Mindfulness based cognitive therapy for psychiatric disorders: a systematic review and meta-analysis.
Mindfulness- based Cognitive Therapy (MBCT) is a meditation program based on an integration of Cognitive behavioural therapy and Mindfulness-based stress reduction. The aim of the present work is to review and conduct a meta-analysis of the current findings about the efficacy of MBCT for psychiatric patients. A literature search was undertaken using five electronic databases and references of retrieved articles. Main findings included the following: 1) MBCT in adjunct to usual care was significantly better than usual care alone for reducing major depression (MD) relapses in patients with three or more prior depressive episodes (4 studies), 2) MBCT plus gradual discontinuation of maintenance ADs was associated to similar relapse rates at 1year as compared with continuation of maintenance antidepressants (1 study), 3) the augmentation of MBCT could be useful for reducing residual depressive symptoms in patients with MD (2 studies) and for reducing anxiety symptoms in patients with bipolar disorder in remission (1 study) and in patients with some anxiety disorders (2 studies). However, several methodological shortcomings including small sample sizes, non-randomized design of some studies and the absence of studies comparing MBCT to control groups designed to distinguish specific from non-specific effects of such practice underscore the necessity for further research.


Pathophysiology of diabetic nephropathy.
Diabetic nephropathy (DN) is now the commonest cause of end-stage renal failure in the Western world. Recent studies examining the pathogenesis of diabetic complications have focused on the complex interaction between genetic and hemodynamic mechanisms in addition to metabolic factors such as advanced glycation, protein kinase C (PKC) activation, and polyol production. The importance of the various components, particularly with regard to the progression of DN, is currently being explored with the assistance of targeted drug intervention studies.


Convenient synthesis of electron-donating substituted benzonitriles by photolysis of phenyl halides and esters.
Irradiation of electron-donating substituted phenyl halides (fluorides and chlorides) or esters (mesylates, triflates and phosphates) in aqueous MeCN in the presence of KCN gives the corresponding benzonitriles in 48 to 100% yield through an ArSN1 reaction with the intermediacy of a triplet phenyl cation.


Improving diagnostic accuracy for probable and definite Ménière's disease using magnetic resonance imaging.
To determine whether magnetic resonance imaging (MRI) can improve diagnostic accuracy for definite and probable Ménière's disease (MD) based on perilymphatic enhancement (PE) and endolymphatic hydrops (EH). 363 patients with unilateral MD (probable MD, n = 75 and definite MD, n = 288) were recruited. A three-dimensional zoomed imaging technique with parallel transmission SPACE real inversion recovery was performed 6 h after intravenous gadolinium injection to investigate the presence of PE and to evaluate the grading and location of EH. PE and EH characteristics were analyzed and compared between the probable and definite MD groups. The cochlear and vestibular EH grading on the affected side was more severe in the definite MD group than that in the probable MD group (P < 0.001). The EH locations within the inner ear on the affected side also differed between the two groups (χ2 = 81.15, P < 0.001). The signal intensity ratio (SIR) on the affected side was significantly higher in the definite MD group than in the probable MD group (t = 2.18, P < 0.05). The assessment of the combination of PE and EH parameters within the inner ear revealed a higher area under the curve (AUC) in the definite MD group (0.82) compared with the AUCs of the parameters assessed alone. The assessment of a combination of PE and EH parameters improved the diagnostic accuracy for probable and definite MD, suggesting that MRI findings may be clinically useful in the diagnosis of MD.


MicroRNA-214-5p involves in the protection effect of Dexmedetomidine against neurological injury in Alzheimer's disease via targeting the suppressor of zest 12.
Alzheimer's disease (AD) is a neurological disease. Dexmedetomidine (Dex) has been evidenced to exert neuroprotective effects on multiple neurological diseases, while the function of microRNA(miR)- 214-5p on Dex-mediated AD progression via targeting the suppressor of zest 12 (SUZ12) remains unclear. This study obligates to investigate the regulatory functions of Dex, miR-214-5p and SUZ12 on AD. The expression of miR-214-5p and SUZ12 in APPswe/PS1dE9 mice (hereinafter referred to as AD mice) was examined. Thereafter, the AD mice were treated with Dex or increased miR-214-5p or reduced SUZ12 to determine the spatial memory ability, apoptosis of hippocampal neurons and the contents of serum inflammatory and oxidative stress factors of AD mice. Finally, the target relationship between miR-214-5p and SUZ12 was detected. MiR-214-5p was reduced and SUZ12 was elevated in AD mice. Dex administration reduced the apoptosis of hippocampal neurons, the contents of serum inflammatory factor and oxidative stress, and attenuated the cognitive impairment of AD mice accompanied by up-regulated miR-214-5p and down-regulated SUZ12, and the overexpression of miR-214-5p or reduction of SUZ12 could effectively enhance the Dex-treated effects on AD mice. MiR-214-5p targeted SUZ12. Dex may have a potential neuroprotective effect on AD via the miR-214-5p/SUZ12 axis. This study provides novel therapeutic targets for AD treatment.


Anti-tumour effect of in situ vaccines combined with VEGFR inhibitors in the treatment of metastatic cervical cancer.
Cervical cancer is the fourth most common malignant tumor in the world, for advanced cervical cancer, more than 30% of patients continue to have tumor and relapse or metastasis after the traditional treatment (concurrent chemoradiotherapy), and the response rate of immune checkpoint inhibitor (PD-1) is less 15%, so additional approaches are required. In situ vaccine is a very promising immunotherapy strategy. In the preclinical study, the combination of CPG and anti-Ox40 antibody can completely resolve injection site tumours and distant tumours and leads to the recovery of most mice with lymphoma. However, our early exploration process found that the effect of CpG + OX40 in the treatment of advanced cervical cancer is not ideal. Hence, we explored the anti-tumor effect of CpG + OX40 combined with anti-angiogenic therapy for the first time. The results showed that the combination significantly inhibited the proliferation of primary and secondary tumor volume and prolonged the survival time of mice, compared with the control group, CD3+, CD4 + and CD8 + T cells in the combined group showed an increasing trend. In addition, in terms of metabolism, the anti-vascular effect of anlotinib can significantly reduce the blood supply and metabolic level of tumor, the expression of Ki67 and CD31 in the control group was significantly higher than that in each administration group. In conclusion, our preclinical research results showed that the combination of in situ vaccine and anti-angiogenic therapy has a good anti-tumor effect, and may potentially offer an effective treatment option for patients with advanced cervical cancer.


Loculated empyema in a neonate successfully treated with chest tube thoracostomy and antibiotics.
Empyema thoracis, defined as the accumulation of pus in the pleural space, is a rare entity in the neonatal period. There are very few cases described in the medical literature and there are still no treatment protocols in the management of empyema in neonates. In older infants and children, intrapleural fibrinolytics and surgery are often utilized since treatment of complicated parapneumonic effusions with chest tube and antibiotics alone often fail due to the viscous fluid and presence of loculations. Presented here is a case of a term neonate who exhibited symptoms of respiratory distress on the sixth day of life. Imaging modalities revealed massive left sided pleural effusion with loculations and mass effects. Pleural fluid was grossly pus and exudative in nature. Gram stain revealed gram-positive cocci but culture was negative. Empiric broad-spectrum antibiotics and chest tube drainage were utilized and patient was discharged after forty-seven days of hospital admission. In spite of prolonged hospital stay, patient survived with no complications. Therefore, nonoperative therapy could still be an option for neonates with loculated empyema. The key to success in treatment is immediate identification of effusion, prompt initiation of antibiotics, and early effective chest tube drainage.


Placental 11β-Hydroxysteroid dehydrogenase type 2 expression: Correlations with birth weight and placental metal concentrations.
Infants born below 2500 g are classified as low birth weight. Excess in utero exposure to cortisol has been linked to restricted fetal growth. Placental production of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) inactivates cortisol before passage into the fetus. The present study tested the hypothesis that placental 11β-HSD2 expression is positively correlated with an individualized birth weight centile and raw birth weight, and examines the relationship between metal concentrations in placental tissue and 11β-HSD2 expression. Placentae from 191 births were collected and samples preserved to maintain mRNA profile. Placental 11β-HSD2 expression was measured via qRT-PCR. Addition samples were collected from placental tissues and uniformly dried in order to quantify 18 metals via ICP-MS (n = 160). A significant, positive correlation between 11β-HSD2 expression and individualized birth weight centile (p = 0.0321) and birth weight (p = 0.0243) was found. Additionally, maternal age and gestational age were positivity correlated with each other (p = 0.0321). Birth weight was significantly different with race, marital status, education and maternal tobacco use. Four metals (Co, Mn, Ni, Zn) demonstrated significant positive correlations (p < 0.05) with 11β-HSD2 expression. Sex specific differences were found; Co, Cu, Fe, Zn, and Ni were positively correlated with 11β-HSD2 expression in males only, no significant correlations were found in the female only sample. These data indicate that the growth potential of a fetus is related to the 11β-HSD2 expression in the placenta, and that 11β-HSD2 expression is related to the trace metals status of the mother.


Zymobacter palmae gen. nov., sp. nov., a new ethanol-fermenting peritrichous bacterium isolated from palm sap.
Zymobacter palmae gen. nov., sp. nov. was proposed for a new ethanol-fermenting bacterium that was isolated from palm sap in Okinawa Prefecture, Japan. The bacterium is gram-negative, facultatively anaerobic, catalase-positive, oxidase-negative, nonsporeforming and peritrichously flagellated. It requires nicotinic acid for growth. It ferments hexoses, alpha-linked di- and tri-saccharides, and sugar alcohols (fructose, galactose, glucose, mannose, maltose, melibiose, saccharose, raffinose, mannitol and sorbitol). Fifteen percent of maltose in broth medium is effectively fermented, whereas glucose with a concentration higher than 10% delayed growth initiation and decreased growth rates. Maltose is fermented to produce ethanol and CO2 with a trace amount of acids. Approximately 2 mol of ethanol are produced from 1 mol moiety of hexose of maltose. The organism possesses ubiquinone-9. The G + C content of the DNA is 55.8 +/- 0.4 mol%. Major cellular fatty acids were palmitic and oleic acids and cyclopropanic acid of C19:0. Characteristic hydroxylated acid was 3-hydroxy dodecanoic acid. The bacterium is distinct from other ethanol-fermenting bacteria belonging to the genera Zymomonas Kluyver and van Niel 1936 and Saccharobacter Yaping et al. 1990 with respect to chemotaxonomic and other phenotypic characters to warrant to compose a new genus and a new species. The type strain is strain T109 (= IAM 14233).


