Health Services was followed by an inductive analysis within the frames of the main constructs: innovation, recipients and context. Gout-related contacts with primary healthcare was described as being patient initiated, diagnostics was in some respects complex and nurse-led care was experienced as a favourable primary healthcare model in general (innovation). Gout was seen as a low-priority condition with acute flares and there was inadequate knowledge of gout, including preventive treatment (recipients). Primary healthcare was perceived as having a holistic but fragmented responsibility for gout care, recommendations against keeping waiting lists complicated follow-up appointments and a need for motivation and support when introducing new practices was emphasised (context). In this study, investigating the perspective of professionals, several factors were found to influence existing gout care. It will be crucial to target these factors in the development of a future implementation strategy.


Textiloma mimicking a pericardial hydatid cyst: a case report.
Textiloma is unusual and uncommon diagnosis which is rarely considered. We report the case of a 13 year-old patient with Holt-Oram syndrome. He was operated on in 2006 for ostium secundum atrial septal defect. The postoperative course was uneventful until 2010 when the child presented paroxysmal dyspnoea. Investigations revealed para-cardiac mass which was thought to be a hydatid cyst, but operative findings showed textiloma.


Muscarinic acetylcholine receptor activation causes inhibition of cyclic AMP accumulation, prolactin and growth hormone secretion in GH3 rat anterior pituitary tumour cells.
Acetylcholine, oxotremorine and carbachol, compounds that exhibit muscarinic agonist activity, maximally inhibited basal prolactin secretion from GH3 cells by approx. 50% and intracellular cyclic AMP levels by approx. 20%. Both parameters were inhibited with similar potencies by each agonist. These inhibitory effects were blocked by a muscarinic but not by a nicotinic receptor antagonist. In the presence of VIP or IBMX, which raise intracellular cyclic AMP levels and stimulate hormone release, the degree of muscarinic inhibition was increased, but the potency remained unchanged. Similar changes in the secretory rate of prolactin and growth hormone occurred in these and in cell perifusion experiments. These results suggest that the inhibition of hormone secretion from GH3 cells by muscarinic agonists is mediated by a decrease in intracellular cyclic AMP levels.


Study of the regulation of oxidation and CO2 assimilation in intact Nitrobacter winogradskyi cells.
1. Changes of the adenine nucleotides in resting and growing Nitrobacter winogradskyi cells were measured in connection with regulating processes during nitrite oxidation and endogenous respiration. 2. After the addition of nitrite to endogenously respiring cells the ATP pool increased strongly during the first 60 sec at the expense of the ADP pool. At this point the energy charge was approx. 0.55. After the first 90 sec the ATP pool dropped, oscillating, to a lower level. The CO2 assimilation began at this point. 3. Under a nitrogen atmosphere the AMP pool increased and the ATP pool decreased. With a value of approx. 0.17 the energy charge was extremely low. When oxygen was added the Nitrobacter cells began to oxidize stored NADH. The ATP pool increased in a few seconds whereas the AMP pool decreased. The P/O ratio of endogenously respiring cells equaled 0.6 under these conditions. 4. During the changeover from anaerobic to aerobic conditions and in the presence of nitrite the nitrite oxidation and CO2 assimilation, opposed to aerobic conditions, were inhibited at first after the nitrite addition. The changeover of the respiratory chain enzymes from a reduced to an oxidized charge and the ATP increase were delayed in comparison with experiments without nitrite. According to these findings the endogenous respiration must be almost nil while nitrite oxidizing cells are growing.


Inhaler-induced pigmentary changes in a 14-year-old girl.
We present a 14-year-old girl with self-induced areas of hypo- and hyperpigmenation on her forearm as a result of applying 10 blasts of an asthmatic aerosol inhaler directly to her skin. We emphasize the importance of being aware of potential danger associated with the common metered-dose inhaler when it is misused.


The dual role of ubiquitin-like protein Urm1 as a protein modifier and sulfur carrier.
The ubiquitin-related modifier Urm1 can be covalently conjugated to lysine residues of other proteins, such as yeast Ahp1 and human MOCS3, through a mechanism involving the E1-like protein Uba4 (MOCS3 in humans). Similar to ubiquitination, urmylation requires a thioester intermediate and forms isopeptide bonds between Urm1 and its substrates. In addition, the urmylation process can be significantly enhanced by oxidative stress. Recent findings have demonstrated that Urm1 also acts as a sulfur carrier in the thiolation of eukaryotic tRNA via a mechanism that requires the formation of a thiocarboxylated Urm1. This role is very similar to that of prokaryotic sulfur carriers such as MoaD and ThiS. Evidence strongly supports the hypothesis that Urm1 is the molecular fossil in the evolutionary link between prokaryotic sulfur carriers and eukaryotic ubiquitin-like proteins. In the present review, we discuss the dual role of Urm1 in protein and tRNA modification.


Methamphetamine absorption by skin lipids: accumulated mass, partition coefficients, and the influence of fatty acids.
Occupants of former methamphetamine laboratories, often residences, may experience increased exposure through the accumulation of the methamphetamine in the organic films that coat skin and indoor surfaces. The objectives of this study were to determine equilibrium partition coefficients of vapor-phase methamphetamine with artificial sebum (AS-1), artificial sebum without fatty acids (AS-2), and real skin surface films, herein called skin oils. Sebum and skin oil-coated filters were exposed to vapor-phase methamphetamine at concentrations ranging from 8 to 159 ppb, and samples were analyzed for exposure time periods from 2 h to 60 days. For a low vapor-phase methamphetamine concentration range of ~8-22 ppb, the equilibrium partition coefficient for AS-1 was 1500 ± 195 μg/g/ppb. For a high concentration range of 98-112 ppb, the partition coefficient was lower, 459 ± 80 μg/g/ppb, suggesting saturation of the available absorption capacity. The low partition coefficient for AS-2 (33 ± 6 μg/g/ppb) suggests that the fatty acids in AS-1 and skin oil are responsible for much high partition coefficients. We predict that the methamphetamine concentration in skin lipids coating indoor surfaces can exceed recommended surface remediation standards even for air concentrations well below 1 ppb.


