Five-year oncological outcomes of endoscopic extraperitoneal radical prostatectomy (EERPE) for prostate cancer: results from a medium-volume UK centre.
To determine the 5-year oncological outcomes of endoscopic extraperitoneal radical prostatectomy (EERPE) from a medium-volume centre, thereby providing much needed data on outcomes from the UK. From January 2006 to January 2012, 575 patients underwent EERPE for localized prostate cancer, performed by a single surgeon who had completed a modular training programme. Follow-up was as per local hospital policy and data were collected in our prospective database. A retrospective review of patient demographics, prostate-specific antigen (PSA) levels, pathological T stages, Gleason scores, surgical margin status and biochemical recurrence (BCR) data was performed. BCR was defined as PSA >0.2 μg/L. The mean (range) patient age was 62 (40.3-76.5) years and the mean (range) follow-up was 30 (12-72) months. The median (interquartile range [IQR]) operating time was 135 (120-170) min and the median (IQR) blood loss was 200 (100-250) mL. Of the 575 patients, 135 (23.5%) had positive surgical margins (PSMs). The PSM rate for pT2 disease was 66/406 patients (16.3%) and for pT3 disease it was 68/168 patients (40.5%). Overall BCR-free survival at 5-years was 81.5%. Multivariate Cox analysis showed that PSMs, Gleason score, D'Amico risk category and pT stage were independent predictors of BCR-free survival. This assessment of the oncological results of EERPE, which included the surgical learning curve, shows that the adoption of EERPE after mentored fellowship training translates into mid-term oncological outcomes in line with those of retropubic/transperitoneal laparoscopic approaches and with large-volume centres worldwide which have pioneered laparoscopic radical prostatectomy. The study shows that EERPE in a medium-volume second generation laparoscopic centre (that introduced EERPE after adequate training in pioneering centres) produces results with good 5-year oncological outcomes, similar to those of other major series, for patients in the UK.


Slow-type C-protein in dystrophic chicken fast pectoralis muscle.
C-protein isoform expression in hereditary dystrophic chicken skeletal muscle was compared with that in normal chicken muscle during postnatal development by immunocytochemical and immunoblot methods. In the pectoralis muscle (PM) of both normal and dystrophic chicken, slow- and fast-type C-proteins were coexpressed in the vast majority of myofibers at neonatal age, but the slow C-protein disappeared, leaving continued expression of only the fast-type C-protein as muscle development progressed up to 2 weeks posthatch. In the dystrophic chicken PM, however, myofibers containing slow-type C-protein reappeared about 1 month posthatch and increased in number with the progression of muscular dystrophy. We conclude that C-protein isoform expression in dystrophic myofibers resembles that in neonatal myofibers and that the expression of slow-type C-protein can be seen as a marker for chicken muscular dystrophy.


Assessment of risk factors in de novo aneurysm development.
Aneurysms that occur anywhere in intracranial except where primary aneurysms develop, are called "de novo aneurysms". The risk factors and formation time of de novo aneurysms are not fully known. Congenital, environmental and hemodynamic factors can play a role in aneurysm development. The 43-year-old female patient was operated with the middle cerebral artery superior trunk aneurysm in our clinic. She came to us again after 17 months with a severe headache. In computed cranial tomography angiography, the middle cerebral artery superior trunk placement aneurysm was found to have a partial clip and "de novo aneurysm" was developed. She was re-operated for "de novo aneurysm". In this study, the risk factors in development of "de novo aneurysms" were discussed in the light of literature through this patient.


Crystal structure, differential scanning calorimetry and vibrational low temperature investigation of C(NH2)3 x HSeO4.
The first X-ray and vibrational spectroscopic analysis of a new molecular complex between guanidinium and selenic acid is reported. The crystal of guanidinium hydrogenselenate at room temperature belongs to P2(1)/n space group of the monoclinic system with Z=4, a=8.330A, b=5.109A, c=14.855A and beta=92.65 degrees . Room temperature powder infrared and Raman spectra for the titled complex (1:1) were measured. The observed IR and Raman spectra are in accordance with this crystallographic structure. The differential scanning calorimetric (DSC) experiment on powder samples indicates on continuous phase transition at ca. 160K. To explain in detail the behavior of the crystal during the phase transition the infrared and Raman powder spectra in low temperature range (10-300K) were measured. The temperature dependencies of bands position and intensities for obtained spectra are analysed.


Altered adrenergic activity in coronary arterial spasm: insight into mechanism based on study of coronary hemodynamics and the electrocardiogram.
To elucidate the pathophysiologic mechanism of coronary arterial spasm, the hypothesis was examined that underlying alterations in sympathetic activity may account for this syndrome in some patients. Observations were directed to alterations in coronary arterial hemodynamics and the electrocardiogram. Spasm of the left anterior descending coronary artery produced a mean increase in coronary vascular resistance of 107 percent (P less than 0.05) in four patients in whom coronary sinus blood flow was measured with the thermodilution technique. The alpha adrenergic blocking agent phentolamine, given intravenously, acutely reversed coronary spasm and its clinical manifestations in eight patients and reduced coronary resistance. In four patients, administration of the long-acting oral alpha blocking agent phenoxybenzamine (20 to 80 mg/day) caused disappearance of symptoms during a follow-up period of 3 to 12 months. Transient prolongation of the corrected Q-T interval preceded spontaneous or ergonovine maleate-provoked coronary spasm in 11 patients with variant angina pectoris, whereas no significant change in the Q-T interval followed ergonovine administration in 27 control patients with atypical chest pain who did not have coronary spasm. T wave inversions in the resting electrocardiogram were normalized by isoproterenol infusion in one patient and by long-term phenoxybenzamine treatment in four patients with variant angina pectoris. These Q-T and T wave changes are analogous to those described with unilateral or asymmetric stellate ganglion stimulation in animals. These observations suggest that alterations in the sympathetic nervous system that are consistent with asymmetric stellate ganglion activity and transient alpha adrenergic receptor stimulation can presage the development of coronary arterial spasm in some patients with variant angina pectoris.


Solute-solvent interaction and DFT studies on bromonaphthofuran 1,3,4-oxadiazole fluorophores for optoelectronic applications.
In the present work, computational and experimental studies were carried out to explore the photophysical properties of bromonaphthofuran substituted 1,3,4-oxadiazole derivatives for optoelectronic applications. Density functional theory (DFT) was used to demonstrate the electronic and optical properties of the synthesised molecules. The theoretical ground state dipole moments of the fluorophores in gas and solvent environments were also computed using Gaussian 09W software. Further, the HOMO-LUMO energies of the fluorophores determined using DFT agree well with the experimental values. Molecular electrostatic potential 3D plots were used to identify the sites which are electrophilic and nucleophilic in nature. Dipole moment of both the fluorophores in ground and excited states were determined experimentally. The excited state dipole moments being higher than that of the ground state shows the redistribution of electron densities in the excited state than in the ground state in both the fluorophores. The solute-solvent interactions, both specific and non-specific, were assessed using Catalan parameters. Further, the nature of chemical reactivity was determined based on global descriptors. The photophysical properties of the fluorophores studied suggest their potential use as promising candidates for organic light emitting diode (OLED), solar cell and chemosensor applications.


Immunological changes after long-term feeding of germfree piglets with protein isolates and yeast cell walls from Candida utilis as food additives.
Germfree piglets were fed a diet supplemented with cell walls and a protein isolate from Candida utilis for 54 days. Besides morphological signs of activation of the lymphoid tissue which occurred primarily in the intestine of piglets which had been fed yeast cell walls, even an increased serum immunoglobulin level could be detected. In sera and intestinal content of piglets fed both with cell walls and isolated protein, specific antibodies capable of agglutinating yeasts were present. Even though a limited number of experimental animals was employed it can be concluded that the yeast material added to the diet elicited an immune response.


Gata is ubiquitously required for the earliest zygotic gene transcription in the ascidian embryo.
In ascidian embryos, the earliest transcription from the zygotic genome begins between the 8-cell and 16-cell stages. Gata.a, a maternally expressed Gata transcription factor, activates target genes specifically in the animal hemisphere, whereas the complex of β-catenin and Tcf7 antagonizes the activity of Gata.a and activates target genes specifically in the vegetal hemisphere. Here, we show that genes zygotically expressed at the 16-cell stage have significantly more Gata motifs in their upstream regions. These genes included not only genes with animal hemisphere-specific expression but also genes with vegetal hemisphere-specific expression. On the basis of this finding, we performed knockdown experiments for Gata.a and reporter assays, and found that Gata.a is required for the expression of not only genes with animal hemisphere-specific expression, but also genes with vegetal hemisphere-specific expression. Our data indicated that weak Gata.a activity that cannot induce animal hemisphere-specific expression can allow β-catenin/Tcf7 targets to be expressed in the vegetal cells. Because genes zygotically expressed at the 32-cell stage also had significantly more Gata motifs in their upstream regions, Gata.a function may not be limited to the genes expressed specifically in the animal or vegetal hemispheres at the 16-cell stage, and Gata.a may play an important role in the earliest transcription of the zygotic genome.


Influence of high hydrostatic pressure pretreatment on properties of vacuum-freeze dried strawberry slices.
Effects of high hydrostatic pressure (HHP) (50, 100, 150, 200 and 250 MPa) pretreatment on water mobility and distribution, drying duration, microstructure, color, cell wall fraction and tissue structure of strawberry slices were investigated. HHP significantly increased water mobility of the strawberry slices, resulting in the reduction of drying duration by 9-24%. As the pretreatment pressure was increased, redness value and anthocyanin content continuously increased, soluble pectin (SBP) content increased and then decreased, while the contents of protopectin (PTP) and cellulose decreased. After the HHP pretreatment, chromoplasts and moisture was distributed more uniformly in the strawberry slices. Microscopy images showed the formation of microscopic holes or channels in the matrix and the breakdown of tissue structure by HHP. Results suggested HHP pretreatment disrupted the integrity of the fresh strawberry which enhanced the drying efficiency and migration of the chromoplasts during the vacuum-freeze drying process.