Cloning of the Major Capsid Protein (MCP) of Grouper Iridovirus of Taiwan (TGIV) and Preliminary Evaluation of a Recombinant MCP Vaccine against TGIV.
Fish iridoviruses cause systemic diseases with high mortality in various species of wild and farm-raised fish, resulting in severe economic losses. In 1998, we isolated a new epizootic iridovirus in cultured grouper (Epinephelus sp.) in Taiwan, thus named as grouper iridovirus of Taiwan (TGIV). We report here the cloning of TGIV major capsid protein (MCP). Phylogenetic analysis of the iridoviral MCPs confirmed the classification of TGIV into the Megalocytivirus genus. Recombinant TGIV MCP and GIV MCP were then generated to produce polyclonal antibodies. Western blot analysis revealed that the two antisera were species-specific, indicating no common epitope shared by the MCPs of the two viruses. We further assayed the potency of a subunit vaccine containing recombinant TGIV MCP. The vaccine effectively protected grouper from TGIV infection. The result demonstrated that MCP is a suitable antigen for anti-TGIV vaccines.


Full wave 3D inverse scattering transmission ultrasound tomography in the presence of high contrast.
We present here a quantitative ultrasound tomographic method yielding a sub-mm resolution, quantitative 3D representation of tissue characteristics in the presence of high contrast media. This result is a generalization of previous work where high impedance contrast was not present and may provide a clinically and laboratory relevant, relatively inexpensive, high resolution imaging method for imaging in the presence of bone. This allows tumor, muscle, tendon, ligament or cartilage disease monitoring for therapy and general laboratory or clinical settings. The method has proven useful in breast imaging and is generalized here to high-resolution quantitative imaging in the presence of bone. The laboratory data are acquired in ~ 12 min and the reconstruction in ~ 24 min-approximately 200 times faster than previously reported simulations in the literature. Such fast reconstructions with real data require careful calibration, adequate data redundancy from a 2D array of 2048 elements and a paraxial approximation. The imaging results show that tissue surrounding the high impedance region is artifact free and has correct speed of sound at sub-mm resolution.


Twin Support Vector Regression for complex millimetric wave propagation environment.
In this article, an effective millimetric wave channel estimation algorithm based on Twin Support Vector Regression (TSVR) is proposed. This algorithm exploits Discrete Wavelet Transform (DWT) in order to denoise samples in learning phase and then enhance fitting performance. An indoor complex conference room environment full of furniture and electronic equipments is adopted for experiments. Through the proposed approach, channel frequency responses are directly estimated using the Orthogonal Frequency Division Multiplexing (OFDM) reference symbol pattern by solving two quadratic programming problems in order to improve generalization aptitude and computational speed. We consider in this work a Channel Impulse Response (CIR) of 60 GHz multipath transmission system generated by the "Wireless InSite" ray tracer by Remcom. The numerical experiments confirm the performance of the proposed approach compared to other conventional algorithms for several configuration scenarios with and without mobility.


[Coronary ventricular fistula as a late complication of permanent pacing].
A coronary angiography performed for the occurrence of atypical chest pain allowed us to discover a coronary-right ventricular fistula as a rare complication of myocardial penetration by a tined ventricular catheter implanted some years earlier.


Response surface methodology combined Box-Behnken design optimized green kinetic spectrophotometric and HPLC methods to quantify angiotensin receptor blocker valsartan in pharmaceutical formulations.
The high-performance liquid chromatographic (HPLC) and kinetic spectrophotometric methods were established to compute valsartan (VAL) in pharmaceutical formulations. The spectrophotometric procedures adopted initial rate, fixed time, and equilibrium strategies to assess VAL. The method was based on the carboxylic acid group of the oxidized VAL with a mixture of potassium iodate (KIO3) and potassium iodide (KI) at room temperature, producing a stable, yellow-coloured absorb at 352 nm. The critical parameters were optimized using green process optimization methodology such as Box-Behnken design (BBD) which belongs to response surface methodology (RSM). After the screening, experiments identified them as significant, and then three crucial factors were optimised: KI volume, KIO3 volume, and reaction time against response as absorbance. The HPLC procedure was also optimized based on the desirability function on RSM-BBD. The parameters such as pH, methanol (%), and flow rate (ml/min) were optimized with the best responses: peak area, symmetry, and theoretical plates. The linearity of spectrophotometric and HPLC methods was within the range of 2-24 and 0.25-11.25 µg/ml, respectively. The developed procedures produced excellent accuracy and precision. The design of the experiment (DoE) setting explained and discussed the individual steps and the importance of independent and dependent variables used to develop the model and optimization. The method was validated as per the International Conference on Harmonization (ICH) guidelines. Furthermore, Youden's robustness study was applied with factorial combinations of the preferred analytical parameters and explored their influence with alternative conditions. The analytical Eco-Scale score was calculated and was found a better option as green methods to quantify VAL. The results were reproducible with the analysis completed with biological fluid and wastewater samples.


Are the favorable outcomes of splenectomy predictable inpatients with idiopathic thrombocytopenic purpura (ITP)?
Historically, splenectomy has been an accepted procedure in the management of immune thrombocytopenic purpura (ITP). However, it is also true that the response to splenectomy in patients with ITP seems to be unpredictable. Therefore, the purpose of this study was to identify clinical variables that might predict a favorable response to splenectomy in patients with ITP. Data were collected retrospectively for 40 adult patients with ITP who underwent laparoscopic (LS) and open (OS) splenectomy at Emory University Hospital between 1992 and 1999. Demographics and outcomes were recorded. Age, sex, disease duration, comorbidities (ASA > 2), previous response to steroids and/or other medications, and preoperative platelet count were analyzed by univariate (t-test, Fisher's exact test) and multivariate statistical methods. Of the 20 patients in each group, improved platelet counts were noted in 18 patients (90%) in the LS group and 20 patients (100%) in the OS group. Follow-up (16 +/- 3 months) was obtained in 19 LS patients (95%) and 16 OS patients (80%), with 84% and 87.5% sustained response rates, respectively. After univariate analysis, two variables (age and disease duration) were found to be significantly related to the outcome of splenectomy (p <lt; 0.01). However, after multiple logistic regression analysis, only disease duration (relative risk = 1.083; CI, 1.004-1.167) was an independent prognostic factor for a sustained response to splenectomy. These results suggest that the response to splenectomy (laparoscopic and open) in patients with ITP cannot be adequately predicted on the basis of presplenectomy clinical variables. However, disease duration and patient age should be taken into consideration when selecting patients for splenectomy.


Incidence of subcortical lesions not increased in nonarteritic ischemic optic neuropathy on magnetic resonance imaging.
We performed magnetic resonance imaging on nine patients with nonarteritic ischemic optic neuropathy and 11 control patients with sensorineural hearing loss and suspected acoustic neuroma. We then counted the number of subcortical lesions in each patient, which may represent an index of generalized cerebral vascular disease. Although patients in the ischemic optic neuropathy group had an average of 3.2 subcortical lesions and those in the control group had an average of 0.9 lesions, this difference was not significant. Based on the presence of subcortical lesions, patients with nonarteritic ischemic optic neuropathy do not appear to have an increased incidence of generalized cerebral vascular disease.


Homograft banking in Singapore: two years of cardiovascular tissue banking in Southeast Asia.
Established in 2008, the National Cardiovascular Homograft Bank (NCHB) has been instrumental in creating an available supply of cardiovascular tissues for implantation in Singapore. This article introduces its collaboration with Singapore General Hospital Skin Bank Unit. The procedure of homograft recovery, processing, cryopreservation and quality assurance are presented. Since its establishment, the NCHB has followed the guidelines set by the Ministry of Health Singapore and the American Association of Tissue Banks. A total of 57 homografts had been recovered and 40 homografts were determined to be suitable for clinical use. The most significant reasons for non-clinical use are positive microbiological culture or unsuitable graft condition. Crucial findings prompted reviews and implementation of new procedures to improve the safety of homograft recipients. These include (1) a change in antibiotic decontamination regime from penicillin and streptomycin to amikacin and vancomycin after a review and (2) mandating histopathogical examination since the discovery of cardiac sarcoidosis in a previously undiagnosed donor. Further, the NCHB also routinely performs dengue virus screening, for donors suspected of dengue infection. Cultural factors which affect the donation rate are also briefly explored. By 2010, 31 homografts had been implanted into recipients with congenital or acquired heart valve conditions. More than half of these recipients were children. Post-operative outcomes had been encouraging, with no report of adverse events attributed to implanted homografts.


The use of biologic therapies in uveitis.
Non-infectious uveitis has been long controlled with the use of corticosteroids with many side effects and poor control in some cases. The purpose of this paper was to assess the different biologic agents (in this case infliximab and adalimumab) and to compare their efficacy in the treatment of uveitis. Adalimumab has been proven very successful in replacing or aiding corticosteroid therapy in different autoimmune mediated uveitis (Juvenile Idiopathic Arthritis, Rheumatoid arthritis, sarcoidosis) whereas infliximab has been used intravenously and recently intravitreally with very promising results in controlling Behcet's related uveitis. Biologic Response Modifiers represent the future of therapy in immune-mediated uveitis. Abbreviations AU = Anterior Uveitis, BCVA = Best Corrected Visual Acuity, BRM = Biologic Response Modifiers, CME = Cystoid Macular Oedema, CPR = C Protein Reactive, ESR = Erythrocyte Sediment Rate, HSV = Herpes Simplex Virus, ICAM = Intercellular Adhesion Molecules, IMT = Immunomodulatory Therapy, JIA = Juvenile Idiopathic Arthritis, MMP = Matrix Metalloproteinases, MTX = Methotrexate, RA = Rheumatoid Arthritis, TB = Tuberculosis, VCAM = Vascular Adhesion Molecules.


Surgeon accuracy in the selection of the flexion-extension axis of the elbow: an in vitro study.
The incorrect determination of the flexion-extension axis of the elbow may result in poor clinical outcomes for patients undergoing ligament repairs, joint arthroplasties, and procedures requiring articulated external fixators. The variability in the selection of the flexion-extension axis based on a visual approximation of bony landmarks on the distal humerus was studied within a group of surgeons. Three surgeons of different experience levels independently selected points through which they believed the flexion-extension axis passed on the medial and lateral surfaces of 23 distal humeri. One surgeon repeated the point selection on three separate occasions. These surgeon points were compared with an axis calculated by use of a computer-assisted method that relied on the centers of the trochlear sulcus and capitellum via digitization of these structures. Relative to the computer-generated flexion-extension axis, the error in the surgeons' selections resulted in a mean frontal plane angle of 1.5 degrees +/- 3.0 degrees valgus (range, 6.3 degrees varus to 9.6 degrees valgus) and a coronal plane angle of 1.6 degrees +/- 3.3 degrees external rotation (range, 8.3 degrees internal rotation to 10.2 degrees external rotation). These results suggest that the use of a computer-assisted surgical technique will allow a more accurate determination of the flexion-extension axis of the elbow, which may lead to improved clinical outcomes in patients treated with ligament repairs or reconstructions, elbow arthroplasties, or articulated external fixators.


