LRRC59 Regulates Trafficking of Nucleic Acid-Sensing TLRs from the Endoplasmic Reticulum via Association with UNC93B1.
Compartmentalization of nucleic acid (NA)-sensing TLR3, 7, 8, and 9 is strictly regulated to direct optimal response against microbial infection and evade recognition of host-derived NAs. Uncoordinated 93 homolog B1 (UNC93B1) is indispensable for trafficking of NA-sensing TLRs from the endoplasmic reticulum (ER) to endosomes/lysosomes. UNC93B1 controls loading of the TLRs into COPII vesicles to exit from the ER and traffics with the TLRs in the steady state. Ligand-induced translocation also happens on NA-sensing TLRs. However, the molecular mechanism for ligand-dependent trafficking of TLRs from the ER to endosomes/lysosomes remains unclear. In this study, we demonstrated that leucine-rich repeat containing protein (LRRC) 59, an ER membrane protein, participated in trafficking of NA-sensing TLRs from the ER. Knockdown of LRRC59 reduced TLR3-, 8-, and 9-mediated, but not TLR4-mediated, signaling. Upon ligand stimulation, LRRC59 associated with UNC93B1 in a TLR-independent manner, which required signals induced by ligand internalization. Endosomal localization of endogenous TLR3 was decreased by silencing of LRRC59, suggesting that LRRC59 promotes UNC93B1-mediated translocation of NA-sensing TLRs from the ER upon infection. These findings help us understand how NA-sensing TLRs control their proper distribution in the infection/inflammatory state.


Interstitial Release of Cisplatin from Triggerable Liposomes Enhances Efficacy against Triple Negative Breast Cancer Solid Tumor Analogues.
Liposomal cisplatin, a promising triple negative breast cancer treatment modality, has been shown to decrease toxicities associated with cisplatin's free agent form. However, the heterogeneous intratumoral distributions of the liposomes themselves, combined with limited release of cisplatin from them contribute to limited penetration of cisplatin within tumors reducing efficacy. This study uses pH-responsive liposomes designed to release cisplatin within the acidic tumor interstitium (7.0 > pH ≥ 6.0) with a dual aim (1) to improve the penetration of the free drug within tumors on the assumption of greater diffusivities based on the free drug's much smaller size than its carrier's size and (2) to increase the availability of the free agent near cancer cells deep into the tumor. On cell monolayers treated with pH-releasing liposomal cisplatin, acidification of the extracellular solution resulted in decreased LD50 values, which were significantly lower than the LD50 values for non-pH-releasing liposomal cisplatin. In multicellular spheroids with acidic interstitia, pH-releasing liposomal cisplatin significantly decreased spheroid volumes relative to non-pH-releasing liposomal cisplatin. Improved efficacy was correlated with increased spheroid penetration of a fluorescent cisplatin surrogate. These findings demonstrate that interstitial release of cisplatin by pH-responsive liposomes may improve the intratumoral distributions of the free drug enhancing efficacy.


Near full-length sequence analysis of a Unique CRF01_AE/B recombinant from Kuala Lumpur, Malaysia.
A new HIV-1 circulating recombinant form (CRF), CRF33_01B, has been identified in Malaysia. Concurrently we found a unique recombinant form (URF), that is, the HIV-1 isolate 06MYKLD46, in Kuala Lumpur, Malaysia. It is composed of B or a Thai variant of the B subtype (B') and CRF01_AE. Here, we determined the near full-length genome of the isolate 06MYKLD46 and performed detailed phylogenetic and bootscanning analyses to characterize its mosaic composition and to further confirm the subtype assignments. Although the majority of the 06MYKLD46 genome is CRF01_AE, we found three short fragments of B or B' subtype inserted along the genome. These B or B' subtype regions were 716 and 335 bp, respectively, in the protease-reverse transcriptase (PR-RT) region, similar to those found in CRF33_01B, as well as an extra 590 bp in the env gene region. Thus we suggest that 06MYKLD46 is a possible second-generation HIV-1 recombinant derived from CRF33_01B.


Activation of microglial NADPH oxidase is synergistic with glial iNOS expression in inducing neuronal death: a dual-key mechanism of inflammatory neurodegeneration.
Inflammation-activated glia are seen in many CNS pathologies and may kill neurons through the release of cytotoxic mediators, such as nitric oxide from inducible NO synthase (iNOS), and possibly superoxide from NADPH oxidase (NOX). We set out to determine the relative role of these species in inducing neuronal death, and to test the dual-key hypothesis that the production of both species simultaneously is required for significant neuronal death. Primary co-cultures of cerebellar granule neurons and glia from rats were used to investigate the effect of NO (from iNOS, following lipopolysaccharide (LPS) and/or cytokine addition) or superoxide/hydrogen peroxide (from NOX, following phorbol 12-myristate 13-acetate (PMA), ATP analogue (BzATP), interleukin-1beta (IL-1beta) or arachidonic acid (AA) addition) on neuronal survival. Induction of glial iNOS caused little neuronal death. Similarly, activation of NOX alone resulted in little or no neuronal death. However, if NOX was activated (by PMA or BzATP) in the presence of iNOS (induced by LPS and interferon-gamma) then substantial delayed neuronal death occurred over 48 hours, which was prevented by inhibitors of iNOS (1400W), NOX (apocynin) or a peroxynitrite decomposer (FeTPPS). Neurons and glia were also found to stain positive for nitrotyrosine (a putative marker of peroxynitrite) only when both iNOS and NOX were simultaneously active. If NOX was activated by weak stimulators (IL-1beta, AA or the fibrillogenic prion peptide PrP106-126) in the presence of iNOS, it caused microglial proliferation and delayed neurodegeneration, which was prevented by iNOS or NOX inhibitors, a peroxynitrite decomposer or a NMDA-receptor antagonist (MK-801). These results suggest a dual-key mechanism, whereby glial iNOS or microglial NOX activation alone is relatively benign, but if activated simultaneously are synergistic in killing neurons, through generating peroxynitrite. This mechanism may mediate inflammatory neurodegeneration in response to cytokines, bacteria, ATP, arachidonate and pathological prions, in which case neurons may be protected by iNOS or NOX inhibitors, or scavengers of NO, superoxide or peroxynitrite.


A theoretical framework for determining cerebral vascular function and heterogeneity from dynamic susceptibility contrast MRI.
Mapping the complex heterogeneity of vascular tissue in the brain is important for understanding cerebrovascular disease. In this translational study, we build on previous work using vessel architectural imaging (VAI) and present a theoretical framework for determining cerebral vascular function and heterogeneity from dynamic susceptibility contrast magnetic resonance imaging (MRI). Our tissue model covers realistic structural architectures for vessel branching and orientations, as well as a range of hemodynamic scenarios for blood flow, capillary transit times and oxygenation. In a typical image voxel, our findings show that the apparent MRI relaxation rates are independent of the mean vessel orientation and that the vortex area, a VAI-based parameter, is determined by the relative oxygen saturation level and the vessel branching of the tissue. Finally, in both simulated and patient data, we show that the relative distributions of the vortex area parameter as a function of capillary transit times show unique characteristics in normal-appearing white and gray matter tissue, whereas tumour-voxels in comparison display a heterogeneous distribution. Collectively, our study presents a comprehensive framework that may serve as a roadmap for in vivo and per-voxel determination of vascular status and heterogeneity in cerebral tissue.


Bayes factor design analysis: Planning for compelling evidence.
A sizeable literature exists on the use of frequentist power analysis in the null-hypothesis significance testing (NHST) paradigm to facilitate the design of informative experiments. In contrast, there is almost no literature that discusses the design of experiments when Bayes factors (BFs) are used as a measure of evidence. Here we explore Bayes Factor Design Analysis (BFDA) as a useful tool to design studies for maximum efficiency and informativeness. We elaborate on three possible BF designs, (a) a fixed-n design, (b) an open-ended Sequential Bayes Factor (SBF) design, where researchers can test after each participant and can stop data collection whenever there is strong evidence for either [Formula: see text] or [Formula: see text], and (c) a modified SBF design that defines a maximal sample size where data collection is stopped regardless of the current state of evidence. We demonstrate how the properties of each design (i.e., expected strength of evidence, expected sample size, expected probability of misleading evidence, expected probability of weak evidence) can be evaluated using Monte Carlo simulations and equip researchers with the necessary information to compute their own Bayesian design analyses.


Nitric oxide enhances endothelin production in pancreas transplantation.
The role of endothelin and its relationship with nitric oxide (NO) production in ischemia-reperfusion associated with pancreas transplantation has been explored. For this purpose, pancreatic levels of endothelin were evaluated in an experimental model of pancreas transplantation after different periods of cold preservation. The effects of NO synthase inhibition were also evaluated. Results show posttransplantation increases in lipase and endothelin production. The release of lipase and endothelin was only prevented by NG-nitro-L-arginine methyl ester after a short ischemic period. Thus, endothelin synthesis could be a consequence of stimulation with NO in the ischemia-reperfusion associated with pancreas transplantation.


Effect of initial body mass index on survival outcome of patients with myelodysplastic syndrome: a single-center retrospective study.
Multiple studies have associated elevated body mass index (BMI) and increased incidence of hematologic malignancies, including myelodysplastic syndrome (MDS). The purpose of the present study was to evaluate the association between BMI at diagnosis and overall survival (OS) in a retrospective cohort of 92 patients with MDS. The median age at diagnosis was 63 (14-84) years. The median BMI was 22.75 (15.94-34.26) kg/m2. Eleven (12.0%) patients were underweight, 64 (69.6%) were normal weight, 17 (18.5%) were overweight or obese. Three-year OS rates differed significantly when the three BMI groups were compared (p = .0449). Multivariate Cox regression analysis indicated that normal weight (versus underweight) had a marginally significant effect on OS (hazard ratio = 0.456, p = .127), and overweight/obese (versus underweight) had a significant effect on OS (hazard ratio = 0.171, p = .015). Further investigations are required to elucidate the mechanisms responsible for this association.