Intriguing roles of hippocampus-synthesized 17β-estradiol in the modulation of hippocampal synaptic plasticity.
Accumulated studies have shown that 17β-estradiol (E2) can be de novo synthesized in the hippocampus, and its role in the regulation of hippocampal synaptic plasticity, which is the basis of learning and memory, has long been exploring. Steroidogenic enzymes (e.g., aromatase) that are essential to the hippocampus-synthesized synthesis of E2 have been detected in the hippocampus. Inhibition of E2 synthesis by aromatase inhibitors significantly reduces the density of hippocampal spine synapses, levels of some synaptic proteins such as spinopholin and synaptophysin. Moreover, the electrophysiological properties of hippocampal neurons are also changed in response to this inhibition. The influences of gonadal and hippocampal E2 on synaptic plasticity may exist some differences, since some reports showed that gonadal (or circulating) estrogens have no obvious effects in the modulation of hippocampal synaptic proteins as evidenced in some ovariectomized animals and postmenopausal women who suffered from Alzheimer's disease (AD). These evidences leads to a hypothesis that hippocampal E2 may play a more important role in modulation of synaptic plasticity than gonadal E2. The signaling pathways, whereby hippocampal E2 modulates synaptic plasticity, insist of classical chronic genomic pathway and rapid nongenomic pathway, which mediated by nonnuclear estrogen receptor (GPER) and/or nuclear or nonnuclear estrogen receptors, which require coactivators for their transcription activity. Among which steroid receptor coactivator-1 (SRC-1) is the predominant coactivator p160 family members in the brain. Several clues have shown that SRC-1 is expressed in hippocampus and is highly correlated with some key synaptic proteins developmentally or after orchidectomy but not ovariectomy, indicating SRC-1 may be regulated by hippocampus-synthesized E2 and profoundly involved in the mediation of hippocampal E2 regulation of hippocampal synaptic plasticity. Further studies about the exact roles of hippocampus-synthesized E2 and therefore SRC-1 are urgently needed in order to facilitate our understanding of hippocampal E2, which will be very important to the development of novel strategies of estrogen replacement therapy against neurodegenerative deficits such as Alzheimer's disease (AD).


A new practical guide to the Luria-Delbrück protocol.
Since 2000 several review papers have been published about the analysis of experimental data obtained using the Luria-Delbrück protocol. These timely papers cleared much of the confusion surrounding various methods for estimating or comparing mutation rates. As a result, today the fluctuation test is more widely applied with much improved accuracy. The present paper provides guidelines on a few remaining problems that continue to baffle mutation researchers. Among the issues addressed are incomplete plating, relative fitness, and comparison of experiments where average final cell population sizes differ. It also offers a fresh view on the estimation methods that are based on the sample median.


Charcot-Marie-Tooth disease and the cavovarus foot.
This article focuses on the cavovarus foot shape, with particular emphasis on those patients who have Charcot-Marie-Tooth disease. Recent greater understanding of this deformity has led to a better appreciation of how the underlying condition drives deformity progression and treatment of the problems associated with it. The basic science underpinning the development of Charcot-Marie-Tooth disease is reviewed and some elements of the importance of the genetic variability are emphasized. The mechanics of the development of the cavovarus foot deformity in patients who have this neuromuscular condition are reviewed and the evaluation of such patients is described. The surgical options for treatment are reviewed and the outcomes of studies relevant to surgical planning for this patient population are summarized.


Diagnostic Utility of Ultrasound-Guided Fine-Needle Aspiration Cytology in Gall Bladder Lesions: An Experience from a Tertiary Care Cancer Center in Eastern India.
Gallbladder cancer (GBC) is the most common malignancy, representing 80-95% of biliary tract cancers. Although ultrasonography-guided fine-needle aspiration cytology (USG-FNAC) has emerged as an effective diagnostic the tool for the precise diagnosis of gallbladder lesions, data on its diagnostic utility and cytomorphological categorization of gallbladder lesions are lacking. To study the diagnostic utility of USG-FNAC in gallbladder lesions. This study was the conducted prospectively on patients who came with clinical and radiological evidence of gallbladder space-occupying lesion and then advised to USG-FNAC over 2 years and 6 months from January 2018 to June 2020. A total of 314 cases were included. The mean age was 56 years, with a range of 17-88 years. Women predominated over men (Male:Female = 1:2.3). Primary adenocarcinoma of the gallbladder was most common. On cyto-histological correlation, the sensitivity, specificity, and diagnostic accuracy of USG-FNAC of gallbladder lesions were found to be 98.82, 87.23, and 96.3%, respectively. The USG-FNAC of gallbladder lesion was found to be an easy, quick, cost-effective, and presumptive diagnostic procedure. It should be opted as an initial preoperative diagnostic modality in high incidence areas to avoid inappropriate management with unnecessary morbidity and cost. Moreover, a close cytological examination of the architectural pattern and the cytomorphological features would help in the sub-typing and prognosticating the tumor.


Pronephric tumour cell lines from herpesvirus-transformed cells.
Pronephric tumor cell lines have been established from tumours induced after inoculation of embryos with herpesvirus cultivated in vitro. Neoplastic properties of the lines are characterized.


Aspergillus fumigatus Majocchi's granuloma in a patient with acquired immunodeficiency syndrome.
Majocchi's granuloma, also known as nodular granulomatous perifolliculitis, is an uncommon fungal infection of the skin and subcutaneous tissue. It can occur in healthy and immunocompromised patients. The most common cause of Majocchi's granuloma is Trichophyton rubrum. We report a case of a Majocchi's granuloma caused by Aspergillus fumigatus in a patient with acquired immunodeficiency syndrome.


Mass transfer kinetics and quality attributes of osmo-dehydrated candied pumpkins using nutritious sweeteners.
The aim of this study was to investigate the mass transfer and quality properties changes during the osmotic dehydration (OD) step of the candying process in pumpkins. The goal was to obtain nutritious, low calorie candied pumpkins improving the time-consuming and inconsistent traditional technique. The osmotic agents were sucrose, oligofructose and mixture of sucrose-oligofructose (1:1), while the concentration of each solution was constant (70° Brix). The process temperature varied in three levels (75, 85 and 95 °C) and the duration was 180 min for sucrose and 240 min for the other osmotic agents. The determined parameters during OD include solid gain, water loss, water activity, chroma, hardness and compression work. An empirical model based on a first-order kinetic equation was developed to predict the products' properties, in which the rate constant is a function of the process temperature. The process temperature (Tosm ) had a significant effect on the water loss and solid gain as well as on the physiochemical characteristics of processed pumpkins. The chroma of osmo-dehydrated pumpkins was affected significantly by process parameters. Both hardness and compression work decreased until an equilibrium value was reached as time and temperature of the process increased, regardless the osmotic agent used.