Deconstructing Mechanisms of Diet-Microbiome-Immune Interactions.
Emerging evidence suggests that the effect of dietary intake on human health and disease is linked to both the immune system and the microbiota. Yet, we lack an integrated mechanistic model for how these three complex systems relate, limiting our ability to understand and treat chronic and infectious disease. Here, we review recent findings at the interface of microbiology, immunology, and nutrition, with an emphasis on experimentally tractable models and hypothesis-driven mechanistic work. We outline emerging mechanistic concepts and generalizable approaches to bridge the gap between microbial ecology and molecular mechanism. These set the stage for a new era of precision human nutrition informed by a deep and comprehensive knowledge of the diverse cell types in and on the human body.


Double negative Treg cells promote nonmyeloablative bone marrow chimerism by inducing T-cell clonal deletion and suppressing NK cell function.
The establishment of immune tolerance and prevention of chronic rejection remain major goals in clinical transplantation. In bone marrow (BM) transplantation, T cells and NK cells play important roles for graft rejection. In addition, graft-versus-host-disease (GVHD) remains a major obstacle for BM transplantation. In this study, we aimed to establish mixed chimerism in an irradiation-free condition. Our data indicate that adoptive transfer of donor-derived T-cell receptor (TCR) αβ(+) CD3(+) CD4(-) CD8(-) NK1.1(-) (double negative, DN) Treg cells prior to C57BL/6 to BALB/c BM transplantation, in combination with cyclophosphamide, induced a stable-mixed chimerism and acceptance of C57BL/6 skin allografts but rejection of third-party C3H (H-2k) skin grafts. Adoptive transfer of CD4(+) and CD8(+) T cells, but not DN Treg cells, induced GVHD in this regimen. The recipient T-cell alloreactive responsiveness was reduced in the DN Treg cell-treated group and clonal deletions of TCRVβ2, 7, 8.1/2, and 8.3 were observed in both CD4(+) and CD8(+) T cells. Furthermore, DN Treg-cell treatment suppressed NK cell-mediated BM rejection in a perforin-dependent manner. Taken together, our results suggest that adoptive transfer of DN Treg cells can control both adoptive and innate immunities and promote stable-mixed chimerism and donor-specific tolerance in the irradiation-free regimen.


Disopyramide kinetics in renal impairment: determinants of interindividual variability.
Disopyramide kinetics were studied in 30 patients with normal to severely impaired renal function (endogenous creatinine clearance 7.6 to 116.9 ml/min/1.73 m2) after intravenous bolus injection. Serum concentration-time curves were fitted to an open two-compartment model. There was close correlation between renal disopyramide clearance and creatinine clearance (r = 0.922). Disopyramide body clearance or elimination rate constant (kel beta) and creatinine clearance did not correlate as closely (r = 0.756 and 0.644). Volume of distribution at steady state and extrarenal clearance of disopyramide both correlated slightly positively with renal function. Disopyramide body clearance and volume of distribution, but not kel beta, were found to be dose dependent. Disopyramide kinetics in renal impairment were not sufficiently predictable from clinical data of the patient because of great interindividual variation in drug disposition and renal and extrarenal elimination. Dosage regimen must therefore be based on individual response and controlled by the clinical effect and estimates of disopyramide serum concentration.


Maturation of replicating simian virus 40 DNA molecules in isolated nuclei by continued bidirectional replication to the normal termination region.
Mature SV40 DNA synthesized for different periods of time either in isolated nuclei or in intact cells was highly purified and then digested with restriction endonucleases in order to relate the time of synthesis of newly replicated viral DNA to its location in the genome. Replication in nuclei supplemented with a cytosol fraction from uninfected cells was a faithful continuation of the bidirectional process observed in intact cells, but did not exhibit significant initiation of new replicons. SV40 DNA replication in cells at 37 degrees C proceeded at about 145 nucleotides/min per replication fork. In the absence of cytosol, when DNA synthesis was limited and joining of Okazaki fragments was retarded, bidirectional SV40 DNA replication continued into the normal region where separation yeilded circular duplex DNA molecules containing one or more interruptions in the nascent DNA strands. In the presence of cytosol, this type of viral DNA was shown to be a precursor of covalently closed, superhelical SV40 DNA, the mature from of viral DNA.


Prognostic Significance of p16 Protein Expression in Breast Cancer.
Breast cancer is the most common cancer in Sudan. The p16 protein plays a vital role in the regulation of the cell cycle. This study analysed the protein expression of p16 in 202 paraffin blocks from Sudanese women with breast cancer using immunohistochemistry. This study included 168 (83.2%), 16 (7.9%), and 18 (8.9%) patients with invasive ductal carcinoma, invasive lobular carcinoma, and papillary carcinoma, respectively. There were 95 cases (47.0%) with grade III, 70 cases (34.6%) with grade II, and 23 cases (11.4%) with grade I breast cancer. The hormone receptor status was available for 119 of the cases, and 31 (15.3%), 25 (12.4%), and 63 (31.2%) cases were positive for oestrogen, progesterone, and HER2 receptors, respectively. p16 protein expression was associated with high histologic grade, lymph node metastasis, and poor prognosis. p16 protein expression may potentially be used as a prognostic marker.


Endoscopic Endonasal Approach for Trigeminal Schwannomas: Tailored Approaches Based on Lesion Traits.
To describe four endoscopic endonasal subapproaches, namely, the trans-lamina papyracea, trans-prelacrimal recess, trans-Meckel's cave, and transclival approaches for trigeminal schwannomas (TSs). This retrospective study reviewed the medical records and intraoperative videos of 38 patients with TSs who underwent endoscopic endonasal approach (EEA) between Jan 2013 and Dec 2021. According to Jeong's classification, for TS equally in middle and posterior fossae (MP), a purely trans-Meckel's cave approach was carried out in 2 cases, and a combined transclival approach was carried out in 4 cases. The four tumors that involved infratemporal fossa (two E3, one mE3, and one Mpe3) were performed via a trans-prelacrimal recess approach, and type Mpe3 was also assisted by the trans-Meckel's cave approach. One patient with type E1 was treated with a trans-lamina papyracea approach. The other 27 cases, including type M, Mp, ME2, and MpE2, were all removed by a purely trans-Meckel's cave approach. Thirty-six patients (97.4%) received total resection under a purely EEA. The functional abilities and preoperative symptoms of 31 patients (88.6%) improved. Eight (21.1%) patients experienced permanent neurological function deficits. Postoperative cerebrospinal fluid and intraoperative internal carotid artery injury occurred in 1 (2.6%) patient. According to the specific endoscopic endonasal subapproaches corresponding to the different TS locations, satisfactory results can be obtained for most types of tumors. It represents an effective alternative to the open transcranial approach and can also be properly used in most types of TS with experienced hands. 4 Laryngoscope, 133:2564-2571, 2023.


Removal of dimethyl sulfide by the combination of non-thermal plasma and biological process.
A bench scale system integrated with a non-thermal plasma (NTP) and a biotricking filtration (BTF) unit for the treatment of gases containing dimethyl sulfide (DMS) was investigated. DMS removal efficiency in the integrated system was up to 96%. Bacterial communities in the BTF were assessed by PCR-DGGE, which play the dominant role in the biological processes of metabolism, sulfur oxidation, sulfate-reducing and carbon oxidation. The addition of ozone from NTP made microbial community in BTF more complicated and active for DMS removal. The NTP oxidize DMS to simple compounds such as methanol and carbonyl sulfide; the intermediate organic products and DMS are further oxidized to sulfate, carbon dioxide, water vapors by biological degradation. These results show that NTP-BTF is achievable and open new possibilities for applying the integrated with NTP and BTF to odour gas treatment.


Immunization: vital progress, unfinished agenda.
Vaccination against infectious diseases has changed the future of the human species, saving millions of lives every year, both children and adults, and providing major benefits to society as a whole. Here we show, however, that national and sub-national coverage of vaccination varies greatly and major unmet needs persist. Although scientific progress opens exciting perspectives in terms of new vaccines, the pathway from discovery to sustainable implementation can be long and difficult, from the financing, development and licensing to programme implementation and public acceptance. Immunization is one of the best investments in health and should remain a priority for research, industry, public health and society.


Slit-lamp visualization of aqueous flow through an inferior iridectomy.
To demonstrate how an inferior iridectomy prevents a pupillary block in aphakic patients with a silicone oil tamponade. Observational case series. Photographs of two patients who had undergone vitrectomy, lensectomy, membrane peeling, silicone oil tamponade, and inferior iridectomy for a complex retinal detachment were evaluated. In the thin layer of erythrocytes covering the endothelium, we observed an arc clear of erythrocytes anterior to the inferior iridectomy. With silicone oil blocking the pupil, aqueous humor was channeled through the inferior iridectomy with sufficient force to sweep the endothelium anterior to the iridectomy clean of erythrocytes, thus visualizing the mechanism that prevents a pupillary block glaucoma.


Public Health Coverage and Access to Mental Health Care for Youth with Complex Behavioral Healthcare Needs.
Drawing upon the National Survey of Children with Special Healthcare Needs (2009/2010), multilevel logistic regression analysis assessed the relationship between parent report of a youth having an emotional, behavioral, or developmental problem (EBDP), their level of reported functional limitations, and parents' report of unmet mental health care needs and experience with cost-barriers to accessing needed healthcare services. Results indicate that, compared to all privately insured youth with special health care needs, parents of privately insured youth with EBDP are much more likely to report their child having unmet mental health care needs (OR 12.16; p < 0.001) and experiencing cost barriers to care (OR 2.37; p < 0.001). Parents of privately insured youth with EBDP with functional limitations are even more likely to report these concerns (Unmet Mental Health Needs: OR 17.09; p < 0.001; Cost Barriers: OR 5.77; p < 0.001). However, findings suggest that having public insurance is associated with reductions in the odds of having unmet needs for youth with SED by 50%. Public insurance and dual coverage is associated with reductions in the odds of encountering cost barriers to care by almost 50% for children with EBDP, and by more 50% for youth with EBDP and functional impairments.