Comparison of electroconvulsive therapy and magnetic seizure therapy in schizophrenia: Structural changes/neuroplasticity.
Electroconvulsive therapy (ECT) can effectively reduce the symptoms of schizophrenia, but may also impair cognitive function. A potential alternative is magnetic seizure therapy (MST), which has shown comparable efficacy with less severe cognitive disruption. This study compared ECT to MST for clinical efficacy and cognitive side effects. In addition, we examined the possible contributions of hippocampal volume changes and enhanced brain derived neurotrophic factor (BDNF) signaling to the therapeutic responses. Thirty-four confirmed schizophrenia patients were allocated to receive ECT (n = 16) or MST (n = 18) over a 4-week period. Schizophrenia symptoms were measured by PANSS, cognition by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and serum BDNF and its precursor proBDNF by ELISA at baseline and following ECT or MST. Both treatments reduced PANSS scores with comparable efficacy, while MST was superior for preservation of RBANS language score. ECT significantly increased the volumes of the bilateral hippocampus and multiple subfields, while MST had no effect on hippocampal volume. The change in right hippocampal volume was correlated with proBDNF change among ECT and MST non-responders (< 25% decrease in PANSS score). MST reduced schizophrenia symptoms as effectively as ECT with slightly better preservation of cognitive function.


Mycobacterium abscessus VapC5 toxin potentiates evasion of antibiotic killing by ribosome overproduction and activation of multiple resistance pathways.
Mycobacterium abscessus (Mab) infections are inexplicably intractable to clearing after aggressive and lengthy treatment regimens. Here we discovered that acquisition of a single toxin-antitoxin system enables Mab to activate a phenotypic switch that enhances survival upon treatment with current first-line antibiotics. This switch is tripped when the VapC5 toxin inactivates tRNASerCGA by cleavage at only one site within its anticodon, leading to growth arrest. Concomitant tRNASerCGA depletion then reprograms the transcriptome to favor synthesis of proteins naturally low in the cognate Ser UCG codon including the transcription factor WhiB7 and members of its regulon as well as the ribosomal protein family. This programmed stockpiling of ribosomes is predicted to override the efficacy of ribosome-targeting antibiotics while the growth arrest phenotype attenuates antibiotics targeting cell wall synthesis. In agreement, VapC5 increases Mab persister formation upon exposure to amikacin and the next-generation oxazolidinone tedizolid (both target ribosomes) or cefoxitin (inhibits cell wall synthesis). These findings expand the repertoire of genetic adaptations harnessed by Mab to survive assaults intended to eradicate it, as well as provide a much-needed framework for selection of shorter and more efficacious alternate treatment options for Mab infections using currently available antimicrobials whose targets are not confounded by VapC5.


Pavlov and appetite.
Before working on conditioned reflexes, Pavlov completed a research program designed to investigate the physiological controls of salivary, gastric, and pancreatic secretions. The originality and significance of this work resulted in a Nobel Prize in 1904, the first awarded to a physiologist. The first part of this manuscript focuses on the experimental analysis of the controls of gastric secretion. This demonstrates Pavlov's experimental skill and his ability to draw strong inferences about how a psychic factor like appetite grew into a physiological effect, such as gastric secretion. The second part of the manuscript reviews Pavlov's ideas about the central neural mechanism for appetite and its stimulatory effect on gastric secretion, and demonstrates that Pavlov's "conceptual nervous system" is very similar to our own.


Comparison of Tensilon and antivenom for the treatment of cobra-bite paralysis.
We prospectively compared the ability of anti-venom and edrophonium (Tensilon) to improve paralytic symptoms in 8 patients envenomed by the Philippine cobra (Naja naja philippinensis). Twenty, 50 or 100 ml of Philippine cobra antivenom were administered in a double-blind fashion by constant intravenous infusion over 30 min. Even the largest dose of antivenom failed to produce marked improvement within 2 h, though enzyme-linked immunosorbent assays and neutralization tests demonstrated that it possessed high titres of anti-neurotoxin antibodies. Tensilon given at 2 h was significantly more effective than antivenom at increasing the duration of upward gaze (78 +/- 28 vs 43 +/- 26 sec, P less than 0.001), and either completely reversed or markedly decreased paralysis in every patient. The Tensilon test should be given to all patients with paralytic envenoming by cobras, and anticholinesterases administered to those with a positive response.


Effect of causes of surgical delay on early and late mortality in patients with proximal hip fracture.
The purpose of this study was to investigate the reasons for delayed surgery in patients with proximal hip fracture and to compare differences in mortality between delayed surgery cases and non-delayed surgery cases. In addition, we evaluated causal factors for delayed surgery that affected differences in mortality. From 2003 to 2013, 1290 patients (1290 hips) with unilateral femoral neck or intertrochanteric fractures who underwent surgery were categorized into Group Ia (402 patients, early surgery group) and Group Ib (888 patients, delayed surgery group). The delayed surgery group was categorized as Group IIa (270 patients, pre-hospital delay group) and Group IIb (618 patients, post-hospital delay group). Among 618 patients with post-hospital delay, 165 patients in Group IIIa were defined as delayed surgery cases due to patient factors, and 453 patients in Group IIIB were defined as delayed surgery cases due to hospital factors. Early and late mortality was compared between each group. Of 1290 patients, 888 patients underwent delayed surgery (mean 7.5 days, range 3-167 days) after hip fracture. The cumulative mortality rate at 30, 60 days, 3, and 12 months was 0.7, 2.0, 3.0, and 9.5% in Group Ia, respectively, and 2.4, 4.5, 5.2, and 14.5% in Group Ib, respectively (p = 0.047, p = 0.027, p = 0.078, and p = 0.012, respectively). Of 618 patients with post-hospital surgery delay, the cumulative mortality rate at 30 days and 12 months was 4.8 and 21.2% in Group IIIa, respectively, and 1.8, and 12.6% in Group IIIb, respectively (p = 0.033 and p = 0.008, respectively). After adjustments, patient factors for delayed surgery (HR 2.780; 95% CI 1.012-7.640, p = 0.047) were significantly associated with death after hip fracture. This study demonstrated that delayed surgery was significantly related to 30-day and 1-year mortality. Surgery delay due to drugs' hold and medical comorbidity was related to 30-day mortality after adjustment.


Heparin-bonded cardiopulmonary bypass circuits reduce the rate of red blood cell transfusion during elective coronary artery bypass surgery.
This study compared the transfusion rates of patients treated with heparin-bonded circuits with the transfusion rates of patients treated with standard bypass circuits with and without -aminocaproic acid (EACA). Prospective double-blind (drugs), open trial (cardiopulmonary bypass circuits). University medical center. Seventy-one patients undergoing elective am admission coronary artery bypass graft surgery. Patients were randomized to receive either heparin-coated cardiopulmonary bypass circuits (HBCPB), nonheparin-coated cardiopulmonary bypass circuits and EACA (EACPB), or nonheparin-coated bypass circuits and placebo (control). Patients were transfused if their hematocrit was <18% while on cardiopulmonary bypass or <25% at any time after the cardiopulmonary bypass period. The rate and number of transfused packed red blood cells (pRBCs), platelets, fresh frozen plasma, and cryoprecipitate were measured. A Fisher exact test showed that the transfusion rate was as follows: the HBCPB group (5.0%), the EACPB group (18.2%), and the control group (36%), (p = 0.034). The heparin-bonded cardiopulmonary bypass-treated patients in this study received fewer pRBCs than did the control group. A nonsignificant reduction in the pRBC transfusion rate was found between those with heparin-bonded bypass circuits and those with standard circuits who received epsilon-aminocaproic acid.


Effect of promethazine on biofilms of gram-positive cocci associated with infectious endocarditis.
This study evaluated the antimicrobial activity of promethazine against Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus mutans and its effect on the antimicrobial susceptibility of biofilms grown in vitro and ex vivo on porcine heart valves. Promethazine was evaluated alone and in combination with vancomycin and oxacillin against Staphylococcus spp. and vancomycin and ceftriaxone against S. mutans in planktonic form and biofilms grown in vitro and ex vivo. Promethazine minimum inhibitory concentration range was 24.4-95.31 μg/mL and minimum biofilm eradication concentration range was 781.25-3.125 μg/mL. Promethazine interacted synergistically with vancomycin, oxacillin and ceftriaxone against biofilms in vitro. Promethazine alone reduced (p < 0.05) the CFU-counts of biofilms grown on heart valves for Staphylococcus spp., but not for S. mutans, and increased (p < 0.05) the activity of vancomycin, oxacillin and ceftriaxone against biofilms of Gram-positive cocci grown ex vivo. These findings bring perspectives for repurposing promethazine as adjuvant in the treatment of infective endocarditis.


Centrifugal concentrator for the substitution of nitrogen blow-down micro-concentration in dioxin/polychlorinated biphenyl sample preparation.
A centrifugal concentrator was applied for the substitution of nitrogen blow-down micro-concentration in dioxin/PCB sample preparation. Automation was achieved through this apparatus and resulted in significant improvements in sample preparation productivity, along with excellent reproducibility and recovery rate of dioxin/PCB. Mean recoveries of dioxin congeners were 90-106%, respectively.


Long-Term Outcome of Arterial Switch Operation Conversion After Failed Senning/Mustard Procedure.
We evaluated long-term outcomes of the arterial switch operation (ASO) conversion after a failed Senning/Mustard operation among patients with dextro-transposition of the great arteries. Between 1986 and 2006, 9 patients with dextro-transposition of the great arteries underwent ASO conversion at our institute. All patients had systemic right ventricle failure, 6 had supraventricular tachycardia, and 8 had moderate or severe tricuspid valve regurgitation. All patients had New York Heart Association classification II or III. The median age of patients at the ASO conversion operation was 7.4 years (range, 0.6 to 32.4 years). Pulmonary artery banding for left ventricle training was performed in 8 of the 9 patients before conversion. There was 1 early death from low-output syndrome at 5 days postoperatively and 1 late sudden death at 5 months. Median follow-up time was 23.1 years (range, 0.08 to 28.0 years). The actuarial survival rate was 76.1% at 20 years. Long-term survivors revealed good New York Heart Association classification (class I, 6 patients; class II, 1 patient), with less than mild tricuspid regurgitation and brain natriuretic peptide levels of 40.6 ± 16.2 pg/mL. Cardiac catheterization revealed significant improvements of right ventricle end-diastolic volume (decreased from 243.2% to 117.7% of normal), and right ventricle ejection fraction (increased from 0.42 to 0.572; p < 0.05). Three patients underwent new pacemaker implantation for sick sinus syndrome, and moderate neoaortic valve regurgitation developed in 1 patient. Excellent long-term outcomes can be achieved after ASO conversion; however, careful observation for new-onset sick sinus syndrome and aortic regurgitation is mandatory.