Alphafetoprotein: the genesis.
A historical account of the finding of alphafetoprotein is presented. The problems in its initial isolation, purification and source are described. Some interesting potential future studies are also discussed.


Fourier analysis applied to the characterization of optical wedges with small angles.
A technique for the measurement of optical wedge parameters is shown. It is based on the analysis of the Fourier transform of an interferogram-intensity register. In this domain the angle and the edge orientations of the optical wedge can be determined through a much simpler procedure than the usual interferogram fringe analysis.


The effects of scalpel, harmonic scalpel and monopolar electrocautery on the healing of colonic anastomosis after colonic resection.
In our study, the effects of harmonic scalpel, scalpel, and monopolar electrocautery usage on the health and healing of colon anastomosis after resection was investigated. In this study, 120 female albino Wistar rats were divided into 3 groups each containing 40 rats. Group A, resection with scalpel; group B, resection with monopolar electrocautery; group C, resection with harmonic scalpel. The groups were divided into 4 subgroups consisting of 10 rats and analysed in the postoperative 1st, 3rd, 5th, and 7th days. Anastomotic bursting pressures, hydroxyproline levels and histopathological parameters were surrogate parameters for evaluating wound healing. The tissue hydroxyproline levels did not show any significant difference between the groups and subgroups. The mean bursting pressure of group A on the 5th day was significantly higher than groups B and C (P < 0.001). When the fibroblast and fibrosis scores were evaluated, scores of group C on the 5th day were significantly higher than the other groups, but the results of bursting pressures and biochemical parameters did not support the fibroblast and fibrosis scores. There were not any significant differences between the groups in other histopathologic parameters. The use of monopolar electrocautery needs more attention since the device causes tissue destruction. The obliterating effect of harmonic scalpel on luminal organs is an important problem, especially if an anastomosis is planned. Despite the disadvantages of scalpel, its efficacy on early wound healing is better than the other devices.


Onychomycosis in Adana, Turkey: a 5-year study.
Onychomycosis results from invasion of the nail plate by dermatophytes, yeasts or mould species of fungi. This report documents the etiological agents of onychomycosis in Adana, Turkey. Results of mycological tests of nail clippings or subungal scrapings collected in the period between 1998 and 2002 were analyzed. Both the direct microscopy and the cultures of the nail material were performed to identify the causative agent. Out of a total of 388 cases examined, finger (12.4%) and toenail (87.6%) involvement, 155 (39.9%), were mycologically proven cases of onychomycosis (15 finger, 140 toenail). Among the 98 specimens from positive fungal cultures, dermatophytes were isolated in 74 (75.5%), and yeasts in 24 (24.5%). Trichophyton rubrum was the most common causative agent (48.0%), followed by T. mentagophytes var. interdigitale (26.6%), Candida tropicalis (11.2%), C. albicans (9.2%), C. glabrata (2.0%), C. krusei (2.0%) and Epidermophyton floccosum (1.0%). Dermatophyte fungi, especially T. rubrum and T. mentagrophytes var. interdigitale, were responsible for most of the infections.


Differential roles of cerebellar cortex and deep cerebellar nuclei in the learning of the equilibrium behavior: studies in intact and cerebellectomized lurcher mutant mice.
Three- to 6-month-old lurcher mutant mice (+/lc), which exhibit a massive loss of neurons in the cerebellar cortex and in the inferior olivary nucleus but whose deep cerebellar nuclei are essentially intact, were trained daily, for 9 days, to maintain their equilibrium upon a rota rod rotating at 20 or 30 revolutions per minute (rpm). Their scores were measured and their behavior upon the rotating rod quantified in comparison to those of matched control (+/+) mice. Lurcher mice were able to learn to maintain their equilibrium efficiently when rotated at 20 rpm but were not when rotated at 30 rpm. After cerebellectomy, the equilibrium capabilities of the animals were much altered, especially in +/lc. These results show that the deep cerebellar nuclei are sufficient for motor learning, provided the task is not too difficult (20 rpm), but that the cerebellar cortex is required when the task is more difficult (30 rpm). Therefore, it can be concluded that the adaptive motor capabilities of lurcher mice are less developed than those of control animals.


Graded doses of recombinant interleukin-1beta induce generalized osteopenia in rats without altering skeletal growth and joint integrity.
Whereas a primary role of interleukin-1beta (IL-1beta) in local bone remodelling and articular inflammation has been well established, the effect of prolonged systemic administration of this cytokine on total skeletal Ca, somatic growth and joint tissue has not yet been investigated. Five groups of 14 rats each, aged 7-8 weeks, had miniosmotic pumps (Alzet 200 microl) implanted and primed to release 100, 200, 500, 1,000 and 2,000 ng/kg/24 h of human recombinant IL-1beta (rIL-1beta) daily for 14 days. On days 0 and 14 total skeletal mineral content (BMC) was assessed by means of X-ray absorptiometry and vertebral and tibial growth was measured by computer-assisted radiometry. On the same days, blood was drawn and analyzed for rat growth hormone (rGH), insulin-like growth factor (IGF-1), and osteocalcin. Also 24-hour urine was collected for d-pyridinoline (dpd) determinations. Hind- and forepaw diameter as a parameter of joint inflammation was assessed using a micrometric calliper. Subsequently the animals were sacrificed and one tibia dissected for measurement of trabecular volume by computerized histomorphometry. BMC decreased in a dose-dependent manner reaching significance at 1,000 and 2,000 ng/kg (p < 0.03 and 0.04) in close correlation with tibial trabecular volumes (r = 0.84; p < 0.02). Normal vertebral and tibial growth was recorded at all dosages. There was no evidence of joint involvement. Blood rGH and IGF-1 remained normal as did osteocalcin, the latter reflecting lack of osteoblast activation. In contrast dpd increased in a dose-dependent manner indicating enhanced bone matrix turnover. It is concluded that graded infusions of supraphysiological doses of rIL-1beta capable of inducing osteopenia did not affect skeletal growth in the absence of articular reaction. This is in contrast with the experience recorded in experimental arthritis in which growth retardation, in addition to osteopenia, may be caused by factors other than circulating IL-1beta.


Dermoscopy of Inflammatory Genital Diseases: Practical Insights.
Diagnosis of genital inflammatory disorders may be difficult for several reasons, such as their similar appearance, possible misdiagnosis with infectious and malignant conditions, and peculiar anatomic conditions that may lead to modification of clinical features. Dermoscopy could be included as a part of the clinical inspection of genital diseases to support diagnosis, as well as to ideally avoid unnecessary invasive investigation. Practical guidance for the use of dermoscopy in the assessment of the main inflammatory genital diseases is provided, namely for lichen sclerosus, lichen planus, psoriasis, lichen simplex chronicus, and plasma cell mucositis.