[Temporal stimulation by active fixation lead.]
To determine the efficacy and safety of temporary pacing with an active fixation lead placed trough the internal jugular vein and/or subclavian vein. We analyzed a consecutive series of 25 out of 73 patients that had a pacemaker extraction and were pacing dependent requiring temporary pacing with an active fixation lead until the new pacemaker implant, from 2017 to 2021. After extraction 25 patients age 68 years ±16 years, required temporary pacing, the media for temporary pacing was 5 days. There were no mortality associated to temporary stimulation. Only one patient (4%) had a complication 4 days after the implant with capture fail due to a microdislogement requiring reintervention. Conclusion. Temporary stimulation through active fixation pacemaker lead it is safe and effective.


Efficacy and acceptability of early mifepristone-misoprostol medical abortion in Ukraine: results of two clinical trials.
Abortion services are legally available in Ukraine although there are issues in quality and access. Two studies were conducted in Ukraine to expand options for women, and to determine the efficacy and acceptability of medical abortion. Two open-label clinical trials were conducted at six clinics in Ukraine. Women were given 200 mg mifepristone followed after 48 hours by 400 μg oral misoprostol (Study One) and mifepristone followed after 24 hours by 400 μg sublingual misoprostol (Study Two). Follow-up visits were scheduled for two weeks after mifepristone administration to assess whether complete uterine evacuation had occurred. Success rates were 97% in the first study and 98% in the second one. The vast majority of participants were satisfied or very satisfied with their abortion method (Study One: 94%; Study Two: 98%). The two studies demonstrate high rates of success and acceptability of early medical abortion in Ukraine.


pH-sensitive biocompatible chitosan/sepiolite-based cross-linked citric acid magnetic nanocarrier for efficient sunitinib release.
In this study, the magnetite nanoparticles were immobilized on the sepiolite needles via co-precipitation of iron ions. Then, the resulted magnetic sepiolite (mSep) nanoparticles were coated with chitosan biopolymer (Chito) in the presence of citric acid (CA) to prepare mSep@Chito core-shell drug nanocarriers (NCs). TEM images showed magnetic Fe3O4 nanoparticles with small sizes (less than 25 nm) on the sepiolite needles. Sunitinib anticancer drug loading efficiencies were ⁓45 and 83.7 % for the NCs with low and high content of Chito, respectively. The in-vitro drug release results exhibited that the mSep@Chito NCs have a sustained release behavior with high pH-dependent properties. Cytotoxic results (MTT assay) showed that the sunitinib-loaded mSep@Chito2 NC had a significant cytotoxic effect on the MCF-7 cell lines. Also, the in-vitro compatibility of erythrocytes, physiological stability, biodegradability, and antibacterial and antioxidant activities of NCs was evaluated. The results showed that the synthesized NCs had excellent hemocompatibility, good antioxidant properties, and were sufficiently stable and biocompatible. Based on the antibacterial data, the minimal inhibitory concentration (MIC) values for mSep@Chito1, mSep@Chito2, and mSep@Chito3 were obtained as 125, 62.5, and 31.2 μg/mL towards S. aureus, respectively. All in all, the prepared NCs could be potentially used as a pH-triggered system for biomedical applications.


Elemental metals as electron sources for biological methane formation from CO2.
Several elemental metals were examined as potential electron donors for methanogenic bacteria, using both a single tube system where the metal was in direct contact with the cells, and a two-flask system, where metal and cells were not in direct contact, but had contact via the gas phase. With all organisms examined in the direct contact system, Fe degree, Al degree and Zn degree served as electron donors for methanogenesis; some organisms used Ni degree or Sn degree as low-level electron donors. Of the metals tested, methanogenesis from H2 + CO2 was inhibited by direct contact with Zn degree or Cu degree, but not by Fe degree or Al degree. Ni degree and Co degree were inhibitory to some methanogens, with Ni degree being particularly inhibitory to the thermophilic strains tested. With all organisms examined in the two-flask system, Fe degree and Zn degree served as good electron sources for both methanogenesis and growth; Co degree generated a very low level of methane and Cu degree did not work at all. In either system V degree, Ti degree or Cd degree did not serve as electron donors. The results suggest that some elemental metals (notably Fe degree, Al degree and Zn degree) produce gaseous H2 by cathodic depolarization which is then consumed by the methanogen, thus accelerating oxidation of the metal by its metabolic activity. All of these reactions are thermodynamically favorable; however, some other metals that are clearly favorable for such a reaction on thermodynamic grounds (Ti degree and V degree) are very stable and do not serve as electron donors.


A single dilution enzyme-linked immunosorbent assay for the quantitative detection of antibodies to African horsesickness virus.
A single dilution enzyme-linked immunosorbent assay (ELISA), utilizing a reference serum with a known, predetermined end-titre was used to compute antibody titres of serum samples against African horsesickness virus. Compared to the complement fixation test it was found to be highly reproducible and sensitive. The assay also reduced the effect of between-test variations on test results and proved superior to an existing single-dilution ELISA method.


Ample glycosylation in membrane and cell envelope proteins may explain the phenotypic diversity and virulence in the Mycobacterium tuberculosis complex.
Multiple regulatory mechanisms including post-translational modifications (PTMs) confer complexity to the simpler genomes and proteomes of Mycobacterium tuberculosis (Mtb). PTMs such as glycosylation play a significant role in Mtb adaptive processes. The glycoproteomic patterns of clinical isolates of the Mycobacterium tuberculosis complex (MTBC) representing the lineages 3, 4, 5 and 7 were characterized by mass spectrometry. A total of 2944 glycosylation events were discovered in 1325 proteins. This data set represents the highest number of glycosylated proteins identified in Mtb to date. O-glycosylation constituted 83% of the events identified, while 17% of the sites were N-glycosylated. This is the first report on N-linked protein glycosylation in Mtb and in Gram-positive bacteria. Collectively, the bulk of Mtb glycoproteins are involved in cell envelope biosynthesis, fatty acid and lipid metabolism, two-component systems, and pathogen-host interaction that are either surface exposed or located in the cell wall. Quantitative glycoproteomic analysis revealed that 101 sites on 67 proteins involved in Mtb fitness and survival were differentially glycosylated between the four lineages, among which 64% were cell envelope and membrane proteins. The differential glycosylation pattern may contribute to phenotypic variabilities across Mtb lineages. The study identified several clinically important membrane-associated glycolipoproteins that are relevant for diagnostics as well as for drug and vaccine discovery.


Evaluation of new enzyme-linked immunosorbent assay based on a supernatant containing Staphylococcus aureus alpha-toxin produced by Bacillus subtilis.
The gene encoding alpha-toxin from Staphylococcus aureus was cloned into a Bacillus subtilis expression vector (pEF 231/alpha-Tox). The protease-deficient B. subtilis strain DB 104 transformed with pEF 231/alpha-Tox expressed and secreted 5 mg of alpha-toxin per liter into the growth medium. The alpha-toxin-containing supernatant was diluted 200-fold and used as coating antigen in an enzyme-linked immunosorbent assay (ELISA) for serodiagnosis of septicemia and endocarditis caused by S. aureus. Paired sera from patients in acute and convalescent stages of S. aureus and non-S. aureus infections were used to evaluate this ELISA. To evaluate the effectiveness of the crude preparation, the results were compared with those of an ELISA based on a commercially available alpha-toxin. Similar rises in serum titers were obtained with either type of alpha-toxin preparation. This is the first time a crude supernatant without any further purification has been used as an ELISA coating antigen. We therefore conclude that B. subtilis is a suitable host organism for cheap and simple production of prokaryotic recombinant antigens to be used in serodiagnosis.


Systemic innate myeloid responses to acute ischaemic and haemorrhagic stroke.
Acute ischaemic and haemorrhagic stroke account for significant disability and morbidity burdens worldwide. The myeloid arm of the peripheral innate immune system is critical in the immunological response to acute ischaemic and haemorrhagic stroke. Neutrophils, monocytes, and dendritic cells (DC) contribute to the evolution of pathogenic local and systemic inflammation, whilst maintaining a critical role in ongoing immunity protecting against secondary infections. This review aims to summarise the key alterations to myeloid immunity in acute ischaemic stroke, intracerebral haemorrhage (ICH), and subarachnoid haemorrhage (SAH). By integrating clinical and preclinical research, we discover how myeloid immunity is affected across multiple organ systems including the brain, blood, bone marrow, spleen, and lung, and evaluate how these perturbations associate with real-world outcomes including infection. These findings are placed in the context of the rapidly developing field of human immunology, which offers a wealth of opportunity for further research.


Auditory category learning is robust across training regimes.
Multiple lines of research have developed training approaches that foster category learning, with important translational implications for education. Increasing exemplar variability, blocking or interleaving by category-relevant dimension, and providing explicit instructions about diagnostic dimensions each have been shown to facilitate category learning and/or generalization. However, laboratory research often must distill the character of natural input regularities that define real-world categories. As a result, much of what we know about category learning has come from studies with simplifying assumptions. We challenge the implicit expectation that these studies reflect the process of category learning of real-world input by creating an auditory category learning paradigm that intentionally violates some common simplifying assumptions of category learning tasks. Across five experiments and nearly 300 adult participants, we used training regimes previously shown to facilitate category learning, but here drew from a more complex and multidimensional category space with tens of thousands of unique exemplars. Learning was equivalently robust across training regimes that changed exemplar variability, altered the blocking of category exemplars, or provided explicit instructions of the category-diagnostic dimension. Each drove essentially equivalent accuracy measures of learning generalization following 40 min of training. These findings suggest that auditory category learning across complex input is not as susceptible to training regime manipulation as previously thought.


Should cardiac resynchronization therapy be a rescue therapy for inotrope-dependent patients with advanced heart failure?
Although the "off-label usage" of cardiac resynchronization therapy with defibrillator (CRT-D) has spread recently in advanced heart failure (HF) patients in the real-world practice, its clinical effect remained uncertain. A total of 84 in-hospital <65-year old patients with advanced HF undergoing CRT-D were enrolled. Seventeen patients (20%) had been dependent on inotropes at the time of CRT-D implantation, and 17 suffered cardiac death within a year. Both inotrope dependence and elevated plasma levels of B-type natriuretic peptide (BNP) (>690 pg/mL) at the time of CRT-D implantation were independent predictors of cardiac death within a year by Cox regression analyses (P < 0.05 for both). These 2 parameters could significantly stratify 1-year ventricular assist device (VAD)-free survival: inotrope-free low (1) or high BNP (2), or inotrope-dependent low (3) or high BNP groups (4) (98, 77, 57, and 17%, respectively, P < 0.001). In contrast, there were no significant differences in actual 1-year survival among the four groups. Patients dependent on inotropes sometimes receive CRT-D therapy as the last treatment resort in clinical practice, but LVAD implantation should be considered instead of CRT-D in advanced HF patients because of their poor prognosis with CRT-D therapy.