[Idiopathic lung fibrosis].
Idiopathic pulmonary fibrosis (IPF), also called interstitial pneumonia or fibrosing alveolitis, is a progressive interstitial lung disease of unknown origin. Two distinct forms are known which differ in course, morphologic features and cytological findings in bronchoalveolar lavage: a cellular "desquamative interstitial pneumonia" and a hypocellular and more fibrotic "usual interstitial pneumonia". The two types appear to represent different stages of the same disease. The clinical findings in IPF are dyspnoea, unproductive cough, clubbing and rales. Pulmonary function tests reveal restriction, reduced diffusion capacity and hypoxaemia during exercise. Chest X-rays show localized linear or nodular densities usually accentuated at the lung bases; in 10% of patients with IPF, chest radiography is normal. To assess the inflammatory process bronchoalveolar lavage and transbronchial or open lung biopsy have proven necessary. Before beginning treatment the activity of the inflammatory process and degree of lung function impairment should be established. Therapy of IPF is unspecific and its aim is to suppress alveolitis and the fibrotic process. Corticosteroids are the initial therapy. If there is no improvement after two months, immunosuppressive agents are added. Regular clinical and functional follow-up is required. Course and prognosis vary in different forms of IPF. Without treatment, median survival in the cellular form is over 10 years and in the hypocellular form between 3.2 and 5.6 years. Only 12-30% of patients respond to antiinflammatory treatment.


[Anticoagulation status and adherence in patients with atrial fibrillation hospitalized for ACS and the impact on 1-year prognosis: a multicenter cohort study].
Objective: For patients with atrial fibrillation (AF) complicated with acute coronary syndrome (ACS), both anticoagulant and antiplatelet therapy should be applied, but the use of anticoagulation therapy is still poor in these patients in China. The purpose of this study was to explore the status and adherence of antithrombotic therapy in AF patients with ACS and the impact on 1 year clinical outcomes. Methods: Patients with AF hospitalized for ACS were retrospectively included from 6 tertiary hospitals in China between July 2015 and December 2020. According to the use of anticoagulant drugs at discharge, patients were divided into two groups: anticoagulant treatment group and non-anticoagulant treatment group. Logistic regression model was used to analyze the main factors influencing the use of anticoagulant drugs in patients with atrial fibrillation complicated with ACS. Major adverse cardiac events (MACEs) were defined as all-cause death, non-fatal myocardial infarction or coronary revascularization, and ischemic stroke and Bleeding Academic Research Consortium (BARC) 3 bleeding events were also collected at 1 year after discharge. After propensity score matching, Cox proportional hazards models and Kaplan-Meier analysis were used to evaluate the effect of anticoagulant treatment and non-anticoagulant treatment on 1-year prognosis. The patients were divided into different groups according to whether anticoagulation was performed at discharge and follow-up, and the sensitivity of the results was analyzed. Results: A total of 664 patients were enrolled, and 273 (41.1%) were treated with anticoagulant therapy, of whom 84 (30.8%) received triple antithrombotic therapy, 91 (33.3%) received double antithrombotic therapy (single antiplatelet combined with anticoagulant), and 98 (35.9%) received single anticoagulant therapy. Three hundred and ninety-one (58.9%) patients were treated with antiplatelet therapy, including 253 (64.7%) with dual antiplatelet therapy and 138 (35.3%) with single antiplatelet therapy. After 1∶1 propensity score matching between the anticoagulant group and the non-anticoagulant group, a total of 218 pairs were matched. Multivariate logistic regression analysis showed that history of diabetes, HAS-BLED score≥3, and percutaneous coronary intervention were predictors of the absence of anticoagulant therapy, while history of ischemic stroke and persistent atrial fibrillation were predictors of anticoagulant therapy. At 1-year follow-up, 218 patients (79.9%) in the anticoagulant group continued to receive anticoagulant therapy, and 333 patients (85.2%) in the antiplatelet group continued to receive antiplatelet therapy. At 1-year follow-up, 36 MACEs events (13.2%) occurred in the anticoagulant group, and 81 MACEs events (20.7%) in the non-anticoagulant group. HR values and confidence intervals were calculated by Cox proportional risk model. Patients in the non-anticoagulant group faced a higher risk of MACEs (HR=1.802, 95%CI 1.112-2.921, P=0.017), and the risk of bleeding events was similar between the two group (HR=0.825,95%CI 0.397-1.715, P=0.607). Conclusions: History of diabetes, HAS-BLED score≥3, and percutaneous coronary intervention are independent factors for the absence of anticoagulant therapy in patients with AF complicated with ACS. The incidence of MACEs, death and myocardial infarction is lower in the anticoagulant group, and the incidence of bleeding events is similar between the two groups. The risk of bleeding and ischemia/thrombosis should be dynamically assessed during follow-up and antithrombotic regiments should be adjusted accordingly.


Effect of electrode size on impedance images of two- and three-dimensional objects.
The sensitivity of an impedance imaging system to small cylindrical inhomogeneities in two-dimensional (2-D) and three-dimensional (3-D) saline tanks was studied for different height electrodes and different height targets. Experimental results were compared with analytical models. Inhomogeneities in the 3-D tank having limited vertical extent were detected by electrodes of vertical size comparable to that of the inhomogeneity. Taller electrodes had increased sensitivity to short targets to only a limited extent. When the electrode height was more than twice that of the target, sensitivity decreased or remained the same with further increases in electrode height. The system was less sensitive to inhomogeneities in the 3-D tank than to those in the 2-D tank. The distinguishability of conductors was greater than that of insulators in the 3-D tank, and the opposite was true in the 2-D tank, consistent with an analytical result.


Protein inhibitor of activated STAT genes are differentially expressed in breast tumor tissues.
Aim: Protein inhibitor of activated STAT (PIAS) family includes transcriptional regulator proteins with SUMO E3 ligase activity. They regulate expression of several genes involved in cell proliferation, differentiation and survival. Method: We evaluated expression of PIAS1-4 genes in 54 breast cancer tissues and their paired adjacent noncancerous tissues. Results:PIAS2 and PIAS3 genes were significantly downregulated in tumoral tissues compared with adjacent noncancerous tissues. PIAS1-3 expressions were significantly lower in estrogen receptor (ER+) samples compared with ER- samples while PIAS4 had the opposite trend. PIAS3 expression was significantly higher in grade 1 samples compared with grade 2 samples. Conclusion: These findings highlight the role of PIAS genes in the pathogenesis of breast cancer and their association with determinants of response to antihormone therapies.


An anomaly within the genital system in a female Ascaris suum Goeze.
The authors describe an individual of the female Ascaris suum Goeze with a unique genital system. A female with such an anomaly was found during laboratory classes of Invertebrate Zoology at the Faculty of Biology and Environmental Protection, NCU. The specimen was about 200 mm long, and the total length of the reproductive system was 1970 mm. Further comparative analysis between unchanged and changed individuals revealed differences in the length of individual sections of the studied system, as well as in the diameter of the uterus. The described case is extremely interesting because of the phenomenon of eutely occurring in nematodes. The exact cause and mechanism of abnormalities described in Ascaris suum are not known and difficult to explain experimentally because of the extremely small number of these anomalies. Moreover, the interpretation of the anomaly is difficult because of the specific behavior and complex morphogenesis of this endoparasite.


[Effect of the beta blockader carazolol (Suacron) on parturition in sows].
It was the aim of this study to investigate the effects of the betablocker carazolol (Suacron) on the birth process of the sow. The drug occupies the betareceptors in different organs without causing the stimulation of adrenaline which induces in part the stress reactions of the organism at these receptors. During delivery the stimulation of the betareceptors of the uterus causes a relaxation of the smooth muscles and, hence, prolongs parturition. It could be illustrated that the intravenous injection of the adrenaline-antagonist carazolol (0.5 mg i.e. 1 ml Suacron/50 kg b.w.) increased the contractions of the uterus sub partu in sows. In a double-blind-trial the same dose of the beta-blocker was administered to sows intramuscularly (n = 523). The rate of deliveries lasting six hours or more was reduced (11.0% vs. 14.5%) in the treated group in comparison with the control group (n = 543) that only received a salt solution. Additionally, the beta-blocker prophylaxis led to a reduced stillbirth rate (7.1% vs. 8.3%), caused less necessity for external aid (6.1% vs. 7.8%), decreased the use of oxytocine (28.9% vs. 34.8%) and managed to diminish the occurrence of puerperal disorders (15.5% vs. 19.5%). These beneficial effects on the farrowing are significant at the 5% level and particularly apparent in sows giving birth to the first litter.


Lectin histochemical characteristics of the canine female mammary gland.
Twelve biotinylated lectins and an avidin-biotin-peroxidase method were used to detect and localize specific carbohydrate residues on formalin-fixed, paraffin-embedded female canine mammary gland sections. Histologic sections from 3 lactating and 7 nonlactating mixed-breed dogs (age 5.6 +/- 0.35 years) were incubated with Arachis hypogea agglutinin (peanut agglutinin; PNA), Concanavalia ensiformis agglutinin (conA), Dolichos biflorus agglutinin (DBA), Glycine max agglutinin (SBA), Griffonia simplicifolia agglutinin-I (GS-I), Lens culinaris agglutinin (LCA), Lycopersicon esculentum agglutinin (LEA), Phytolacca americana mitogen (pokeweed mitogen; PWM), Ricinus communis agglutinin-I and -II (RCA-I and -II), Triticum vulgaris (WGA), and Ulex europaeus agglutinin-I (UEA-I). Each lectin had a specific binding pattern, except SBA and DBA. In nonlactating glands, PNA, conA, LEA, and UEA-I stained duct cells in a linear-binding pattern, with a mean percentage of positive ducts per section of 28.7 (+/- 0.6), 65.7 (+/- 0.3), 100 (+/- 0), and 8.4 (+/- 0.2), respectively. Strong apical, lateral, basal, and cytoplasmic positivity on duct cells was seen after incubation of the sections with RCA-I, RCA-II, and WGA in all ducts. In acinar cells, the binding pattern and the staining distribution of all the lectins studied were similar to those in duct cells. However, for PNA, conA, and UEA-I, the mean percentage of positive lobules per section was 33.7 (+/- 0.9), 62 (+/- 0.5), and 10.5 (+/- 0.2), respectively. In glands from lactating dogs, conA and UEA-I did not stain. The cytoplasm of all myoepithelial cells was moderately stained with RCA-I, RCA-II, and WGA.(ABSTRACT TRUNCATED AT 250 WORDS)


One-year clinical performance of a self-etching adhesive in class V resin composites cured by two methods.
This study evaluated the clinical performance of a self-etching adhesive for resin composites over one year. Thirty pairs of restorations of Pertac II, using the adhesive Prompt L-Pop, were placed in caries-free cervical erosion/abfraction lesions without tooth preparation. One of each pair was cured using "soft-start" polymerization, while the other was polymerized with high-intensity halogen light. Restorations were clinically evaluated at baseline, six and 12 months using modified Ryge/USPHS criteria. Although no significant difference (p>0.05) was observed between the curing methods, adhesive performance was poor, with a 35% loss of restorations overall.