Finite-Time Extended Dissipative Filtering for Singular T-S Fuzzy Systems With Nonhomogeneous Markov Jumps.
This article investigates the finite-time extended dissipative filtering for singular T-S fuzzy Markov jump systems with time-varying transition probabilities (TPs). The time-varying TPs are considered to reside in a polytope. By resorting to a generalized performance index, the H∞ , L2-L∞ , passive, and dissipative performance can be solved in a unified framework. Combining the free-weighting method and the proposed recursive method, a sufficient condition on singular stochastic extended dissipative finite-time boundedness (SSEDFTB) for a fuzzy filtering error system is obtained. By proposing a decoupling principle called double variables-based decoupling principle (DVDP) and a variable substitution principle (VSP), a novel condition on the existence of the fuzzy filter is presented in terms of linear matrix inequalities (LMIs). Compared with the existing works, the assumption on state variables and the constraints of slack matrices are overcome, which leads to more practical and less conservative results. A practical example is provided to demonstrate the effectiveness of the design methods.


Suppression of protein tyrosine phosphatase PTPN22 gene induces apoptosis in T-cell leukemia cell line (Jurkat) through the AKT and ERK pathways.
The aim of this study was to investigate the effect of specific PTPN22 small interfering RNAs (siRNAs) on the viability and induction of apoptosis in Jurkat cells and to evaluate apoptosis signaling pathways. In this study, Jurkat cells were transfected with specific PTPN22 siRNA. Relative PTPN22 mRNA expression was measured by Quantitative Real-time PCR. Western blotting was performed to determine the protein levels of PTPN22, AKT, P-AKT, ERK, and P-ERK. The cytotoxic effects of PTPN22 siRNA were determined using the MTT assay. Apoptosis was quantified using TUNEL assay and flow cytometry. Results showed that in Jurkat cells after transfection with PTPN22 siRNA, the expression of PTPN22 in both mRNA and protein levels was effectively reduced. Moreover, siRNA transfection induced apoptosis on the viability of T-cell acute leukemia cells. More importantly, PTPN22 positively regulated the anti-apoptotic AKT kinase, which provides a powerful survival signal to T-ALL cells as well as the suppression of PTPN22 down regulated ERK activity. Our results suggest that the PTPN22 specific siRNA effectively decreases the viability of T-cell acute leukemia cells, induces apoptosis in this cell line, and therefore could be considered as a potent adjuvant in T-ALL therapy.


Misalignment of foveal pit and foveal bulge determined by ultrahigh-resolution SD-OCT in normal eyes.
The foveal bulge (FB) results from a lengthening of the outer segments of the photoreceptors which then makes the central fovea arcuate in shape. The purpose of this study was to evaluate the morphological features and locations of the FB relative to the foveal pit (FP) in a single B-scan image. One hundred and forty-seven eyes of 147 healthy volunteers were studied. Horizontal and vertical B-scan optical coherence tomographic (OCT) images through the fovea were recorded by an ultrahigh-resolution spectral domain OCT (UHR-SD-OCT) instrument (Bi-μ, KOWA, Japan). The vertex of the FB and the center of the FP were identified with the ImageJ software. The distance between the FB and FP and the height of the FB were measured. In the horizontal images, the vertex of the FB was on the nasal side of the center of the FP in 97 eyes (66%), on the temporal side in 42 eyes (29%), and the same position in 8 eyes (5%). In the vertical images, the vertex of the FB was superior to the center of the FP in 82 eyes (55%), inferior to the center of the FP in 45 eyes (31%), and the same position in 20 eyes (14%). The mean distance (± SD) between the FB and the FP was + 16.8 ± 30.1 μm in the horizontal images and + 8.27 ± 28.0 μm in the vertical images. The mean height (± SD) of the FB was 77.0 ± 4.78 μm in the horizontal images and 77.9 ± 5.05 μm in the vertical images. The height of the FB in the horizontal images was significantly correlated with refractive error in the multiple regression analysis (P = 0.041). These results indicate that the vertex of the FB was not aligned with the center of the FP in the majority of the eyes of normal Japanese individuals in a single B-scan image. Analysis showed that eyes with less severe myopia had the higher height of the FB. This must be considered when interpreting the location of the vertex of the FB and the center of the FP in clinical situations.


The conceptual framework of monitoring mutagens/carcinogens: a critical appraisal.
The main theme of this paper is an analysis of the present knowledge and conceptual framework in the field of monitoring for carcinogenic and mutagenic agents. The conclusions of the International Symposium on "Monitoring human exposure to carcinogenic and mutagenic agents" (Helsinki, 1983) were taken as a starting point for a series of considerations; methods suitable for the quantitative treatment of the information were applied to evidence the profile of current research in this area. The analysis indicated that the major underlying paradigms were related to technical considerations, such as chemical specificity, precision, reproducibility or ease of execution, as well as to the concept of mechanism of action of genotoxic agents. On the other hand, the lack of reliable information about the operational relevance of the systems for assessing health effects was dramatically evidenced. As a conclusion, the dangers of relying on a scientific background derived only from the basic research, without a critical re-examination in terms of real, operational performances of the systems, are emphasized.


Codon choice and gene expression: synonymous codons differ in their ability to direct aminoacylated-transfer RNA binding to ribosomes in vitro.
Phe-tRNA (anticodon GAA)--polypeptide-chain elongation factor Tu-GTP ternary complexes react faster with ribosomes programmed with UUC codons than with ribosomes programmed with UUU codons. A similar preference is shown by Leu-tRNA2 (anticodon GAG) complexes, which react faster with ribosomes programmed with CUC than with those programmed with CUU. The difference is seen in the rate of ternary-complex binding to the ribosome; no differences are seen in peptide-bond formation. Highly expressed mRNAs in Escherichia coli favor codons terminating in cytosine rather than uracil when both codons are read by a single tRNA with an anticodon beginning with guanine. The results suggest that intrinsic differences between the efficiencies of synonymous codons play an important role in modulating gene expression in E. coli.


