[IFL].
An IFL regimen combining irinotecan, a bolus administration of 5-fluorouracil (5-FU) and leucovorin (LV) was associated with a significantly better response rate, progression-free survival and median overall survival, compared to 5-FU/LV against metastatic colorectal cancer. Despite a favorable initial report, randomized trials have suggested that triple therapy may be more toxic (severe neutropenia, diarrhea), leading to unacceptably high rates of early treatment-related mortality. On the other hand,a survival benefit for the oxaliplatin-containing regimen (FOLFOX 4) compared to bolus IFL, has been shown from INT trial 9741, and a European trial (V 308) suggests similar efficacy for combinations of irinotecan or oxaliplatin with short-term infusional 5-FU/LV (FOLFIRI or FOLFOX 6). Overall, FOLFIRI or FOLFOX regimen is now a standard option for first-line treatment of metastatic CRC.


Using 24-h intraocular pressure-related patterns to identify open-angle glaucoma in thyroid eye disease.
Our study aims to develop a diagnostic model using 24-h intraocular pressure (IOP) patterns to differentiate between open-angle glaucoma (OAG) and dysthyroid optic neuropathy (DON) in thyroid eye disease (TED) patients with glaucoma-like symptoms. TED patients with elevated IOP, abnormal optic disc, and/or visual fields were prospectively recruited. The subjects whose symptoms were relieved by DON first-line treatments were divided into the DON group, and the subjects with previous diagnosis of OAG before TED onset were divided into the OAG group. The 24-h IOP was monitored by Tono-Pen in a sitting position during awake time and in a supine position during sleep time. All subjects were divided into a training set and a testing set. The diagnostic models were generated from training set by using either IOP curve-derived parameters or principal component (PC) factors. The discrimination ability was tested in training set based on area under curve (AUC), and the calibration ability was verified in testing set by Hosmer-Lemeshow goodness-of-fit. The sensitivity and specificity were calculated by two-by-two table with the cutoff value determined by Youden's index. Thirty-two cases were recruited in each group. The 24-h IOP curves revealed a nocturnal pattern in both groups, with the acrophase moving slightly forward in the DON group (21:00 pm-24:00 pm) compared to the OAG group (22:00 pm-3:00 am). Several IOP curve-derived parameters differed between the two groups, with larger amplitude during sleep time (P < 0.000) and longer duration of IOP ≥ 21 mmHg at awake time (P = 0.004) in the DON group than the OAG group. However, the diagnostic model generated from IOP parameters showed poor reliability (P = 0.001) in calibration test and was rejected. The other model built on PC factors achieved good performance of discrimination (AUC = 0.943) and calibration (P = 0.139) with a sensitivity of 87.50% and a specificity of 95.83% at cutoff value of 0.538 to identify OAG cases. The diagnostic model facilitates discrimination between OAG and DON in TED patients based on 24-h IOP-related patterns. This work was registered on Chinese Clinical Trial Registry (ChiCTR1900025394).


[Early complications of endoscopic retrograde cholangiopancreatography performed from January 1998 to December 2000 at the Daniel Alcides Carrion National Hospital "ELCALLAO", Peru].
The aim of this study was to determine the procedure characteristics of ERCP, indications and frequency of complications, as well as analyzing the associated risk factors. ERCPs carried out from January 1998 to December 2000 in the Gastroenterology Service of Daniel Alcides Carri n Hospital were evaluated retrospectively; 17 risk factors were analyzed. A total of 202 ERCPs were carried out in 182 patients, of which 70.3% were patients aged under 60 years and 66.5% were female patients. The most frequent indication was bile duct stone suspect (59.4%). Therapeutic ERCPs were carried out in 49.5% of total ERCPs, diagnostic ERCPs were 33.2%, and failure ERCPs 17.3%. Post-ERCP complications occurred in 5.9% (12 cases), and the most frequent were: acute pancreatitis 3.4% and hemorrhage 1%. There was no mortality case related with complications. A risk factor related with the procedure: pancreatic cannulation or pancreatic contrast injections reached the highest statistic significance (p= 0.063). Therapeutic or failed ERCPs presented significant higher frequency of complications than diagnostic ERCPs: (p=0.0085 and p=0.0381). the frequency of early post-ERCP complications is 5.9%, and has a direct relation with therapeutic or failed ERCPs. This marks a difference with regards to diagnostic ERCPs. There was no mortality, and pancreatic cannulation or pancreatic contrast injections would be able to determine the development of complications.


Photocatalytic degradation effect of malachite green and catalytic hydrogenation by UV-illuminated CeO2/CdO multilayered nanoplatelet arrays: Investigation of antifungal and antimicrobial activities.
CeO2/CdO multi-layered nanoplatelet arrays have been synthesized by sol-gel method at two different temperatures using Citrus limonum fruit extract and the effect of particle size on the photocatalytic performance is studied. The particle size and phases was analysed by X-ray diffraction pattern (XRD) which brought out the formation of cubic phase in the synthesized samples. Field Emission Scanning electron microscopy (FESEM) revealed the surface morphology and made up of cumulative form of platelet shaped arrays with an average size of 10nm. The elemental composition and the purity of the nanomaterials were confirmed by Energy Dispersive X-ray spectroscopy (EDX). CeO2/CdO multilayered binary metal oxide nanoplatelet arrays were formed which was further explored with Fourier transform infrared spectroscopy (FTIR), it reveals that the nanocomposites contain CeO and CdO bonds. Determination of the direct and indirect bandgap energy of the nanoplatelet arrays was carried out by UV-Vis-DRS studies. In MG degradation, both the hole (h+) and hydroxyl radical (OH) played a major role than the superoxide radical (O2-). Possible photo degradation mechanisms are proposed and discussed in this article. CeO2/CdO multi-layered nanoplatelet arrays showed antibacterial activity and among the tested ones, it showed better growth inhibition towards P. aeruginosa MTCC73. Thus, this greener synthetic procedure was a highly effective method due to low-cost, highly effective UV light responsive material for environmental safety.


Heteropolymetallic Architectures as Snapshots of Transmetallation Processes at Different Degrees of Transfer.
Novel heteropolymetallic architectures have been built by integrating Pd, Au and Ag systems. The dinuclear [(CNC)(PPh3 )Pd-G11 M(PPh3 )](ClO4 ) (G11 M=Au (3), Ag (4); CNC=2,6-diphenylpyridinate) and trinuclear [{(CNC)(PPh3 )Pd}2 G11 M](ClO4 ) (G11 M=Au (6), Ag (5)) complexes have been accessed or isolated. Structural and DFT characterization unveil striking interactions of one of the aryl groups of the CNC ligand(s) with the G11 M center, suggesting these complexes constitute models of transmetallation processes. Further analyses allow to qualitatively order the degree of transfer, proving that Au promotes the highest one and also that Pd systems favor higher degrees than Pt. Consistently, Energy Decomposition Analysis calculations show that the interaction energies follow the order Pd-Au > Pt-Au > Pd-Ag > Pt-Ag. All these results offer potentially useful ideas for the design of bimetallic catalytic systems.


A new type of Kazal proteinase inhibitor related to shrimp Penaeus (Litopenaeus) vannamei immunity.
A clone encoding a four-Kazal domain-containing protein was isolated from the hemostats of a Penaeus vannamei cDNA library. The full-length cDNA sequence is 975 bp in length and encodes a 24.4 kDa protein (228 residues). Four Kazal domains, each 43-46 residues in length, were detected in the deduced primary structure. The first, third and fourth domains have the CPLREELPVC, CPAVYDPVC and CPLYVDPVC motifs, respectively, suggesting that they are able to inhibit chymotrypsin and elastase. The mRNA levels of the Kazal protein were modified after the injection of Vibrio alginolyticus, indicating the probable role of this protein in the immune response. All these characteristics are similar to previously reported shrimp Kazal, however, based on both domain architecture and expression profile following Vibrio stimulation, this protein represents a new type of Kazal inhibitor associated with shrimp immunity.


The production and application of a regenerable filter system for adsorption of some atmospheric contaminants.
In this work, a new filter, used to prevent atmospherical pollution, has been developed. Spherical amorphous shaped silicates (such as KC-Siliperl AF 125 and Aluminium silicate 596 FA) were coated with different materials which were prepared from the hydrolysis-condensation products of organically modified silanes and metal alkoxides. The adsorption capacities of such silicates for different solvents; ethylacetate, toluene, n-hexane and cyclohexanone were investigated. It was found that KC-Siliperl AF 125 coated with IMEO (a commercial silane) adsorbed all the solvents better than Aluminium silicate 596 FA, and ethylacetate was adsorbed more than the other solvents.


[Antibiotic Stewardship].
The adequate management of infections is an important task in critical care medicine which has an effect on patient outcome. As a result, the prevalence of antiinfective therapy is high in intensive care units. In the face of an unsettling development of worldwide microbial resistance, an optimization and reduction of antiinfective therapy is necessary. Antibiotic stewardship tries to improve antiinfective therapy with an interdisciplinary approach. One overall objective of antibiotic stewardship is the reduction of resistance induction in order to preserve the therapeutic efficiency of antibiotics. Intensive care units are important fields of action for antibiotic stewardship interventions. This article reviews available evidence and some practical aspects for antibiotic stewardship.


Ketamine-induced rotational asymmetry in evaluation of motor disturbances in rats with middle cerebral artery occlusion.
Intraperitoneal injection of ketamine in subanesthetic doses to Wistar rats with unilateral occlusion of the middle cerebral artery caused ipsilateral rotation (2-10 rpm), which was recorded in an automatic rotameter. The optimal dose of ketamine was 50 mg/kg. The animals were examined in an automatic rotameter for 40 min. Motor asymmetry persisted for no less than 2 months after surgery. According to the neurological test (Menzies scale) motor asymmetry in animals with focal brain ischemia persisted for no more than 30 days. The degree of ketamine-induced motor asymmetry in intact rats was 0.10 0.03 rpm.


Dynamic entangled framework based on an iridium-organic unit showing reversible luminescence turn-on sensing.
A new entangled metal-organic framework shows reversible structural dynamics and luminescence changing in response to the loss of guest H2O molecules. Furthermore, an intense and sensitive luminescence turn-on sensing was observed by the naked eye for 1 upon detection of the volatile organic solvent molecule CH3CN, accompanied by reversible structural transformation.