[Leukocyte intracellular metabolism and phagocytic activity in patients with an erysipelatous inflammation].
A total of 118 patients with erysipelatous inflammation were examined for functional-metabolic activity of leukocytes. The consistent changes in the content of glycogen, cationic protein, in phosphatase and myeloperoxidase activity and in the NBT test of neutrophils--the most important components of the microbicidal system of leukocytes--attest to the status of nonspecific reactivity of the body in erysipelatous inflammation.


Biosynthesis of glycoproteins in human placenta: processing of oligosaccharides.
The processing of the high-mannose asparagine-linked oligosaccharides synthesized by first-trimester human placenta has been investigated. Tissue was pulsed for 1 h with [2-3H]mannose and chased for zero, 45, 90, and 180 min in media containing unlabeled mannose. Glycopeptides, prepared by Pronase digestion of the delipidated membrane pellets at each time point, were treated with endo-beta-N-acetylglucosaminidase-H to release the high-mannose asparagine-linked oligosaccharides. The largest major processing intermediate isolated was Glc1Man9GlcNAc, which was converted into Man9GlcNAc, and then into Man8GlcNAc, Man7GlcNAc, Man6GlcNAc, and Man5GlcNAc. There was also a minor pathway in which mannosyl residues were removed prior to the glucose. By carrying out the detailed structural characterization of the individual processing intermediates, it was possible to demonstrate that processing of the Man9GlcNAc to Man5GlcNAc proceeded by the nonrandom removal of the alpha 1,2-linked mannosyl residues. Specifically, of 12 possible sequences of removal of the four alpha 1,2-linked mannosyl residues present in Man9GlcNAc, first-trimester human placenta utilized only two of these in the processing of asparagine-linked oligosaccharides. It is suggested that the limited number of processing pathways reflects a high degree of specificity of these reactions in human placenta.


Biplanar temple lift for lateral brow ptosis: comparison with uniplanar dissection technique.
The amount of lift achievable in the temple region has been limited by traditional uniplanar dissection techniques. A biplanar temple-lifting technique (BTL), involving a biplanar dissection both deep and superficial to the superficial musculoaponeurotic system (SMAS) of the temporal region, is described. This study compares the amount of temporal lifting that can be achieved using a uniplanar dissection with that achieved using a biplanar dissection. Thirty-seven patients underwent bilateral temple lifting. Deep dissection was performed on the surface of the deep temporalis fascia. The skin flap was pulled in a superolateral direction and the skin overlap at the wound edge was measured. A SMAS flap was then dissected beneath the dermis from the anterior wound edge to the temporal hairline. The SMAS flap was suspended superolaterally and fixated to the deep temporalis fascia. The skin flap was again pulled in a superolateral direction and the amount of skin overlap was measured and compared. The average potential temple skin that could be excised using the traditional dissection technique was 15.1 mm (range, 7-24 mm). The average temple skin that was excised using the biplanar dissection technique was 21.8 mm (range, 14-30 mm). The biplanar technique was shown to offer, on average, a 48% increase in lift relative to the skin-only approach. There were no cases of wound dehiscence, necrosis, or overcorrection. Using the BTL technique to create a temporal SMAS flap, dissected free from overlying dermis as well as from deep temporal fascia, provides a more secure suspension of the temporal flap and significantly greater temple lift than a uniplanar dissection. The deep layering absorbs the tension of the lift, allowing for tensionless skin closure, thus decreasing the potential for scarring, hair loss, and necrosis. The increased mobility and higher suspension of the temporal flap allows for more skin excision and therefore a more pleasing lateral brow height.


The legacy effect of hyperglycemia and early use of SGLT-2 inhibitors: a cohort study with newly-diagnosed people with type 2 diabetes.
A delay in reaching HbA1c targets in patients with newly-diagnosed type 2 diabetes (T2D) is associated with an increased long-term risk of developing cardiovascular diseases (CVD), a phenomenon referred to as legacy effect. Whether an early introduction of glucose-lowering drugs with proven benefit on CVD can attenuate this phenomenon is unknown. Using data derived from a large Italian clinical registry, i.e. the AMD Annals, we identified 251,339 subjects with newly-diagnosed T2D and without CVD at baseline. Through Cox regressions adjusted for multiple risk factors, we examined the association between having a mean HbA1c between 7.1 and 8% or >8%, compared with ≤7%, for various periods of early exposure (0-1, 0-2, 0-3 years) and the development of later (mean subsequent follow-up 4.6 ± 2.9 years) CVD, evaluated as a composite of myocardial infarction, stroke, coronary or peripheral revascularization, and coronary or peripheral bypass. We performed this analysis in the overall cohort and then splitting the population in two groups of patients: those that introduced sodium-glucose transport protein 2 inhibitors (SGLT-2i) during the exposure phase and those not treated with these drugs. Considering the whole cohort, subjects with both a mean HbA1c between 7.1 and 8% and >8%, compared with patients attaining a mean HbA1c ≤ 7%, showed an increased risk of developing the outcome in all the three early exposure periods assessed, with the highest risk observed in patients with mean HbA1c > 8% in the 3 years exposure period (hazard ratio [HR]1.33; 95% confidence interval [CI] 1.063-1.365). The introduction of SGLT-2i during the exposure periods of 0-1 and 0-2 years eliminated the association between poor glycemic control and the outcome (p for interaction 0.006 and 0.003, respectively, vs. patients with the same degree of glycemic control but not treated with these drugs). Among patients with newly diagnosed T2D and free of CVD at baseline, a poor glycemic control in the first three years after diagnosis is associated with an increased subsequent risk of CVD. This association is no longer evident when SGLT-2i are introduced in the first two years, suggesting that these drugs attenuate the phenomenon of legacy effect. An early treatment with these drugs might thus promote a long-lasting benefit in patients not attaining proper glycemic control after T2D diagnosis. This work was supported, in part, by the Italian Ministry of Health (Ricerca Corrente) to IRCCS MultiMedica.


Influence of Weight-Control Attempts as Based on Self-Perception of Macronutrient Intake Among Young Females and Its Association with Mood Disorder.
There are a few studies on the association between macronutrients and mood, but none on weight control based on self-perception of specific macronutrients and mood. To assess the association between anxiety and depression levels and weight-control attempts among young females based on self-perception of diet that impacts weight by limiting or boosting a certain macronutrient. A cross-sectional survey conducted on young females (n=302) with an age range of 19 to 29. Dietary intake was measured using the Food frequency questionnaire (FFQ) and 24h-dietary recall. Anxiety and depression were measured using the Hospital Anxiety and Depression Scale (HADS) questionnaire. Analysis of the data showed a significant and inverse association of macronutrients - carbohydrates (OR 0.86; 95% CI 0.77-0.95; p < 0.01), protein (OR 0.87; 95% CI 0.78-0.97; p < 0.05), and fat (OR 0.79; 95% CI 0.63-0.99; p < 0.05) - with the odds of abnormal anxiety was noted. In addition, lower omega-3 intake was significantly associated with abnormal anxiety score (OR 0.85; 95% CI 0.76-0.97; p < 0.05) and abnormal depression score (OR 0.31; 95% CI 0.14-0.68; p < 0.01). Increased calorie intake is associated with an increased risk of anxiety scores. This preliminary study found the importance of monitoring dietary intake, especially macronutrients, among the young population to screen for any onset of mood symptoms, especially for those who are following a specific diet without any supervision. Young people should be aware of the importance of following a balanced diet and seek dietitians' consultation.


Difficulty of follow-up and outcome of alcoholism treatment.
Patients who are difficult to follow up after alcoholism treatment have poorer treatment outcome than do patients who are followed up more easily.


Right ventricular metastasis of endometrial carcinoma: a case report.
Although between 5 and 20% of cancer deaths have cardiac metastasis at postmortem examination, pelvic malignancy is a seldom-reported primary source. Endometrial carcinoma rarely results in distant metastasis. A patient is described who presented with a large symptomatic right ventricular metastasis 15 months after a total abdominal hysterectomy and bilateral salpingo-oophorectomy for Stage I poorly differentiated adenocarcinoma of the uterine corpus.


A Fuzzy mathematical model to estimate the effects of global warming on the vitality of Laelia purpurata orchids.
This study aimed to develop a fuzzy mathematical model to estimate the impacts of global warming on the vitality of Laelia purpurata growing in different Brazilian environmental conditions. In order to develop the mathematical model was considered as intrinsic factors the parameters: temperature, humidity and shade conditions to determine the vitality of plants. Fuzzy model results could accurately predict the optimal conditions for cultivation of Laelia purpurata in several sites of Brazil. Based on fuzzy model results, we found that higher temperatures and lacking of properly shading can reduce the vitality of orchids. Fuzzy mathematical model could precisely detect the effect of higher temperatures causing damages on vitality of plants as a consequence of global warming.


Relative bioavailability of a newly developed pediatric formulation of bosentan vs. the adult formulation.
Bosentan is a dual endothelin receptor antagonist approved for the treatment of pulmonary arterial hypertension (PAH). Since bosentan is frequently used to treat pediatric PAH patients, a pediatric formulation was developed. To evaluate the pharmacokinetic properties of bosentan and its active metabolite, Ro 48-5033, of the quadrisected, dispersible pediatric vs. the adult tablet after single-dose administration to healthy subjects. Secondary objectives of the study were to compare the pharmacokinetics of two inactive metabolites and the safety of both formulations. In this open-label, two-way crossover study, subjects (20 - 43 years) were randomized to receive single oral doses of 62.5 mg of bosentan as 1 adult tablet and 64 mg as 2 pediatric tablets of 32 mg. Blood samples were drawn over a 48-hour period to measure bosentan and its metabolites. 16 subjects were enrolled and completed the study. Following treatment with the pediatric formulation, values for Cmax and AUC0-∞ of bosentan were lower than with the adult formulation with geometric mean ratios (90% confidence interval) of 0.82 (0.65, 1.04) and 0.87 (0.78, 0.97), respectively. Similar results were obtained for the primary active metabolite Ro 48-5033. Both treatments were well tolerated. Although the 90% confidence intervals of the geometric mean ratios of Cmax and AUC0-∞ were not entirely within the conventional bioequivalence range (0.80 - 1.25), no clinically relevant effect of formulation on the pharmacokinetics of bosentan and Ro 48-5033 was detected. Both formulations were well tolerated.