Neonatal repair of atypical double outlet right ventricle.
A complex and rare form of double outlet right ventricle needs careful attention when choosing the optimal strategy for repair. To point out retrospectively what could have been done differently in our unique patient. Primary repair was arranged in a neonate with double outlet right ventricle (of a non-committed ventricular septal defect type and lack of the outlet septum between the semilunar valves) with right aortic arch and dextro-malposition of great arteries. We managed to achieve intraventricular rerouting via a right ventricular incision concomitantly with the arterial switch maneuver. The patient is doing well with an excellent hemodynamic status. We considered that the radical approach we chose appeared to be sensible in this particular patient, although some other options could have been available.


Modification of agonist binding moiety in hybrid derivative 5/7-{[2-(4-aryl-piperazin-1-yl)-ethyl]-propyl-amino}-5,6,7,8-tetrahydro-naphthalen-1-ol/-2-amino versions: impact on functional activity and selectivity for dopamine D2/D3 receptors.
The goal of the present study was to explore, in our previously developed hybrid template, the effect of introduction of additional heterocyclic rings (mimicking catechol hydroxyl groups as bioisosteric replacement) on selectivity and affinity for the D3 versus D2 receptor. In addition, we wanted to explore the effect of derivatization of functional groups of the agonist binding moiety in compounds developed by us earlier from the hybrid template. Binding affinity (K(i)) of the new compounds was measured with tritiated spiperone as the radioligand and HEK-293 cells expressing either D2 or D3 receptors. Functional activity of selected compounds was assessed in the GTPγS binding assay. In the imidazole series, compound 10a exhibited the highest D3 affinity whereas the indole derivative 13 exhibited similar high D3 affinity. Functionalization of the amino group in agonist (+)-9d with different sulfonamides derivatives improved the D3 affinity significantly with (+)-14f exhibiting the highest affinity. However, functionalization of the hydroxyl and amino groups of 15 and (+)-9d, known agonist and partial agonist, to sulfonate ester and amide in general modulated the affinity. In both cases loss of agonist potency resulted from such derivatization.


Insights on action observation and imitation abilities in children with Developmental Coordination Disorder and typically developing children.
Children with Developmental Coordination Disorder (DCD) face difficulties in motor learning. Action observation and imitation are strategies frequently used to teach motor skills. (1) To study action observation and imitation abilities in children with DCD compared with typically developing peers with a new protocol. (2) To gain insights in the relation between action observation, imitation, motor performance and activities of daily living (ADL). Twenty-one children with DCD (mean age 7 years 9 months, range 6-10 years) and 20 age-matched controls (mean age 7 years 8 months, range 6-10 years) were included. A newly developed protocol was used for testing action observation and imitation proficiency. Motor performance were evaluated with the Movement Assessment Battery for Children-2. ADL were investigated with DCD Questionnaire'07. Children with DCD presented significantly lower action observation (p = .037) and imitation abilities (p < .001) than peers. Worse action observation and imitation abilities were related to lower motor performance and ADL skills and a younger age. Non-meaningful gestures imitation proficiency had predictive value for global motor performance (p = .009), manual dexterity (p = .02) and ADL (p = .004). The new protocol for action observation and imitation abilities can be helpful for detecting motor learning difficulties and for delineating new opportunities for motor teaching approaches in children with DCD.


A cruciform phthalocyanine pentad-based NIR-II photothermal agent for highly efficient tumor ablation.
Photothermal therapy in the second near-infrared window (NIR-II, 1000-1700 nm) exhibits a significant advantage over the first near-infrared window (NIR-I, 650-950 nm) in terms of both maximum permissible exposure (MPE) and penetration depth. However, the thus far reported NIR-II photothermal agents (PTAs) have been focused just on inorganic semiconducting and organic polymeric semiconducting nanoparticles. Herein a novel cruciform phthalocyanine pentad was designed, synthesized, and characterized for the first time. The water-soluble nanoparticles (Zn4-H2Pc/DP NPs) assembled from this single molecular material with the help of DSPE-PEG2000-OCH3 exhibit characteristic absorption in the NIR-II region at 1064 nm with a large extinction coefficient of 52 L g-1 cm-1, high photothermal conversion efficiency of 58.3%, and intense photoacoustic signal. Moreover, both in vitro and in vivo studies reveal the good biocompatibility and notable tumor ablation ability of Zn4-H2Pc/DP NPs under 1064 nm laser irradiation. Theoretical density functional theory calculations interpret the two-dimensional compressional wave energy-dissipation pathway over the broad saddle curved framework of the cruciform conjugated phthalocyanine pentad, rationalizing the efficient photothermal properties of corresponding Zn4-H2Pc/DP NPs in the NIR-II window.


A capture-rate model of net-spinning caddisfly communities.
Empirical research suggests that net-spinning caddisflies require two basic resources, suspended particulate foods, and the currents which deliver them. I present a theoretical model of caddisfly communities based on quantitative differences in the capture rate produced by different catchnet designs. It assumes that catchnet architecture reflects a tradeoff between water filtration rate (flux through the net) and capture efficiency (the proportion of suspended items retained), and that the marginal resource concentration required by species with different catchnet morphologies should reflect the product of these parameters. The model hypothesizes a) that downstream changes in the physical morphology of the stream channel cause a shift in the relative importance of population limitations imposed by food and current-substrate availability, b) that the interaction of these physical changes with the filtering biota results in a seston resource gradient, and c) that the distribution of each taxon along this resource gradient reflects a marginal resource requirement determined by the functional morphology of its catchnet.


[Role of sorbed enzymes in the digestion and absorption of nutrient substances from the chyme].
In poly--fistula dogs, a significant suppression of the fermentative hydrolysis and of the absorption ability was revealed in excluded from the digestion intestinal loops. The experiments showed that suppression of the cave enzyme sorption in the area of wall digestion was the factor slowing down the flow of feeding substances from the enteral milieau.