Modelling potential human exposure to the urease inhibitor NBPT through the environment-food pathway.
The urease inhibitor N-(n-butyl) thiophosphoric triamide (NBPT) has recently attracted a lot of attention attributing to its efficiency in reducing ammonia loss from urea fertiliser applied to temperate grassland soils. Ammonia gas lost to the environment causes soil acidification, eutrophication and contributes to global warming through increased greenhouse gas emissions and ozone layer depletion. The active chemical NBPT blocks the soil microbial enzyme (urease) and reduces ammonia emission. Furthermore, NBPT's use in agriculture might benefit farmers by reducing reliance on expensive nitrate fertiliser and aiding in a shift to more urea-based fertiliser (using NBPT co-applied with urea is more cost-effective). The present study was carried out to characterise the potential transfer of NBPT from grass to liquid milk and compute the associated human health risks. Using probabilistic risk assessment techniques, an exposure assessment model was developed to calculate the Estimated Daily Intake (EDI) of NBPT from milk, following co-application of NBPT with a urea N-fertiliser. Results show that the predicted mean concentration of NBPT in milk is 2.5 × 10-8 mg NBPT/kg milk, while the mean daily intake (EDI) of NBPT is 5 × 10-11 mg NBPT /kg BW/day). Back-calculations revealed that, under the studied conditions, for the EDI to exceed ADI of 3 × 10-2 mg NBPT/kg BW/ day, the NBPT application rate would need to exceed the NBPT fertiliser limit (0.09-0.2% by mass of urea nitrogen) set in the Commission Regulation (EC) No 1107/2008, and the bio-transfer factor would need to be over 100% (implausible). Sensitivity analysis revealed soil pH (SPH), phytoaccumulation factor (PF), NBPT permissible levels in fertiliser (NBPT%), pasture cover (P), and grazing rotation length (t) as critical factors influencing the EDI of NBPT. The present study concludes that NBPT presents negligible risk to human health under the conditions and assumptions studied.


Electrophysiologic evidence of regeneration of lamprey spinal neurons.
Morphologic evidence has shown that the anteriorly projecting axons of giant interneurons (GIs) can regenerate after spinal transection in larval sea lampreys (19). In the present study, we showed that the regenerating neurites of GIs were electrically excitable. We also showed evidence for regeneration of descending afferent connections to GIs. Spinal cords were transected at the level of the cloaca. After at least 70 days recovery, GIs located 1.5 to 17.0 mm below the scar were impaled with microelectrodes. Stimulating electrodes were placed at various distances above the scar. Six of 13 GIs located 4 to 17 mm below the scar could be activated antidromically. For 1 GI, the rostralmost point of stimulation which elicited these responses was 13.5 mm above the scar. For the others, the range was 0.5 to 4.5 mm. Estimated average conduction velocity in regenerated neurites was 0.50 m/s compared with 1.94 m/s for the parent axon. Twelve GIs could be orthodromically activated by fixed-latency EPSPs. The most rostral point of stimulation that could elicit such responses was 0.5 to 8.5 mm above the scar. There was an inverse relationship between the farthest distance of stimulation and the distance of the GI from the scar. These findings are consistent with the hypothesis that regeneration of axons across a spinal transection is limited to neurons whose cell bodies are situated within 1 to 2 cm from the transection, and that regenerating neurites grow only a few millimeters beyond the scar.


Expression of cyclooxygenase-2 in prostate carcinoma.
Nonsteroidal antiinflammatory drugs inhibiting cyclooxygenase (COX) enzyme activity in both its constitutive (COX-1) and inducible (COX-2) isoforms were shown also to inhibit the development of colon carcinoma in animal models. COX-2 is an inducer of angiogenesis of new blood vessels. The expression of COX-1 and COX-2 in prostate tissues from patients with prostate carcinoma was investigated using reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry. Tumor specimens were obtained from 28 prostate carcinoma (PC) patients, 8 benign prostatic hyperplasia (BPH) patients, 1 prostatic intraepithelial neoplasia (PIN) patient, and 8 specimens of normal prostate tissue (NP). Affinity-purified COX-1 and COX-2 antibodies were used in immunochemistry. Very weak expression of COX-1 and marked expression of immunoreactive COX-2 in tumor cells was obtained. In contrast, expression of both isoforms was very weak in all cases of BPH and in the NP tissues. Immunoreactive COX-1 also was very weak in all cases of benign tissues. The extent and intensity of immunoreactive COX-2 polypeptides in tumor cells was statistically much greater than those of cells from BPH. Immunostaining with normal rabbit immunoglobulin G was completely negative. By RT-PCR analysis, enhanced expression of COX-2, but not COX-1, was observed in PC tissue. BPH displayed faint expression of COX-2. The results of the current study demonstrated that human prostate carcinoma cells generated COX-2, and that COX-2 might play an important role in the proliferation of prostate carcinoma cells. These findings suggest that inhibition of COX-2 development may lead not only to inhibition of the proliferation and metastasis of prostate carcinoma but also to the inhibition of prostate carcinogenesis.


Coronary sinus diverticulum as a cause of resistant posteroseptal pathway ablation.
Coronary sinus (CS) anomalies such as diverticulum, persistent left superior vena cava or CS ostium dilatation are predominantly found in patients with accessory pathway-related tachycardias. Diverticulum of the proximal CS found in 7-11% of patients with postero-septal or left posterior manifests accessory pathways. We reported a 28 year old gentleman with manifested postero-septal accessory pathway, who underwent repeat electrophysiological study (EPS) and radiofrequency ablation for previously failed ablation. Huge CS diverticulum was identified by angiography as a reason for resistant accessory pathway. Successful RF ablation was achieved at the neck of the diverticulum without complications. Other associated anomalies were ruled out by cardiac computerized tomography (CT) and trans-esophageal echocardiography.


Waxholm Space atlas of the Sprague Dawley rat brain.
Three-dimensional digital brain atlases represent an important new generation of neuroinformatics tools for understanding complex brain anatomy, assigning location to experimental data, and planning of experiments. We have acquired a microscopic resolution isotropic MRI and DTI atlasing template for the Sprague Dawley rat brain with 39 μm isotropic voxels for the MRI volume and 78 μm isotropic voxels for the DTI. Building on this template, we have delineated 76 major anatomical structures in the brain. Delineation criteria are provided for each structure. We have applied a spatial reference system based on internal brain landmarks according to the Waxholm Space standard, previously developed for the mouse brain, and furthermore connected this spatial reference system to the widely used stereotaxic coordinate system by identifying cranial sutures and related stereotaxic landmarks in the template using contrast given by the active staining technique applied to the tissue. With the release of the present atlasing template and anatomical delineations, we provide a new tool for spatial orientation analysis of neuroanatomical location, and planning and guidance of experimental procedures in the rat brain. The use of Waxholm Space and related infrastructures will connect the atlas to interoperable resources and services for multi-level data integration and analysis across reference spaces.


Blood and Cerebrospinal Fluid Biomarkers in Vascular Dementia and Alzheimer's Disease: A Brief Review.
The Maintenance of brain health is a lifelong process whereby potentially deleterious exposures such as cardiovascular risks, amyloid beta, and phosphorylated tau may adversely affect the brain decades before there are clinical manifestations. Thus, the early structural and neuropathological foundation for the development of cognitive impairment and its allied features later in life may provide precursor targets such that interventions may be applied to prevent or slow cognitively impairing processes if the underlying mechanism(s) can be addressed in time.


The Role of Reactive Oxygen Species in Tumor Treatment and its Impact on Bone Marrow Hematopoiesis.
Reactive oxygen species (ROS), an important molecule inducing oxidative stress in organisms, play a key role in tumorigenesis, tumor progression and recurrence. Recent findings on ROS have shown that ROS can be used to treat cancer as they accelerate the death of tumor cells. At present, pro-oxidant drugs that are intended to increase ROS levels of the tumor cells have been widely used in the clinic. However, ROS are a double-edged sword in the treatment of tumors. High levels of ROS induce not only the death of tumor cells but also oxidative damage to normal cells, especially bone marrow hemopoietic cells, which leads to bone marrow suppression and (or) other side effects, weak efficacy of tumor treatment and even threatening patients' life. How to enhance the killing effect of ROS on tumor cells while avoiding oxidative damage to the normal cells has become an urgent issue. This study is a review of the latest progress in the role of ROS-mediated programmed death in tumor treatment and prevention and treatment of oxidative damage in bone marrow induced by ROS.


Rat mast cells permeabilized with Sendai virus secrete histamine in response to Ca2+ buffered in the micromolar range.
In the presence of low extracellular Ca2+, Sendai virus generates permeability lesions in the membrane of rat mast cells. This causes leakage of intracellular phosphorylated metabolites and lactate dehydrogenase; it also permits uptake of normally impermeant aqueous solutes such as the complex of Ca2+ with N-hydroxyethylethylenediaminetriacetic acid. We have used this system to buffer the concentration of cytosol Ca2+ in the micromolar range and thus to cause release of the contents of the secretory granules such as histamine and beta-N-acetylglucosaminidase. We argue that such release occurs by a normal exocytotic secretory mechanism for the following reasons. (1) While leakage of cytosol components is progressively inhibited by Ca2+ in the range 1-10 microM, release of histamine is dependent on Ca2+ in this range. Higher concentrations of Ca2+ are inhibitory to both permeabilization and histamine release. (2) While leakage of phosphorylated metabolites is enhanced in metabolically inhibited cells and the leakage of lactate dehydrogenase is insensitive to metabolic inhibition, the release of histamine and beta-N-acetylglucosaminidase is strictly dependent on an intact metabolic process.


Presentation and outcome of purpura fulminans associated with peripheral gangrene in 12 patients at Mayo Clinic.
Dermatologists may be called to assist in the diagnosis and management of purpura fulminans. This retrospective case series details the clinical presentation and outcomes of patients presenting with purpura fulminans associated with peripheral gangrene between 1989 and 2004. All 12 patients presented with sudden onset of purpuric patches and evolving gangrene of the extremities in association with a shock syndrome (hypotension, oliguria). Eleven patients had disseminated intravascular coagulation. The cause of purpura fulminans was infectious in 9 patients, surgical in two, and cancer in one. Three patients died (25%) within a week of onset of purpura fulminans. Of the 9 surviving patients, 8 required amputation of at least one limb. Four patients required amputation of all 4 limbs. Retrospective study design, varying clinical descriptions, and potential referral bias are limitations. Purpura fulminans in association with symmetric peripheral gangrene is an ominous clinical presentation.


Role of mTOR1 signaling in the antidepressant effects of ketamine and the potential of mTORC1 activators as novel antidepressants.
Conventional antidepressant medications act on monoaminergic systems and have important limitations, including a therapeutic delay of weeks to months and low rates of efficacy. Recently, clinical findings have indicated that ketamine, a dissociative anesthetic that blocks N-methyl-d-aspartate receptor channel activity, causes rapid and long-lasting antidepressant effects. Although the exact mechanisms underlying the antidepressant effects of ketamine are not fully known, preclinical studies have demonstrated a key role for mechanistic target of rapamycin complex 1 (mTORC1) signaling and a subsequent increase in synapse formation in the medial prefrontal cortex. In this review, we discuss the role of mTORC1 and its subsequent signaling cascade in the antidepressant effects of ketamine and other compounds with glutamatergic mechanisms of action. We also present the possibility that mTORC1 signaling itself is a drug discovery target.