Infectious complications of endourological treatment of kidney stones: A meta-analysis of randomized clinical trials.
Endourological treatment is associated with a risk of postoperative febrile urinary tract infections and sepsis. The aim of this study was to review the reported rate of infectious complications in relation to the type and modality of the endourologic procedure. This systematic review was conducted in accordance with the PRISMA guidelines. Two electronic databases (PubMed and EMBASE) were searched. Out of 243 articles retrieved we included 49 studies after full-text evaluation. Random-effects meta-analysis demonstrated that retrograde intrarenal surgery (RIRS) and percutaneous nephrolithotomy (PCNL) were associated with not significantly different odds of getting fever (OR = 1.54, 95% CI: 0.99 to 2.39; p = 0.06) or sepsis (OR = 1.52, 95% CI: 0.37 to 6.20, p = 0.56). The odds of getting fever were not significantly different for mini PCNL compared to standard PCNL (OR = 1.11, 95% CI: 0.85 to 1.44; p = 0.45) and for tubeless PCNL compared to standard PCNL (OR = 1.34 95% CI: 0.61 to 2.91, p = 0.47). However, the odds for fever after PCNL with suctioning sheath were lower than the corresponding odds for standard PCNL (OR = 0.37, 95% CI: 0.20 to 0.70, p = 0.002). The odds of getting fever after PCNL with perioperative prophylaxis were not different from the corresponding odds after PCNL with perioperative prophylaxis plus a short oral antibiotic course (before or after the procedure) (OR = 1.31, 95% CI: 0.71 to 2.39, p = 0.38). The type of endourological procedure does not appear to be decisive in the onset of infectious complications, although the prevention of high intrarenal pressure during the procedure could be crucial in defining the risk of infectious complications. on behalf of U-merge Ltd. (Urology for emerging countries), London-Athens-Dubai.


Molluscum contagiosum-like lesions in lepromatous leprosy.
A 23-year old male presented with multiple, asymptomatic, raised lesions of 4 months' duration. The lesions were well demarcated. Dome-shaped papules and nodules were seen on normal looking skin; some were shiny, pearly white and umbilicated. Bilateral greater auricular, ulnar, radial cutaneous and lateral popliteal nerves were thickened. Slit skin smear from an umbilicated nodule had a BI of 6+. Biopsy showed features of lepromatous leprosy.


Current Research on the Epidemiology, Pathogenesis, and Management of Necrotizing Enterocolitis.
Despite decades of research on necrotizing enterocolitis, we still do not fully understand the pathogenesis of the disease, or how to prevent or how to treat it. However, as a result of recent significant advances in the microbiology, molecular biology, and cell biology of the intestine of preterm infants and infants with necrotizing enterocolitis, there is some hope that research into this devastating disease will yield some important translation into effective prevention, more rapid diagnosis, and novel therapies.


A mathematical analysis of an extended MHD Darcy-Forchheimer type fluid.
The presented analysis has the aim of introducing general properties of solutions to an Extended Darcy-Forchheimer flow. The Extended Darcy-Forchheimer set of equations are introduced based on mathematical principles. Firstly, the diffusion is formulated with a non-homogeneous operator, and is supported by the addition of a non-linear advection together with a non-uniform reaction term. The involved analysis is given in generalized Hilbert-Sobolev spaces to account for regularity, existence and uniqueness of solutions supported by the semi-group theory. Afterwards, oscillating patterns of Travelling wave solutions are analyzed inspired by a set of Lemmas focused on solutions instability. Based on this, the Geometric Perturbation Theory provides linearized flows for which the eigenvalues are provided in an homotopy representation, and hence, any exponential bundles of solutions by direct linear combination. In addition, a numerical exploration is developed to find exact Travelling waves profiles and to study zones where solutions are positive. It is shown that, in general, solutions are oscillating in the proximity of the null critical state. In addition, an inner region (inner as a contrast to an outer region where solutions oscillate) of positive solutions is shown to hold locally in time.


Idiopathic Intracranial Hypertension Masking as Obstructive Hydrocephalus: A Case Report.
Idiopathic intracranial hypertension (IIH) is a poorly understood phenomenon and its presentation can both mimic and co-exist with other intra-cranial processes. Accurate diagnosis is imperative as ongoing advancements in treatment can yield dramatic positive results. Here we present the case of an individual with signs and symptoms of obstructive hydrocephalus who was ultimately found to have IIH secondary to venous sinus stenosis. After correction of the venous sinus stenosis, resolution in the patient's symptoms was noted. The case highlights some of the unique considerations in approaching patients with IIH and provides a framework for review of current literature related to IIH and venous sinus stenosis.


An Interdigital Electrode Probe for Detection, Localization and Evaluation of Surface Notch-Type Damage in Metals.
Available microwave notch-type damage detection sensors are typically based on monitoring frequency shift or magnitude changes. However, frequency shift testing needs sweep-frequency data that make scanning detection becomes difficult and time-consuming. This work presents a microwave near-field nondestructive testing sensor for detecting sub-millimeter notch-type damage detection in metallic surfaces. The sensor is loaded with an interdigital electrode element in an open-ended coaxial. It is simple to fabricate and inexpensive, as it is etched on the RC4003 patch by using printed circuit board technology. The detection is achieved by monitoring changes in reflection amplitude, which is caused by perturbing the electromagnetic field around the interdigital structure. The proposed sensor was tested on a metallic plate with different defects, and the experimental results indicated that the interdigital electrode probe can determine the orientation, localization and dimension of surface notch-type damage.


Serine Protease Inhibitors in Ticks: An Overview of Their Role in Tick Biology and Tick-Borne Pathogen Transmission.
New tick and tick-borne pathogen control approaches that are both environmentally sustainable and which provide broad protection are urgently needed. Their development, however, will rely on a greater understanding of tick biology, tick-pathogen, and tick-host interactions. The recent advances in new generation technologies to study genomes, transcriptomes, and proteomes has resulted in a plethora of tick biomacromolecular studies. Among these, many enzyme inhibitors have been described, notably serine protease inhibitors (SPIs), whose importance in various tick biological processes is only just beginning to be fully appreciated. Among the multiple active substances secreted during tick feeding, SPIs have been shown to be directly involved in regulation of inflammation, blood clotting, wound healing, vasoconstriction and the modulation of host defense mechanisms. In light of these activities, several SPIs were examined and were experimentally confirmed to facilitate tick pathogen transmission. In addition, to prevent coagulation of the ingested blood meal within the tick alimentary canal, SPIs are also involved in blood digestion and nutrient extraction from the meal. The presence of SPIs in tick hemocytes and their involvement in tick innate immune defenses have also been demonstrated, as well as their implication in hemolymph coagulation and egg development. Considering the involvement of SPIs in multiple crucial aspects of tick-host-pathogen interactions, as well as in various aspects of the tick parasitic lifestyle, these molecules represent highly suitable and attractive targets for the development of effective tick control strategies. Here we review the current knowledge regarding this class of inhibitors in tick biology and tick-borne pathogen transmission, and their potential as targets for future tick control trials.


Ultrasound Stimulation of Insulin Release from Pancreatic Beta Cells as a Potential Novel Treatment for Type 2 Diabetes.
Type 2 diabetes mellitus is a complex metabolic disease that has reached epidemic proportions in the United States and around the world. This disease is characterized by loss of insulin secretion and, eventually, destruction of insulin-producing pancreatic beta cells. Controlling type 2 diabetes is often difficult as pharmacological management routinely requires complex therapy with multiple medications, and loses its effectiveness over time. The objective of this study was to explore the effectiveness of a novel, non-pharmacological approach that uses the application of ultrasound energy to augment insulin release from rat INS 832/13 beta cells. The cells were exposed to unfocused ultrasound for 5 min at a peak intensity of 1 W/cm2 and frequencies of 400 kHz, 600 kHz, 800 kHz and 1 MHz. Insulin release was measured with enzyme-linked immunosorbent assay and cell viability was assessed via the trypan blue dye exclusion test. A marked release (approximately 150 ng/106 cells, p < 0.05) of insulin was observed when beta cells were exposed to ultrasound at 400 and 600 kHz as compared with their initial control values; however, this release was accompanied by a substantial loss in cell viability. Ultrasound application at frequencies of 800 kHz resulted in 24 ng/106 cells released insulin (p < 0.05) as compared with its unstimulated base level, while retaining cell viability. Insulin release from beta cells caused by application of 800-kHz ultrasound was comparable to that reported by the secretagogue glucose, thus operating within physiological secretory capacity of these cells. Ultrasound has potential as a novel and alternative method to current approaches aimed at correcting secretory deficiencies in patients with type 2 diabetes.


Factors affecting quality of life in Hungarian adults with epilepsy: A comparison of four psychiatric instruments.
We investigated the impact of 19 factors on life quality in Hungarian patients with epilepsy. Wellbeing was evaluated by several inventories to investigate the impact of factors in more detail. A cross-sectional study was performed in 170 patients. Wellbeing was evaluated with the WHO-5 Well-being Index (WHOQOL-5), Diener Satisfaction with Life Scale (SwLS), and the Quality of Life in Epilepsy-31 Questionnaire (Qolie-31). We investigated their association with demographic characteristics, general health status, epilepsy, and its treatment. The impact of these factors on illness perception (Illness Perception Questionnaire, IPQ) was also studied. The four measures correlated highly significantly. In addition, the predictive power of factors was comparable with the four inventories as evaluated by Multiple Regression. Factors explained 52%, 41%, 63% and 46% in the variance of WHOQOL-5, SwLS, Qolie-31, and IPQ scores, respectively. However, associations with particular factors were instrument-specific. The WHOQOL-5 was associated with factors indicative of general health. SwLS scores were associated with health-related and several demographic factors. Neither showed associations with epilepsy-related factors. All four categories of factors were associated with Qolie-31 and IPQ scores. Factors had an additive impact on IPQ, but not on Qolie-31. Our findings reveal interactions between the method of life quality assessment and the factors that are identified as influencing life quality. This appears to be the first study that analyses the factors that influence illness perception in epilepsy patients, and suggests that the IPQ may become a valuable tool in epilepsy research.