Effectiveness of an educational intervention to reduce the burden on home care workers and facilitating factors: A pre-post study.
To determine if a training program, aimed at home care workers, for caring for the elderly and for providing their own self-care is effective for reducing workers burden in the short and long terms and to identify the associated variables that can influence burden across 12 months. An increasing number of older adults rely on home care workers as a complement to the care received from family caregivers. However, these workers do not usually have any formal training in nursing care and occasionally suffer burden. A pre- and post-intervention study with a follow-up at 12 months including 86 participants. An 85-hour training course, which included a practical module lasting 35 h, was offered on five separate occasions between 2014 and 2017 in Barcelona (Spain). The care burden was measured according the Zarit Burden Interview and care knowledge and perceived difficulty performing care tasks were assessed. We also gathered data on the physical and psychological status of the care recipients. The educational intervention was effective after training (-7.45% p = .020) and although the initial burden on caregivers did not worsen significantly despite spending 12 months caring for people with moderate physical and psychological dependence, the decrease in the burden was not maintained over time. Associated variables that can influence the burden over 6 months were the caregivers' baseline perception of lacking knowledge and/or having no difficulty with care tasks. The variable that could influence overburden in caregivers at 12 months was becoming ill before the intervention. For the first time, the effectiveness of home workers-specific training has been demonstrated: a reduction in the perceived burden was observed immediately following training completion, but this reduction was not sustained at 6/12 months. The practical interpretation is that a remedial/follow-up training course may be needed. Whether difficulty in providing care or having sufficient knowledge and having an illness influence self-care maintenance requires further verification.


Cardiopulmonary resuscitation (CPR) complications encountered in forensic autopsy cases.
Cardiopulmonary resuscitation (CPR) provides a significant increase in survival rate, even if performed by bystanders. However, bystanders may refrain from performing CPR for fear of eventual malpractice litigation. Currently lack Guidelines specifying whether a particular CPR-related complication is in all likelihood unavoidable or not. To fulfill this gap a great number of studies is required to be published in the most relevant leading academic literature. This paper aims at making a contribution to addressing such a challenge. A retrospective observational study based on forensic autopsy material aiming at recording injuries resulting from the application of CPR. The severity of injuries was forensically evaluated. Out of 88 cases autopsied, only 26.7% had rib fractures (only 20% of which were located in the 6 lower ribs), 17.4% had sternal fractures (85.7% of which were detected in the body of the sternum and 14.3% in the manubrium). The ratio of sternal fractures to rib fractures is similar to the ratio cited in other studies reported in the literature (2:3, approximately). The number of fractures was 7.86 (4.11 on the right side and 4.75 on the left side). 16% of the cases were found to be mild, 48% were moderate, and 35% of the cases were severe. When a physician was present, a (not statistically significant) trend towards more severe complications was found. The findings are in accordance with other similar studies reported in the literature referring to the classic external CPR. This study offers a proposal aiming at making a contribution to develop Guidelines specifying whether a particular CPR-related complication is in all likelihood unavoidable or not.


Limbness in the early chick embryo lateral plate.
In order for the limb to be useful in the evaluation of early determinants of morphogenesis, it is necessary to understand some of the characteristics associated with "limbness" and, more importantly at the beginning at least, it is necessary to know what regions of the early embryo exhibit limbness qualities. Previous investigators have assumed, without direct experimental evidence, that the flank does not have limbness qualities, even at early stages of development. However, there are a few studies suggesting that the early flank does possess limbness qualities. The purpose of the present study was to determine how extensively the qualities of limbness exist in the early chick embryo. Tissues from the future neck, wing, flank, and leg regions were grafted to host celoms and evaluated for their abilities to form limbs. Limbs developed from all four regions of stage 11-14 embryos, but after stage 14 only grafts from the wing and leg regions formed limbs.


Radiofrequency thermoablation in locally advanced breast cancer.
The authors report their experience of 8 cases of breast cancer in six patients, treated by radiofrequency thermoablation. Two patients had bilateral breast cancer infiltrating the skin. All patients, but one, were alive at two years follow-up. The age range was 54-75 years old (median, 71 years old). We observed complete regression in one patient, regression with residual scar in two patients and partial regression in the remaining three patients. The authors believe that radiofrequency, alone or associated with other treatments, is an easy and useful alternative for the management of breast cancer, in selected patient who cannot undergo surgery or refuse surgical treatment and other treatments.


Pleural Empyema Caused by Streptococcus intermedius and Fusobacterium nucleatum: A Distinct Entity of Pleural Infections.
Many community-acquired pleural infections are caused by facultative and anaerobic bacteria from the human oral microbiota. The epidemiology, clinical characteristics, pathogenesis, and etiology of such infections are little studied. The aim of the present prospective multicenter cohort study was to provide a thorough microbiological and clinical characterization of such oral-type pleural infections and to improve our understanding of the underlying etiology and associated risk factors. Over a 2-year period, we included 77 patients with community-acquired pleural infection, whereof 63 (82%) represented oral-type pleural infections. Clinical and anamnestic data were systematically collected, and patients were offered a dental assessment by an oral surgeon. Microbial characterizations were done using next-generation sequencing. Obtained bacterial profiles were compared with microbiology data from previous investigations on odontogenic infections, bacteremia after extraction of infected teeth, and community-acquired brain abscesses. From the oral-type pleural infections, we made 267 bacterial identifications representing 89 different species. Streptococcus intermedius and/or Fusobacterium nucleatum were identified as a dominant component in all infections. We found a high prevalence of dental infections among patients with oral-type pleural infection and demonstrate substantial similarities between the microbiology of such pleural infections and that of odontogenic infections, odontogenic bacteremia, and community-acquired brain abscesses. Oral-type pleural infection is the most common type of community-acquired pleural infection. Current evidence supports hematogenous seeding of bacteria from a dental focus as the most important underlying etiology. Streptococcus intermedius and Fusobacterium nucleatum most likely represent key pathogens necessary for establishing the infection.


A hybrid ring-opening metathesis polymerization catalyst based on an engineered variant of the β-barrel protein FhuA.
A β-barrel protein hybrid catalyst was prepared by covalently anchoring a Grubbs-Hoveyda type olefin metathesis catalyst at a single accessible cysteine amino acid in the barrel interior of a variant of β-barrel transmembrane protein ferric hydroxamate uptake protein component A (FhuA). Activity of this hybrid catalyst type was demonstrated by ring-opening metathesis polymerization of a 7-oxanorbornene derivative in aqueous solution.