Multimodal analgesia reduces narcotic requirements and antiemetic rescue medication in laparoscopic Roux-en-Y gastric bypass surgery.
After bariatric surgery, patients are at risk for narcotic-related side effects. Multimodal pain management strategies should be used when possible to reduce the consumption of narcotic medication. The purpose of this study was to investigate whether multimodal analgesia reduces narcotic consumption and may have an influence on opioid-related side effects in patients undergoing laparoscopic Roux-en-Y gastric bypass surgery (LRYGB). In this retrospective data analysis, we examined the data of a total of 181 consecutive patients undergoing LRYGB. In January 2011, i.v. acetaminophen became clinically available. Hydromorphone patient controlled analgesia (PCA) was replaced by i.v. acetaminophen and i.v. ketorolac (TNT-Tylenol and Toradol). The first 89 patients received postoperative hydromorphone PCA (PCA group). The next 92 patients received i.v. acetaminophen and i.v. ketorolac every 6 hours for the first 24 hours (TNT group). In the TNT group, 8 patients were excluded in the analysis. There were no differences in clinical characteristics between the groups except for smoking history. Patients treated with PCA required 4.2 mg hydromorphone in the postoperative period. Patients in the TNT group required 1.1 mg hydromorphone. This was a statistically significant reduction of opioids by 73.8%. After discharge from postanesthesia care unit, 34.8% of patients required antiemetic rescue medication (AERM) compared with 20.2% in the TNT group (P<.001). The relative risk (AERM/no AERM) in the postoperative period after postanesthesia care unit discharge is 1.75 (95% CI, 1.05-2.92). This study suggests that a multimodal analgesic regimen (TNT) can reduce postoperative narcotic consumption, which may lead to a reduction in the number of patients requiring AERM.


Rigid mask-like face, ear anomalies, deafness, preaxial polydactyly and toe malformations in a patient with normal intelligence: a new entity?
We describe a patient with deafness, normal intellect and a unique phenotype characterized by a rigid mask-like face, narrow, upslanting palpebral fissures, flat malar bones, thick lower lip, malformed auricles, preaxial polydactyly with triphalangeal thumbs, syn-ectrodactyly of toes and first degree hypospadias.


An alternate-day corticosteroid regimen for pemphigus vulgaris. A 13-year prospective study.
Pemphigus vulgaris (PV) at the early, usually oral and relatively stable stage, represents the majority of PV patients. Treatment modalities usually do not differ compared to those for the fully established disease. To prospectively assess a standardized and effective therapeutic approach that aims at less morbidity due to adverse reactions. The following regimen, also known as Lever's mini treatment (LMT), was used. Forty mg of oral prednisone on alternate days plus 100 mg azathioprine every day were administered until the complete healing of all lesions. A gradual monthly and later bimonthly decrease of prednisone was followed by the tapering of a second immunosuppressive agent, in a one-year period. Seventy-four patients suffering from early-stage-PV, and representing 70% of all PV patients seen through the years 1991-2003, were eligible in the study. Total follow-up period was 76 +/- 37 (26-180) months. During the 53 +/- 26 months of LMT, 6 (8%) patients dropped out of therapy, 9 (12%) required a change to another treatment, two (3%) died and 57 (77%) achieved a lesion-free condition. Forty-five (61%) patients were in complete remission for 27 +/- 29 months. Significant morbidity was estimated 4/74 (5.2%). Disease 'breakthroughs' necessitating treatment adjustments occurred in 30 patients, usually throughout the last phase of therapy and post-treatment follow-up. LMT may be a standardized therapeutic approach for the early and relatively stable stage of PV, resulting in high efficacy, safety and quality of life profile.


Clinical usefulness of myocardial innervation imaging using Iodine-123-meta-iodobenzylguanidine scintigraphy in evaluating the effectiveness of pharmacological treatments in patients with heart failure: an overview.
This study was designed to review published data regarding the clinical usefulness of iodine-123-meta-iodobenzyl-guanidine (MIBG) scintigraphy in evaluating the effectiveness of pharmacological treatments in patients with heart failure (HF). A comprehensive computer literature search of the PubMed/MEDLINE and Embase databases was conducted to find relevant published articles about the clinical usefulness of MIBG scintigraphy in evaluating the effectiveness of pharmacological treatments in patients with HF. Thirty-three studies, comprising a total sample size of 1124 patients with HF, were included in this review. Main findings of the included studies are presented. Myocardial innervation imaging using MIBG scintigraphy can be successfully used to assess changes in cardiac sympathetic neuronal function caused by several pharmacological interventions in patients with HF.


Rupture of a saphenous vein coronary artery bypass graft due to Aspergillus necrotizing vasculitis.
We present the first, unusual case of a lethal mediastinal hemorrhage caused by rupture of a saphenous vein aortic coronary bypass graft due to Aspergillus species necrotizing vasculitis in an immunocompetent patient 18 days after redo coronary artery bypass surgery. The patient had neither signs for mediastinitis nor for another source of Aspergillus infection.


Glucose, glycogen, and insulin responses in the hypothermic rat.
The rat appears to be unable to utilize glucose during hypothermia. The objective of this study was to examine carbohydrate homeostasis during induction, hypothermia, and rewarming phases. Groups of normothermic animals were euthanized to serve as time controls for comparison. Hypothermia (15 degrees C) was produced by exposure to helox (80% helium:20% oxygen) at 0 +/- 1 degree C. Hyperglycemia was noted during the induction process (169 +/- 8 in control vs 326 +/- 49 mg/dl). Serum glucose increased further during 4 hr of hypothermia, but following rewarming (Tre of 33 +/- 1 degrees C) was reduced (153 +/- 16 mg/dl) significantly (P less than 0.05). Serum insulin was depressed during hypothermic induction (from 48 +/- 4 in controls to 19 +/- 3 microU/ml in hypothermic rats) and increased only slightly during the arousal process, remaining significantly lower than in normothermic subjects. Initial hepatic, skeletal muscle, and cardiac glycogen concentrations were reduced 34, 68, and 75%, respectively, during hypothermic induction. While liver glycogen decreased further during 4 hr of hypothermia, skeletal and cardiac stores increased markedly. During rewarming, hepatic glycogen was markedly decreased, while skeletal and cardiac stores were maintained. These data suggest that hyperglycemia in the hypothermic rat can be accounted for by glycogenolysis and hypoinsulinemia. In addition, this study indicates repletion of skeletal and cardiac muscle glycogen during maintained hypothermia and sparing of muscle glycogen during rewarming.


Redox signalling and regulation of the blood-brain barrier.
Neurological disorders are associated with increased oxidative stress. Reactive oxidants damage tissue and promote cell death, but it is apparent that oxidants can have more subtle effects on cell function through the modulation of redox-sensitive signalling pathways. Cells of the blood-brain barrier regulate the brain microenvironment but become dysfunctional during neurological disease. The blood-brain barrier is maintained by many cell types, and is modulated by redox-sensitive pathways, ranging from the cytoskeletal elements responsible for establishing a barrier, to growth factor and cytokine signalling pathways that influence neurovascular cells. During neurological disease, blood-brain barrier cells are exposed to exogenously generated oxidants from immune cells, as well as increasing endogenously oxidant production. These oxidants impair the function of the blood-brain barrier, leading to increased leakage and reduced blood flow. Reducing the impact of oxidants on the function of blood-brain barrier cells may provide new strategies for delaying the progression of neurological disease.


STAT3 interacts with Skp2/p27/p21 pathway to regulate the motility and invasion of gastric cancer cells.
The interleukin-6 (IL-6)/Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway mediates cell proliferation and migration. S-phase kinase-associated protein-2 (Skp2) catalyzes the ubiquitylation of p27 and p21. Here we investigated that the cross-talk of the two pathways regulates motility and invasion of gastric cancer SGC7901 and MGC803 cells. Both cell lines endogenously secret IL-6, and blockage of IL-6 or JAK2 inhibited the activation of JAK2 and STAT3. Depletion of STAT3 downregulated Skp2 expression, and thereby increased the expression of p27 and p21. The depletion of STAT3 inhibited the ability of cells to migrate and invade, and impaired the cellular cytoskeleton mainly microtubules; while the depletion of p27 partially restored the impaired ability to migrate, and reversed the impaired microfilaments, further inhibited the ability to invade, but had little effect on microtubules and cellular adhering ability of STAT3-depleted cells. STAT3 depletion inhibited the activity of RhoA and the interaction with stathmin, downregulated the expression of pFAK (phosphorylated focal adhesion kinase), acetylated-tubulin, RECK (reversion-inducing-cysteine-rich protein with kazal motifs) and Sp1, upregulated E-cadherin, and reduced the activities of MMP (matrix metalloproteinase)-2 and -9. The depletion of p27 increased RhoA (Ras homolog family member A) activity, upregulated RECK, and downregulated E-cadherin and Sp1 in STAT3-depleted cells. The results indicate that the interaction between STAT3 and Skp2/p27/p21 pathway plays an important role in mediating the motility, migration and invasion of gastric cancer cells, and inhibition of STAT3 may be a useful therapeutic approach for metastasis of gastric cancer, but caution needs to be taken for its effects on Skp2/p27/p21 pathway.


In situ synthesized novel biocompatible titania-chitosan nanocomposites with high surface area and antibacterial activity.
A series of titania-chitosan nanocomposites (2:x (0.12, 0.25, 0.5, 1.0 and 2.0g)) were synthesized using in situ sol-gel method and comprehensively characterized using conventional techniques. The resultant particles showed anatase phase, spherical and irregular morphology with particle size of 4.5-10.5nm. Nanocomposites with higher surface area (114-265m(2)/g) and high purity were obtained. The characterized samples were analyzed in 1.5mM simulated body fluid (1.5 SBF) and human gastric adenocarcinoma cell line to explore the bioactivity and biocompatibility. Antibacterial activity against Staphylococcus aureus was also evaluated. The formation of apatite layer on 1.5 SBF-immersed samples confirms the bioactivity of all the nanocomposites. High surface area, appropriate hydroxyapatite formation, specific antibacterial action, increased cell viability, controlled swelling and degrading rate are favorably achieved at 2:1 nanocomposite ratio. This study shows titania-chitosan nanocomposites as the promising biomaterial for orthopedic and tissue engineering applications.