Polymer hydrogel from carboxymethyl guar gum and carbon nanotube for sustained trans-dermal release of diclofenac sodium.
Novel carboxymethyl guar gum (CMG)-chemically modified multiwalled carbon nanotube (MCNT) hybrid hydrogels were synthesized at different MCNT levels as potential device for sustained trans-dermal release of diclofenac sodium. Spectroscopy together with morphology, thermogravimetry, and rheological studies proved relatively strong CMG-MCNT interaction at 0.5 and 1 wt% levels of MCNT whereas de-wetting was increased with higher MCNT concentration. Drug encapsulation tendency increased with addition of MCNT; maximum entrapment was noticed at 1 wt% MCNT level. Hydrogels containing 0.5, 1 and 3 wt% MCNT exhibited slower trans-dermal release than neat CMG due to slightly higher gel viscosity and more drug entrapment. Slowest but steady release was obtained from 1 wt% MCNT loaded hydrogel due to highest viscous resistance among all other hybrid nanocomposites.


The von Hippel-Lindau protein pVHL inhibits ribosome biogenesis and protein synthesis.
pVHL, the product of von Hippel-Lindau (VHL) tumor suppressor gene, functions as the substrate recognition component of an E3-ubiquitin ligase complex that targets hypoxia inducible factor α (HIF-α) for ubiquitination and degradation. Besides HIF-α, pVHL also interacts with other proteins and has multiple functions. Here, we report that pVHL inhibits ribosome biogenesis and protein synthesis. We find that pVHL associates with the 40S ribosomal protein S3 (RPS3) but does not target it for destruction. Rather, the pVHL-RPS3 association interferes with the interaction between RPS3 and RPS2. Expression of pVHL also leads to nuclear retention of pre-40S ribosomal subunits, diminishing polysomes and 18S rRNA levels. We also demonstrate that pVHL suppresses both cap-dependent and cap-independent protein synthesis. Our findings unravel a novel function of pVHL and provide insight into the regulation of ribosome biogenesis by the tumor suppressor pVHL.


The potential impact of a prophylactic herpes simplex vaccine.
Herpes simplex virus (HSV) infections have a significant impact on health causing a wide range of diseases. Oral-facial and genital sites are the most common locations of infection and may lead to recurrent painful lesions. HSV infection acquired perinatally may result in severe sequelae or even death despite appropriate therapy. Furthermore, it is becoming increasingly clear that genital HSV infections significantly raise the risk of HIV transmission. To describe the strategies, impediments, and advancements in the development of vaccines to prevent HSV disease. A review of the literature was performed, limited to prophylactic HSV vaccines and their potential effect on genital herpes, oral-facial disease, and perinatal herpes. There are several vaccine strategies under development that show promise for the treatment these diseases.


Assessment of availability, accessibility, and affordability of magnetic resonance imaging services in Ghana.
The aim of this study was to assess the availability, accessibility, and affordability of MRI services to patients in Ghana. A descriptive quantitative research method which involve the use of a structured email 3-page survey questionnaire was employed, and addressed to the MRI radiographer-in-charge for completion. A response rate of 92% was achieved. Sixty-seven percent (8) of the facilities were located in the Greater Accra region of Ghana with most (6[75%]) being private health facilities. The Western, Eastern, Brong Ahafo, Upper East, and Upper West lacked MRI scanners. MRI scanners per million population was 0.5. The mean cost per MRI examination, was lower in the public (i.e. GHȻ 563-GHȻ 686, p < 0.05 for non-contrast MRI examinations) compared to the private (i.e. GHȻ 618-GHȻ 775, p < 0.05 also for non-contrast MRI examinations). Most facilities (9[75%]) accept card bearers of some private health insurance to access MRI services, but none accepts that of the public-funded health insurance. There is wide disparity in the distribution of MRI scanners nationwide, with most of them located in the Greater Accra region. With only 5 regions having MRI scanners, it does imply that close to 40% of the general population do not readily have access to MRI services. Government can achieve an increase in availability, accessibility, and affordability of MRI by providing more public health facilities with MRI scanners and reimbursing MRI services via the NHIS (National Health Insurance Scheme).


Improving Perioperative Pain Education for Patients Prescribed Opioids: An Integrative Review.
Postoperative pain is still inadequately managed for a significant number of patients despite the extensive use of opioids. Among several pain management strategies, patient education is a vital component of perioperative pain management. However, perioperative education practices remain inconsistent and incomplete in many hospital settings. This integrative review aims to synthesize current evidence regarding pain education interventions across all phases of perioperative care in order to promote the safe use of opioids among patients prescribed opioids. The literature search identified 443 records published since 2016 through Cochrane Library, PubMed, the Cumulative Index of Nursing and Allied Health Literature Plus, and Embase. This review process was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. A total of 12 articles met the inclusion criteria. The study settings varied from a general surgery center to multiple settings in the United States or Canada, with sample sizes ranging from 27 to 536. The main themes from the analysis include the key components of education, the optimal timing and frequency of education, education delivery methods, and a multidisciplinary team approach. The findings from this review will help nursing professionals across surgical specialties identify effective educational approaches for patients prescribed opioids during the perioperative period. Developing education interventions based on these findings would enhance the quality and effectiveness of pain education, improve patient understanding and their preparedness to manage pain at home, and, ultimately, promote the safe use of opioids postoperatively.


Synthesis of diverse pyrazole-4-sulfonyl chlorides starting from 2-(benzylthio)malonaldehyde.
A series of pyrazole-4-sulfonyl chlorides was obtained by a convenient 2-step method starting from synthetically available 2-(benzylthio)malonaldehyde. The method can be applied for the effective multi-gram synthesis of diverse pyrazole-containing sulfonyl chlorides which are mostly not available by other methods.


4-[(1H-imidazol-4-yl) methyl] benzamidines and benzylamidines: novel antagonists of the histamine H3 receptor.
A series of amidine substituted phenyl-, benzyl-, and phenethylimidazoles based on the known H3 agonist SK&F 91606 (4) has been synthesized and tested as ligands for the histamine H3 receptor. Insertion of a phenyl ring between the imidazole ring and the amidine moiety produces antagonists. The benzyl series was found to be the most potent and was further investigated. Compounds 9c and 18 (entries 5 and 12, Table 1) are potent ligands for the H3 receptor with K(i) values of 16 nM and 7.2 nM respectively. In vivo, both compounds were shown to be equipotent to thioperamide (2), the standard H3 antagonist.


Complete AV block following mediastinal radiation therapy: electrocardiographic and pathologic correlation and review of the world literature.
The clinical, features, serial electrocardiograms, and autopsy findings of a patient with symptomatic complete AV block, who had received mediastinal radiation therapy 8 1/2 years previously, are presented. The cardiac histopathology disclosed immense fibrosis of the conduction system and of the atria and ventricles. The enormous amount of fibrosis was similar in location and intensity to that observed in our previously reported patient (Cohen et al., Arch Intern Med 1981; 141:676-679) who had undergone mediastinal radiation. We conclude that the severe fibrosis was primarily due to radiation, rather than secondary to atherosclerotic coronary artery disease, which also has been described as a consequence of mediastinal radiotherapy. This patient's serial electrocardiograms disclosed evidence of complete block both in the AV nodal area and infra His system, which correlated well with the histopathology. The characteristic clinical features of patients with symptomatic complete AV block post mediastinal radiation therapy are presented, along with a review of the world literature.


Congress of neurological surgeons systematic review and evidence-based clinical practice parameter guidelines for the treatment of adults with newly diagnosed glioblastoma: Introduction and Methods.
This is an update of the evidence-based guideline for management of newly diagnosed glioblastomas sponsored by the American Association of Neurological Surgeons (AANS) and Congress of Neurological Surgeons (CNS) initially published in 2008. The objective is to update evidence-based management of newly diagnosed glioblastomas over all commonly used diagnostic and treatment modalities in regularly encountered clinical situations. A multidisciplinary writing group was assembled to create documents related to imaging, cytoreductive surgery, neuropathology, radiation therapy, chemotherapy and emerging developments. Questions from the prior set of guidelines, and new and modified questions were used to guide a search of the scientific literature since the last guideline search was completed in June 2005. Citations were screened, classified and used as evidence to create recommendations addressing the questions in a manner that was directly linked to this evidence. The sixteen writers produced 34 questions resulting in eight Level I recommendations, eleven Level II recommendations, and 27 Level II recommendations across all the topics. In some instances, insufficient data was available to answer all or part of a question and this is stated and explained. This series of guidelines is based upon relevant evidence in the literature related to the management of newly diagnosed glioblastomas. They set a benchmark for the management of this disease while highlighting key areas of weakness in our knowledge and suggest directions for future basic and clinical research to improve evidence quality and recommendation strength.


Renal imaging in pyelonephritis.
Pyelonephritis accounts for a significant number of hospital admissions. It is unclear from existing literature whether all patients requiring admission to hospital should undergo renal imaging or if there is a subset that indicates clinical parameters for those who are more likely to have significant renal imaging abnormalities. We undertook a retrospective study of 60 consecutive patients hospitalized with pyelonephritis, the majority of whom underwent renal ultrasound at the time of admission. Clinical data collected included age, sex, fever, serum creatinine, days for resolution of fever, premorbid conditions, and results of renal imaging. Sixteen per cent were found to have new and clinically significant abnormal findings; predominantly, urinary tract obstruction. We found no significant difference between the groups with abnormal and normal renal imaging in terms of any easily detectable clinical parameter such as change in serum creatinine, premorbid conditions, age, days for fever to resolve or white cell count on admission. We found a high proportion of Escherichia coli resistant to ampicillin (46%) but not to amoxycillin/clavulinic acid. Although our study did not test whether immediate imaging is more advantageous than delaying imaging for those who fail to respond to treatment, our findings suggest that early imaging is a cost-effective part of management. On the basis of these data, we recommend renal imaging for all patients requiring hospital admission for pyelonephritis, and suggest that initial empirical therapy should include an intravenous dose of cephalosporin but not ampicillin.


Assessment of contamination and misclassification biases in a randomized controlled trial of a social network peer education intervention to reduce HIV risk behaviors among drug users and risk partners in Philadelphia, PA and Chiang Mai, Thailand.
Controlled trials of HIV prevention and care interventions are susceptible to contamination. In a randomized controlled trial of a social network peer education intervention among people who inject drugs and their risk partners in Philadelphia, PA and Chiang Mai, Thailand, we tested a contamination measure based on recall of intervention terms. We assessed the recall of test, negative and positive control terms among intervention and control arm participants and compared the relative odds of recall of test versus negative control terms between study arms. The contamination measures showed good discriminant ability among participants in Chiang Mai. In Philadelphia there was no evidence of contamination and little evidence of diffusion. In Chiang Mai there was strong evidence of diffusion and contamination. Network structure and peer education in Chiang Mai likely led to contamination. Recall of intervention materials can be a useful method to detect contamination in experimental interventions.