Segment Based Decision Tree Induction With Continuous Valued Attributes.
A key issue in decision tree (DT) induction with continuous valued attributes is to design an effective strategy for splitting nodes. The traditional approach to solving this problem is adopting the candidate cut point (CCP) with the highest discriminative ability, which is evaluated by some frequency based heuristic measures. However, such methods ignore the class permutation of examples in the node, and they cannot distinguish the CCPs with the same or similar frequency information, thus may fail to induce a better and smaller tree. In this paper, a new concept, i.e., segment of examples, is proposed to differentiate the CCPs with same frequency information. Then, a new hybrid scheme that combines the two heuristic measures, i.e., frequency and segment, is developed for splitting DT nodes. The relationship between frequency and the expected number of segments, which is regarded as a random variable, is also given. Experimental comparisons demonstrate that the proposed scheme is not only effective to improve the generalization capability, but also valid to reduce the size of the tree.


Developing FAITHH: Methods to Develop a Faith-Based HIV Stigma-Reduction Intervention in the Rural South.
Human immunodeficiency virus (HIV) disproportionately affects Blacks/African Americans, particularly those residing in the southern United States. HIV-related stigma adversely affects strategies to successfully engage people in HIV education, prevention, and care. Interventions targeting stigma reduction are vital as additional tools to move toward improved outcomes with HIV prevention and care, consistent with national goals. Faith institutions in the South have been understudied as partners in HIV stigma-reduction efforts, and some at-risk, Black/African American communities are involved with southern faith institutions. We describe the collaborative effort with rural, southern faith leaders from various denominations to develop and pilot test Project Faith-based Anti-stigma Initiative Towards Healing HIV/AIDS (FAITHH), an HIV stigma-reduction intervention that built on strategies previously used with other nonrural, Black/African American faith communities. The eight-module intervention included educational materials, myth-busting exercises to increase accurate HIV knowledge, role-playing, activities to confront stigma, and opportunities to develop and practice delivering a sermon about HIV that included scripture-based content and guidance. Engaging faith leaders facilitated the successful tailoring of the intervention, and congregation members were willing participants in the research process in support of increased HIV awareness, prevention, and care.


Emergence and control of multidrug resistant organisms in small cities in India: a wake up call.
Urinary tract infections (UTIs) is one of the most common bacterial infections in general practice. Antimicrobial resistance in urinary pathogens, particularly the most common being Escherichia coli, is directly associated with prescribing in primary care. Diagnosis of UTI requires laboratory examination of urine sample in addition to clinical evaluation, which may lead to higher cost of treatment, but the proper treatment of the case that will lead to complete recovery with no recurrence episodes far outweigh the cost issue of microbiological investigation. Even though UTIs are a very common diagnosis, management of this condition is not consistent in general practice. This study was conducted in an effort to see the extent of presence of multi drug resistant organisms in local set up . To describe the common urine isolates observed in the small cities of India and also to test for drug resistance among them with simple manageable tests in small-scale laboratories. A retrospective review was conducted of Gram negative bacilli and Gram positive cocci isolated from the clinical urine samples collected from various hospitals and private practitioners in Shimoga City, Karnataka and Jamshedpur City, Jharkhand. The study period was between November 2011 to January 2012. A total of 788 urine samples were included in the study. It was seen that 55.8% of the total isolated organisms were multidrug resistant (MDR) in Shimoga city, Karnataka and 38.8% of the total isolated organisms were MDR in Jamshedpur city, Jharkhand. Only with the combined efforts of the local laboratories and clinicians, the looming threat of the pandrug resistant organisms in small cities can be avoided. However, more such studies are required from both clinicians and laboratory health care professionals in order to arrive at a common consensus, and uniformity can be brought about in the community regarding prescription practices.


[Predictive value of single and combined indexes in the diagnosis of sarcoidosis].
To evaluate the predictive value of single and combined indexes in the diagnosis of sarcoidosis. Eighty-eight patients suspected of having sarcoidosis were retrospectively investigated. The diagnostic predictive value of lymphocyte percentage and CD4/CD8 ratio in bronchoalveolar lavage (BAL), angiotensin converting enzyme (ACE) and their combination was evaluated by ROC curve method and Bayes' rule. Final diagnosis of sarcoidosis by biopsy was available in 59 patients (67%), 16 were males (27%), 43 were females (73%), with a mean age of (48 +/- 10) years. The diagnosis of non-sarcoidosis was available in 29 patients (33%), 12 were males (41%), 17 were females (59%), with a mean age of (49 +/- 13) years. The ROC curve area of lymphocyte percentage, CD4/CD8 ratio and ACE were 0.64, 0.74 and 0.69 respectively; CD4/CD8 ratio had the best diagnostic efficiency. The optimized cut-offs of the three single indexes, lymphocyte percentage > or = 30%, CD4/CD8 ratio > or = 4.0 and ACE > or = 40 U/L, were determined by the tangential points and coordinates of the ROC curve. The positive predictive values were 76.7%, 80.4% and 76.8% respectively; CD4/CD8 ratio had the best predictive value. The ROC curve area of the combined CD4/CD8 ratio and ACE was 0.81, and the combination of lymphocyte percentage, CD4/CD8 ratio and ACE was 0.78. They were both higher than those of the respective single indexes. The combination of CD4/CD8 ratio and ACE had the best diagnostic efficiency. On the other hand, it had the best positive predictive value of 90.5% in all the diagnostic indexes. CD4/CD8 ratio in BAL is still a useful index in the auxiliary diagnosis of sarcoidosis. The combination of CD4/CD8 ratio and ACE can improve the diagnostic efficiency and predictive value of sarcoidosis.


Hamartomas of mature cardiac myocytes.
We present two paediatric cases of a very rare, pathologically benign, and primary cardiac tumour composed of mature cardiac myocytes with disorganized cytoarchitecture called hamartoma of mature cardiac myocyte. The patients are usually asymptomatic, may have non-specific electrocardiogram findings, and rarely have associated sudden death. The clinical presentation and pathological and imaging findings of this rare tumour are discussed. Cardiac magnetic resonance imaging may help differentiate this tumour from other common differential diagnosis like cardiac fibroma and hypertrophic cardiomyopathy.


Rockets, gauges, and pendulums: applying engineering principles to cell biology.
From flight to radar to Velcro, biological form and function have inspired engineers for centuries. It is equally valuable to consider whether concepts in engineering might provide insights into core biological processes. To explore this idea, cell cycle checkpoints, biological clocks, and signaling pathways are viewed here from an engineering perspective. Engineering concepts covered include gauge error, the distinction between precision and accuracy, and the Taguchi method of robust design. Also discussed is the Pareto principle, which describes the observation that, in complex systems, a minority of the components (or inputs) are responsible for a majority of the outputs. These concepts enable engineers to manage complexity, both in system design and in operation. Thus, with new techniques and large data sets revealing ever-increasing levels of biological complexity, an engineering mindset may be particularly valuable for the study of living systems.


Use of a gamma-labeled bile acid (75SeHCAT) as a test of ileal function. Methods of improving accuracy.
The object of the present study was to improve the accuracy of measurements of ileal function obtained by abdominal scanning and fecal counting after oral administration of the gamma-labeled bile acid 75seleno-homocholic acid-taurine (75SeHCAT), as current techniques do not distinguish between retention of the bile acid within the enterohepatic circulation from retention within the colon, and are also affected by incomplete stool collection when using the fecal method. We have therefore introduced the following modifications: (a) simultaneous ingestion of 51CrCl3 as a nonabsorbable correction marker for both the abdominal scanning and fecal counting methods; and (b) the use of 75SeHCAT counts over the gallbladder area on abdominal scanning, because these counts should be independent of colonic retention. We have studied 42 subjects, including 6 healthy controls, 6 ileal resection subjects, 15 ulcerative colitis patients, and 15 patients with unresected ileal Crohn's disease. Colonic retention (0%-68% per day) caused a variable overestimate of 75SeHCAT absorption. Corrected measurements of the fecal absorption index determined by a gamma-counter and of the abdominal absorption coefficient determined by a gamma-camera correlated well with each other (r = 0.92, p less than 0.0001), providing an internal validation of the 51CrCl3 modification. The fecal absorption index could also be determined from the carmine-rich stool collection of a single day, and this also correlated well with the abdominal absorption coefficient (r = 0.81, p less than 0.0001). Gallbladder scanning alone was simpler, involving only one isotope, but it correlated less well with the fecal absorption index than did the abdominal absorption coefficient (r = -0.64, p less than 0.001).


Application of Linear Mixed-Effects Models in Human Neuroscience Research: A Comparison with Pearson Correlation in Two Auditory Electrophysiology Studies.
Neurophysiological studies are often designed to examine relationships between measures from different testing conditions, time points, or analysis techniques within the same group of participants. Appropriate statistical techniques that can take into account repeated measures and multivariate predictor variables are integral and essential to successful data analysis and interpretation. This work implements and compares conventional Pearson correlations and linear mixed-effects (LME) regression models using data from two recently published auditory electrophysiology studies. For the specific research questions in both studies, the Pearson correlation test is inappropriate for determining strengths between the behavioral responses for speech-in-noise recognition and the multiple neurophysiological measures as the neural responses across listening conditions were simply treated as independent measures. In contrast, the LME models allow a systematic approach to incorporate both fixed-effect and random-effect terms to deal with the categorical grouping factor of listening conditions, between-subject baseline differences in the multiple measures, and the correlational structure among the predictor variables. Together, the comparative data demonstrate the advantages as well as the necessity to apply mixed-effects models to properly account for the built-in relationships among the multiple predictor variables, which has important implications for proper statistical modeling and interpretation of human behavior in terms of neural correlates and biomarkers.


The Program in Medical Humanities at the University of Missouri-Kansas City School of Medicine.
The University of Missouri-Kansas City School of Medicine opened officially in 1971, offering a combined BA/MD in a six-year program. The program has a defined goal of offering humanities courses throughout the curriculum. The Sirridge Office of Medical Humanities was established in 1992, and it assumed the responsibility of developing conveniently scheduled courses in medical humanities, making more specific requirements for such courses in the medical curriculum. The goal of these courses has been to provide students a different way of looking at things by giving them insight into the ways that reading literature and writing stories helps medical students better read patient experiences. A course entitled " A Healing Art" was first offered in 1992. In 1994, The Body Image in Medicine and the Arts course was added. With the help of a Culpeper grant in 1995, five interdisciplinary undergraduate courses were created. In 1999 Medicine, LITERATURE, and Law was developed from two previous courses. Bioethics is offered as part of a series called Correlative Medicine and in a required course, Behavioral Science. The present director of the Office of Medical Humanities has resigned and at present there is a search for a replacement. A new director may decide to change some of the offerings and add new activities. The medical school remains committed to supporting the office and its programs in keeping with the goals of the original academic plan to educate safe and caring physicians.