Removing high contrast artifacts via digital inpainting in cryo-electron tomography: an application of compressed sensing.
To cope with poor quality in cryo-electron tomography images, electron-dense markers, such as colloidal goldbeads, are often used to assist image registration and analysis algorithms. However, these markers can create artifacts that occlude a specimen due to their high contrast, which can also cause failure of some image processing algorithms. One way of reducing these artifacts is to replace high contrast objects with pixel densities that blend into the surroundings in the projection domain before volume reconstruction. In this paper, we propose digital inpainting via compressed sensing (CS) as a new method to achieve this goal. We show that cryo-ET projections are sparse in the discrete cosine transform (DCT) domain, and, by finding the sparsest DCT domain decompositions given uncorrupted pixels, we can fill in the missing pixel values that are occluded by high contrast objects without discontinuities. Our method reduces visual artifacts both in projections and in tomograms better than conventional algorithms, such as polynomial interpolation and random noise inpainting.


Random local neighbor joining: a new method for reconstructing phylogenetic trees.
We have developed a new method for reconstructing phylogenetic trees called random local neighbor-joining (RLNJ). Our method is different from the neighbor-joining method (NJ) of Saitou and Nei and affords a more thorough sampling of solution space by randomly searching for local pair of neighbors in each step. Results using the RLNJ method to analyze yeast data show an increasing possibility to get a smaller S value (sum of branch lengths) compared with the NJ method as cases with more taxa are analyzed and many individual runs using the RLNJ method usually generate more than one topology with small S values. Computer simulation shows the fact that the RLNJ method can improve the possibility of recovering correct topology significantly by affording more than one topology. In addition, when using the RLNJ method, computer simulation also shows that the proportion of correct topologies (P(C)) will increase as the number of different topologies decreases and as the proportion of "most frequent topology" increases. Thus, the number of different topologies and the proportion of "most frequent topology" can be used as auxiliary criteria to evaluate reliability of a phylogenetic tree.


Linking denitrification and pesticide transformation potentials with community ecology and groundwater discharge in hyporheic sediments in a lowland stream.
Contamination of rivers by nitrate and pesticides poses a risk for aquatic ecosystems in lowland catchments that are often intensively used for agriculture. Here, the hyporheic zone, the streambed underneath the stream, plays a vital role due to its efficient self-purification capacity. The present study aims to evaluate the denitrification and transformation potential of 14 pesticides and three transformation products in the hyporheic sediment from a lowland stream with a high N load and by comparing an agricultural straightened section to a natural meandering part of the stream influenced by different groundwater discharges. Batch experiments were set up to evaluate the denitrification and pesticide transformation potentials in hyporheic sediment from two depths (5-15 cm (a) and 15-25 cm (b)). Our results revealed that (i) differences between the agricultural and natural sections of the river did not influence pollutant attenuation, (ii) both the nitrate and pesticide attenuation processes were more rapid in the upper "a" layer compared to the "b" layer due to higher microbial abundance, (iii) high groundwater discharge reduced the denitrification potential while pesticide transformation was unaffected, (iv) denitrification correlated with denitrifier abundance (nirK) in the "b" layer, while this correlation was not seen in the "a" layer, and (v) a microbial community with low diversity can explain limited transformation for the majority of tested pesticides. Overall, our results suggest that high groundwater discharge zones with reduced residence time in the hyporheic zone can be an important source of pesticides and nitrate to surface water.


Intermittent Broca's aphasia management in an emergency unit: from theory to practice.
Although Broca's aphasia (BA) may mimic different neurological illness, its sudden onset often requires an emergency approach. In this paper, the management of a case of intermittent BA occurred in a young woman without history of neurological, cardiovascular and arrhythmic diseases is discussed. Diffusion-weighted magnetic resonance imaging showed two areas of hypoperfusion in the terminal branches of the left medial cerebral artery not previously diagnosed by computed tomography. Although there were no eligibility criteria for thrombolysis, patient received intravenous treatment with recombinant tissue-type plasminogen activator (rt-PA) over 1 h and at the end of rt-PA infusion aphasia completely disappeared without neurological sequelae. Transesophageal echocardiography revealed a thrombus in the left atrial appendage not previously detected by transthoracic echocardiography. In the month following the cardioembolic stroke, heart rhythm was monitored for 30 days by an external loop recorder and during this test two episodes of silent lone atrial fibrillation were collected.


Morphological and phenotypical features of ovarian metastases in breast cancer patients.
Autotransplantation of frozen-thawed ovarian tissue is a method to preserve ovarian function and fertility in patients undergoing gonadotoxic therapy. In oncology patients, the safety cannot yet be guaranteed, since current tumor detection methods can only exclude the presence of malignant cells in ovarian fragments that are not transplanted. We determined the need for a novel detection method by studying the distribution of tumor cells in ovaries from patients with breast cancer. Furthermore, we examined which cell-surface proteins are suitable as a target for non-invasive tumor-specific imaging of ovarian metastases from invasive breast cancer. Using the nationwide database of the Dutch Pathology Registry (PALGA), we identified a cohort of 46 women with primary invasive breast cancer and ovarian metastases. The localization and morphology of ovarian metastases were determined on hematoxylin-and-eosin-stained sections. The following cell-surface markers were immunohistochemically analyzed: E-cadherin, epithelial membrane antigen (EMA), human epidermal growth receptor type 2 (Her2/neu), carcinoembryonic antigen (CEA), αvβ6 integrin and epithelial cell adhesion molecule (EpCAM). The majority of ovarian metastases (71%) consisted of a solitary metastasis or multiple distinct nodules separated by uninvolved ovarian tissue, suggesting that ovarian metastases might be overlooked by the current detection approach. Combining the targets E-cadherin, EMA and Her2/neu resulted in nearly 100% detection of ductal ovarian metastases, whereas the combination of EMA, Her2/neu and EpCAM was most suitable to detect lobular ovarian metastases. Examination of the actual ovarian transplants is recommended. A combination of targets is most appropriate to detect ovarian metastases by tumor-specific imaging.


Dose- and time-dependent effects of interferon tau on bovine endometrial gene expression.
Failure by the developing conceptus to secrete sufficient interferon tau (IFNT), required for maternal recognition of pregnancy (MRP), at the appropriate time is related to early pregnancy loss in cattle. We aimed to test the hypothesis that there is a dose- and time-dependent relationship between IFNT and the endometrial expression of key interferon-stimulated genes (ISGs) involved in the signalling cascade leading to MRP in cattle. Candidate genes were identified first through a bioinformatic approach, where integrated transcriptomic data from two previous studies were analyzed to identify endometrial genes induced by IFNT. Next, expression of selected candidate genes was investigated in vitro in endometrial explants. Endometrial explants collected from cows (n = 8) in the late luteal phase of the estrous cycle were cultured in medium without (control) or with recombinant ovine IFNT (1, 10, 100 ng/mL) for 6 h. Simultaneously, endometrial explants were cultured in medium containing 100 ng/mL IFNT for different time periods (15 min, 30 min, 1 h, 3 h, 6 h). Gene expression was analyzed by RT-qPCR. We identified 54 endometrial genes responding to IFNT and to some degree to the conceptus, from which five ISGs (CMPK2, BPNT1, IFI35, TNFSF10 and TRIM38) were further selected for the dose- and time-dependent experiments. Classical ISGs (ISG15, OAS1, MX1 and MX2) were up-regulated (P < 0.05) in endometrium by 1 ng/mL IFNT. However, other selected ISGs (CMPK2, BPNT1, IFI35, TNFSF10 and TRIM38) were induced only by higher concentrations (10 and 100 ng/mL) of IFNT (P < 0.05). In terms of duration of exposure, IFNT at 100 ng/mL induced a significant (P < 0.05) increase in ISG15 and CMPK2 expression after 1 h incubation, while all other studied ISGs in the endometrium were upregulated when cultured for 3 or 6 h, but did not affect expression when the duration of culture was for 1 h or less. These results suggest that IFNT acts on the uterus in both a dose- and time-dependent manner in cattle and that timely exposure of the endometrium to sufficient IFNT is essential for appropriate signalling to ensure successful pregnancy establishment.


Foster-Kennedy syndrome due to optochiasmatic arachnoiditis.
A case of optochiasmatic arachnoiditis mimicking Foster-Kennedy syndrome is reported. The difficulties in establishing diagnosis are considered, and the literature of optochiasmatic arachnoiditis presenting in this unusual manner is reviewed.


Practical assessment of the NBT-PABA pancreatic function test using high performance liquid chromatography determination of p-aminobenzoic acid in urine.
A practical method for determining p-aminobenzoic acid in urine by high-performance liquid chromatography has been assessed. The technique is quick, requires no extraction steps and has good precision. Using this method, healthy individuals had a p-aminobenzoic acid excretion index of 94% +/- 18 (mean +/- 1 SD). Patients with proven, severe chronic exocrine pancreatic dysfunction had index values of less than 5-25%. Unlike chemical methods available, there were no interferences in any of the urines tested, nor did 12 compounds tested interfere with the analysis.


Tympanosclerosis: long-term hearing results after ossicular reconstruction.
The study goal was to analyze long-term hearing results and factors likely to affect outcome after ossicular reconstruction in patients with tympanosclerosis, particularly tympanosclerotic stapes fixation. We conducted a retrospective chart review of the past 10 years. The short- and long-term (up to 9(1/2) years) hearing results of first-stage and second-stage operations for middle ear tympanosclerosis in 203 consecutive patients, performed in a tertiary referral otologic private practice, are presented. There were 160 tympanoplasties and 43 tympanoplasties with mastoidectomy performed, with ossicular fixation secondary to tympanosclerosis in 135 cases. Of these 203, 42.9% were primary cases, with the majority being planned second-stage or revision procedures. The average preoperative air-bone gap (ABG) was 30.9 dB. The average short-term postoperative ABG was 17.4 dB with closure of the ABG within 20 dB in 64.6%. The success rate (ABG < or = 20 dB) for patients with ossicular fixation was 65.3%. Partial sensorineural hearing loss occurred in 1.0% of the patients, and none experienced profound sensorineural hearing loss (dead ears). There was no statistically significant change from short-term to long-term follow-up in either ABG or air PTA, with mean differences of only 0.3 and 2.0 dB, respectively. The mean time to the last follow-up was 1.6 years. Ossicular reconstruction in individuals with tympanosclerosis can yield satisfactory, lasting hearing results with a low incidence of complications and no dead ears.


Sleep and synaptic changes.
Several recent studies, using molecular, electrophysiological, or structural approaches, have investigated how synapses are affected by sleep, spontaneous wake, chronic sleep restriction, and acute sleep deprivation. Overall, the results have found that even a few hours of sleep or wake can modify the molecular composition of excitatory synapses, change their efficacy, and make synapses grow or shrink. Moreover, partial and total loss of sleep affect the ability of synapses to undergo long-term potentiation, an effect that may underlie some of the negative consequences of sleep deprivation on memory and other cognitive functions.