Breast cancer in the elderly patient: early detection with mammography.
To determine the mammographic features and differences in stage of breast carcinomas in elderly women with malignancies detected with palpation or mammography at presentation. The mammograms and clinical records of 60 patients (aged 75 years or older) with 62 breast carcinomas, detected during 40 consecutive months, were retrospectively reviewed. A variety of dedicated devices and processing equipment were used. The histologic features, mammographic appearance, mode of detection, and stage of disease were determined. Statistically significant differences between subgroups were calculated with the Student t and chi 2 tests. Sixty cancers (97%) were seen on mammograms. Seventeen tumors detected with annual mammography differed significantly from the 45 carcinomas in nonscreened patients in diameter (1.1 vs 2.1 cm; P < .0005) and stage (14 minimal [82%] of 17 tumors vs 15 minimal [33%] of 45 tumors; P < .0005). Thirty-five nonpalpable malignancies differed significantly from 27 palpable masses in diameter (1.2 vs 2.3 cm; P = .01) and stage (25 tumors minimal [71%] vs four tumors minimal [15%]; P < .0005). Screening mammography enabled detection of statistically significantly smaller and earlier-stage tumors, most of which were minimal disease.


Ultrastructural observations on chick bone processed by quick-freezing and freeze-substitution.
The ultrastructure of newly formed bone was examined with the use of quick-freezing followed by freeze-substitution. Osteoblasts and young osteocytes were characterized by a smooth cell contour, whereas old osteocytes were irregular in shape. The plasma and intracytoplasmic membranes were clearly identifiable as trilaminar substructures. With the method described herein the tissue is handled in the anhydrous state. Thus mitochondrial granules could be demonstrated in all samples, since their preservation is not affected by non-aqueous solutions. The matrices of intact mitochondria were densely stained with post-staining. The contents of the Golgi complex, rough-surfaced endoplasmic reticulum (RER), nuclear envelope, vesicles, and vacuoles were stained to various degrees. Lacunar spaces were always filled with flocculent and filamentous materials, and the plasma membrane was in direct contact with them. Membrane-bounded matrix vesicles were clearly visible within the osteoid extracellular matrix which was the initial site of mineral crystal deposition. In heavily mineralized bone matrix, the periodic pattern of collagen fibrils was retained, and the electron density of mineralized matrix in freeze-substituted and unstained sections which had been floated on ethylene glycol was greater than that encountered in sections processed in aqueous reagents.


Magnetic resonance imaging and trigeminal schwannoma.
A case of trigeminal schwannoma, extending from the posterior fossa into Meckel's cave, is reported. The information provided by computed tomography, angiography, and magnetic resonance imaging allowed a correct preoperative diagnosis to be obtained. Due to the excellent sensitivity, the absence of bone artifacts, and the ease of imaging in any plane, magnetic resonance imaging best defined the "dumbbell" nature of the tumor, the atrophy of the masticatory muscles, and the infiltration of the third division of the trigeminal nerve.


Measurement of histone acetyltransferase and histone deacetylase activities and kinetics of histone acetylation.
Dynamic histone acetylation has a role in chromatin remodeling and in the regulation of transcription. Histone deacetylases (HDACs) and histone acetyltransferases (HATs) catalyze reversible histone acetylation. HATs and HDACs exist as multiprotein complexes that have coactivator and corepressor activities, respectively. The steady-state level of acetylation at a chromatin site is determined by the local net activities of these enzymes. Here we describe methods to isolate different subcellular fractions (cytosol, nuclei, tightly bound nuclear, loosely bound nuclear, immunoprecipitated multiprotein complexes, and nuclear matrix) to determine the subcellular distribution of HAT and HDAC activities. Procedures to assay the activities of these enzymes and to measure the kinetics of histone acetylation and deacetylation are presented.


Laparoscopic fundoplication for a case of esophageal hiatal hernia after gastroschisis repair.
Esophageal hiatal hernia and gastroesophageal reflux have been recognized as inevitable complications after the definitive gastroschisis operation. Patients with refractory gastroesophageal reflux require anti-reflux surgery; however, the surgical adhesions may complicate subsequent surgical therapy, especially in the cases treated by staged repair. A male infant who showed a severe gastroesophageal reflux due to hiatal hernia after staged abdominal fascial closure of gastroschisis. In spite of continuous conservative management, frequent vomiting and hematemesis had become progressively worse at the age of 8 months. Laparoscopic Nissen fundoplication was attempted and completed with no adverse events. Laparoscopic fundoplication may be applied, as a first-line approach, for the treatment of gastroesophageal reflux in this difficult group of patients, after the repair of congenital abdominal wall defect.


Acquired adenomatous hyperplasia of the rete testis: an immunohistochemical study of its pathogenesis.
Adenomatous hyperplasia of the rete testis (AHRT) is an uncommon abnormality first described by Nistal and Paniagua in 1988. Congenital and acquired forms of AHRT are recognized. We present a case of AHRT in a patient who underwent bilateral orchiectomy for penile carcinoma; he had received chemotherapy for Hodgkin lymphoma 18 years prior. Proposed causes for this disorder include developmental, hormonal, and paracrine induction by adjacent testicular tumors and exposure to chemicals, based on clinical contexts but without experimental support. We performed immunohistochemical studies using markers of cell cycle (cyclin D1, p16), proliferation (Ki-67), apoptosis (bcl2), senescence (γ-H2AX), and androgen receptors to try to provide scientific support for or refute existing hypotheses. Our results indicate that, in this case of acquired AHRT after chemotherapy, the process is neither adenomatous nor hyperplastic but rather represents abnormal accumulation of rete testis cells with acquired senescence.


Detection of Plasmodium berghei and Plasmodium yoelii Liver-Stage Parasite Burden by Quantitative Real-Time PCR.
Direct detection and quantification of liver-stage Plasmodium parasites became possible with the development of quantitative real-time PCR (qPCR). Here we describe the measurement of parasite burden in the livers of mice infected with the rodent malaria species, Plasmodium berghei and Plasmodium yoelii. This method is based on detection of expression of parasite ribosomal 18S RNA and can serve as an endpoint to accurately evaluate the efficacy of vaccines targeting the preerythrocytic stages of malaria. This approach is fast and highly reproducible and allows quantification of liver-stage parasite burden in different mouse strains and different Plasmodium species after infection with a range of sporozoite challenge doses.


Analysis of Small Ischemic Lesions in the Examinees of a Brain Dock and Neurological Examination of Animals Subjected to Cortical or Basal Ganglia Photothrombotic Infarction.
We analyzed cases of small brain ischemic lesions found in examinees of a brain dock (neurological health screening center). Small cerebral infarction was found in 17 % of the examinees (733 cases). White matter lesions were found in 24 %. Infarctions were located in the cortex or subcortical white matter in 31 % and in the basal ganglia in 44 % of cases. Infratentorial infarction was found in 1.6 %. We have developed an animal model of small infarction in the cortex or basal ganglia induced by photothrombosis in rodents. Sprague-Dawley rats or Mongolian gerbils were anesthetized and photothrombotic infarction was induced in the left caudate nucleus or parietal cortex by light exposure via an optic fiber and intravenous Rose Bengal dye injection. Histological examination revealed development of a small spherical infarction surrounding the tip of the optic fiber. The lesion turned to a cyst by 6 weeks after lesioning. Neurological deficits were found in animals both with cortical and caudate infarction. Behavioral changes in an open field test differed with the lesion site. Neurological deficits were sustained longer in animals with larger infarctions. Thus, photothrombotic infarction is useful for analyzing location-dependent and size-dependent neurological and neuropathological changes after cerebral infarction.


Development of Endothelial-Specific Single Inducible Lentiviral Vectors for Genetic Engineering of Endothelial Progenitor Cells.
Endothelial progenitor cells (EPC) are able to migrate to tumor vasculature. These cells, if genetically modified, can be used as vehicles to deliver toxic material to, or express anticancer proteins in tumor. To test this hypothesis, we developed several single, endothelial-specific, and doxycycline-inducible self-inactivating (SIN) lentiviral vectors. Two distinct expression cassettes were inserted into a SIN-vector: one controlled by an endothelial lineage-specific, murine vascular endothelial cadherin (mVEcad) promoter for the expression of a transactivator, rtTA2S-M2; and the other driven by an inducible promoter, TREalb, for a firefly luciferase reporter gene. We compared the expression levels of luciferase in different vector constructs, containing either the same or opposite orientation with respect to the vector sequence. The results showed that the vector with these two expression cassettes placed in opposite directions was optimal, characterized by a robust induction of the transgene expression (17.7- to 73-fold) in the presence of doxycycline in several endothelial cell lines, but without leakiness when uninduced. In conclusion, an endothelial lineage-specific single inducible SIN lentiviral vector has been developed. Such a lentiviral vector can be used to endow endothelial progenitor cells with anti-tumor properties.


Restrictive guideline reduces platelet count thresholds for transfusions in very low birth weight preterm infants.
Platelet transfusions are performed almost entirely according to expert experience. This study assessed the effectiveness of a restrictive guideline to reduce platelet transfusions in preterm infants. A retrospective cohort of preterm infants with a birth weight of <1500 g had been born in 2 periods. In Period 1, a transfusion was indicated for a platelet count of <50,000/ml in clinically stable neonates or <100,000/ml in bleeding or clinically unstable infants. In Period 2, the indications were restricted to <25,000/ml in clinically stable neonates, or <50,000/ml in newborns who were either on mechanical ventilation, subject to imminent invasive procedures, within 72 h following a seizure, or extremely premature and <7 days old. A count of <100,000/ml was indicated for bleeding or major surgery. Periods 1 and 2 comprised 121 and 134 neonates, respectively. The rates of ventricular haemorrhage and intrahospital death were similar in both periods. The percentage of transfused infants, the odds of receiving a platelet transfusion, the mean platelet count before transfusion and the percentage of transfusions with a platelet count >50,000/ml were greater in Period 1. Among thrombocytopenic neonates, the percentage of transfused neonates and the number of transfusions were similar in both groups. The restrictive guideline for platelet transfusions reduced the platelet count thresholds for neonatal transfusions without increasing the rate of ventricular haemorrhage.