Multifunctional Tannic Acid/Silver Nanoparticle-Based Mucoadhesive Hydrogel for Improved Local Treatment of HSV Infection: In Vitro and In Vivo Studies.
Mucoadhesive gelling systems with tannic acid modified silver nanoparticles were developed for effective treatment of herpes virus infections. To increase nanoparticle residence time after local application, semi solid formulations designed from generally regarded as safe (GRAS) excipients were investigated for their rheological and mechanical properties followed with ex vivo mucoadhesive behavior to the porcine vaginal mucosa. Particular effort was made to evaluate the activity of nanoparticle-based hydrogels toward herpes simplex virus (HSV) type 1 and 2 infection in vitro in immortal human keratinocyte cell line and in vivo using murine model of HSV-2 genital infection. The effect of infectivity was determined by real time quantitative polymerase chain reaction, plaque assay, inactivation, attachment, penetration and cell-to-cell assessments. All analyzed nanoparticle-based hydrogels exhibited pseudoplastic and thixotropic properties. Viscosity and mechanical measurements of hydrogels were found to correlate with the mucoadhesive properties. The results confirmed the ability of nanoparticle-based hydrogels to affect viral attachment, impede penetration and cell-to-cell transmission, although profound differences in the activity evoked by tested preparations toward HSV-1 and HSV-2 were noted. In addition, these findings demonstrated the in vivo potential of tannic acid modified silver nanoparticle-based hydrogels for vaginal treatment of HSV-2 genital infection.


SpatialCPie: an R/Bioconductor package for spatial transcriptomics cluster evaluation.
Technological developments in the emerging field of spatial transcriptomics have opened up an unexplored landscape where transcript information is put in a spatial context. Clustering commonly constitutes a central component in analyzing this type of data. However, deciding on the number of clusters to use and interpreting their relationships can be difficult. We introduce SpatialCPie, an R package designed to facilitate cluster evaluation for spatial transcriptomics data. SpatialCPie clusters the data at multiple resolutions. The results are visualized with pie charts that indicate the similarity between spatial regions and clusters and a cluster graph that shows the relationships between clusters at different resolutions. We demonstrate SpatialCPie on several publicly available datasets. SpatialCPie provides intuitive visualizations of cluster relationships when dealing with Spatial Transcriptomics data.


Multi-omic network analysis identified betacellulin as a novel target of omega-3 fatty acid attenuation of western diet-induced nonalcoholic steatohepatitis.
Clinical and preclinical studies established that supplementing diets with ω3 polyunsaturated fatty acids (PUFA) can reduce hepatic dysfunction in nonalcoholic steatohepatitis (NASH) but molecular underpinnings of this action were elusive. Herein, we used multi-omic network analysis that unveiled critical molecular pathways involved in ω3 PUFA effects in a preclinical mouse model of western diet induced NASH. Since NASH is a precursor of liver cancer, we also performed meta-analysis of human liver cancer transcriptomes that uncovered betacellulin as a key EGFR-binding protein upregulated in liver cancer and downregulated by ω3 PUFAs in animals and humans with NASH. We then confirmed that betacellulin acts by promoting proliferation of quiescent hepatic stellate cells, inducing transforming growth factor-β2 and increasing collagen production. When used in combination with TLR2/4 agonists, betacellulin upregulated integrins in macrophages thereby potentiating inflammation and fibrosis. Taken together, our results suggest that suppression of betacellulin is one of the key mechanisms associated with anti-inflammatory and anti-fibrotic effects of ω3 PUFA on NASH.


The use of case studies to drive bottom-up leadership in community-oriented integrated care and health promotion (COIC).
London Journal of Primary Care is supporting a collaborative network of multidisciplinary colleagues with an interest in community-oriented health care and health promotion (COIC). Case study methodology is well suited to generating knowledge from the frontline of health and social care service delivery and is a much under-developed resource. It is most effective when dealing with wicked problems, namely, the sort of complex, entangled and multi-faceted problems that successful COIC programmes must overcome. Used collaboratively, it supports effective networking across professional and community boundaries.


[Prevention of the anti-interferon effect of exogenous leukocyte interferon in children].
The preventive effect of exogenous leukocyte interferon used twice weekly at a 3-day interval in the period of an influenza epidemic as well as the effect of this preparation on the capacity of leukocytes to produce endogenous interferon were studied in young infants brought to nurseries. The observations covered 146 infants varying in ages from 11 months to 31/2 years, of them 104 infants were given interferon intranasally from an automizer (conditional experimental group) and 42 received no interferon (conditional) control group). During the period of interferon prophylaxis (5 weeks) a significant. 7-fold, reduction in the morbidity rate was observed in the group given interferon as compared to the control group. Observations in the time course showed a reduced incidence in the experimental group for a year. During the use of interferon in infants there was an increase in the capacity to produce endogenous interferon as manifested by a significant rise in titres by the end of interferon prophylaxis.


Raman Fingerprints of SARS-CoV-2 Omicron Subvariants: Molecular Roots of Virological Characteristics and Evolutionary Directions.
The latest RNA genomic mutation of SARS-CoV-2 virus, termed the Omicron variant, has generated a stream of highly contagious and antibody-resistant strains, which in turn led to classifying Omicron as a variant of concern. We systematically collected Raman spectra from six Omicron subvariants available in Japan (i.e., BA.1.18, BA.2, BA.4, BA.5, XE, and BA.2.75) and applied machine-learning algorithms to decrypt their structural characteristics at the molecular scale. Unique Raman fingerprints of sulfur-containing amino acid rotamers, RNA purines and pyrimidines, tyrosine phenol ring configurations, and secondary protein structures clearly differentiated the six Omicron subvariants. These spectral characteristics, which were linked to infectiousness, transmissibility, and propensity for immune evasion, revealed evolutionary motifs to be compared with the outputs of genomic studies. The availability of a Raman "metabolomic snapshot", which was then translated into a barcode to enable a prompt subvariant identification, opened the way to rationalize in real-time SARS-CoV-2 activity and variability. As a proof of concept, we applied the Raman barcode procedure to a nasal swab sample retrieved from a SARS-CoV-2 patient and identified its Omicron subvariant by coupling a commercially available magnetic bead technology with our newly developed Raman analyses.


Clinical characteristics, molecular profile and outcomes of myeloid sarcoma: a single institution experience over 13 years.
Myeloid sarcoma (MS) is characterized by extramedullary infiltration by immature myeloid cells. Owing to rarity of this disease, the clinical features and overall outcomes are yet to be clarified. To define clinical characteristics, epidemiology, pathologic findings, treatment options and outcomes in MS. We conducted a retrospective review of 23 patients diagnosed with MS at our institute over a period of 13 years (2002-2015). MS presented mostly as a manifestation of relapsed acute myeloid leukemia, seen in 39% of patients. Skin and subcutaneous soft tissues were the most common sites of anatomic involvement (69.5%). Ninety five percent (n = 19) were positive for classical myeloid markers with either cytochemical staining (chloracetate-esterase, MPO), flow-cytometry (CD33, CD34, CD13 and CD117), or immunohistochemistry (CD34, CD43, CD68 and lysozyme). Of these, 52% were positive for CD33 (n = 12), 35% for CD68 (n = 8), 30% for CD34 (n = 7), and 26% for lysozyme (n = 6). Cytogenetic abnormalities were seen in 63% (n = 12/19) patients on bone-marrow aspirate, with five patients displaying a complex (n = 3) or monosomal (n = 2) karyotype. Twenty seven percent patients with a normal karyotype had presence of deleterious mutations (FLT3, ASXL, STAG and JAK2) on further testing with myeloid mutation panel. The Median overall survival (OS) of the entire cohort was 15.9 months (95% CI, 7.4-24.4 months). The OS was significantly better for patients <65 years (24.6 vs. 3.4 months, p = 0.009) of age, and for those attaining a complete remission (CR) to induction therapy (25.7 vs. 0.8 months, p < 0.001). All patients who underwent allogeneic hematopoietic stem cell transplant attained long-term remissions, with a median follow-up of 54 (range 32-120) months. Failure to achieve CR with induction therapy, and age >65 years are associated with poor outcomes in MS. Allogeneic stem-cell transplant in first remission appears to be the most effective modality for achieving long-term remissions.


d-Glucosamine as the Green Ligand for Cu(I)-Catalyzed Regio- and Stereoselective Domino Synthesis of (Z)-3-Methyleneisoindoline-1-ones and (E)-N-Aryl-4H-thiochromen-4-imines.
d-Glucosamine, a natural, inexpensive, and conveniently accessible sugar, has been explored as an efficient ligand for the Cu(I)-catalyzed regio- and stereoselective synthesis of an array of (Z)-3-methyleneisoindoline-1-ones and (E)-N-aryl-4H-thiochromen-4-imines in good-to-excellent yield in a tandem fashion via the reaction of 2-halobenzamide and 2-halobenzothioamide with terminal alkynes, respectively. The water solubility and biocompatible nature of the ligand offer easy separation of the catalytic system toward the aqueous phase as well as change in the reaction path in terms of the product also demonstrated the variation of the reaction temperature. The domino reaction proceeds by the Sonogashira and Ullmann type cross-coupling reaction, followed by Cu(I)-promoted additive cyclization of heteroatom to the triple bond. In addition, d-glucosamine causes successful Glaser-Hay coupling of terminal alkynes under Cu catalysis to produce a high yield of respective 1,3-diynes.