Gestational Age-Dependent Regulation of Transthyretin in Mice during Pregnancy.
Our prior studies have shown that protein misfolding and aggregation in the placenta are linked to the development of preeclampsia, a severe pregnancy complication. We identified transthyretin (TTR) as a key component of the aggregated protein complex. However, the regulation of native TTR in normal pregnancy remains unclear. In this study, we found that pregnant mice exhibited a remarkable and progressive decline in serum TTR levels through gestational day (gd) 12-14, followed by an increase in late pregnancy and postpartum. Meanwhile, serum albumin levels showed a modest but statistically significant increase throughout gestation. TTR protein and mRNA levels in the liver, a primary source of circulating TTR, mirrored the changes observed in serum TTR levels during gestation. Intriguingly, a similar pattern of TTR alteration was also observed in the serum of pregnant women and pregnant interleukin-10-knockout (IL-10-/-) mice with high inflammation background. In non-pregnant IL-10-/- mice, serum TTR levels were significantly lower than those in age-matched wild-type mice. Administration of IL-10 to non-pregnant IL-10-/- mice restored their serum TTR levels. Notably, dysregulation of TTR resulted in fewer implantation units, lower fetal weight, and smaller litter sizes in human TTR-overexpressing transgenic mice. Thus, TTR may play a pivotal role as a crucial regulator in normal pregnancy, and inflammation during pregnancy may contribute to the downregulation of serum TTR presence.


Anomalously slow crystal growth of the glass-forming alloy CuZr.
Our ability to exploit the benefits of metallic glasses depends on identifying alloys of high glass-forming ability (GFA). So far, the established empirical correlations of GFA (ref. ) are statistical guides at best and lack a microscopic rationale. Although simulations have the potential to provide this physical insight into the maximum crystallization rate, crystal nucleation is often too slow to be observed. In contrast, measuring the growth rate of a planar crystal surface represents an accessible route to understanding ordering kinetics. Here we use molecular dynamics simulations to show that the crystal growth rate for an important binary glass former, CuZr, is significantly slower than that of a poor glass former, NiAl. In accounting for this difference, we find that the crystal/liquid interface in NiAl exhibits a significantly greater width than that of CuZr. Our results suggest that the crystal/liquid interfacial structure exerts an important influence on the GFA of alloys.


Transposition of the left renal vein in nutcracker syndrome.
Mesoaortic compression of left renal vein produces left renal vein hypertension resulting in left flank pain, hematuria and pelvic-ureteral varices. This is called the nutcracker syndrome. The nutcracker syndrome has been treated in various ways. We recently experienced two cases of patients with nutcracker syndrome. We treated the patients with transposition of their left renal vein.


Preoperative cardiac assessment for patients with infrarenal abdominal aortic aneurysms: a survey of current practice by vascular surgeons in New South Wales and Australian Capital Territory.
The reported mortality rate following open elective repair of abdominal aortic aneurysm (AAA) varies between 0 and 12%. Much of the mortality and major morbidity is caused by cardiac events. The evidence regarding best practice for cardiac assessment and optimization of this patient group is unclear. The aim of the present study was to evaluate current practice of cardiac risk factor assessment by vascular surgeons in New South Wales (NSW) and Australian Capital Territory (ACT) for patients undergoing open elective repair of infrarenal AAA. A postal questionnaire was sent to 46 surgeons in NSW and ACT identified as expressing a principal or major interest in vascular surgery. If no response was received within 3 weeks, a second questionnaire was sent and if no response was received after the second mailing, a telephone survey of non-responders was conducted. Data were collated regarding the importance of risk factors elicited by clinical history, preoperative investigation, referral for cardiological opinion, use of perioperative beta-blockade and the timing of aortic surgery in relation to coronary artery revascularization and acute myocardial infarction. The overall response rate was 87% (40/46) and the median (range) response time was 14 (4-109) days. Only 22 of 40 and 23 of 40 surgeons consider diabetes mellitus or renal impairment, respectively, to be important when assessing cardiac risk and 34 of 40 surgeons do not employ a validated risk index in preoperative assessment. Sixteen of 40 surgeons refer all patients needing AAA repair to a cardiologist, while 24 of 40 would initiate cardiac investigations themselves (either stress electrocardiography, scintigraphy or echocardiography). Seventeen surgeons always or usually commenced perioperative beta-blockade with wide variations in the commencement (1 to > 28 days preoperatively) and duration (< 1 week to > 28 days postoperatively) of treatment. The timing of AAA repair following coronary revascularization ranged from < 1 week to 6 months and delay in surgical repair of AAA following myocardial infarction ranged from < 1 week to > 6 months. Preoperative assessment of cardiac risk in patients for repair of AAA lacks consensus among vascular surgeons in NSW and ACT. The diversity of clinical practice may rest with the paucity of prospective trials published in the medical literature or the influence of local institutional facilities.


Leonurine (SCM-198) improves cardiac recovery in rat during chronic infarction.
Leonurine, an alkaloid typically found in Herba leonuri, is known to have both antioxidant and cardioprotective properties. In the present study, we investigated the cardioprotective mechanism of leonurine the in vivo rat model of chronic myocardial ischemia and in vitro H9c2 cardiac myocyte model of oxidative stress. Myocardial ischemia was induced by ligating the left anterior descending coronary artery. Rats were divided into sham, myocardial ischemia+saline, and myocardial ischemia+leonurine (15 mg/kg/day). Cardiac function was recorded by catheterization. Apoptosis-related factor vascular endothelial growth factor (VEGF), survivin, Bcl-2 and Bax and pro-survival signaling pathways Akt, hypoxia inducible factor (HIF)-1α were measured by Western blotting or RT-PCR. Our results showed leonurine significantly improved myocardial function as evidenced by the decreased left ventricle end-diastolic pressure and the increased +dP/dt. Interestingly, leonurine increased the phosphorylation of Akt, the protein and gene expression of Bcl-2, but it reduced the protein and gene expression of Bax in vivo. Meanwhile leonurine significantly increased Akt phosphorylation in a concentration-dependent manner in H9c2 cardiac myocyte induced by oxidative stress in vitro, which was abolished by a phosphoinositide 3-kinase (PI3K) inhibitor, LY294002. Furthermore, leonurine not only increased the expression of HIF-1α but also the expression of survivin and VEGF. The results of present study demonstrated, for the first time that leonurine has potent anti-apoptotic effects after chronic myocardial ischemia mediated by activating the PI3K/Akt signaling pathway. Angiogenic mechanisms may be partially responsible for such an effect, which needs to be studied further.