Comparison of early versus delayed timing of left ventricular assist device implantation as a bridge-to-transplantation: An analysis of the UNOS dataset.
Placement of left ventricular assist devices (LVAD) as a bridge-to-heart transplantation (HTx) has rapidly expanded due to organ donor shortage. However, the timing of LVAD implantation is variable and it remains unclear if earlier implantation improves survival. We analyzed 14,187 adult candidates from the United Network of Organ Sharing database. Patients were classified by 3 treatment strategies including patients medically treated alone (MED, n=11,009), patients on LVAD support at listing (Early-LVAD, n=1588) and patients undergoing LVAD placement while awaiting HTx (Delayed-LVAD, n=1590). Likelihood of HTx and event-free survival were assessed in patients subcategorized by clinical strategies and UNOS status at listing. The device support strategy, despite the timing of placement, was not associated with increased likelihood of HTx compared to MED group. However, both LVAD implantation strategies showed better survival compared to MED group (Early-LVAD: HR 0.811 and 0.633, 95% CI 0.668-0.984 and 0.507-0.789, for 1A and 1B; p=0.034 and p<0.001, Delayed-LVAD: HR 0.553 and 0.696, 95% CI 0.415-0.736 and 0.571-0.847, for 1A and 1B; both p<0.001, respectively). Furthermore, there was no significant difference in survival between these LVAD implantation strategies in patients listed as 1B (p=0.500), although Early-LVAD implantation showed worse survival in patients listed as 1A (HR 1.467, 95% CI 1.076-2.000; p=0.015). LVAD support strategies offer a safe bridge-to-HTx. Those candidates who receive urgent upfront LVAD implantation for HTx, and improve to 1B status, would achieve competitive survival with those who receive elective LVAD implantation.


Subxiphoid pericardial window in patients with suspected traumatic pericardial tamponade.
The technique, indications, and results of subxiphoid pericardial window in penetrating chest wounds with suspected traumatic pericardial tamponade are reported. The classic signs of pericardial tamponade (elevated central venous pressure, muffled heart sounds, and paradoxical pulse) are unreliable in an emergency situation. Chest roentgenograms and electrocardiograms are of little diagnostic value. Pericardicentesis was either falsely positive or negative in 50% of our patients. Therefore, unexplained high central venous pressure and hypotension were considered to be pericardial tamponade until disproved by the results of a subxiphoid pericardial window. There were 4 negative and 46 positive findings of tamponade in 50 consecutive patients with suspected traumatic pericardial tamponade who underwent creation of a subxiphoid pericardial window. There were no deaths or complications from the procedures. The early use of subxiphoid pericardial window has been a major factor in reducing our mortality rate from penetrating heart wounds to 12% overall, and 8% in the past three years.


Activity-dependent plasticity of hippocampal place maps.
Hippocampal neurons encode a cognitive map of space. These maps are thought to be updated during learning and in response to changes in the environment through activity-dependent synaptic plasticity. Here we examine how changes in activity influence spatial coding in rats using halorhodopsin-mediated, spatially selective optogenetic silencing. Halorhoposin stimulation leads to light-induced suppression in many place cells and interneurons; some place cells increase their firing through disinhibition, whereas some show no effect. We find that place fields of the unaffected subpopulation remain stable. On the other hand, place fields of suppressed place cells were unstable, showing remapping across sessions before and after optogenetic inhibition. Disinhibited place cells had stable maps but sustained an elevated firing rate. These findings suggest that place representation in the hippocampus is constantly governed by activity-dependent processes, and that disinhibition may provide a mechanism for rate remapping.


Electrophysiological evidence for differences between fusion and combination illusions in audiovisual speech perception.
Incongruent audiovisual speech stimuli can lead to perceptual illusions such as fusions or combinations. Here, we investigated the underlying audiovisual integration process by measuring ERPs. We observed that visual speech-induced suppression of P2 amplitude (which is generally taken as a measure of audiovisual integration) for fusions was similar to suppression obtained with fully congruent stimuli, whereas P2 suppression for combinations was larger. We argue that these effects arise because the phonetic incongruency is solved differently for both types of stimuli.


[Loach spermatozoa transfer foreign DNA, which expression is discovered in the early development stages].
The transfer of plasmid pcDNA3-lacZ by electrotrasfected sperm cells into loach (Misgurnus fossilis L.) ova has been studied. The lacZ gene has been found to express in 3- to 5-day-old prelarvae.


Hepatitis C virus nonstructural protein 5A perturbs lipid metabolism by modulating AMPK/SREBP-1c signaling.
Steatosis is an important clinical manifestation associated with chronic hepatitis C virus (HCV) infection. AMP-activated protein kinase (AMPK), a major mediator of lipid metabolism, regulates HCV-associated hepatic steatosis, but the underlying mechanisms remain obscure. Here we investigated the mechanism of HCV nonstructural protein 5A (NS5A)-induced lipid accumulation by the AMPK/SREBP-1c pathway. We generated model mice by injecting recombinant lentiviral particles expressing the NS5A protein (genotype 3a) via the tail vein. The serum levels of alanine aminotransferase (ALT), free fatty acids (FFAs) and triglycerides (TG) were examined. H&E and Oil Red O staining were used to examine lipid droplets. Immunohistochemistry staining, quantitative real-time PCR and Western blotting were used to determine the expression of lipogenic genes. Our results showed that the serum levels of ALT, FFAs and TG, as well as the accumulation of hepatic lipid droplets, were increased significantly in mice infected with NS5A-expressing lentiviral particles. NS5A inhibited AMPK phosphorylation and increased the expression levels of sterol regulatory element binding protein-1c (SREBP-1c), acetyl-coenzyme A carboxylase 1 (ACC1) and fatty acid synthase (FASN) in vivo and in vitro. Further investigation revealed that pharmacological activation or ectopic expression of AMPK neutralized the upregulation of SREBP-1c, ACC1 and FASN, and ameliorated hepatic lipid accumulation induced by NS5A. Ectopic expression of SREBP-1c enhanced NS5A-induced hepatic lipid accumulation, which was dramatically reversed by pharmacological activation of AMPK. Collectively, we demonstrate that NS5A induces hepatic lipid accumulation via the AMPK/SREBP-1c pathway.


Significance of Omental Infiltration in Gastric Cancer Patients: a Retrospective Cohort Study.
Stomach cancer is a curative disease in early stages. The optimal extent and approach for gastric resection are still evolving. In this study, we examined the value, as well as, the predictors of omental disease spread, retrospectively, in a group of patients with gastric cancer who attended the Oncology Center, Mansoura University, in the period between January 2006 and April 2017. Nodal metastasis, especially heavy disease (N2 and beyond), and advanced stage are predictors of the presence of omental disease. However, neither overall nor disease-free survival is affected by omental infiltration. Omental resection will continue being an integral part of gastric resection, but the level of omental cutting needs further studies.


Anesthesia for plastic surgery in the pediatric patient.
The anesthetic management of pediatric patients for plastic surgical procedures requires close cooperation and understanding between the surgeon and anesthesiologist. Success depends upon avoidance of psychological trauma, establishment and maintenance of a secure airway, and adequate access to the vascular system.


Spin-echo fMRI: The poor relation?
Spin-echo fMRI offers a potentially better intrinsic functional spatial resolution than its gradient echo counterpart, as well as the elimination of signal dropouts in the image. This comes at the price of a significant loss in sensitivity. In this article the main methods for measuring spin-echo fMRI are presented: HASTE, SSFP, RASER and most importantly spin-echo EPI. Their relative merits and limitations are discussed. The BOLD contrast mechanisms responsible for spin echo fMRI are summarised, and the spatial origin of the signal within the neocortex discussed. The major publications concerning the use of spin echo fMRI are examined. At present the most promising application for this methodology would appear to be in the examination of cortical layers and columns. The balance of experimental and theoretical evidence accumulated to date leads the author to propose that: (i) There is little point in conducting spin-echo fMRI at main magnetic field strengths of 3T and below; (ii) There are fundamental limitations to acquiring spin-echo BOLD data at 7T and above; (iii) Whole brain coverage with SE-BOLD at very high static magnetic field strengths could prove valuable; and (iv) SE-BOLD is probably better suited to study cortical columns than cortical layers. Recently gradient-echo approaches for high spatial resolution fMRI have been demonstrated that employ special techniques to avoid the effects of larger post capillary vessels. The coming years will show whether spin-echo techniques can remain the method of choice for high spatial resolution studies, and whether they can extend their range of application at 7T and above.


Sensitivity of petrolatum and aqueous vehicles for detecting allergy to imidazolidinylurea, diazolidinylurea, and DMDM hydantoin: a retrospective analysis from the North American Contact Dermatitis Group.
To determine whether petrolatum or aqueous vehicles are more sensitive for detecting allergy to imidazolidinylurea (IU), diazolidinylurea (DU), and dimethylol dimethyl hydantoin (DM). The relationship of these allergens to formaldehyde sensitivity was also explored. Retrospective analysis of patients patch-tested by the North American Contact Dermatitis Group. All patients were simultaneously tested to seven allergens (formaldehyde, IU in petrolatum [pet], IU aqueous [aq], DU pet, DU aq, DM pet, and DM aq). Data were analyzed in pairs with various "gold standard" definitions of "true allergy" and adjusting for correlated data. Reaction to at least one of the seven allergens occurred in 2,398 patients. In all cases except one (which just approached statistical significance), the petrolatum-based allergen was statistically significantly more sensitive than the same allergen in an aqueous base. Most of the patients allergic to the three preservatives were also allergic to formaldehyde, but most formaldehyde-allergic patients were not allergic to the IU, DU, or DM. Of these two vehicles, petrolatum is significantly more sensitive than an aqueous vehicle is for detecting allergy to IU, DU, and DM.


Electrophysiological evidence that a set of interfascicular cells of the rat anterior commissure are neurons.
In mammals, the anterior commissure (AC) provides a route that interconnects homonymous areas of the basal forebrain. Recently, we reported the presence of short-axon and projection neurons among the axonal fascicles of the rat AC (i.e. interfascicular neurons; IFNs). This, coupled with the commissural inputs to these neurons, suggests that in addition to conveying nerve impulses, the AC may be a site of neural processing. To test this hypothesis, the electrophysiological activity of IFNs was recorded in adult albino rats. From extracellular recordings performed in 11 IFNs, it was found that these cells: (1), have a spontaneous discharge of a relatively low frequency (i.e. 0.04 +/- 0.1 to 5.9 +/- 3.2 spikes per second); (2), application of anodic current in the adjacent commissural fibers decreased this frequency; and (3), application of cathodic current increased the number of action potentials. Since observations made in Golgi-impregnated sections suggest that the main input to IFNs arises from their commissural collaterals, it is concluded that these cells may participate in the integration of interhemispheric nerve impulses.