Influence of written form on reading comprehension in aphasia.
Reading comprehension of 20 aphasic patients was systematically assessed using equivalent stimuli written in both print and cursive form. A Single-Word-to-Picture Matching task and a Sentence-to-Picture Matching task were employed. Performances of the aphasics were not uniformly facilitated by one written form over the other. Furthermore, the reading comprehension of the majority of individual patients was not influenced by written form. Four of the subjects, however, did appear to display real performance discrepancies when reading cursive versus print, particularly on the Sentence-to-Picture Matching task. Two of these patients performed better when reading cursive, while two performed better when reading print. Reevaluation of two of these patients 6 mo after initial testing revealed that they continued to display the same performance patterns originally demonstrated. Clinical implications of these results for the evaluation and treatment of reading comprehension in aphasia are discussed.


Preparation and evaluation of steroid chemiluminescent tracers.
Six different isoluminol derivatives have been synthesized and evaluated as potential labels for conjugation to steroid molecules. The resulting steroid-chemiluminescent tracers have been investigated in terms of detection limit and affinity for the homologous antibody. The conjugation to the steroid molecule did not significantly affect the quantum yield of the chemiluminescent label. Consequently the detection limit was very similar using tracers with the same chemiluminescent label and different steroids and it was always at picomolar levels. The affinity of the chemiluminescent tracer versus the homologous antibody was evaluated using tritiated steroids as reference. The bridge and the chemiluminescent molecule could influence the affinity of the chemiluminescent tracer which could be higher, similar or lower than that of the tritiated steroid. In conclusion some isoluminol derivatives (i.e. ABEI or AEEI) can be considered as universal labelling compounds for steroids and their metabolites, because they possess a high light efficiency (similar to luminal itself) and favourable reaction conditions. Moreover the conjugation to the steroid molecule does not modify their chemiluminescent properties.


Development and psychometric assessment of the sexual-reproductive health profile of women with type-1 diabetes mellitus.
To improve the sexual-reproductive health (SRH) of women with type-1 diabetes mellitus (T1DM), plans should be formulated on the basis of the existing situation. The situation can be examined by a valid tool conforming to the specific domains of SRH in the target group. The present study seeks to develop and assess the psychometric properties of the SRH Profile of Women with T1DM. Based on the extracted concepts of SRH Profile of Women with T1DM in a previously conducted study, a tool was designed using the following steps: The selection of the conceptual model, explaining the objectives, designing the roadmap and development of the tool. In the psychometric assessment phase, the content, face and construct validity (convergent validity and principal component analysis) were assessed with the participation of 365 married women of reproductive age with T1DM. The reliability of the tool was determined by the internal consistency method (Cronbach's alpha) and its stability using the test-retest method (Intraclass Correlation Coefficients). The SRH Profile of Women with T1DM was formed with 53 items in two sections. Twenty-six items were about safe motherhood and reproductive system; 27 items were about the three components of concerns about the reproductive system health and function, sexual health and function, and violence related to T1DM. The three components in the second section explained 49.44% of the total variance. Cronbach's alpha was 0.872 and the total intra-cluster correlation coefficient was 0.946. SRH Profile of Women with T1DM is a valid, reliable, and specific tool for assessing sexual-reproductive health in women with type-1 diabetes mellitus.


Effects of quinoline-containing antimalarials on the erythrocyte membrane and their significance to drug action on Plasmodium falciparum.
Quinoline-containing antimalarials are cationic amphiphiles which accumulate to high levels in lysosomes and are known to interact with membrane phospholipids. It was therefore hypothesized that they could exert their antimalarial effect by compromising the integrity of the parasite's acidic organelles. To test this hypothesis, the effects of chloroquine (CQ), quinine (Q) and mefloquine (MQ) on the osmotic stability of human red blood cells exposed to hypotonic solutions have been investigated. With CQ and Q stabilization was observed at pH 7.8 and destabilization at pH 5, indicating that destabilization is caused by the protonated forms of the drugs. With MQ the pH dependence was reversed, i.e. it destabilized at pH 7.8 and stabilized at pH 5, suggesting that destabilization is caused by the unprotonated drug. MQ caused cell lysis at the tenth millimolar range by a detergent effect. The possible destabilizing effect of drugs on the membranes of Plasmodium falciparum acidic organelles was investigated in metabolically-labelled parasites. We expected an increase in degradation of parasite proteins if drugs did indeed cause the release of acid hydrolases from destabilized organelles to the cytoplasm. No effect of drugs on parasite protein degradation could be observed, but protein synthesis was inhibited at therapeutic drug concentrations. These results imply that quinoline-containing antimalarials do not compromise the integrity of parasite acidic organelles, and that inhibition of protein synthesis results from a limited supply of essential amino acid(s) due to the demonstrable drug-mediated suppression of parasite digestion of host cell cytosol.


Endothelial function in long-term survivors of childhood acute lymphoblastic leukemia: effects of a home-based exercise program.
The risk for cardiovascular disease (CVD) is increased in long-term survivors of childhood acute lymphoblastic leukemia (ALL). Chemotherapy may have direct toxic effects on vascular endothelium, potentially increasing the significance of endothelial dysfunction in the development of CVD in ALL survivors. Endothelial structure and function can be measured with carotid intima media thickness (IMT) and brachial flow mediated dilation (FMD). IMT and FMD are intermediate markers of CVD. We studied endothelial function and the effects of an exercise program on vascular endothelium in long-term survivors of childhood ALL. Twenty-one 16-30 year old long-term survivors of ALL (age at diagnosis ≤16 years) and 21 healthy controls were studied at baseline, and 17 of the ALL survivors participated in a 16 week home-based exercise program. IMT and FMD were studied before and after the exercise program. At baseline, the ALL survivors had impaired overall FMD response (FMDauc, P = 0.02). FMDmax(%) was 22% lower (P = 0.06) and FMD at 40 seconds 44% lower (P = 0.01) compared to healthy controls. After the exercise program, FMD at 40 seconds (P < 0.01) and IMT (P = 0.02) improved. The mean overall FMD response increased by 25% after the exercise program, but this change was not statistically significant (P = 0.27). Our results show that the excess burden of CVD morbidity in this population may possibly be alleviated by simple means. The importance of physical activity on the health of childhood ALL survivors should be emphasized. Longer, controlled studies are needed to confirm our findings.


Radiation therapy of skin carcinomas: results of a hypofractionated irradiation schedule in 675 cases followed more than 2 years.
Six hundred and seventy-five cases of cutaneous epidermoid carcinomas of the face (excluding the lips, ears and eyelids) were treated with superficial irradiation therapy according to an original dose and time schedule (3 fractions of 1020 R over 14 days), with correction for RBE. The reference dose was always set at the deepest portion of the tumor (100% isodose including the lesion) and surface dose was limited to 125% of the depth dose. The energy used varied according to the thickness of the tumor, and the size of the irradiation fields according to the diameter of the tumor. All other parameters remained constant. The results after a minimum follow-up of 2 years show that the failure rate was low (less than 4%) and could be corrected in 85% of cases. Ninety per cent of recurrences appeared within 3 years; they were central and most frequently observed in nasal locations and basal cell carcinomas. Complications were rare (fewer than 3% of cases), and the majority were cured by medical treatment. Cosmetic results were satisfactory in over 90% of cases. The method used for expression of the dose permits a clear and coherent interpretation of the results: complications and sequelae were closely correlated with the irradiated surface and volume. The hypofractionated irradiation protocol described in this paper offers a simple, ambulatory method for the treatment of cutaneous epidermoid carcinomas of the face which have a particularly high incidence among the elderly. The majority of patients can be treated in this way.(ABSTRACT TRUNCATED AT 250 WORDS)


Plasma membrane-bound mechanisms of signal transduction in the control of plant dormancy and resistance.
Data on membrane-bound biochemical mechanisms of control of plant dormancy and resistance to phytopathogens are discussed. Phytohormones are involved in the control of plant dormancy by the modification of activity of membrane-bound enzymes and ion channels. Similar constituents of the plasma membrane are influenced by fungal extracellular metabolites. Proposed interconnections between plasmalemma-bound signaling mechanisms responsible for plant resistance to infection and dormancy regulation are illustrated by a scheme.


Identification and characterization of a novel fermented substance produced by edible Aspergillus oryzae AO-1 that inhibits DPP-IV activity.
We identified a novel fermented substance (FKA) produced by the edible Aspergillus oryzae strain AO-1 that inhibited dipeptidyl peptidase IV (DPP-IV) (IC(50) = 3.41 mg · mL(-1)). HPLC analysis of FKA showed specific one metabolite (WYK-1), which inhibited DPP-IV (IC(50) = 6.98 μM). WYK-1 was identified as a tetrahydroxyisoquinoline derivative. Interestingly, we examined 60 strains of A. oryzae, AO-1 was the only A. oryzae strain that produces WYK-1. This is the first report that an edible A. oryzae strain produces a DPP-IV inhibitor such as WYK-1. This study also suggests that FKA has applications in the development of novel antihyperglycemic therapeutics or functional foods.


The major core histone antigenic determinants in systemic lupus erythematosus are in the trypsin-sensitive regions.
Antibody responses against nucleosome core histones in systemic lupus erythematosus have been shown, by immunoblotting, to be directed largely against the trypsin-sensitive regions of the histones. These occur at the N-terminal regions of all 4 core histones and at the C-terminal ends of H2A and H3. Since these regions are often not the most antigenic when individual histones are used as immunogens, and appear to be exposed in the nucleosome, the active immunogens in systemic lupus erythematosus seem likely to be chromatin-bound, rather than free, histones.


Identification of antithrombotic drugs related to total joint replacement using anonymised free-text notes: a search strategy in the Clinical Practice Research Datalink.
We aimed to design and test a method to extract information on antithrombotic therapy from anonymised free-text notes in the Clinical Practice Research Datalink (CPRD). General practice database representative of the UK. All patients undergoing total hip replacement (THR, n=25,898) or total knee replacement (TKR, n=22,231) between January 2008 and October 2012 were included. Antithrombotic drug use related to THR or TKR was identified using anonymised free text and prescription data. Internal validity of our newly designed method was determined by calculating positive predictive values (PPVs) of hits for predefined keywords in a random sample of anonymised free-text notes. In order to determine potential detection bias, total joint replacement (TJR) patient characteristics were compared as per their status of exposure to antithrombotics. PPVs ranging between 97% and 99% for new oral anticoagulants (NOAC) or low-molecular weight heparins (LMWH) exposure related to TJR were obtained with our method. Our search strategy increased detection rates by 57%, yielding a total proportion of 18.5% of all THR and 18.6% of all TKR surgeries. Identified users of NOACs and LMWHs were largely similar with regards to age, sex, lifestyle, disease and drug history compared to patients without identified drug use. We have developed a useful method to identify additional exposure to NOACs or LMWHs with TJR surgery.