Negative affect and alcohol craving in trauma-exposed young adult drinkers.
Clinical research indicates that successful posttraumatic stress disorder (PTSD) treatment does not lead to improvements in alcohol use outcomes in comorbid PTSD and alcohol use disorder (AUD). Emerging theory suggests that treating PTSD may not disrupt an association between negative affect and alcohol craving, which underlies negative reinforcement drinking. The goal of the current study was to determine the respective influences of PTSD symptoms, coping motives, and negative affect on trauma and alcohol cue reactivity to inform theoretical models of co-occurring PTSD and AUD. The sample consisted of 189 young adults (50.3% women; 49.2% current PTSD; 84.0% current AUD) who endorsed interpersonal trauma (e.g., sexual/physical assault) and current weekly alcohol use. Participants completed a trauma and alcohol cue reactivity assessment, in which subjective (e.g., craving, affect) and physiological (i.e., salivation) measures were recorded in response to 4 narrative (i.e., personalized trauma or standard neutral) and in vivo beverage (i.e., personalized alcohol or water) cue combinations. Forward-fitted linear mixed-effects (LME) models confirmed that trauma cue-elicited craving was elevated among those high but not low in PTSD symptoms, consistent with prior research and theory. Trauma cue-elicited craving was fully explained by increases in negative affect, with no evidence of a direct effect of trauma cue on craving. PTSD symptoms moderated an association between trauma cue and negative affect (but not negative affect and craving), and coping motives for alcohol moderated an association between negative affect and craving (but not trauma cue and negative affect). This study provides novel laboratory evidence for the respective contributions of negative affect, PTSD symptoms, and coping motives on alcohol craving in trauma-exposed drinkers. It offers a methodological framework in which to evaluate novel strategies that aim to disrupt negative reinforcement drinking in individuals with co-occurring PTSD and AUD.


Multiplex one-step Real-time PCR by Taqman-MGB method for rapid detection of pan and H5 subtype avian influenza viruses.
Avian influenza virus (AIV) can infect a variety of avian species and mammals, leading to severe economic losses in poultry industry and posing a substantial threat to public health. Currently, traditional virus isolation and identification is inadequate for the early diagnosis because of its labor-intensive and time-consuming features. Real-time RT-PCR (RRT-PCR) is an ideal method for the detection of AIV since it is highly specific, sensitive and rapid. In addition, as the new quencher MGB is used in RRT-PCR, it only needs shorter probe and helps the binding of target gene and probe. In this study, a pan-AIV RRT-PCR for the detection of all AIVs and H5-AIV RRT-PCR for detection of H5 AIV based on NP gene of AIV and HA gene of H5 AIV were successfully established using Taqman-MGB method. We tested 14 AIV strains in total and the results showed that the pan-AIV RRT-PCR can detect AIV of various HA subtypes and the H5-AIV RRT-PCR can detect H5 AIV circulating in poultry in China in recent three years, including H5 viruses of clade 7.2, clade 126.96.36.199 and clade 22.214.171.124. Furthermore, the multiplex detection limit for pan-AIV and H5-AIV RRT-PCR was 5 copies per reaction. When this multiplex method was applied in the detection of experimental and live poultry market samples, the detection rates of pan-AIV and H5 AIV in RRT-PCR were both higher than the routine virus isolation method with embryonated chicken eggs. The multiplex RRT-PCR method established in our study showed high sensitivity, reproducibility and specificity, suggesting the promising application of our method for surveillance of both pan AIV and prevalent H5 AIV in live poultry markets and clinical samples.


[Dibenzyl trisulfide inhibits proliferation and induces apoptosis of HN30 cells via Akt/ p53 signaling pathway].
To explore the effect of dibenzyl trisulfide (DTS) on cell proliferation and apoptosis in human head and neck squamous cell carcinoma (HNSCC) HN30 cells. The effects of DTS on proliferation of HNSCC cell lines HN30, HN12, and SCC25 were examined by assessing colony formation ability of the treated cells. The effect of different concentrations of DTS on viability of HN30 cells was assessed using MTT assay. HN30 cells were treated with 3, 10, or 30 μmol/L DTS for 24 h, and the cell apoptosis and mitochondrial membrane potential (MMP) were detected using flow cytometry with annexin Ⅴ-FITC/PI double staining and JC-1 fluorescent probe staining. Western blotting was performed to determine the protein expressions of caspase-3, cleaved caspase-3 and Bcl-2 in the treated cells. The phosphorylation levels of Akt and p53 in HN30 cells were detected using Western blotting after treatment with 10 μmol/L DTS for 0.5, 1, 2, 4, 8, or 16 h. DTS at 1 μmol/L significantly inhibited the proliferation of HN30, HN12 and SCC25 cells as shown by colony formation assay. MTT assay showed that DTS dose-dependently decreased HN30 cell viability as compared with the solvent control group, and 100 μmol/L DTS produced the strongest inhibitory effect (P < 0.0001). Treatment with DTS below 30 μmol/L concentrationdependently promoted apoptosis (P < 0.01) and lowered the MMP (P < 0.01) of HN30 cells, and after treatment for 24 h, the cells showed significantly increased cleaved caspase-3 (P < 0.01) and decreased Bcl-2 expression (P < 0.01). Treatment with 10 μmol/L DTS for 16 h significantly inhibited Akt phosphorylation (P < 0.001) and enhanced p53 phosphorylation (P < 0.01) in HN30 cells. DTS inhibits proliferation and induces apoptosis of HN30 cells possibly through mechanisms involving the inhibition of Akt and the activation of p53.


Chemical modification of wheat protein-based natural polymers: cross-linking effect on mechanical properties and phase structures.
Chemical modification of wheat protein-based natural polymer materials was conducted using glyoxal as cross-linker, and the cross-linking effect was studied on mechanical properties under different humidity conditions, the molecular motions of each component, and the phase structures/components of the whole materials. The cross-linking significantly enhanced the mechanical strength of wheat gluten (WG) materials under RH = 50%. The elongation of materials was also increased, which was in contrast to many cross-linked protein systems. The reaction mainly occurred in proteins and starch components, resulting in the formation of a stable cross-linked network with restricted molecular motions and modified motional dynamics. Although the plasticizer glycerol could also take part in the reaction with glyoxal or other components in WG especially when the glyoxal content was higher, the amount of glycerol involved in such reactions was very little. Glycerol was predominantly hydrogen-bonded with the network. The lipid component did not seem to take part in the cross-linking reaction; its mobility was promoted while its interaction with the protein-starch network was weakened after cross-linking. The formation of the cross-linked network did not enhance the hydrophobicity of the materials; the materials still adsorbed a high level of moisture under high humidity conditions (ca. RH = 85%) with no improvement in mechanical strength. In addition, further increasing the amount of glyoxal did not generate an additional strength improvement even at RH = 50%, possibly because the enhanced mobility of lipid promoted the component to be phase-separated from the WG system. To improve the water-resistant properties, the hydrophobicity of the protein macromolecules requires enhancement by other chemical modifications.


[Non small-cell bronchial cancers: toxicity of the association radiotherapy-chemotherapy. Review of the literature].
Radiation therapy is the elective treatment of inoperable non small cell lung cancer, but is potentially curative only for a few of them: failures result from distant metastases and/or from progressive local disease. During the last years, following the progress in chemotherapy, combining radiation and drugs is becoming a more common approach. Nevertheless, one of the main concerns remains the potential interference between both modalities leading to an increased toxicity, which may outweigh all potential benefit. Several organs can be a target for acute or late toxicity: lung (pneumonitis and fibrosis), esophagus (acute esophagitis, stenosis), heart (pericarditis, impaired ventricular functions, heart failure, coronary stenosis), spinal cord (transient myelopathy, radiation myelitis), skin (moist desquamation, fibrosis, telangiectasia). The current published trials combining drug and radiation appear to be a rather safe approach especially when avoiding concomitant treatment. However, several points remain unsolved: the optimal combination scheme, the real risk of late damage observation including the second cancer occurrence risk. This risk is uneasy to evaluate due to the long latency period. The way of describing the late damage is crucial, seeking for a more precise system of evaluating, recording and reporting late effects, taking into account objective damage as well as the patient's symptoms. Therefore, combining drug and radiation should preferentially be performed within prospective studies, with precise evaluation procedures.


Modelling artificial sea salt emission in large eddy simulations.
We study the dispersion of sea salt particles from artificially injected sea spray at a cloud-resolving scale. Understanding of how different aerosol processes affect particle dispersion is crucial when designing emission sources for marine cloud brightening. Compared with previous studies, we include for the first time an explicit treatment of aerosol water, which takes into account condensation, evaporation and their effect on ambient temperature. This enables us to capture the negative buoyancy caused by water evaporation from aerosols. Additionally, we use a higher model resolution to capture aerosol loss through coagulation near the source point. We find that, with a seawater flux of 15 kg s(-1), the cooling due to evaporation can be as much as 1.4 K, causing a delay in particle dispersion of 10-20 min. This delay enhances particle scavenging by a factor of 1.14 compared with simulations without aerosol water. We further show that both cooling and particle dispersion depend on the model resolution, with a maximum particle scavenging efficiency of 20% within 5 h after emission at maximum resolution of 50 m. Based on these results, we suggest further regional high-resolution studies which model several injection periods over several weeks.


Innovative therapies for prostate cancer treatment.
Androgen ablation is effective therapy for metastatic prostate cancer, but the majority of men eventually become refractory to this intervention. Cytotoxic chemotherapy offers palliation to symptomatic patients with hormone-refractory prostate cancer (HRPC); however, no chemotherapy regimen has yet been shown to prolong survival. There is a clear need for new agents and drug targets for the treatment of HRPC. A number of innovative therapeutic approaches that are rationally based and target driven are under investigation. This article reviews the development of antisense oligonucleotides that inhibit the anti-apoptotic bcL-2 protein. Approaches that target the epidermal growth factor receptor, the platelet derived growth factor receptor, and nuclear factor kappa-B are also discussed. There is much expectation that these therapies alone or in combination with cytotoxic chemotherapy will impact the clinical outcome of patients with HRPC.


[A case of cancer in the dilated jejunal pouch after total gastrectomy].
We report a case of cancer in the dilated jejunal pouch after total gastrectomy, in which we resected the jejunal pouch. The patient was a man in his 60s and had a history of total gastrectomy with jejunal pouch ρ-interposition for mucosa-associated lymphoid tissue (MALT) lymphoma in 1994. In late July 2012, he presented to the emergency department with a protracted ileus-like symptom and was admitted to the gastroenterological department after the diagnosis of a dilated jejunal pouch. He was managed conservatively; however, the same symptom recurred. Examinations showed a duodenal carcinoma and cancer in the jejunal pouch; therefore, he was referred for digestive surgery in early August. Endoscopic mucosal resection( EMR) was performed on the duodenal carcinoma, and we resected the jejunal pouch with Roux-en-Y reconstruction for the jejunal cancer. He recovered from postoperative wound infection and was discharged 15 days after the second operation.