Arthroscopic Complete Synovectomy of the Proximal Interphalangeal Joint of the Finger.
Rheumatoid arthritis is characterized by hypertrophic synovitis destroying the involved joints. If medical treatment fails to control the synovitis, synovectomy is a worthwhile prophylactic procedure that might help to delay further distention of the joint capsule and ligament. Synovitis of the proximal interphalangeal joint is usually performed by an open approach. The major complication is scar development around the interphalangeal joint, leading to considerable joint contracture. Arthroscopy of the proximal interphalangeal joint is a minimally invasive technique that can eliminate the risk of joint contracture associated with open surgery. The purpose of this Technical Note is to report the technical details of arthroscopic complete synovectomy of the proximal interphalangeal joint of the finger. This procedure is indicated in patients with rheumatoid synovitis of the proximal interphalangeal joint of the finger recalcitrant to medical treatment. It is contraindicated in case of an established boutonniere or swan-neck deformity, the presence of large dorsal synovial cysts, advanced degeneration of the joint, the presence of joint instability, or a fresh skin lesion near portals.


Enlarged perivascular spaces are associated with the disease activity in systemic lupus erythematosus.
To determine whether any brain MR abnormalities, including enlarged perivascular spaces (EPVS), were associated with disease activity in systemic lupus erythematosus (SLE) as an inflammatory activity. One hundred and thirty SLE patients with normal MR findings were assessed. With regard to MRI abnormalities, patients with brain atrophy and mild white matter hyperintensity (WMH) on T2WI were not excluded. The disease activity was assessed using the SLEDAI and the BILAG scores. The imaging characteristics included centrum semiovale EPVS (CS- EPVS) and basal ganglia EPVS on T2WI, WMH, and brain atrophy. We used univariate and multivariate logistic regression analyses to determine the clinical (vascular risk factors and blood examinations) and imaging characteristics that were associated with the disease activity of SLE. High CS-EPVS to be the only factor that was independently associated with the severity of the SLEDAI and BILAG scores (odds ratio [OR] 5.77; 95% confidence interval [CI] 2.21-15.00; p < 0.001 for the SLEDAI, and OR 2.64; 95% CI 1.03-6.74; p = 0.042 for the BILAG score). The CS-EPVS in the SLE patients are associated with the systemic disease activity, suggesting that CS- EPVS may be indicative of the reactive changes of the white matter due to the inflammatory activity.


[Sarcoid-like granulomatosis in cancer patients treated with immune checkpoints inhibitors].
Immune checkpoint inhibitors are becoming a standard treatment for many different cancers. Their toxicities are variable and include organ-specific dysimmune injuries and the development of systemic diseases. We report 3 cases of sarcoid-like granulomatosis that occurred during treatment of various types of primary cancer by immune checkpoint inhibitors: lung adenocarcinoma, small cell lung cancer and melanoma. The clinical presentation, radiologic pattern and severity of this toxicity were variable. The diagnosis was made on biopsy with pathological examination and exclusion of differential diagnoses, particularly infection. In such cases, immunotherapy should be discontinued and subsequent rechallenge discussed later. Systemic corticosteroids should be considered depending on the severity of symptoms. Knowledge of this toxicity is crucial as the clinical signs and radiological patterns may suggest tumour progression.


A case-control study of risk factor for renal cell cancer in northern Italy.
A hospital-based case-control study of renal cell cancer was conducted in northern Italy between 1986 and 1989, with 240 cases of renal cell cancer (150 males and 90 females), and 665 controls (445 males and 220 females) chosen on the basis of age, sex, and area of residence. No associations were found between renal cell cancer and: body mass index (BMI); number of cigarettes smoked; age at starting to smoke; years of smoking; consumption of wine, beer, spirits, coffee, decaffeinated coffee; tea; intake of animal protein, fruits, and vegetables; various reproductive factors; hormonal use; sexual habits; sexually transmitted diseases; or selected occupational exposures. The odds ratio (OR) was above unity in smokers (OR = 1.34 for greater than or equal to 15 cigarettes/day), but the trends in risk with dose or duration were not statistically significant. Significant positive associations were found between renal cell cancer and sources of fat intake, especially margarine (OR for highest vs lowest intake = 1.71), and oils (OR = 1.89) whereas carrot intake showed a negative association (OR = 0.62). Also, a history of nephrolithiasis and multiple episodes of cystitis showed weak positive associations (OR = 2.00, 95 percent confidence interval (CI) 1.07-3.73; and OR = 1.60, 95 percent CI 0.95-2.70, respectively).


Histopathological biomarkers in gills and liver of Oreochromis niloticus from polluted wetland environments, Saudi Arabia.
Fish live in direct contact with their immediate external environment and, therefore, are highly vulnerable to aquatic pollutants. In this study, Oreochromis niloticus were caught at three different sites in Al-Hassa irrigation channels, namely Al-Jawhariya, Um-Sabah and Al-Khadoud. The histological changes in gills and liver were detected microscopically and evaluated with semi-quantitative analyses. Also, heavy metals have been determined in the water samples in these sites. Results showed that all sites were polluted by different kinds of heavy metals. Cd and Pb were mostly detected at concentrations above the WHO reference values. Meanwhile, various histopathological abnormalities were observed in gills and liver of fish specimens. In the gill filaments, cell proliferation, lamellar cell hyperplasia, lamellar fusion, lifting of the respiratory epithelium, and the presence of aneurysmal areas were observed. In the liver, there was vacuolization of the hepatocytes, sinusoidal congestion, necrosis of the parenchyma tissue, nuclear pyknosis, eosinophilic hepatocellular degeneration, pigment accumulation, an increase in the number and size of melanomacrophage centers. Liver tumors with severe chronic inflammation were occasionally found in fish at Al-Khadoud area (first-time report). The histological lesions were comparatively most severe in the liver. Despite heavy metals assessment did not show marked differences among sites, histopathological biomarkers indicated that the surveyed fish are living under stressful environmental conditions. So, we suggest use those biomarkers in future monitoring of aquatic systems.


Epidemiology of bluetongue in Central America and the Caribbean: initial entomological findings. Regional Bluetongue Team.
Forty-four species of Culicoides (Diptera: Ceratopogonidae) were caught in insect light traps during the first 2 years of studies on the epidemiology of bluetongue virus in the Caribbean and Central America. Traps were operated near sentinel ruminants which were bled monthly for serologic evaluation and then virus isolation. More than 570,000 individuals were identified. Culicoides insignis Lutz accounted for 90% of the catch, C. filarifer Hoffman/C. ocumarensis Ortiz 5%, C. furens Poey 3% and C. pusillus Lutz 2%. Other species accounted for less than 1% of the total catch. Sentinel ruminants became seropositive when C. insignis populations were high at many study sites. At a few sites C. pusillus and C. filarifer/C. ocumarensis were predominant or were present in large numbers during seroconversions of sentinels. Virus isolations were obtained from sentinel ruminants during times when these same species were present in large populations.


Can noninvasive brain stimulation measure and modulate developmental plasticity to improve function in stroke-induced cerebral palsy?
The permanent nature of motor deficits is a consistent cornerstone of cerebral palsy definitions. Such pessimism is disheartening to children, families, and researchers alike and may no longer be appropriate for it ignores the fantastic plastic potential of the developing brain. Perinatal stroke is presented as the ideal human model of developmental neuroplasticity following distinct, well-defined, focal perinatal brain injury. Elegant animal models are merging with human applied technology methods, including noninvasive brain stimulation for increasingly sophisticated models of plastic motor development following perinatal stroke. In this article, how potential central therapeutic targets are identified and potentially modulated to enhance motor function within these models is discussed. Also, future directions and emerging clinical trials are reviewed.


Similar risk of exercise-related hypoglycaemia for insulin degludec to that for insulin glargine in patients with type 1 diabetes: a randomized cross-over trial.
We compared changes in blood glucose (BG) and risk of hypoglycaemia during and after exercise in 40 patients with type 1 diabetes (T1D) treated with insulin degludec (IDeg) or insulin glargine (IGlar) in a randomized, open-label, two-period, crossover trial. After individual titration and a steady-state period, patients performed 30 min of moderate-intensity cycle ergometer exercise (65% peak rate of oxygen uptake). BG, counter-regulatory hormones and hypoglycaemic episodes were measured frequently during and for 24 h after exercise. BG changes during exercise were similar with IDeg and IGlar [estimated treatment difference (ETD) for maximum BG decrease: 0.14 mmol/l; 95% confidence interval (CI) -0.15, 0.42; p = 0.34], as was mean BG (ETD -0.16 mmol/l; 95% CI -0.36, 0.05; p = 0.13). No hypoglycaemic episodes occurred during exercise. Post-exercise mean BG, counter-regulatory hormone response and number of hypoglycaemic episodes in 24 h after starting exercise were similar with IDeg (18 events in 13 patients) and IGlar (23 events in 15 patients). This clinical trial showed that, in patients with T1D treated with a basal-bolus regimen, the risk of hypoglycaemia induced by moderate-intensity exercise was low with IDeg and similar to that with IGlar.


Pilot tone-based motion correction for prospective respiratory compensated cardiac cine MRI.
To evaluate prospective motion correction using the pilot tone (PT) as a quantitative respiratory motion signal with high temporal resolution for cardiac cine images during free breathing. Before cine data acquisition, a short prescan was performed, calibrating the PT to the respiratory-induced heart motion using respiratory-resolved real-time images. The calibrated PT was then applied for nearly real-time prospective motion correction of cine MRI through slice tracking (ie, updating the slice position before every readout). Additionally, in-plane motion correction was performed retrospectively also based on the calibrated PT data. The proposed method was evaluated in a moving phantom and 10 healthy volunteers. The PT showed very good correlation to the phantom motion. In volunteer studies using a long-term scan over 7.96 ± 1.40 min, the mean absolute error between registered and predicted motion from the PT was 1.44 ± 0.46 mm in head-feet and 0.46 ± 0.07 mm in anterior-posterior direction. Irregular breathing could also be corrected well with the PT. The PT motion correction leads to a significant improvement of contrast-to-noise ratio by 68% (P ≤ .01) between blood pool and myocardium and sharpness of endocardium by 24% (P = .04) in comparison to uncorrected data. The image score, which refers to the cine image quality, has improved with the utilization of the proposed PT motion correction. The proposed approach provides respiratory motion-corrected cine images of the heart with improved image quality and a high scan efficiency using the PT. The PT is independent of the MR acquisition, making this a very flexible motion-correction approach.