Decision Making on Vestibular Schwannoma: Lessons from a Multidisciplinary Board.
Management of vestibular schwannoma (VS) is a complex process aimed at identifying a clinical indication for fractionated stereotactic radiotherapy (sRT) or radiosurgery, microsurgical resection, or wait and scan (WS). We describe the experience of our VS multidisciplinary team (MDT) at a tertiary university referral center created for diagnosis, treatment, and follow-up of VS patients. We conducted a retrospective study on 132 consecutive patients referred to the MDT and managed by observation (WS), microsurgery, or fractionated sRT. The analysis included patient age, tumor size, hearing level, facial nerve function, tumor control, complications, and quality of life questionnaires. Among the patients, 21% were subjected to microsurgery, 10% to sRT, and 69% to WS. The median follow-up time was 30 months. Outcomes based on different management modalities are described. Statistically significant differences among groups were detected in terms of quality of life (physical domain). MDT may provide the best individualized therapy for VS patients compared with a single gold-standard strategy.


Exposure of the clam Tapes philippinarum to 4-nonylphenol: changes in anti-oxidant enzyme activities and re-burrowing capability.
The effects of 4-nonylphenol on anti-oxidant enzyme (superoxide dismutase and catalase) activity in both gills and digestive gland and re-burrowing capability of the clam Tapes philippinarum were investigated after 7 days' exposure to various sublethal concentrations of nonylphenol (NP). NP caused a significant decrease in superoxide dismutase activity in both tissues from the lowest concentration tested, whereas no significant alteration with respect to controls was observed in catalase activity. NP effects on re-burrowing of clams were evaluated in two experiments. In the first, clams exposed to the highest NP concentrations showed a marked delay in re-burrowing 48 h after the end of exposure. Modifications in normal burrowing behaviour were also observed, suggesting that NP acts via narcosis and/or neurotoxic mechanisms. In the second experiment, the elapsed time for 50% of the exposed clams to re-burrow into the sediment (RT(50)) was also calculated in a 24-h re-burrowing response test. At the highest NP concentrations, it was not possible to estimate RT(50) values, as the percentage of clams showing complete burial was less than 50%. The present study demonstrates that NP causes oxidative stress by inhibiting superoxide dismutase activity and greatly affects the re-burrowing capability of T. philippinarum, even at environmentally realistic concentrations.


Glycerol uptake and synthesis systems contribute to the osmotic tolerance of Kluyveromyces marxianus.
The accumulation of glycerol is essential for yeast viability upon hyperosmotic stress. In this study, the STL1 homolog KmSTL1, encoding a putative glycerol transporter contributing to cell osmo-tolerance, was identified in Kluyveromyces marxianus NBRC1777. We constructed the KmSTL1, KmGPD1, and KmFPS1 single-deletion mutants and the KmSTL1/KmGPD1 and KmSTL1/KmFPS1 double-deletion mutants of K. marxianus. Deletion of KmSTL1 or KmGPD1 resulted in K. marxianus cell sensitization to hyperosmotic stress, whereas deletion of KmFPS1 improved stress tolerance. The expression of KmSTL1 was osmotically induced, whereas that of KmFPS1 was osmotically inhibited. The expression of KmGPD1 was constitutive and continuous in the ΔKmSTL1 mutant strain but inhibited in the ΔKmFPS1 mutant strain due to feedback suppression by glycerol. In summary, our findings indicated that K. marxianus would increase glycerol synthesis by increasing GPD1 expression, increase glycerol import from the extracellular environment by increasing STL1 expression, and reduce glycerol efflux by reducing FPS1 expression under hyperosmotic stress.


The vascular biology of macrophage migration inhibitory factor (MIF). Expression and effects in inflammation, atherogenesis and angiogenesis.
Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine with chemokine-like functions. MIF is a critical mediator of the host immune and inflammatory response. Dysregulated MIF expression has been demonstrated to contribute to various acute and chronic inflammatory conditions as well as cancer development. More recently, MIF has been identified as an important pro-atherogenic factor. Its blockade could even aid plaque regression in advanced atherosclerosis. Promotion of atherogenic leukocyte recruitment processes has been recognised as a major underlying mechanism of MIF in vascular pathology. However, MIF's role in vascular biology is not limited to immune cell recruitment as recent evidence also points to a role for this mediator in neo-angiogenesis / vasculogenesis by endothelial cell activation and endothelial progenitor cell recruitment. On the basis of introducing MIF's chemokine-like functions, the current article focusses on MIF's role in vascular biology and pathology.


No evidence for tumorigenesis of AAV vectors in a large-scale study in mice.
Six hundred ninety-five mice received adeno-associated virus (AAV) vectors, mostly via portal vein injection. At necropsy, the livers were inspected for tumors, and tissue sections were prepared for histology. We observed only one tumor, a lipoma, resulting in a tumor frequency of 0.14%. This tumor contained fewer vector genomes per total DNA than the surrounding liver tissue, as shown by quantitative PCR. In another mouse we found a macroscopically visible nodule containing lymphocytes. Immunohistochemistry revealed cells not of monoclonal origin, and they contained fewer AAV genomes than the surrounding hepatocytes. There were no macroscopic tumors in 226 control mice. Upon microscopic examination, lymphocytic infiltrates were found in 5% of livers of both control and vector-treated mice; no transgene expression was seen in those infiltrates in AAV-injected animals. Compared to an average frequency of spontaneous liver tumors in C57BL/6 mice (0-10%), and given the absence of high levels of vector DNA in the observed tumor, we conclude that AAV vectors do not predispose these target animals to the formation of liver tumors.


The Brain Trauma Foundation. The American Association of Neurological Surgeons. The Joint Section on Neurotrauma and Critical Care. Pupillary diameter and light reflex.
The pupillary diameter and the pupilloconstrictor light reflex are the two parameters that have been studied extensively in relation to prognosis. Accurate measurement of pupil diameter or the constrictor response or the duration of the response has not been performed in studies on traumatic brain-injured individuals--for lack of a standardized measuring procedure. The following is recommended: 1. Pupillary light reflex for each eye should be used as a prognostic parameter. 2. The duration of pupillary dilation and fixation should be documented. 3. A pupillary size of >4 mm is recommended as the measure for a dilated pupil. 4. A fixed pupil should be defined as no constrictor response to bright light. 5. Right or left distinction should be made when the pupils are asymmetric. 6. Hypotension and hypoxia should be corrected before assessing pupils for prognosis. 7. Direct orbital trauma should be excluded. 8. Pupils should be reassessed after surgical evacuation of intracranial hematomas.


Notch signaling controls cell fate specification along the dorsoventral axis of the Drosophila gut.
Gut formation is a key event during animal development. Recent genetic analysis in chick, mice, and Drosophila has identified Hedgehog and TGFbeta signals as essential players for the development of the primitive gut tube along its anterior-posterior (AP) axis. However, the genetic programs that control gut patterning along its dorsoventral (DV) axis have remained largely elusive. We demonstrate that the activation of the Notch receptor occurs in a single row of boundary cells which separates dorsal from ventral cells in the Drosophila hindgut. rhomboid, which encodes a transmembrane protein, and knirps/knirps-related, which encode nuclear steroid receptors, are Notch target genes required for the expression of crumbs, which encodes a transmembrane protein involved in organizing apical-basal polarity. Notch receptor activation depends on the expression of its ligand Delta in ventral cells, and localizing the Notch receptor to the apical domain of the boundary cells may be required for proper signaling. The analysis of gene expression mediated by a Notch response element suggests that boundary cell-specific expression can be obtained by cooperation of Suppressor of Hairless and the transcription factor Grainyhead or a related factor. Our results demonstrate that Notch signaling plays a pivotal role in determining cell fates along the DV axis of the Drosophila hindgut. The finding that Notch signaling results in the expression of an apical polarity organizer which may be required, in turn, for apical Notch receptor localization suggests a simple mechanism by which the specification of a single cell row might be controlled.


Hydrogen Sulfide Prevents LPS-Induced Depression-like Behavior through the Suppression of NLRP3 Inflammasome and Pyroptosis and the Improvement of Mitochondrial Function in the Hippocampus of Mice.
Hydrogen sulfide (H2S) has been implicated to have antidepressive effects. We sought to investigate the prevention effects of H2S donor NaHS on depression-like behavior induced by lipopolysaccharide (LPS) in mice and its potential mechanisms. Sucrose preference, force swimming, open field, and elevate zero maze were used to evaluate depression-like behavior. NF-κB and NLRP3 inflammasome activation and mitochondrial function in the hippocampus were determined. It was found that depression-like behavior induced by LPS was prevented by NaHS pretreatment. LPS caused NF-κB and NLRP3 inflammasome activation in the hippocampus as evidenced by increased phosphorylated-p65 levels and increased NLRP3, ASC, caspase-1, and mature IL-1β levels in the hippocampus, which were also blocked by NaHS. LPS increased GSDMD-N levels and TUNEL-positive cells in the hippocampus, which was prevented by NaHS. Abnormal mitochondrial morphology in the hippocampus was found in LPS-treated mice. Mitochondrial membrane potential and ATP production were reduced, and ROS production was increased in the hippocampus of LPS-treated mice. NaHS pretreatment improved impaired mitochondrial morphology and increased membrane potential and ATP production and reduced ROS production in the hippocampus of LPS-treated mice. Our data indicate that H2S prevents LPS-induced depression-like behaviors by inhibiting NLRP3 inflammasome activation and pyroptosis and improving mitochondrial function in the hippocampus.


Acute rhabdomyolysis following epidural steroid injection: An unusual complication in a patient with low back pain.
Epidural steroid injection is a very common intervention in the treatment of low back pain and sciatic symptoms. The most common complication for epidural steroid injection is transient headache with or without identifiable dural puncture. Other complications have also been reported, including intravascular entry, local hematoma, bleeding, increased back pain, facial flushing, vasovagal reactions, nausea, and fever. We report a case of rhabdomyolysis following epidural steroid injection for lumbar radiculopathy.