What Kind of Capsule Endoscope Is Suitable for a Controllable Self-Propelling Capsule Endoscope? Experimental Study Using a Porcine Stomach Model for Clinical Application (with Videos).
We have been developing the Self-Propelling Capsule Endoscope (SPCE) that allows for controllability from outside of the body and real-time observation. What kind of capsule endoscope (CE) is suitable for a controllable SPCE is unclear and a very critical point for clinical application. We compared observing ability of three kinds of SPCEs with different viewing angles and frame rates. Eleven buttons were sewed in an excised porcine stomach. Four examiners controlled the SPCE using PillCamSB2, -ESO2, and -COLON2 (Given Imaging Ltd., Israel), for 10 minutes each with the aim of detecting as many buttons and examining them as closely as possible. The ability to find lesions was assessed based on the number of detected buttons. The SPCE-performance score (SPS) was used to evaluate the ability to examine the lesions in detail. The SPCE-ESO2, -COLON2, and -SB2 detected 11 [interquartile range (IQR): 0], 10.5 (IQR, 0.5), and 8 (IQR, 1.0) buttons, respectively. The SPCE-ESO2 and -COLON2 had a significantly better ability to detect lesions than the -SB2 (p < 0.05). The SPCE-ESO2, -COLON2, and -SB2 had significantly different SPS values of 22 (IQR, 0), 16.5 (IQR, 1.5), and 14 (IQR, 1.0), respectively (p < 0.05 for all comparisons; SPCE-SB2 vs. -ESO2, -SB2 vs. -COLON2, and -ESO2 vs. -COLON2). PillCamESO2 is most suitable in different three CEs for SPCE for examining lesions in detail of the stomach.


Modeling ciliopathies in patient-derived primary cells.
Ciliopathies comprise a group of inherited diseases caused by mutations in genes encoding proteins that localize to cilia or centrosomes. They afflict multiple organs and are one of the most frequent monogenic causes of kidney failure in adults, adolescents and children. Primary cilia play diverse roles in cell signaling, cell cycle regulation, planar cell polarity and mechanosensing. The use of patient-derived cells possessing endogenous disease causing mutations enables the study of these processes and their dysregulation in disease. Here we describe methods to cultivate patient-derived dermal fibroblast and renal epithelial cells isolated from urine. Fibroblasts are highly robust, long-lived, and easy to culture cells in which ciliary assembly can be easily induced. Similarly, the ability to acquire and culture ciliated renal epithelial cells without patient-invasive-intervention holds great potential to further our understanding of ciliopathies. In addition to monolayer cultures, we also detail the formation of three-dimensional renal-epithelial organoids-so-called tubuloids-that demonstrate epithelial-polarization and transepithelial transport activities like those seen in vivo renal-tubules. These in vitro models are powerful tools to investigate the underlying disease mechanisms of human ciliopathies that can be employed without the need for heavy-handed genetic or molecular manipulations.


LongStitch: high-quality genome assembly correction and scaffolding using long reads.
Generating high-quality de novo genome assemblies is foundational to the genomics study of model and non-model organisms. In recent years, long-read sequencing has greatly benefited genome assembly and scaffolding, a process by which assembled sequences are ordered and oriented through the use of long-range information. Long reads are better able to span repetitive genomic regions compared to short reads, and thus have tremendous utility for resolving problematic regions and helping generate more complete draft assemblies. Here, we present LongStitch, a scalable pipeline that corrects and scaffolds draft genome assemblies exclusively using long reads. LongStitch incorporates multiple tools developed by our group and runs in up to three stages, which includes initial assembly correction (Tigmint-long), followed by two incremental scaffolding stages (ntLink and ARKS-long). Tigmint-long and ARKS-long are misassembly correction and scaffolding utilities, respectively, previously developed for linked reads, that we adapted for long reads. Here, we describe the LongStitch pipeline and introduce our new long-read scaffolder, ntLink, which utilizes lightweight minimizer mappings to join contigs. LongStitch was tested on short and long-read assemblies of Caenorhabditis elegans, Oryza sativa, and three different human individuals using corresponding nanopore long-read data, and improves the contiguity of each assembly from 1.2-fold up to 304.6-fold (as measured by NGA50 length). Furthermore, LongStitch generates more contiguous and correct assemblies compared to state-of-the-art long-read scaffolder LRScaf in most tests, and consistently improves upon human assemblies in under five hours using less than 23 GB of RAM. Due to its effectiveness and efficiency in improving draft assemblies using long reads, we expect LongStitch to benefit a wide variety of de novo genome assembly projects. The LongStitch pipeline is freely available at https://github.com/bcgsc/longstitch .


A congenial cutaneous bronchogenic sinus of the abdominal wall in an infant.
Cutaneous bronchogenic anomalies are very rare, and we report a child who presented with mucoid discharge from a small opening on her epigastrium that was present since birth. Diagnosis and treatment of congenital bronchogenic anomalies are important because surgical excision is needed to prevent the potential risk of infection and malignant degeneration. To the best to our knowledge, this is the first report of a congenital bronchogenic sinus of the abdominal wall.


Genotypic and phenotypic distinctness of restored and indigenous populations of Pimpinella saxifraga L. 8 or more years after restoration.
The recovery of altered or damaged ecosystems demands large-scale reintroductions of seeds. In the past, ecological restoration in Germany was carried out with non-local seeds of naturally occurring species. We here analysed whether the genetic pattern of the introduced non-local seeds (R = restored) of Pimpinella saxifraga are still detectable several years after application and whether the phenotype differs from that of the regional gene pool (I = indigenous) of the species. We collected material from individuals of R and I sites, conducted a common garden experiment and tested for genetic, morphological and phenotypic differences. In a cutting experiment we investigate treatment effects on indigenous and restored populations. At all investigated sites we only found P. saxifraga individuals with comparatively similar genome sizes. The population genetic analysis revealed two large and quite distinct molecular clusters, separating indigenous and restored individuals along the first axis. None of the vegetative, but two of the reproductive fitness parameters differed between individuals of the R and I sites. Cutting always had a significant influence on all analysed vegetative and reproductive fitness parameters, regardless of the individuals' origin. The effects of mowing always mask origin-specific characteristics, which then disappear. Genotypic coexistence reduces the availability of niches for the local genotype and may eventually lead to genotypic competition or introgression. We therefore recommend not to use non-local genotypes of this species in the region. Instead, we recommend using the genetically diverse local genotypes of P. saxifraga for restoration purposes.


Augmented autophagy suppresses thymocytes development via Bcl10/p-p65 pathway in prenatal nicotine exposed fetal mice.
Tobacco smoke is a common global environmental pollutant. Maternal tobacco smoke/nicotine exposure has long-term toxic effects on immune organs. We previously found that prenatal nicotine exposure (PNE)-induced programmed immune diseases caused by fetal thymic hypoplasia, but the mechanism still unknown. Autophagy has important functions in maintaining thymopoiesis, whether autophagy was involved in PNE-inhibited fetal thymocytes development is also obscure. Therefore, this study aimed to investigate how nicotine changed the development of fetal thymocytes from the perspective of autophagy in vivo and in vitro. PNE model was established by 3 mg/kg nicotine administration in Balb/c mice from gestational day 9 to 18. The results showed that PNE reduced the percentage and absolute number of CD69-CD4+SP cells, suggesting a block of fetal thymocytes mature. PNE promoted autophagosome formation, autophagy related proteins (Beclin1, LC3I/II) expression, and upregulated α7 nAChR as well as AMPK phosphorylation in fetal thymus. Moreover, PNE promoted Bcl10 degradation via autophagy-mediated proteolysis and inhibited p65 activation, blocking the transition of thymocytes between the DP to SP stage. Further, primary thymocytes were treated with nicotine in vitro and showed induced autophagy in a dose- and time-dependent manner. In addition, nicotine-inhibited CD69-CD4+SP cells and the Bcl10/p-p65 pathway have been reversed by an autophagy inhibitor. The α7 nAChR specific antagonist abrogated nicotine-induced AMPK phosphorylation and autophagy initiation. In conclusion, our findings showed that PNE repressed the Bcl10/p-p65 development pathway of CD4+SP cells by triggering autophagy, and illuminated the developmental origin mechanism of programmed immune diseases in PNE offspring.


[Electrophoretic and immunoelectrophoretic characteristics of serums of mice bearer of S. 180 (author's transl)].
The AA. start fully verified that neoplastic cells produce and pour out abnormal products, operating in favour of taking root of proliferation and penetration before, and with an action of mass in generalized phase of the illness. They have employed adequate immunologic techniques and antiserums prepared against plasmaproteins of the mouse bearer of tumour, succeeding in making evident with electrophoresis and immunoelectrophoresis the S. 180 of Cobs mouse.


A question of time: tissue adaptation to mechanical forces.
While much attention has been focused on the force-generating mechanisms responsible for shaping developing embryos, less is known about the ways in which cells in animal tissues respond to mechanical stimuli. Forces will arise within a tissue as the result of processes such as local cell death, growth and division, but they can also be an indirect consequence of morphogenetic movements in neighbouring tissues or be imposed from the outside, for example, by gravity. If not dealt with, the accumulation of stress and the resulting tissue deformation can pose a threat to tissue integrity and structure. Here we follow the time-course of events by which cells and tissues return to their preferred state following a mechanical perturbation. In doing so, we discuss the spectrum of biological and physical mechanisms known to underlie mechanical homeostasis in animal tissues.


Use of Mesenchymal Stem Cells to Enhance the Efficacy of Gene Therapy.
Herein, a method to use of mesenchymal stem cells (MSCs) to modulate immune response against rAAV transduction in a canine Duchenne muscular dystrophy (DMD) model is presented. The aim is to overcome the immune response against adeno-associated virus (AAV) capsid itself as well as against the AAV-derived transgene.AAV is currently the most used viral vector because of its relative safety and high efficiency of gene transfer to nondividing cells. Since DMD is caused by a deficiency of dystrophin protein due to mutation or deletion in the dystrophin gene, dystrophin replacement therapy using AAV vectors carrying dystrophin as a therapeutic gene is an effective treatment as shown by animal experiments and clinical trials. Because DMD is a systemic disease, the amount of AAV vector required to achieve efficacy is impractically large. MSC have been used in combination with organ transplants due to their immunomodulatory effects. By using MSCs and AAVs in combination as described below, we are able to decrease the immune response to AAV capsid and the transgene as well as to reduce the dose of AAV to approximately 1/100 of the dose used in conventional clinical trials.