The anatomy of the pectoral nerves and its significance in breast augmentation, axillary dissection and pectoral muscle flaps.
In many plastic surgeries, a detailed understanding of the pectoral nerve anatomy is often required. However, the information available on the anatomy of pectoral nerves is sparse and unclear. The purpose of this study is to provide detailed anatomical information on the pectoral nerves to allow for their easy intra-operative localisation and to improve the understanding of the pectoral muscle innervation. We dissected 26 brachial plexuses from 15 fresh cadavers. The origins, locations, courses and branches of the pectoral nerves were recorded. We found three constant branches of the pectoral nerve. The superior branch travelled in a straight course to the pectoralis major to innervate the clavicular aspect. The middle branch coursed on the under-surface of the pectoralis major near the pectoral branch of the thoraco-acromial artery to innervate the muscle's sternal aspect. The inferior branch passed beneath the pectoralis minor muscle to innervate the pectoralis minor muscle and the costal aspect of the pectoralis major muscle. Knowing the pectoral nerves' origins, courses and connections, in addition to understanding the functional consequences of iatrogenically severing these nerves, leads to a better understanding of the pectoral muscle's innervation. Precise anatomical data on the pectoral nerve allow for its easy localisation during axillary breast augmentation, axillary dissection, removal of the pectoralis minor muscle and harvesting the pectoralis major muscle island flap.


Myc-like transcriptional factors in wheat: structural and functional organization of the subfamily I members.
Myc-like regulatory factors carrying the basic helix-loop-helix (bHLH) domain belong to a large superfamily of transcriptional factors (TFs) present in all eukaryotic kingdoms. In plants, the representatives of this superfamily regulate diverse biological processes including growth and development as well as response to various stresses. As members of the regulatory MBW complexes, they participate in biosynthesis of flavonoids. In wheat, only one member (TaMyc1) of the Myc-like TFs family has been studied, while structural and functional organization of further members remained uncharacterized. From two Myc-subfamilies described recently in the genomes of Triticeae tribe species, we investigated thoroughly the members of the subfamily I which includes the TaMyc1 gene. Comparison of the promoter regions of the Myc subfamily I members in wheat suggested their division into two groups (likely homoeologous sets): TaMyc-1 (TaMyc-A1/TaMyc1, TaMyc-B1, TaMyc-D1) and TaMyc-2 (TaMyc-A2 and TaMyc-D2). It was demonstrated that the TaMyc-D1 copy has lost its functionality due to the frame shift mutation. The study of functional features of the other four copies suggested some of them to be involved in the biosynthesis of anthocyanins. In particular, TaMyc-B1 is assumed to be a co-regulator of the gene TaC1-A1 (encoding R2R3-Myb factor) in the MBW regulatory complex activating anthocyanin synthesis in wheat coleoptile. The mRNA levels of the TaMyc-A1, TaMyc-B1, TaMyc-A2 and TaMyc-D2 genes increased significantly in wheat seedlings exposed to osmotic stress. Salinity stress induced expression of TaMyc-B1 and TaMyc-A2, while TaMyc-A1 was repressed. The features of the structural and functional organization of the members of subfamily I of Myc-like TFs in wheat were determined. Myc-like co-regulator (TaMyc-B1) of anthocyanin synthesis in wheat coleoptile was described for the first time. The Myc-encoding genes presumably involved in response to drought and salinity were determined in wheat. The results obtained are important for further manipulations with Myc genes, aimed on increasing wheat adaptability.


Protein kinase CK2 activates the atypical Rio1p kinase and promotes its cell-cycle phase-dependent degradation in yeast.
Using co-immunoprecipitation combined with MS analysis, we identified the alpha' subunit of casein kinase 2 (CK2) as an interaction partner of the atypical Rio1 protein kinase in yeast. Co-purification of Rio1p with CK2 from Deltacka1 or Deltacka2 mutant extracts shows that Rio1p preferentially interacts with Cka2p in vitro. The C-terminal domain of Rio1p is essential and sufficient for this interaction. Six C-terminally located clustered serines were identified as the only CK2 sites present in Rio1p. Replacement of all six serine residues by aspartate, mimicking constitutive phosphorylation, stimulates Rio1p kinase activity about twofold in vitro compared with wild-type or the corresponding (S > A)(6) mutant proteins. Both mutant alleles (S > A)(6) or (S > D)(6) complement in vivo, however, growth of the RIO1 (S > A)(6) mutant is greatly retarded and shows a cell-cycle phenotype, whereas the behaviour of the RIO1 (S > D)(6) mutant is indistinguishable from wild-type. This suggests that phosphorylation by protein kinase CK2 leads to moderate activation of Rio1p in vivo and promotes cell proliferation. Physiological studies indicate that phosphorylation by CK2 renders the Rio1 protein kinase susceptible to proteolytic degradation at the G(1)/S transition in the cell-division cycle, whereas the non-phosphorylated version is resistant.


[Clinical study of tolerance and effectiveness of a F(ab')(2) polyvalent antienom for African snake bites in Kindia, Guinea].
An open, pragmatic, phase IV clinical trial was undertaken to measure tolerance and assess the effectiveness of Antivipmyn® Africa, antivenom composed of lyophilized F(ab')(2) fragments of immunoglobulin G in field conditions. The study was conducted at the Institut Pasteur of Guinea (IPG) from August 2009 to February 2010. Two hundred twenty-eight victims of snakebites presented at the processing center of the IPG during this period, including one hundred fifty (65.8%) envenomations, mostly young men. One hundred twenty-four of them (82.7%) suffered from viper envenomations and 26 (17.3%) from elapid ones. All patients were treated by intravenous Antivipmyn® Africa, averaging 1.4 (± 1.0) vials, more in patients with neurotoxic envenomation than others (P < 10(-5)). Four patients (2.7%), showing cobralike envenomation, died shortly after their arrival at the IPG despite the administration of the antivenom. Ten patients showed mild side effects (rash or pruritus), out of which 5 (3.3%) were probably due to treatment. This study confirms the efficacy and safety of Antivipmyn® Africa.


Nurses' experiences of managing cognitive problems in intensive care unit patients: A qualitative study.
Nurses hold a key position in identifying symptoms and initiating preventive strategies for cognitive impairment in delirious and non-delirious intensive care unit patients. However, it remains unclear whether nurses consider cognitive impairment as a distinct concern from delirium. By understanding nurses' perspectives, we may identify barriers and facilitators in caring for patients with cognitive challenges in the intensive care unit. The objective of this study was to explore nurses' experiences of cognitive problems in patients admitted to an intensive care unit. A phenomenological-hermeneutic study of interviews with ten nurses from intensive care units. Data were collected in March-April 2022 and analysed using a Ricœur-inspired method of interpretation. Three themes related to nurses' experiences of cognitive problems emerged through analysis; 1) Cognitive problems and delirium are seen as two sides of the same coin, 2) Searching for the person behind the patient, and 3) Maintaining a sense of normality in a confusing environment. The interconnected concept of cognitive impairment and delirium syndrome meant that nurses assessed and managed cognitive problems in intensive care unit patients by focusing on preventing delirium. Apart from delirium screening, nurses relied on relatives' knowledge to assess patients' cognition. Most significantly, our study revealed a previously unexplored approach by nurses to manage patients' cognition, which involved "shielding" patients from the noisy and disruptive intensive care unit environment. Effective communication methods, coupled with family involvement may aid nurses in identifying patients' cognitive problems. In the acute phase of critical illness, distinguishing between delirium and cognitive problems may not be clinically relevant, as delirium protocols may protect patients' cognition. Further investigating the concept of shielding may reveal previously unexplored nursing approaches to manage cognitive problems.


Outcomes of dura-splitting technique compared to conventional duraplasty technique in the treatment of adult Chiari I malformation: a systematic review and meta-analysis.
Chiari malformation type I is a developmental abnormality with an array of surgical techniques introduced for the management of it. The most common technique is foramen magnum decompression with duraplasty. Dura-splitting technique as one of the non-dura-opening techniques is a less known procedure that spares the internal layer of the dura and can theoretically result in fewer complications compared to duraplasty. So, we performed a review of literature and meta-analysis on different clinical and radiological aspects of this technique and compared its outcomes to duraplasty. MOOSE guidelines were followed. A systematic search of three databases based on predefined search strategy and inclusion/exclusion criteria was performed. After quality assessment and data extraction by two authors, summarized data were presented in form of tables, and meta-analysis results were illustrated in forest plots. A review of 10 included studies consisting of 370 patients revealed significantly shorter operation duration and less intraoperative blood loss in the dura-splitting technique compared to duraplasty. Interestingly, there was no significant difference between these two techniques in terms of clinical and radiological outcomes. Overall complication rate and incidence of CSF-related complications or infections were significantly in favor of the dura-splitting technique. Dura-splitting technique can be considered as a safe and effective surgical procedure for Chiari I malformation with comparable outcomes and fewer complications compared to duraplasty, although this interpretation is derived from retrospective observational studies and lack of a prospective clinical trial is evident.


Antiallergic activity of nylidrin hydrochloride (RHC 3432-A). I. Effect on release of histamine in vitro from rat peritoneal mast cells, guinea pig lung slices and human basophils.
Nylidrin (RHC 3432-A) has been investigated for its antiallergic activity in three in vitro models. Nylidrin was an effective inhibitor of IgE-mediated release of histamine from passively sensitized rat peritoneal mast cells and human basophils, and of IgG1-mediated release of histamine from passively sensitized guinea pig lung slices. The inhibition of the release of histamine by nylidrin in all three models was not antagonized by propranolol, indicating that nylidrin does not inhibit histamine release via stimulation of beta-adrenergic receptors. Isoproterenol and epinephrine were effective as inhibitors of the release of histamine only from guinea pig lung while salbutamol and terbutaline had no effect on immunologic release of histamine in all three models. Detailed comparative studies with disodium cromoglycate (DSCG) indicated that the mechanism of action of nylidrin in the rat mast cell model is different from that of DSCG.