[Conformational regulation of amyloid beta-peptide by lipid membranes and metal ions].
Conformational transition of monomeric amyloid beta-peptide (Abeta) to a self-associated beta-sheet structure is considered to be an initial step in the development of Alzheimer's disease. Several lines of evidence suggest that physiologically abundant lipid membranes and metal ions are involved in this step. We have demonstrated that Abeta binds to the phosphatidylcholine membrane in the lamellar gel phase but not in the liquid crystalline phase by using fluorescence and circular dichroism spectroscopy. The membrane-bound Abeta molecule takes alpha-helical or beta-sheet structure depending on the temperature. Tightly packed phosphatidylcholine membranes appear to serve as a platform for non-electrostatic binding and self-association of Abeta. We have also examined Zn(II) and Cu(II) binding modes of Abeta by Raman spectroscopy. The Raman spectra demonstrate that three histidine residues in the N-terminal region of Abeta provide primary metal binding sites. Zn(II) binds to the N(tau) atom of histidine and the peptide aggregates through intermolecular His-Zn-His bridges. In contrast, Cu(II) ion is chelated by the N(pi) atom of histidine and deprotonated main-chain amide nitrogens to form a soluble complex. Our findings on the conformational regulation of Abeta may help in better understanding the molecular basis for the development of Alzheimer's disease.


Impairment of the oral stereognosis in the partial anterior open bite.
The study was performed in 20 children with partial anterior open bite and in 20 children of a control group. Stereognosis was evaluated on the basis of correct recognition responses to silicone pieces of the different shapes. Pieces were put on the dorsal surface of the tongue close to its apex. It was evident that the stereognostic ability was impaired in children with anterior open bite. This ability also decreased after infiltration anaesthesia of the tongue. The study indicated that the tongue plays an important role in oral stereognosis.


Intravascular-ultrasound-guided percutaneous transluminal coronary angioplasty/provisional stent implantation strategy: impact on long-term clinical follow-up.
Two hundred and eighty-four consecutive patients with 438 native coronary artery stenoses were enrolled prospectively in a study of intravascular ultrasound (IVUS)-guided percutaneous transluminal coronary angioplasty (PTCA) with provisional stenting: (1) aggressive lesion-site media-to-media balloon-sizing; (2) IVUS-assessment of residual lumen dimensions to identify optimal PTCA results (minimum lumen area = 65% of the average of the proximal and distal reference lumen areas or = 6.0 mm(2) and no major dissection); and (3) liberal stent crossover. Overall, 206 stenoses in 134 patients (47%) were treated with PTCA alone. Reasons for crossover were flow-limiting or lumen-compromising dissections in 28% of patients and suboptimal IVUS minimum lumen area in 72% of patients. At one year, 8% of stenoses in the PTCA group and 16% in the stent crossover group required revascularization. In approximately half of the patients treated using an IVUS-guided aggressive PTCA strategy, stent implantation could be avoided without sacrificing an increase in acute complications or worse clinical outcome.


[Control of morphogenesis of woody plant by gravity on earth].
Using the weeping branch of Japanese flowering cherry tree and its woody stem of the seedling grown under simulated microgravity condition by three dimensional clinostat, it was elucidated that the morphogenesis of its secondary xylem supporting the plant itself to grow upward is seriously controlled by gravity on earth with a sedimentable amyloplast as its sensor. Space experiment of woody plant is expected to elucidate such problem.


Bone densitometry with L125 in the study of uraemic osteropathy: semeiological signifiance and limitations.
Bone densitometry using I125 is a very easy method of investigation; it may be used repeatedly and simultaneously at different bone levels without distress to patients. The problems involved were those of the value, semeiological significance and possible limitations of this method in the investigation of uraemic osteopathy. These problems were solved successfully in tests carried out on 87 patients of both sexes suffering from various degrees of chronic nephropathy and on chronic haemodialysis patients. The method is reliable: reproducibility tests in normal and uraemic subjects were satisfactory; the indexes remain constant, usually in normal subjects. The parameters are "Bone Mineral Content" and "Bone Index". Trabecular bone is more sensitive than cortical bone, although comparisons between the two types of bone produce interesting data. There are difference dependent on sex. The method which is more sensitive than others enables: 1) Normal and nephropathic subjects, to be distinguished from one another. The latter generally show a lower mineral content and bone index (clinical picture of osteomalacia, osteoporosis, hyperparathyroidism) seldom a higher or a normal one. 2) The same bone sites to be examined over a given period. 3) Treatment of patients to be monitored.


Traumatic third nerve palsy.
Twenty patients with a traumatic third nerve palsy had sustained a closed head injury with prolonged loss of consciousness in a high-speed deceleration accident. Sixteen were male, and the average age was 25 years. Seven had skull or facial fractures, 15 damage to the anterior visual pathways, and 16 other permanent neurological damage. Nineteen developed the misdirection/regeneration syndrome. Thirteen had strabismus surgery, and an area of binocular single vision was enlarged or achieved in three.


Severe sinus bradycardia in a patient with Rett syndrome: a new cause for a pause?
Rett syndrome is a progressive disorder seen primarily in young females. It is characterized by autonomic dysfunction affecting many organ systems. Although sudden death is common in these patients, little is known about the cardiovascular manifestations of this dysautonomia. Earlier reports focused on the role of sympathetic overactivity manifest as reduced heart rate variability and prolonged QT intervals indicating a propensity for lethal ventricular arrhythmias. Bradyarrhthmias and sinus node dysfunction, however, have not previously been reported. We describe a 2-year-old with Rett syndrome and severe sinus bradycardia requiring a pacemaker implant. This case represents the first description of a new cardiovascular manifestation of Rett syndrome and may provide an explanation for sudden and unexpected death in some of these patients.


Structural insight into a novel human CCR5-V130I variant associated with resistance to HIV-1 infection.
We report the identification of a novel CC chemokine receptor 5 (CCR5) variant that seems associated with resistance to HIV-1 infection. The V130I mutation of the CCR5 receptor is located in the intracellular loop ICL2 known as DRY box and described in the literature as a nonsynonymous mutation present in nonhuman primates group. Extensive molecular modeling and dynamics simulations were performed to elucidate the mechanism by which the V130I mutation may induce conformational change of the CCR5 folding protein and prevent the interaction with the β-arrestin protein. Our study provides new mechanistic insight into how a specific mutation in the regulatory domain of CCR5 might alter the structural folding of the DRY box and the possible ICL2 loop binding with the β-arrestin protein, as described in our previous computational study. The results from our large-scale simulations complement recent experimental results and clinical features and offer useful insights into the mechanism behind CCR5 protein folding and signal transduction. In order for HIV, the entry of the virus to the cells must fuse with the CCR5 receptor that sits on the surface of T-helper immune cells. The described V130I mutation in the gene encoding the CCR5 protein may results in a defective CCR5-Arrestin binding complex that blocks entry of the virus.


[Autologous transfusion in obstetrics and fetal safety].
It is common knowledge that for modern medicine transfusion therapy represents a precious resource and an often mandatory option. It is equally known that autohemotransfusion (or autologous transfusion) provides further advantages: certainty of blood availability when necessary, absence of transfusion reactions, elimination of the risk of infections that is still associated with the traditional homologous transfusions. In its most widespread application, autotransfusion provides for the donation of one or more units of autologous blood, mostly before elective surgery. Even in obstetrics the practice of autologous blood donation with the aim of autotransfusion is finding increasing employment. However, there are still controversial aspects and the need is pointed out for more authoritative verifications as refers to the alleged innocuity to the fetus of acute maternal blood loss. The present study was performed to contribute personal experience to a better definition of the possible interactions between autologous blood donation during pregnancy and unborn child welfare. To this end, 80 term pregnant women underwent fetal heart rate electronic monitoring before, during and after the donation of one unit of autologous blood. Both during and after the phlebotomy there were no cardiotocographic signs of fetal hypo-oxygenation. Even the non stress tests performed at a distance of 24 hours and those that were periodically repeated afterwards were normal, confirming the safety of autologous predonation during pregnancy. However, the authors think that in obstetrics it is still premature to consider the experimental phase of autotransfusion as definitively exhausted.


Development of QSAR-Improved Statistical Potential for the Structure-Based Analysis of ProteinPeptide Binding Affinities.
Proteinpeptide interactions have recently been found to play an essential role in constructing intracellular signaling networks. Understanding the molecular mechanism of such interactions and identification of the interacting partners would be of great value for developing peptide therapeutics against many severe diseases such as cancer. In this study, we describe a structure-based, general-purpose strategy for fast and reliably predicting proteinpeptide binding affinities. This strategy combines unsupervised knowledge-based statistical potential derived from 505 interfacially diverse, non-redundant proteinpeptide complex structures and supervised quantitative structure-activity relationship (QSAR) modeling trained by 250 proteinpeptide interactions with known structure and affinity data. The built partial least squares (PLS) model is confirmed to have high stability and predictive power by using internal 5-fold cross-validation and rigorous Monte Carlo cross-validation (MCCV). The model is further employed to analyze two large groups of HLA- and SH3-binding peptides based upon computationally modeled structures. Satisfactorily, although the PLS model is originally trained with dissociation constants (Kd ) of proteinpeptide binding, it shows a good correlation with other two affinity qualities, i.e. SPOT signal intensities (BLU) and half maximal competitive concentrations (IC50 ). Furthermore, we perform systematic comparisons of our method with several widely used, representative affinity predictors, including molecular mechanics-based MM-PB/SA, knowledge-based DFIRE and docking score HADDOCK, on a small panel of elaborately selected proteinpeptide systems. It is demonstrated that (i) the QSAR-improved statistical potential exhibits a comparable predictive performance with but can work faster than these traditional methods, and (ii) the crystal structure-derived statistical potential also supports the modeled and solution structures of proteinpeptide complexes. We expect that this hybrid method can be exploited as a new scoring tool to facilitate, for example, peptide docking and virtual screening.