Comparative analysis of laparoscopic sleeve gastrectomy and Roux-en-Y gastric bypass procedures for the treatment of morbid obesity.
Roux-en-Y gastric bypass (RYGB) has been considered as the most efficient method in bariatric surgery. Indeed, Laparoscopic Sleeve Gastrectomy (LSG) which is easier to do, has been increasingly used in the recent years. The aim of the present study was to compare short-and mid-term outcomes of RYGB and LSG. Medical records of 62 patients who underwent either RYGB (GroupR) or LSG (GroupL) in our General Surgery Department between 2010 and 2013 were retrospectively reviewed. Demographics, comorbidities, preoperative laboratory values, length of hospital stay and postoperative complications were recorded. During follow-up in the postoperative period, body-mass-index (BMI), excess weight loss (EWL), triglyceride levels (TG), and low-density lipoprotein (LDL) levels were recorded at the 1st, 3rd, 6th, and 12th months. Mean length of hospital stay was significantly higher in GroupR (p = 0.001), which was also correlated with BMI. EWL at 1st, 3rd, 6th, and 12th months was significantly higher in GroupR. Hair loss was significantly higher in GroupR (p < 0.05). The rates of diabetes mellitus and hypertension in the preoperative period and at 6th and 12th months did not significantly differ between the groups. Preoperative TG and LDL values were significantly higher in GroupR (p < 0.05). This study indicated, that RYGB is statistically more effective than LSG, but LSG has clinically almost the same effect as RYGB, and also hospital stay, postoperative complications as hair loss are decreased in LSG. Laparoscopic Sleeve Gastrectomy, Morbid Obesity, Roux-en-Y Gastric Bypass.


Evolution of concomitant use of veno-arterial extracorporeal membrane oxygenation support with Impella in cardiogenic shock: From percutaneous femoral Impella to axillary Impella 5.5.
Little is known about safety and efficacy of the use of Impella 5.5 compared to previous iterations in the setting of Impella with Veno-Arterial Extracorporeal Membrane Oxygenation Support as ECPELLA. Consecutive patients who were treated by ECPELLA with surgically implanted axillary Impella 5.5 (N = 13) were compared with patients supported by ECPELLA with percutaneous femoral Impella CP or 2.5 (Control, N = 13). The total ECPELLA flow was higher in ECPELLA 5.5 group (6.9 vs. 5.4 L/min, p = 0.019). Actual hospital survival was higher than predicted and comparable in both groups (ECPELLA 5.5, 61.5% vs. Control, 53.8%, p = 0.691). Both total device complications (ECPELLA 5.5, 7.7% vs. Control, 46.1%, p = 0.021) and Impella-specific complications (ECPELLA 5.5, 0% vs. Control, 30.8%, p = 0.012) were significantly lower in the ECPELLA 5.5 group. Utilization of Impella 5.5 in the setting of ECPELLA provides greater hemodynamic support with a lower risk of complications compared to Impella CP or 2.5.


Impacts of plasma microbial lipopolysaccharide translocation on B cell perturbations and anti-CD4 autoantibody production in people with HIV on suppressive antiretroviral therapy.
. Up to 20% of people with HIV (PWH) who undergo virologically suppressed antiretroviral therapy (ART) fail to experience complete immune restoration. We recently reported that plasma anti-CD4 IgG (antiCD4IgG) autoantibodies from immune non-responders specifically deplete CD4 + T cells via antibody-dependent cytotoxicity. However, the mechanism of antiCD4IgG production remains unclear. . Blood samples were collected from 16 healthy individuals and 25 PWH on suppressive ART. IgG subclass, plasma lipopolysaccharide (LPS), and antiCD4IgG levels were measured by ELISA. Gene profiles in B cells were analyzed by microarray and quantitative PCR. Furthermore, a patient-derived antiCD4IgG-producing B cell line was generated and stimulated with LPS in vitro. B cell IgG class switch recombination (CSR) was evaluated in response to LPS in splenic B cells from C57/B6 mice in vitro. . Increased plasma anti-CD4 IgGs in PWH were predominantly IgG1 and associated with increased plasma LPS levels as well as B cell expression of TLR2, TLR4, and MyD88 mRNA in vivo. Furthermore, LPS stimulation induced antiCD4IgG production in the antiCD4IgG B cell line in vitro. Finally, LPS promoted CSR in vitro. . Our findings suggest that persistent LPS translocation may promote anti-CD4 autoreactive B cell activation and antiCD4IgG production in PWH on ART, which may contribute to gradual CD4 + T cell depletion. This study suggests that reversing a compromised mucosal barrier could improve ART outcomes in PWH who fail to experience complete immune restoration.


A novel nutritional risk score and prognosis of oral cancer patients: A prospective study.
To evaluate the prognostic performance of a novel nutritional risk score based on serum iron, hemoglobin, and body mass index (BMI) in oral cancer patients, and to predict the response to chemotherapy in patients with different nutritional status. X-tile analysis was performed to determine the optimal cutoff values of serum iron, hemoglobin, and BMI. A nutritional risk score was established by using the HR values of serum iron, hemoglobin, and BMI. Kaplan-Meier curve and multivariable Cox proportional hazards models were used to evaluate the prognostic value of the nutritional risk score in overall survival (OS) and oral cancer-specific survival (OCSS). Serum iron, hemoglobin, and body mass index were all inversely related to the prognosis of oral cancer. The adjusted HR of serum iron, hemoglobin, and BMI were 1.562, 1.886, and 1.465 for OS, and 1.653, 1.865, and 1.443 for OCSS. Patients with higher nutritional risk score had a poorer OS and OCSS. Additionally, chemotherapy was only associated with improved OCSS in patients with the lowest nutritional risk score, but not in patients with higher one. Nutritional risk score is of prognostic value in oral cancer patients. Favorable response to chemotherapy may only be observed in well-nourished oral cancer patients with lower nutritional risk score.


Olecranon fracture fixation utilizing a bioabsorbable tension band construct: analysis of stability with motion in a cadaveric model.
This study was performed to determine if tension band suturing with bioabsorbable materials can maintain fracture (osteotomy) reduction when subjected to an early motion protocol. Olecranon osteotomies were created in 13 cadaveric upper extremities and then sequentially fixed with axial Kirschner wires, and tension band wiring/suturing utilizing: musical #1 PDS (Ethicon Inc., Somerville, New Jersey, USA), musical #1 Panacryl (Ethicon Inc.), musical #2 Panacryl (Ethicon Inc.), and 18 gauge surgical wire. Specimens were cycled through a range of motion in a continuous passive motion machine. Specimens fixed with K-wires only, musical #1PDS and musical #1 Panacryl tension band suturing failed to maintain osteotomy reduction. Only surgical steel and musical #2 Panacryl maintained osteotomy reduction; both were superior to the other fixation methods (P<0.001). The musical #2 Panacryl suture is an excellent choice for a tension band suture construct; it retains 80% of its breaking strength at 3 months, is fully absorbed, and maintains osteotomy reduction throughout a passive motion protocol.