Anaphylaxis triggers in a large tertiary care hospital in Qatar: a retrospective study.
Anaphylaxis is a serious allergic disease that may lead to death if not immediately recognized and treated. Triggers of anaphylaxis including food, drugs, and insect stings can vary widely. The incidence of anaphylaxis seems to be affected by age, sex, atopy, and geographic location. This study aims to examine the common triggers of anaphylaxis in Qatar. A total of 1068 electronic medical records were audited using power chart system: 446 from the medical coding system of anaphylaxis and 622 from the epinephrine auto-injectors (EAIs) dispensed during January 2012-December 2017. Of 1068 patients, 574 (53.5%) had anaphylaxis; male to female ratio was 1.2, and 300 patients (77.9%) were less than 10 years old. The common triggers were food (n = 316, 55.0%), insect stings (n = 161, 28.0%), and drugs (n = 103, 17.9%). Common anaphylaxis food triggers were nuts (n = 173, 30.1%), eggs (n = 89, 15.5%), and seafood (n = 72, 12.5%), and common anaphylaxis medication triggers were antibiotics (n = 49, 8.5%) and nonsteroidal anti-inflammatory drugs (n = 30, 5.2%). Interestingly, 135 anaphylactic patients (23.5%) were due to black ant stings. The anaphylaxis triggers varied significantly between children and adults. Among children (less than 10 years), three quarters of the events were triggered by food (223, 74.3%) while among adults (20-55 years), insect stings (n = 59, 43.0%) and drugs (n = 44, 32.0%) were dominant. This is the first national study stratifying anaphylaxis triggers among different age groups in Qatar. This study will serve as a guide for clinical practice in allergy clinics in Qatar and will help to assess future trends of anaphylaxis in Qatar.


Up-regulated ephrinB3/EphB3 expression in intractable temporal lobe epilepsy patients and pilocarpine induced experimental epilepsy rat model.
EphB family receptor tyrosine kinases, in cooperation with cell surface-bound ephrinB ligands, play a critical role in maintenance of dendritic spine morphogenesis, axons guidance, synaptogenesis, synaptic reorganization and plasticity in the central nervous system (CNS). However, the expression pattern of ephrinB/EphB in intractable temporal lobe epilepsy (TLE) and the underlying molecular mechanisms during epileptogenesis remain poorly understood. Here we investigated the expression pattern and cellular distribution of ephrinB/EphB in intractable TLE patients and lithium chloride-pilocarpine induced TLE rats using real-time quantitative polymerase chain reaction (RT-qPCR), immunohistochemistry, double-labeled immunofluorescence and Western blot analysis. Compared to control groups, ephrinB3 and EphB3 mRNA expression were significantly up-regulated in intractable TLE patients and TLE rats, while the mRNA expression trend of ephrinB1/2 and EphB1/2/4/6 in intractable TLE patients and TLE rats were inconsistent. Western blot analysis and semi-quantitative immunohistochemistry confirmed that ephrinB3 and EphB3 protein level were up-regulated in intractable TLE patients and TLE rats. At the same time, double-labeled immunofluorescence indicate that ephrinB3 was expressed mainly in the cytoplasm and protrusions of glia and neurons, while EphB3 was expressed mainly in the cytoplasm of neurons. Taken together, up-regulated expression of ephrinB3/EphB3 in intractable TLE patients and experimental TLE rats suggested that ephrinB3/EphB3 might be involved in the pathogenesis of TLE.


The impact of nitrogen oxides on electrochemical carbon dioxide reduction.
The electroreduction of carbon dioxide offers a promising avenue to produce valuable fuels and chemicals using greenhouse gas carbon dioxide as the carbon feedstock. Because industrial carbon dioxide point sources often contain numerous contaminants, such as nitrogen oxides, understanding the potential impact of contaminants on carbon dioxide electrolysis is crucial for practical applications. Herein, we investigate the impact of various nitrogen oxides, including nitric oxide, nitrogen dioxide, and nitrous oxide, on carbon dioxide electroreduction on three model electrocatalysts (i.e., copper, silver, and tin). We demonstrate that the presence of nitrogen oxides (up to 0.83%) in the carbon dioxide feed leads to a considerable Faradaic efficiency loss in carbon dioxide electroreduction, which is caused by the preferential electroreduction of nitrogen oxides over carbon dioxide. The primary products of nitrogen oxides electroreduction include nitrous oxide, nitrogen, hydroxylamine, and ammonia. Despite the loss in Faradaic efficiency, the electrocatalysts exhibit similar carbon dioxide reduction performances once a pure carbon dioxide feed is restored, indicating a negligible long-term impact of nitrogen oxides on the catalytic properties of the model catalysts.


Trimethylation of histone H3K4 is associated with the induction of fructose-inducible genes in rat jejunum.
We previously reported that fructose force-feeding rapidly induces jejunal Slc2a5 gene expression in rats. In this study, we conducted microarray analyses using total RNA to identify genes upregulated in rat jejunum by fructose force-feeding. Rats were force-fed fructose, glucose or distilled water for 6h. Genes such as Slc2a5, Cdkn1c, Cabp2, Ranbp3, Vwce and Gcgr were induced by force-feeding with fructose compared with glucose or distilled water. Chromatin immunoprecipitation assays revealed that trimethylation of histone H3K4, and acetylation of histones H3 and H4, on the transcribed region of these fructose-inducible genes were enhanced by force-feeding of fructose, but not glucose or distilled water. These results suggest that the induction of genes in the rat jejunum by fructose force-feeding is coordinately regulated by histone modifications, particularly trimethylation of histone H3K4.


Peripubertal suicide attempts in offspring of suicide attempters with siblings concordant for suicidal behavior.
The authors sought to determine 1) whether the risk for familial transmission of suicidal behavior is greater with increased family loading for suicide attempts, and 2) whether the transmission of suicidal behavior is mediated by impulsive aggression. A reanalysis of a high-risk study compared the offspring of three mood disorder proband groups: suicide attempters with a sibling who also attempted suicide (N=19), suicide attempters whose siblings never made a suicide attempt (N=73), and nonsuicidal probands whose siblings also never engaged in suicidal behavior (N=73). Probands and offspring were assessed with respect to psychopathology, suicide attempt history, impulsive aggression, and exposure to familial adversity. Offspring of suicide attempters with siblings concordant for suicidal behavior showed a higher risk of suicide attempt than did offspring of nonsuicidal probands and had an earlier age at onset of suicidal behavior than offspring of suicide attempters with siblings discordant for suicidal behavior. Probands from sibling pairs concordant for suicidal behavior and their offspring reported greater lifetime impulsive aggression compared with each of the other two proband/offspring groups. In the offspring, impulsive aggression was the most powerful predictor of early age at first suicide attempt. Familial loading for suicide attempts may affect rates of transmission as well as age at onset of suicidal behavior, and its effect may be mediated by the familial transmission of impulsive aggression.


Sphincteromyectomy and sphincteroplasty in chronic constipation with megarectum.
An operative procedure for patients with chronic constipation with megarectum and its results is presented. Eleven cases of idiopathic chronic constipation showing megarectum on barium enema underwent this operation. Bowel habits of operated patients were evaluated at 1 to 5 years after the operation. Complete cure was obtained in eight cases. Three cases were improved but needed occasional suppositories. This procedure, sphincteromyectomy and sphincteroplasty, may be an operation of choice for chronic constipation with megarectum, when nonoperative methods fail.


Involvement of PI 3 kinase/Akt-dependent Bad phosphorylation in Toxoplasma gondii-mediated inhibition of host cell apoptosis.
Toxoplasma gondii-infected cells are resistant to various apoptotic stimuli, however, the role of the pro-apoptotic BH3-only Bad protein in T. gondii-imposed inhibition of host cell apoptosis in connection with the phosphoinositide 3-kinase (PI3K)-PKB/Akt pathway was not well delineated. Here, we investigated the signaling patterns of Bad, Bax and PKB/Akt in T. gondii-infected and uninfected THP-1 cells treated with staurosporine (STS) or PI3K inhibitors. STS treatment, without T. gondii infection, reduced the viability of THP-1 cells in proportion to STS concentration and triggered many cellular death events such as caspase-3 and -9 activation, Bax translocation, cytochrome c release from host cell mitochondria into cytosol, and PARP cleavage in the host cell. However, T. gondii infection eliminated the STS-triggered mitochondrial apoptotic events described above. Additionally, T. gondii infection in vitro and in vivo induced the phosphorylation of PKB/Akt and Bad in a parasite-load-dependent manner which subsequently inhibited Bax translocation. The PI3K inhibitors, LY294002 and Wortmannin, both blocked parasite-induced phosphorylation of PKB/Akt and Bad. Furthermore, THP-1 cells pretreated with these PI3K inhibitors showed reduced phosphorylation of Bad in a dose-dependent manner and subsequently failed to inhibit the Bax translocation, also these cells also failed to overcome the T. gondii-imposed inhibition of host cell apoptosis. These data demonstrate that the PI3K-PKB/Akt pathway may be one of the major route for T. gondii in the prevention of host cell apoptosis and T. gondii phosphorylates the pro-apoptotic Bad protein to prevent apoptosis.


Theoretical bounds of generalization error for generalized extreme learning machine and random vector functional link network.
Ensuring the prediction accuracy of a learning algorithm on a theoretical basis is crucial and necessary for building the reliability of the learning algorithm. This paper analyzes prediction error obtained through the least square estimation in the generalized extreme learning machine (GELM), which applies the limiting behavior of the Moore-Penrose generalized inverse (M-P GI) to the output matrix of ELM. ELM is the random vector functional link (RVFL) network without direct input to output links Specifically, we analyze tail probabilities associated with upper and lower bounds to the error expressed by norms. The analysis employs the concepts of the L2 norm, the Frobenius norm, the stable rank, and the M-P GI. The coverage of theoretical analysis extends to the RVFL network. In addition, a criterion for more precise bounds of prediction errors that may give stochastically better network environments is provided. The analysis is applied to simple examples and large-size datasets to illustrate the procedure and verify the analysis and execution speed with big data. Based on this study, we can immediately obtain the upper and lower bounds of prediction errors and their associated tail probabilities through matrices calculations appearing in the GELM and RVFL. This analysis provides criteria for the reliability of the learning performance of a network in real-time and for network structure that enables obtaining better performance reliability. This analysis can be applied in various areas where the ELM and RVFL are adopted. The proposed analytical method will guide the theoretical analysis of errors occurring in DNNs, which employ a gradient descent algorithm.


Network convergence zones in the anterior midcingulate cortex.
Situated medially and centrally in the brain, the anterior midcingulate cortex (aMCC) is a nexus of control. This specialized neocortical brain region participates in large-scale brain networks underlying attention, motor, and limbic processes. The functional diversity and proximity of cognitive and affective subdivisions within this region are its distinguishing features, rendering it an effective site for integration across domains. Here we review comparative neuroanatomic, meta-analytic, and connectomic analyses contributing to the emerging picture of the aMCC as comprising functionally diverse, flexible network nodes involved in multiple regulatory behaviors. We further present data providing evidence for an organizing gradient along the anterior and midcingulate cortex and explore the implications of these findings for understanding the functional role of the anterior midcingulate within this spectrum. We conclude by highlighting open questions and proposing future directions for investigations into the functional role of this important network convergence zone.