Vitamin D Receptor Gene Polymorphism and the Risk of Multiple Sclerosis in the Azeri Population of Iran.
Multiple sclerosis (MS), a disease of the central nervous system (CNS), is associated with damage to the myelin sheath of neurons. It is demonstrated that vitamin D deficiency plays an important role in the development of the disease. Binding of vitamin D to its specific nuclear receptors is a way to exert its function. Possible correlation between the vitamin D receptor (VDR) gene and MS was evaluated in the Azeri population of Iran. Different genotypes of the Bsml site were determined by using the PCR-RFLP method in 148 MS patients and 220 non-relative healthy controls. In MS patients, genotype bb was significantly higher than the healthy controls (p<0.05). Additionally, most subjects of the MS group had been insufficiently exposed to sunlight before the age of 15 (p<0.001). Our findings indicated that the red meat intake in MS patients was significantly higher than the healthy controls (p<0.001). In addition, the healthy controls had appropriate dieting behaviors in comparison to MS patients (excessive intake of some foods) (p=0.0001). In conclusion, genotype BB and sufficient exposure to sunlight before the age of 15 were the protective factors against MS. Although, excessive consumption of red meat and inappropriate dieting behaviors were predisposing factors to MS disease.


Solitary pulmonary nodule as the initial manifestation of isolated metastasis from prostate cancer without bone involvement: A case report.
Isolated lung metastases from prostate cancer without any other organ involvement are rare. They are commonly in the form of diffuse or multiple lesions and rarely emerge as a solitary pulmonary nodule. A 61-year-old man who had undergone a laparoscopic-assisted radical prostatectomy for prostate cancer 16 months prior presented with a growing solitary pulmonary nodule. Positron emission tomography/computed tomography showed an abnormal uptake in the nodule without any other organ involvement. A surgical specimen by a thoracoscopic wedge resection proved a diagnosis of a metastasis from prostate cancer. He is currently alive only with worsening pulmonary metastases at 7 years after the lung surgery. A rare entity of isolated pulmonary metastases could be a sole finding of metastatic prostate cancer over the years and its initial manifestation could emerge as a solitary pulmonary nodule. It poses a diagnostic challenge because primary lung cancer is the leading differential diagnosis of solitary pulmonary nodules and is also one of the most frequent second primary malignancies in prostate cancer survivors. An aggressive surgical biopsy is essential for definitive histopathological and immunohistochemical analyses of solitary pulmonary nodules to distinguish a rare form of an isolated pulmonary relapse from a second primary lung cancer in prostate cancer survivors.


Accelerating next-generation vaccine development for global disease prevention.
Vaccines are among the greatest successes in the history of public health. However, past strategies for vaccine development are unlikely to succeed in the future against major global diseases such as AIDS, tuberculosis, and malaria. For such diseases, the correlates of protection are poorly defined and the pathogens evade immune detection and/or exhibit extensive genetic variability. Recent advances have heralded in a new era of vaccine discovery. However, translation of these advances into vaccines remains impeded by lack of understanding of key vaccinology principles in humans. We review these advances toward vaccine discovery and suggest that for accelerating successful vaccine development, new human immunology-based clinical research initiatives be implemented with the goal of elucidating and more effectively generating vaccine-induced protective immune responses.


Patterns and Influencing Factors of Medial Meniscus Tears in Varus Knee Osteoarthritis.
To investigate the patterns of medial meniscus (MM) tears in patients with varus knee osteoarthritis who underwent total knee arthroplasty and analyze the factors that could affect MM tears. The patients (365 knees, 268 patients) were classified into three groups; group I with MM posterior horn (PH) tear only; group II with MM root tear only; and group III with MMPH plus root tear. The following factors were evaluated: age, gender, body mass index, varus deviation of the mechanical axis, medial proximal tibial angle, posterior tibial slope (PTS), and anterior cruciate ligament (ACL) integrity (normal, degeneration, and tear or absence). MM tears were identified in all knees. The patterns of the combined MMPH tears in group III were less complex than those in group I. Varus deviation and PTS were significantly greater in group III than groups I and II. In group III, there were significantly more cases of ACL tear or absence than groups I and II. The others showed no differences among three groups. Severe varus knee osteoarthritis was always accompanied by MM tears. Risk factors for MMPH plus root tears were severe varus deformity, great PTS, and ACL tear or absence.


Scoliosis may be the first symptom of the tethered spinal cord.
Tethered cord syndrome (TCS) is a progressive clinical entity that arises from abnormal spinal cord tension. Scoliosis may be a unique symptom in TCS. The aim of this study is to investigate prognosis after releasing the filum terminale in scoliosis due to TCS with/without findings in magnetic resonance imaging (MRI) and to draw attention to the importance of somatosensorial evoked potentials (SSEP) on the differential diagnosis of idiopathic scoliosis versus scoliosis due to TCS with normal appearance of filum terminale and conus medullaris. Eleven female and seven male patients with progressive scoliosis were included in the study. They were evaluated radiologically, SSEP and urodynamical studies. Preoperative and postoperative anteroposterior full spine X-rays were obtained for measuring the Cobb's angle. MRI was performed in all cases for probable additional spinal abnormalities. All patients underwent filum terminale sectioning through a L5 hemilaminectomy. The resected filum terminale were subjected to histopathological examination. The mean Cobb angle was 31.6° (range 18°-45°). Eight patients (44.45%) had a normal appearance of filum terminale and normal level conus medullaris in MRI, but conduction delay and/or block was seen on SSEP. In the histopathological examination of filum terminale dense collagen fibers, hyaline degeneration and loss of elastic fibers were observed. Postoperatively none of the patients showed worsening of the Cobb angle. Three patients showed improvement of scoliosis. In TCS presented with scoliosis, untethering must be performed prior to the corrective spinal surgery. Absence of MRI findings does not definitely exclude TCS. SSEP is an important additional guidance in the diagnosis of TCS. After untethering, a followup period of 6 months is essential to show it untethering helps in stopping the progress of the scoliotic curve. In spite of non progression (curve stopped lesser than 45°) or even improvement of scoliosis, there may be no need for major orthopedic surgical intervention.


Functional Abnormalities of Cerebellum and Motor Cortex in Spinal Muscular Atrophy Mice.
Spinal muscular atrophy (SMA) is a devastating genetic neuromuscular disease. Diffuse neuropathology has been reported in SMA patients and mouse models, however, functional changes in brain regions have not been studied. In the SMNΔ7 mouse model, we identified three types of differences in neuronal function in the cerebellum and motor cortex from two age groups: P7-9 (P7) and P11-14 (P11). Microelectrode array studies revealed significantly lower spontaneous firing and network activity in the cerebellum of SMA mice in both age groups, but it was more profound in the P11 group. In the motor cortex, however, neural activity was not different in either age group. Whole-cell patch-clamp was used to study the function of output neurons in both brain regions. In cerebellar Purkinje cells (PCs) of SMA mice, the input resistance was larger at P7, while capacitance was smaller at P11. In the motor cortex, no difference was observed in the passive membrane properties of layer V pyramidal neurons (PN5s). The action potential threshold of both types of output neurons was depolarized in the P11 group. We also observed lower spontaneous excitatory and inhibitory synaptic activity in PN5s and PCs respectively from P11 SMA mice. Overall, these differences suggest functional alterations in the neural network in these motor regions that change during development. Our results also suggest that neuronal dysfunction in these brain regions may contribute to the pathology of SMA. Comprehensive treatment strategies may consider motor regions outside of the spinal cord for better outcomes.


Uneventful epidural labor analgesia in a parturient with immune thrombocytopenic purpura and platelet count of 26,000/mm3 which was unknown preoperatively.
We report a case of a parturient with immune thrombocytopenic purpura and platelet count of 26,000/mm3, unknown before induction of labor analgesia, who presented in active labor and received continuous epidural labor analgesia for an uneventful vaginal delivery. No neurologic or hematological complications were reported.


Investigations of 'transfer factor' activity in the transfer of immunity to Trichostrongylus axei infections in sheep.
Three investigations are described in which non-dialysed and dialysed leucocyte lysates, 'transfer factor' prepared from the blood of sheep infected with Trichostrongylus axei successfully transferred immunity to challenge infection with that parasite in susceptible lambs. Similar leucocyte lysates from parasite-free lambs failed to transfer a similar resistance to challenge infection. 'Transfer factor' treatment produced a 30--72 per cent reduction in a total worm burden compared to susceptible control lambs. In the first two investigations the donor and recipient lambs were genetically dissimilar and in the third investigation were of different breeds. The resistance transfer was considered to operate independently of immune incompetence.


Aesthetic and functional implications following rotation of the maxillomandibular complex in orthognathic surgery: a systematic review.
The manipulation of the maxillomandibular complex (MMC) in orthognathic surgery has been used widely in the treatment of dentofacial deformities so as to optimize aesthetic and functional results, making these more stable in the long term. The aim of the present study was to perform a systematic literature review of the aesthetic and functional implications following rotation of the occlusal plane in orthognathic surgery, by evaluating skeletal stability, facial harmony, respiratory function, and temporomandibular joint (TMJ) function after clockwise or counterclockwise rotation of the MMC. A survey of Scopus, PubMed, and Cochrane databases was performed through which 10 papers were selected for the final review. From this review, it could be concluded that facial aesthetics, TMJ function, and skeletal and occlusal stability in the orthosurgical treatment of dentofacial deformities may be influenced by the surgical manipulation of the MMC (clockwise or counterclockwise rotation). However, although this treatment technique is used widely today, the results of the present study do not provide sufficient scientific evidence with regard to the choice of this approach.


Incidence of new-onset diabetes and impaired fasting glucose in patients with recent myocardial infarction and the effect of clinical and lifestyle risk factors.
Individuals with diabetes are at higher risk of myocardial infarction than non-diabetics. However, much less is known about the incidence of, and risk factors for, development of diabetes and impaired fasting glucose in patients who have had a myocardial infarction. We set out to estimate this incidence and investigate whether lifestyle factors such as dietary habits might alter this risk. We used prospectively obtained data for 8291 Italian patients with a myocardial infarction within the previous 3 months, who were free of diabetes (determined by medication use, a physician-reported diagnosis, or fasting glucose > or =7 mmol/L) at baseline. Incidence of new-onset diabetes (new diabetes medication or fasting glucose > or =7 mmol/L) and impaired fasting glucose (fasting glucose > or =6.1 mmol/L and <7 mmol/L) were assessed at follow-up at 0.5, 1.0, 1.5, 2.5, and 3.5 years. Baseline data for body-mass index (BMI), other risk factors, dietary habits, and medications were updated during follow-up. A Mediterranean diet score was assigned according to consumption of cooked and raw vegetables, fruit, fish, and olive oil. Associations of demographic, clinical, and lifestyle risk-factors with incidence of diabetes and impaired fasting glucose were assessed with multivariable Cox proportional hazards. During 26 795 person-years (mean follow-up 3.2 years [SD 0.9]), 998 individuals (12%) developed new-onset diabetes (incidence 37 cases per 1000 person-years). Of the 7533 without impaired fasting glucose at baseline, 2514 (33%) developed new-onset impaired fasting glucose or diabetes (incidence 123 cases per 1000 person-years), rising to 3859 (62%) of 6229 with the lower cutoff for impaired fasting glucose of 5.6 mmol/L (incidence 321 cases per 1000 person-years). Independent risk factors for new-onset diabetes or impaired fasting glucose included older age, hypertension, use of beta-blockers, lipid-lowering medications (protective), and diuretic use. Independent lifestyle risk-factors included higher BMI, greater BMI gain during follow-up, current smoking, a lower Mediterranean dietary score, and wine consumption of more than 1 L/day. Data for physical activity were unavailable, but inability to perform exercise testing was associated with higher incidence of diabetes and impaired fasting glucose. Compared with population-based cohorts, patients with a recent myocardial infarction had a higher annual incidence rate of impaired fasting glucose (1.8 vs 27.5% in our study) and diabetes (0.8-1.6% compared with 3.7%) in this study. Thus, our results indicate that myocardial infarction could be a prediabetes risk equivalent. Smoking cessation, prevention of weight gain, and consumption of typical Mediterranean foods might lower this risk, which emphasises the need for guidance on diet and other lifestyle factors for patients who have had a myocardial infarction.