Vein of Marshall ethanol infusion: First-step or adjunctive choice for perimitral atrial tachycardia?
Perimitral atrial tachycardia (PMAT) is the most frequent type of iatrogenic atrial tachycardia (AT) after atrial fibrillation (AF) ablation. Vein of Marshall ethanol infusion (EIVOM) is a promising technique in mitral isthmus (MI) ablation. A total of 165 patients with PMAT were divided into three groups according to ablation strategies, including RF only group (n = 89), RF-EIVOM group (initial RF ablation with adjunctive EIVOM, n = 28), and EIVOM-RF group (first-step EIVOM with touch-up RF ablation, n = 48). Acute and follow-up procedure outcomes were evaluated. PMAT terminated in 89.9%, 89.3%, and 93.7% of patients in RF only, RF-EIVOM and EIVOM-RF groups, respectively (p = .715), with complete MI block achieved in 80.9%, 89.3%, and 95.8% of patients (EIVOM-RF vs. RF only, p = .012). First-step utilization of EIVOM was associated with a significant shortening of RF ablation time at MI (EIVOM-RF 2.1 ± 1.3 min, RF only 7.9 ± 5.9 min, RF-EIVOM 6.8 ± 5.8 min; p < .001) and a decrease in the proportion of patients need ablation within coronary sinus (CS, EIVOM-RF 14.6%, RF only 61.8%, RF-EIVOM 64.3%; p < .001). After a mean follow-up of 12.1 ± 6.2 months, AF/AT recurred in 39 (43.8%), 6 (21.4%), and 12 (25.0%) patients in RF only, RF-EIVOM, and EIVOM-RF group (RF-EIVOM vs. RF only, p = .026; EIVOM-RF vs. RF only, p = .022). EIVOM was associated with an enhanced acute MI block rate as well as reduced AF/AT recurrence. First-step utilization of EIVOM promises to significantly simplify the RF ablation process. PMAT is the most common type of iatrogenic AT after AF ablation procedures. EIVOM contributed to a higher acute MI block rate and lower arrhythmia recurrence risk during follow-up. First-step utilization of EIVOM significantly reduced the need for radiofrequency ablation at MI and inside CS with the advantage of creating a homogenous, transmural lesion and eliminating epicardial connections.


Synergistic interactions between β-lapachone and fluconazole in the inhibition of CaCdr2p and CaMdr1p in Candida albicans.
Mortality rate of invasive Candida infections is raising mainly amongst immunocompromised patients. These infections are hard-to-treat mainly due to the increasing incidence of resistance. The overexpression of ATP-binding cassette and major facilitator superfamily transporters is the main responsible for the failure of antifungal therapies. In a Saccharomyces cerevisiae model, β-lapachone inhibited Pdr5p, a transporter homologous to those found in Candida albicans. To determine whether β-lapachone reverses the resistance phenotype mediated by efflux transporters in C. albicans clinical isolates. The antifungal activity of β-lapachone combined with fluconazole was measured by agarose chemosensitization and microdilution assays. CaCdr2p and CaMdr1p activities were evaluated through fluorescent dyes accumulation. ATPase activity was assessed using transporter-enriched plasma membranes. β-lapachone reverted antifungal resistance of S. cerevisiae and C. albicans strains overexpressing CaCdr2p and CaMdr1p transporters by inhibiting these proteins activities. CaCdr2p ATPase activity was not impaired by the compound. β-lapachone is a promising drug candidate to be used as an adjuvant in the treatment of candidiasis caused by fluconazole-resistant C. albicans strains.


Impact of irrigant sequence on mechanical properties of human root dentin.
To get the root canal system free of organic debris and the smear layer, it has been recommended to irrigate with a NaOCl solution during instrumentation, followed by a rinse with a chelating agent such as ethylenediaminetetraacetic acid (EDTA) and a final irrigation with NaOCl. However, both hypochlorite and EDTA weaken dentin through dissolution of its organic and inorganic components, respectively. EDTA exposes the organic dentin matrix, which could then be attacked more easily by hypochlorite. It was the aim of this study to assess the impact of different irrigation sequences of NaOCl (2.5% w/v; total exposure time, 24 minutes) and EDTA (17%; 3 minutes) on the elastic modulus and flexure strength of standardized human root dentin bars (n = 11 per group). Exposures to solely EDTA (3 minutes), NaOCl (24 minutes), and water were used as control treatments. Specimens were subjected to 3-point bending tests; modulus of elasticity and flexure strength values were compared between groups with one-way analysis of variance followed by Fisher probable least-squares difference test. The alpha-type error was set at .05. The 24-minute exposure to the hypochlorite solution caused a significant drop in flexure strength compared with water- or EDTA-treated controls (P < .05), whereas the elastic modulus remained unaffected. In contrast, the short exposure to EDTA as is clinically recommended did not affect the mechanical dentin parameters under investigation, regardless of the irrigant sequence that was used.


SU6668 inhibits Flk-1/KDR and PDGFRbeta in vivo, resulting in rapid apoptosis of tumor vasculature and tumor regression in mice.
SU6668 is a small molecule inhibitor of the angiogenic receptor tyrosine kinases Flk-1/KDR, PDGFRbeta, and FGFR1. In mice, SU6668 treatment resulted in regression or growth arrest of all large established human tumor xenografts examined associated with loss of tumor cellularity. The events underlying loss of tumor cellularity were elucidated in detail in several tumor models. SU6668 treatment induced apoptosis in tumor microvessels within 6 h of the initiation of treatment. Dose-dependent decreases in tumor microvessel density were observed within 3 days of the first treatment. These changes were accompanied by decreased tumor cell proliferation and increased tumor cell apoptosis. Rapid increases in VEGF transcript levels were seen, consistent with the induction of tumor hypoxia. Using Western blot analyses, we determined that these in vivo antiangiogenic and proapoptotic effects of SU6668 occur at doses comparable to those required to inhibit Flk-1/KDR and PDGFRbeta phosphorylation in tumors. Potent, dose-dependent inhibition of Flk-1/KDR activity in vivo was independently demonstrated using vascular permeability as a readout. These data demonstrate that SU6668-induced inhibition of angiogenic receptor tyrosine kinase activity in vivo is associated with rapid vessel killing in tumors, leading to broad and potent antitumor effects.


Parental Stress as the Mediator Between Symptom Burden and the Quality of Life of Chinese Children With Cancer.
Because of their cancer and treatment adverse effects, most pediatric oncology patients will experience 1 or more symptoms at one time that can seriously affect their quality of life. Because these children are attached to parents, their symptom burden directly influences the parental stress level and parental interpretations of their children's quality of life. The aim of this study was to examine the association between child-reported symptom burden and the pediatric quality of life reported by children with cancer and their parents, and whether parental perceived stress mediates these relationships. In a cross-sectional design, convenience sampling was used to recruit 80 parent-child dyads. Advanced statistical methods were adopted to analyze the mediating effects of parental stress between children's symptom burden and their quality of life. The results revealed that parental stress was the mediator in the relationship between child-reported symptom burden and children's quality of life reported by parents. The results also showed that parental stress was not a mediator in the relationship between child-reported symptom burden and their quality of life. This underscored the differences in interpretations of quality of life reported by children and their parents. Children's symptom burden is an important factor in predicting parental stress level and the quality of life reported by the children. Children's voice should be incorporated whenever possible. The knowledge gained from this study will facilitate intervention development to enhance parents' abilities in stress management and symptom management for their children with the support of the nursing profession.


Right Ventricular Free Wall Rupture After Myocardial Infarction.
This paper describes the case of a 68-year-old man who presented in cardiac tamponade due to a right ventricular free wall rupture after a recent ST-segment elevation myocardial infarction. After a pericardiocentesis, the ventricular defect resolved spontaneously. The patient was managed medically and avoided surgical intervention. (Level of Difficulty: Intermediate.).


Continuous atmospheric in-situ measurements of the CH4/CO ratio at the Mt. Cimone station (Italy, 2165 m a.s.l.) and their possible use for estimating regional CH4 emissions.
Methane (CH4) is an important climate forcer, contributing about 17% of the total radiative forcing by long living greenhouse gases. The Po basin is one of the most polluted and densely populated areas in Europe representing an important source region for CH4. The aim of this work was to test an inter-species correlation approach to derive estimates of anthropogenic CH4 emissions for the period 2015-2019 from the Po basin by combining CO bottom-up inventory data and continuous CH4 and CO observations from a mountain site in the northern Italy. The tested methodology suggested lower emissions in respect to EDGAR (-17%) and the Italian National Inventory (-40%) for the Po basin. However, despite the two bottom-up inventories, the emissions derived from the atmospheric observations reported an increasing tendency from 2015 to 2019 for the CH4 emissions. A sensitivity study revealed that using different subsets of the atmospheric observations implied a difference of 26% in the CH4 emission estimates. The highest agreement with two bottom-up CH4 inventories (EDGAR and the Italian national inventory) were obtained when atmospheric data were strictly selected for periods representative of air mass transport from the Po basin. Our study identified various challenges when using this methodology as a benchmark to verify bottom-up CH4 inventories. Issues could be attributed to the annual aggregation of the proxies used to derive the emission amounts, to the CO bottom-up inventory used as input information and to the relatively high sensitivity of the results to the different subsets of the atmospheric observations. However, the use of different bottom-up inventories as input data for CO emissions can potentially provide information that should be carefully considered for the purpose of integrating CH4 bottom-up inventories.


Ontogeny of central melatonin receptors in tadpoles of the anuran Rana perezi: modulation of dopamine release.
The objective of this work was to study melatonin receptors in the eye and the brain and their possible functionality in the ontogeny of Rana perezi. The binding of 2-[(125)I]melatonin increases throughout embryonic larval development in both tissues. The most pronounced increase takes place at the end of premetamorphosis and during early prometamorphosis. This rise coincides temporarily with the appearance of the rhythmic melatonin-synthesizing capacity in the retina. In the three studied developmental stages (32G, 40G and 49-50G), melatonin-binding sites are coupled to G proteins and become functional. Moreover, melatonin inhibits dopamine (DA) release by the eyecups and brain of R. perezi tadpoles in vitro (stage 40G). Thus, the modulation of DA release could be one mechanism by which melatonin interacts with hormones, like prolactin and thyroxine that are involved in the regulation of anuran development and metamorphosis. Finally, we show that melatonin decreases K(+)-evoked cAMP content in the frog retina in vitro, suggesting that the effect of melatonin on DA release in the frog retina is mediated by the inhibition of this intracellular messenger.