Higher-order structure formation using refined monomer structures of lipid raft markers, Stomatin, Prohibitin, Flotillin, and HflK/C-related proteins.
Currently, information on the higher-order structure of Stomatin, Prohibitin, Flotillin, and HflK/C (SPFH)-domain proteins is limited. Briefly, the coordinate information (Refined PH1511.pdb) of the stomatin ortholog, PH1511 monomer, was obtained using the artificial intelligence, ColabFold: AlphaFold2. Thereafter, the 24mer homo-oligomer structure of PH1511 was constructed using the superposing method, with HflK/C and FtsH (KCF complex) as templates. The 9mer-12mer homo-oligomer structures of PH1511 were also constructed using the ab initio docking method, with the GalaxyHomomer server for artificiality elimination. The features and functional validity of the higher-order structures were discussed. The coordinate information (Refined PH1510.pdb) of the membrane protease PH1510 monomer, which specifically cleaves the C-terminal hydrophobic region of PH1511, was obtained. Thereafter, the PH1510 12mer structure was constructed by superposing 12 molecules of the Refined PH1510.pdb monomer onto a 1510-C prism-like 12mer structure formed along the crystallographic threefold helical axis. The 12mer PH1510 (prism) structure revealed the spatial arrangement of membrane-spanning regions between the 1510-N and 1510-C domains within the membrane tube complex. Based on these refined 3D homo-oligomeric structures, the substrate recognition mechanism of the membrane protease was investigated. These refined 3D homo-oligomer structures are provided via PDB files as Supplementary data and can be used for further reference.


Fatal attraction in glycolysis: how Saccharomyces cerevisiae manages sudden transitions to high glucose.
In the model eukaryote Saccharomyces cerevisiae, it has long been known that a functional trehalose pathway is indispensable for transitions to high glucose conditions. Upon addition of glucose, cells with a defect in trehalose 6-phosphate synthase (Tps1), the first committed step in the trehalose pathway, display what we have termed an imbalanced glycolytic state; in this state the flux through the upper part of glycolysis outpaces that through the lower part of glycolysis. As a consequence, the intermediate fructose 1,6-bisphosphate (FBP) accumulates at low concentrations of ATP and inorganic phosphate (Pi). Despite significant research efforts, a satisfactory understanding of the regulatory role that trehalose metabolism plays during such transitions has remained infamously unresolved. In a recent study, we demonstrate that the startup of glycolysis exhibits two dynamic fates: a proper, functional, steady state or the imbalanced state described above. Both states are stable, attracting states, and the probability distribution of initial states determines the fate of a yeast cell exposed to glucose. Trehalose metabolism steers the dynamics of glycolysis towards the proper functional state through its ATP hydrolysis activity; a mechanism that ensures that the demand and supply of ATP is balanced with Pi availability under dynamic conditions. [van Heerden et al. Science (2014), DOI: 10.1126/science.1245114.].


Effects of electrochemotherapy on CaSki cells derived from a cervical squamous cell carcinoma.
Electrochemotherapy is a new approach to the treatment of tumors that takes advantage of the permeabilization of the cell membranes by electric pulses to facilitate the intracellular delivery of chemotherapeutic drugs into cells. Using the female genital squamous cell carcinoma cell line, CaSki, the antitumor effectiveness of electrochemotherapy was tested. In vitro studies showed that the cytotoxicity of some anticancer drugs, especially bleomycin, can be greatly enhanced by exposing cells to noncytotoxic electric pulses. This enhancement was significantly greater when the electric treatment was given after exposure to the drug than when applied preexposure. Treatment of nude mice bearing subcutaneous transplanted tumors with noneffective intraperitoneal doses of bleomycin followed by local delivery of electric pulses similar to those performed in vitro resulted in tumor reduction and complete disappearance after 12 days this electrochemotherapy. Histological changes in tumor tissue such as necrosis and degeneration were extensive even 6 hr after the electrochemotherapy. Thus the antitumor effects of bleomycin in mice can be considerably potentiated by local electric pulses, suggesting that electrochemotherapy with bleomycin may have promise for treatment of vulvar or ectocervical squamous cell carcinomas with early invasion.


Small-cell neuroendocrine tumor of the bladder: Unexpected long-term survival with carboplatin-etoposide therapy in a patient with metastatic stage disease.
Neuroendocrine small-cell bladder cancer is an extremely rare and aggressive entity, it constitutes <1% of all bladder malignancies. The small-cell neuroendocrine histological variant has a worse prognosis than the classical subtypes. A case of a 53-year-old female consulting with gross hematuria is presented. Cystoscopy revealed a solid aspect lesion involving the posterior wall and dome that was resected. Histopathological findings showed small-cell pure variant carcinoma, high grade, with lymph, vascular, and perineural infiltration, infiltrating the muscle layer. The extension study made by hole body computed tomography scan, showed evidence of multiple lymph nodes and multiple visceral radiological involvements, with pulmonary, hepatic, and peritoneal implants. More than 10 years later, after receiving nine cycles of carboplatin-etoposide remains in complete remission and without radiological evidence of the disease. This is, to our knowledge, one of the longest disease-free survival cases in metastatic small-cell bladder cancer published nowadays.


Renal pelvis and ureteropelvic junction incarceration in a Grynfeltt-Lesshaft hernia: a case report and review of the literature.
Grynfeltt-Lesshaft hernia is a kind of lumbar abdominal wall hernia in which clinical presentations may vary from an asymptomatic bulge in the lumbar area to a symptomatic lumbar mass with back pain. It has been accepted to be a rare entity, and incarceration of the kidney through this hernia is shown to be very rare, and very few previous cases have been reported in this regard. We present a case of renal pelvic and ureteropelvic junction incarceration in a Grynfeltt-Lesshaft hernia and provide an overview of the existing literature on it. A 76-year-old lady presented to the outpatient clinic with the chief complaint of right flank pain and swelling. Computed tomography (CT) scan of the abdomen was revealed a large herniated sac (60*30 mm) in the upper lumbar triangle with protrusion of retroperitoneal and omental fat, right renal pelvis, ureteropelvic junction and proximal ureter with consecutive hydronephrosis. Herniated retroperitoneal and omental fat was reduced, and closure of the abdominal wall defect was done using retro-muscular Mesh and was fixed to the fascia. The patient was discharged 24 h after the surgery without any complications. Kidney herniation through the lumbar triangle is extremely rare, and the diagnosis requires careful clinical evaluation. CT scan is the modality of choice for the assessment. Management through surgery should be done in symptomatic patients.


Aggressive coronary artery vasculopathy after combined heart-lung transplantation.
Combined heart-lung transplantation remains as a treatment option for patients with cardiopulmonary failure. There is speculation that lung grafts protect the heart from developing graft vasculopathy after combined heart-lung transplantation. This protective mechanism is more likely, at best, a delay in the onset of coronary artery vasculopathy. We present our experiences in two cases of an aggressive form of cardiac allograft vasculopathy after combined heart-lung transplantation that resulted in the death of both patients.


[Evaluation of the advantages of laparoscopic procedures for hysterectomy].
The objective of this publication was the analysis of 102 laparoscopic hysterectomy. The results were discussed in comparison with traditional laparotomy. There was the analysis of 102 hysterectomy by the means of laparoscopy done in 2000-2002. Following parameters were evaluated: duration of the operation, blood loss, complication, the day of introducing enteral nutrition and duration of hospitalization. It was observed, that laparoscopic operation took more time than laparotomy (average time: 96.4 min vs 62.37 min). Blood loss was similar in both procedures. Comparing the changes of hemoglobin concentration in serum before and after the procedures it was observed average change 1.75 g% for laparoscopy and 1.71 g% for laparotomy. Time introducing enteral nutrition and duration of hospitalization was shorter for laparoscopic procedures. 87.25% of patients was able to eat in next day after laparoscopic operation. Average amount of days of hospitalization after laparoscopic procedures was 3.75 days, after laparotomy 6.44 days. The infections were the most common postoperative complications. The infections were more common in laparotomy group. The new method causes: shortened time of hospitalization, quicker introducing of general diet, avoiding the large wound of abdominal segments, small amount of complications.


A process for determining content for a nurse internship program.
The purpose of this study was to determine the essential content of a surgical nurse internship program. Five groups of senior nursing students, nursing faculty, and nursing service staff ranked and weighted 68 topics separated into five categories: professional, personal, patient/family, broad clinical, and surgical nursing. Kendall's Coefficient of Concordance was used to determine the agreement within each of the nurse groups, between each two nurse groups, and among all nurses. All nurses showed a significantly high agreement in ranking topics of all five categories. The associate degree faculty was the only nurse group to have a significant agreement within the group. Of the five nurse groups, the nursing service staff had the most significant rankings with other nurse groups. Because the topics ranked are broad in context, the study is applicable to nurse internship programs of other areas and to continuing education (CE) and staff development (SD) programs for newly graduated nurses.


Benign tumours of the bronchus and trachea, 1951-1981.
A review has been made of 128 benign tumours of the bronchus seen at a Regional Thoracic Surgery Centre during the 30-year period, 1951-1981. These have included 74 cases of carcinoid tumour of the bronchus and 38 cases of hamartoma. The similarity of the histological appearances of carcinoid to oat cell carcinoma is stressed, together with its clinical implications. A 5-30-year follow-up of the cases of bronchial carcinoid shows that it is essentially a benign tumour, though late recurrence may occur. The use of the somewhat forgotten technique of a Gebauer skin graft in bronchoplastic surgery is described.


Effectiveness of interventions to increase screening for gastric and colorectal cancer in Korea.
Public health centers in Korea play an important role at the community level in encouraging residents to participate in cancer screening, usually by sending reminders in the mail and by making phone calls. However, there have not been any studies on the effectiveness of these interventions by public health centers in Korea. The purpose of this study was to evaluate this question. The study was limited to male subjects aged 50-59 years living in one district of Daegu, Korea. A total of 923 subjects were selected for the study among the target population for gastric and colorectal cancer screening as part of the National Cancer Screening Program in 2012. The subjects were randomly assigned to one of four groups: control, postal intervention, telephone intervention, and telephone and postal intervention. Three months after the interventions, the results were confirmed by the National Health Insurance Corporation. Logistic regression analyses were performed to find differences in participation rates in cancer screening for each group. Men who received telephone and postal intervention were most likely (40.5%) to undergo gastric cancer screening, in comparison to the men who received telephone intervention only (31.7%), postal intervention only (22.2%) and those in the control group (17.9%). Also, men who received telephone and postal intervention were most likely (27.8%) to participate in colorectal cancer screening, followed by the men who received telephone intervention only (24.3%), postal intervention only (16.5%), and men in the control group (13.5%). Combined telephone and postal intervention and telephone only intervention as well produced significantly increased rates of participation in cancer screening in comparison to the control group. There was no significant difference, however, between the postal intervention only and control groups for either colorectal or gastric cancer screening.