Breast Cancer and Lifestyle Factors: Umbrella Review.
Lifestyle factors play a major role in the risk of breast cancer. This review aimed to examine the size of the effect of select lifestyle factors on risk for breast cancer and assess the quality of existing evidence. The authors performed an umbrella review of systematic reviews. The authors found an increased risk for breast cancer associated with obesity, alcohol intake, and smoking and a decreased risk due to physical activity. The evidence for sleep disruption and duration indicates risk for breast cancer, but it is limited in size, statistical significance, and quality of evidence.


Analysis of aberrant splicing and nonsense-mediated decay of the stop codon mutations c.109G>T and c.504_505delCT in 7 patients with HMG-CoA lyase deficiency.
Eukaryotic cells can be protected against mutations that generate stop codons by nonsense-mediated mRNA decay (NMD) and/or nonsense-associated altered splicing (NAS). However, the processes are only partially understood and do not always occur. In this work, we study these phenomena in the stop codon mutations c.109G>T (p.Glu37*) and c.504_505delCT; the second and third most frequent mutations in HMG-CoA lyase deficiency (MIM #246450). The deficiency affects the synthesis of ketone bodies and produces severe disorders during early childhood. We used a minigene approach, real-time quantitative PCR and the inhibition of NMD by puromycin treatment, to study the effect of stop codons on splicing (NAS) and NMD in seven patients. Surprisingly, none of the stop codons studied appears to be the direct cause of aberrant splicing. In the mutation c.109G>T, the splicing is due to the base change G>T at position 109, which is critical and cannot be explained by disruption of exonic splicing enhancer (ESE) elements, by the appearance of exonic splicing silencer (ESS) elements which were predicted by bioinformatic tools or by the stop codons. Moreover, the mutation c.504_505delCT produces two mRNA transcripts both with stop codons that generate simultaneous NMD phenomena. The effects of the mutations studied on splicing seemed to be similar in all the patients. Furthermore, we report a Spanish patient with 3-hydroxy-3-methylglutaric aciduria and a novel missense mutation: c.825C>G (p.Asn275Lys).


An enzyme-linked immunosorbent assay (ELISA) for urinary growth hormone suitable for use in the routine laboratory. The Wessex Growth Study.
An avidin-biotin enzyme-linked immunoassay was developed to measure human growth hormone (hGH) in urine. The assay was validated in terms of sensitivity, specificity and reproducibility. Parallelism was demonstrated between the standard curve (4-500 pg/ml) and serially concentrated urine. There was no interference from 125 ng/ml of adrenocorticotrophin, follicle stimulating hormone, luteinising hormone, prolactin or thyroid stimulating hormone. Recovery of exogenous human growth hormone in urine ranged from 91 to 103%. Intra- and interassay variations were less than 10% and sensitivity was 1.4 pg/ml. Application to timed overnight urine samples from both normal and short children or from acromegalic patients suggests the assay may be useful for simple, non-invasive assessment of growth hormone secretion. Moreover, use of standard laboratory equipment and commercially available components, together with the avoidance of radioisotopes, facilitate its use as a routine screening assay.


Cardiac echinococcal cyst: diagnosis by two-dimensional echocardiography.
A case of an intracardiac echinococcal cyst is presented. The diagnosis was made by two-dimensional echocardiography, which clearly identified a large multiseptated cystic structure in the right ventricular outflow tract. The findings were verified at surgery. It is suggested that two-dimensional echocardiography may be the procedure of choice in the diagnosis of cardiac echinococcal disease.


Influence of different treatment procedures on the temporomandibular joint after mandibular setback in skeletal class III - A retrospective study.
The aim of this study was to clarify the effects of three different orthognathic surgical procedures on the temporomandibular joint after mandibular setback. Conventional sagittal split ramus osteotomy (SSRO) with segmental fixation (conv-SSRO), intraoral vertical ramus osteotomy (IVRO), or SSRO without fixation followed by the physiological positioning strategy (nonfix-SSRO) was performed for mandibular setback. Temporomandibular joint disorder (TMD) symptoms were clinically assessed, and the condylar head angle was measured. In total, 129 patients participated. Preoperative TMD and treatment procedure were related to postoperative TMD. A menton deviation of 3.43 mm was the cutoff for the risk of postoperative TMD. The incidence rate of postoperative TMD in the conv-SSRO group was higher than that in the IVRO (p = 0.0197) and nonfix-SSRO (p = 0.0001) groups in asymmetric cases. There was no significant postoperative change in the temporomandibular joint space in each group. In symmetric and asymmetric cases, the condylar head was rotated inwards by 5.82 ± 4.75° (p < 0.0001) and 5.44 ± 3.10° (p < 0.0001), respectively, in the conv-SSRO group, and outwards by -7.98 ± 5.05° (p < 0.0001) and -8.32 ± 6.38° (p < 0.0001), respectively, in the IVRO group, but it was almost stable in the nonfix-SSRO group. Within the limitations of the study it seems that nonfix-SSRO should be preferred over conv-SSRO and IVRO whenever appropriate.


Monitoring and meta-metacognition in the own-race bias.
Although there is a great deal of research focused on identification issues related to own-versus other-race faces very few experiments have explored whether metacognitive monitoring contributes to the own-race bias. In the current experiment the typical own-race bias paradigm was modified so that type-2 signal detection measures (e.g. Higham & Arnold, 2007a,b) could be used to directly measure metacognitive monitoring at retrieval. A second goal of the experiment was to explore whether self-reported confidence ratings differed depending on whether they were directed at answer accuracy (e.g., judging a face as "studied") versus at decisions about that answer (e.g., volunteering vs. withholding that answer). Overall the results demonstrated that monitoring does contribute to the own-race bias, in that participants were better at monitoring their memory for own-race faces. Further, there was a significant difference between the two confidence measures, and the pattern of this difference depended on whether responses had been volunteered or withheld.


Fundamental neurochemistry review: Old brain stories - Influence of age and sex on the neurodegeneration-associated lipid changes.
Brain aging is a naturally occurring process resulting in the decline of cognitive functions and increased vulnerability to develop age-associated disorders. Fluctuation in lipid species is crucial for normal brain development and function. However, impaired lipid metabolism and changes in lipid composition in the brain have been increasingly recognized to play a crucial role in physiological aging, as well as in several neurodegenerative diseases. In the last decades, the role of sexual dimorphism in the vulnerability to develop age-related neurodegeneration has increased. However, further studies are warranted for detailed assessment of how age, sex, and additional non-biological factors may influence the lipid changes in brains. The aim of this work is to address the presence of sex differences in the brain lipid changes that occur along aging, and in the two most common age-related neurodegenerative disorders (Alzheimer's and Parkinson's diseases). We included the studies that assessed lipid-related alterations in the brain of both humans and experimental models. Additionally, we explored the influence of sex on lipid-lowering therapies. We conclude that sex exerts a notable effect on lipid modifications occurring with age and neurodegeneration, and in lipid-reducing interventions. Therefore, the application of sex as an experimental variable is strongly encouraged for future research in the field of precision medicine approach.


A Cohort Analysis of Early Outcomes After AlloDerm, FlexHD, and SurgiMend Use in Two-Stage Prepectoral Breast Reconstruction.
Acellular dermal matrix (ADM) is frequently utilized in prepectoral breast reconstruction, but few studies have examined the role of ADM type in complication risk. This study was performed to determine the impact of ADM type on early complication rates in 2-stage alloplastic prepectoral breast reconstruction. We performed a cohort examination of all patients who underwent mastectomy with immediate 2-stage alloplastic prepectoral breast reconstruction with ADM support at Memorial Sloan Kettering Cancer Center from 2018 to 2021. ADM types utilized included AlloDerm (LifeCell Corporation, Branchburg, NJ), FlexHD (MTF Biologics, Edison, NJ), and SurgiMend (Integra LifeSciences Corporation, Princeton, NJ). Complication rates based on the number of tissue expanders (TEs) were determined for each ADM type. Performance of multivariate logistic regression determined the impact of ADM type on complication risk after accounting for confounders. Overall, 726 patients (1054 TEs: 194 AlloDerm, 93 FlexHD, 767 SurgiMend) were included. The 3 cohorts differed in terms of mastectomy type (nipple-sparing: 23.5% of AlloDerm, 33.3% of FlexHD, 19.1% of SurgiMend, P = .038); ADM perforation (perforated: 94.8% of AlloDerm, 98.2% of FlexHD, 100% of SurgiMend, P < .001); and ADM size (AlloDerm: 153.2 cm2 [37.6], SurgiMend: 198.7 cm2 [10.4], FlexHD: 223.7 cm2 [37.9], P < .001). On univariate examination, no differences existed between ADM types for seroma, infection, exposure, malposition, or TE loss. Additionally, after adjustment for confounders with multivariate regression, no ADM type had higher odds of TE loss. In this large cohort of prepectoral reconstruction patients, ADM type did not significantly affect the risk of complications. Additional prospective studies are warranted to better evaluate ADM choice for prepectoral breast reconstruction.


Comparing the Effects of Consuming Almonds or Biscuits on Body Weight in Habitual Snackers: A 1-Year Randomized Controlled Trial.
Almonds are nutrient rich, providing a healthier alternative to many snacks. Studies report health benefits with regular almond consumption without adverse weight gain. However, most interventions have been relatively short or have included additional dietary advice. Taking a pragmatic approach, we compared consumption of almonds compared with biscuits on body weight and other health outcomes in a population of regular snackers of discretionary foods, hypothesizing the almonds will displace some of the less-healthful snacks in their current diets. We randomly assigned 136 nonobese habitual discretionary snackers to receive almonds or biscuits daily for 1 y. These isocaloric snacks provided either 10% of participants' total energy (TE) requirements or 1030 kJ (equivalent to 42.5 g almonds), whichever was greater. Anthropometry, blood biomarkers, diet, appetite, sleep, and physical activity were assessed at baseline, 3, 6, and 12 mo, and body composition and RMR at baseline and 12 mo. The difference in changes for body weight from baseline to 12 mo was not statistically significant (geometric means: 67.1 and 69.5 kg for almonds and 66.3 and 66.3 kg for biscuits, P = 0.275). There were no statistically significant differences in changes for body composition or other nondietary outcomes (all P ≥ 0.112). Absolute intakes of protein; total, polyunsaturated, and monosaturated fat; fiber; vitamin E; calcium; copper; magnesium; phosphorous; and zinc, and % TE from total monounsaturated, and polyunsaturated fat statistically significantly increased from baseline (all P ≤ 0.033), whereas % TE from carbohydrate and sugar statistically significantly (both P ≤ 0.014) decreased from baseline, in the almond compared with the biscuit group. Almonds can be incorporated into the diets of habitual snackers to improve diet quality, without evidence for changes in body weight, compared with a popular discretionary snack food. This trial was registered at the Australian New Zealand Clinical Trials Registry (https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375610&isReview=true), registration number ACTRN12618001758291.


Effect of divalent minerals on the bioaccessibility of pure carotenoids and on physical properties of gastro-intestinal fluids.
During digestion, high concentrations of divalent minerals (DMs) can lead to insoluble lipid-soap complex formation, hampering carotenoid bioaccessibility. The effect of varying concentrations (0-1000 mg/L) of calcium, magnesium, zinc and sodium (control) on the bioaccessibility of lutein, neoxanthin, lycopene and β-carotene, following in vitro gastro-intestinal digestion (GI), was investigated systematically and coupled with physical measurements of the digesta. Addition of DMs significantly decreased (p<0.001) carotenoid bioaccessibility, up to 100% in the case of calcium. Mean half maximal inhibitory concentrations (EC50) for calcium, magnesium and zinc were 270±18, 253±75 and 420±322 mg/L respectively. Increased DM concentrations correlated with decreased viscosity (r>0.9) and decreased carotenoid bioaccessibility. Surface tension of digesta correlated inversely (p<0.05) with the bioaccessibility of carotenoids. This correlation was mineral and carotenoid dependent. Although based on in vitro findings, it is plausible that similar interactions occur in vivo, with DMs affecting the bioaccessibility and bioavailability of carotenoids and other lipophilic micronutrients and phytochemicals.


Unusual portosystemic collateral penetrating the liver parenchyma.
We present a case of an extremely rare portosystemic collateral pathway which arose from the right intrahepatic portal vein, passed through the liver parenchyma, and terminated into the inferior vena cava. We demonstrate the findings of diagnostic imaging and discuss the etiology of the collateral circulation in this unusual case.


In vitro evaluation of the capacity of zeolite and bentonite to adsorb aflatoxin B1 in simulated gastrointestinal fluids.
Anin vitro study using single concentration and isotherm adsorption was carried out to evaluate the capacity of Vietnamese produced zeolite and bentonite to adsorb aflatoxin B1 (AFB1) in simulated gastrointestinal fluids (SGFs), and a commercial sorbent hydrated sodium calcium aluminosilicate (HSCAS) was used as reference. In this study, AFB1 solution was mixed with sorbents (0.3, 0.4 and 0.5% w/v) in SGFs at pH 3 and pH 7 and shaken for 8 h, centrifuged and the supernatant measured by Vicam fluorometer. Adsorption of AFB1 onto zeolite and bentonite varied according to the pH of SGFs and was lower than HSCAS. Linearity between the increased amount of AFB1 adsorbed on sorbents and the decrease of sorbent concentration was observed for bentonite and HSCAS, except for zeolite in SGFs at pH 7. The observed maximum amounts of AFB1 adsorbed on bentonite and HSCAS were 1.54 and 1.56 mg/g, respectively. The adsorption capacities of bentonite and HSCAS for AFB1 were 12.7 and 13.1 mg/g, respectively, from fitting the data to the Freundlich isotherm equation. Improvement in processing and purification for bentonite is needed to enhance the surface area, which would probably result in better adsorptive capacity for this sorbent.


Lipid peroxidation in the liver of carcinogen-resistant rats.
Recently, we developed a new strain of rats that exhibit marked resistance to the hepatotoxic and carcinogenic actions of 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB) and some other carcinogens. In this work, we compared lipid peroxidation in the liver of these carcinogen-resistant (R) rats and the parental Donryu strain rats that are sensitive (S) to hazardous actions of these carcinogens. The liver microsomal fractions of the R group contained less amounts of polyunsaturated fatty acids. Microsomal lipid peroxidation in the presence of exogenous NADPH was much lower in R rats than in S rats. Liver microsomes of R rats were much less active than those of S rats also in producing 4-hydroxynonenal, carbonyl compounds and conjugated diene. The hepatic contents of ascorbic acid, glutathione, alpha-tocopherol and coenzyme Q in the R rats were similar to those in S rats. The activities of the free radical scavenger enzymes, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT), in the two groups were also similar. Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are both thought to function in disposal of these cytotoxic aldehydes. The liver microsomal and mitochondrial ALDH activities of the two groups were similar. The ADH activity of the liver cytosolic fraction of R rats was nearly twice that of S rats, as measured with 4-hydroxynonenal as substrate. The higher ADH activity may explain the decreased lipid peroxidation in R rats at least partly, if this enzyme is involved in lipid peroxidation.


Development of standard methods for activity measurement of natural radionuclides in waterworks as basis for dose and risk assessment--first results of an Austrian study.
A comprehensive study with the aim to evaluate the risks due to radiation exposure for workers in water supply is conducted in 21 Austrian waterworks. The development of standard methods for the assessment of occupational exposure of water work staff is a part of this study. Preliminary results of this study show a wide range of Rn-222 activity concentration in waterworks with values from (28 ± 10)Bq/m(3) to (38,000 ± 4,000)Bq/m(3). Also seasonal variations of the Rn-222 activity concentration could be observed.


Reproducible method to enrich membrane proteins with high purity and high yield for an LC-MS/MS approach in quantitative membrane proteomics.
The proportionately low abundance of membrane proteins hampers their proteomic analysis, especially for a quantitative LC-MS/MS approach. To overcome this limitation, a method was developed that consists of one cell disruption step in a hypotonic reagent using liquid nitrogen, one isolation step using a low speed centrifugation, and three wash steps using high speed centrifugation. Pellets contained plasma, nuclear, and mitochondrial membranes, including their integral, peripheral, and anchored membrane proteins. The reproducibility of this method was verified by protein assay of four separate experiments with a CV of 7.7%, and by comparative LC-MS/MS label-free quantification of individual proteins between two experiments with 99% of the quantified proteins having a CV ≤30%. Western blot and LC-MS/MS results of markers for cytoplasm, nucleus, mitochondria, and their membranes indicated that the enriched membrane fraction was highly pure by the absence of, or presence of trace amounts of, nonmembrane marker proteins. The average yield of membrane proteins was 237 μg/10 million HT29-MTX cells. LC-MS/MS analysis of the membrane-enriched sample resulted in the identification of 2597 protein groups. In summary, the developed method is reproducible, produces a highly pure membrane fraction, and generates a high yield of membrane proteins.


The Effects of Cadmium Exposure on Cadmium Fractionation and Enzyme Activities in the Rhizosphere of Two Radish Cultivars (Raphanus sativus L.).
The effects of increasing Cd additions on plant growth and Cd fractionation and enzyme activities in rhizosphere soil of two radish cultivars were investigated. The results showed that Cd concentrations in shoot and root of cultivar 4 were both higher than for cultivar 19 under different Cd levels. Compared with cultivar 19, the total, shoot and root biomasses of cultivar 4 were significantly reduced with increasing Cd levels. A decrease in soil pH was observed for cultivar 4. The exchangeable Cd concentration of soil from cultivar 4 was significantly higher than for soil from cultivar 19, while the carbonate-bound Cd concentration of soil from cultivar 4 was significantly lower than for cultivar 19. Enzyme activities, especially acid phosphatase activity, were more susceptible to Cd in soil from cultivar 4. These results indicated that cultivar 19 exhibits a stronger ability to adapt to Cd stress than cultivar 4.


Bioactive secondary metabolites from marine microbes for drug discovery.
The isolation and extraction of novel bioactive secondary metabolites from marine microorganisms have a biomedical potential for future drug discovery as the oceans cover 70% of the planet's surface and life on earth originates from sea. Wide range of novel bioactive secondary metabolites exhibiting pharmacodynamic properties has been isolated from marine microorganisms and many to be discovered. The compounds isolated from marine organisms (macro and micro) are important in their natural form and also as templates for synthetic modifications for the treatments for variety of deadly to minor diseases. Many technical issues are yet to overcome before wide-scale bioprospecting of marine microorganisms becomes a reality. This chapter focuses on some novel secondary metabolites having antitumor, antivirus, enzyme inhibitor, and other bioactive properties identified and isolated from marine microorganisms including bacteria, actinomycetes, fungi, and cyanobacteria, which could serve as potentials for drug discovery after their clinical trials.


Transport of critically ill children in a resource-limited setting.
To audit paediatric intensive care unit (PICU) transfer activity and transfer-related adverse events in a resource-limited setting. Twenty-two bed regional PICU of a university children's hospital in Cape Town, South Africa. Prospective 1-year audit of all children transferred directly from other hospitals. Data were collected for patient demographics, diagnostic category, referring hospital, transferring personnel, mode of transport, and technical, clinical, and critical adverse events. Data are median (interquartile range) or percentages. The transfers of 202 children, median age 2.8 months (1.1-14), median weight 3.5 kg (2.5-8.1) were analysed. Most transfers were performed by paramedic personnel (82%) and via road ambulance (76%). One or more technical adverse events occurred in 36%, clinical adverse events in 27%, and critical adverse events in 9% of children. Retrievals by intensive care staff (10%), all from rural hospitals, had a lower incidence of technical adverse events (0%). Children transferred from non-academic hospitals within the metropolitan area had the highest incidence of technical (44%), clinical (39%), and critical (17%) adverse events. Crude mortality was 17% ( n=34). Technical adverse events were not associated with mortality. Non-survivors were more likely to develop shock (32%) or hypoxia (26%) during transfer than survivors (10% and 11%, respectively). There is a high incidence of transfer-related adverse events, most commonly in transfers from non-academic metropolitan hospitals. Further studies are needed to assess the impact of regional paediatric life support training or a specialised retrieval team on clinical adverse events and mortality.


A Rare Cause of Walking Disorder in Childhood.
Teaching point: Guillain-Barre Syndrome is a rare cause of a walking disorder during childhood. MRI is a key role for diagnosis.