Improvements in total mortality and lipid levels after acute myocardial infarction in an English health district (1995-1999).
To quantify changes in 30 day and one year mortality among patients with acute myocardial infarction in southern Derbyshire (population 560 000) in each of five consecutive years (1995-1999) before the publication of the National Service Framework for coronary heart disease, and to assess the proportion of one year survivors in whom serum lipids were measured and were below target values. All hospital admissions coded on the patient administration system (PAS) as "AMI" (ICD codes I-21, I-22, and I-23) and with a creatine kinase measurement in the pathology database were identified over a five year period (n = 4912). All deaths in the district are automatically notified to the PAS. Total mortality after acute myocardial infarction (30 days and one year) and lipid levels were analysed by year of admission, age group (35-74 years v > or = 75 years), and sex using unconditional logistic regression analysis. An acute hospitals trust and pathology laboratory, as sole service providers for a catchment population of 560 000. The number of admissions for acute myocardial infarction was similar in each of the five years (n = 4912, 62% male, 63% < 75 years old). Overall, among patients aged 35-74 years there were 396 deaths (13%) at 30 days and 585 (19%) at one year; mortality was higher in women (1.28-fold at 30 days, p = 0.02) and in subjects aged 75 years or more (3.26-fold at 30 days, p < 0.0001). There was a progressive reduction in 30 day mortality of 9%/year over the five year period (95% confidence interval, 4% to 13%, p = 0.012). The proportion of one year survivors (35-74 years) in whom serum lipids were measured at least once increased from 74% in 1995 to 88% in 1999; of these, 27% of men and 23% of women had a total serum cholesterol of < 5 mmol/l in 1995, increasing to 65% and 74%, respectively, in 1998 and 1999 (p < 0.0001). In the five year period 1995-1999, there was a significant year on year decline in 30 day and one year mortality after admission for acute myocardial infarction, and progressively more patients achieved cholesterol levels below 5 mmol/l. Men were more likely than women to have their lipids measured after myocardial infarction. Mortality at one year was 1.32-fold higher among women than among men.


Isolation and structure elucidation of pectic polysaccharide from rose hip fruits (Rosa canina L.).
A pectic polysaccharide from rose hip (RH) fruits has been obtained by extraction with 1% aqueous citric acid. It was found that the polysaccharide fraction mainly consisted of galacturonic acid (45.5%) next to galactose (5.5%) and arabinose (4.7%). RH pectin is having a relatively high degree of methylesterification (62%) and acetylation (10%) and consists of different molecular weight populations in the range of 10-100kDa. Enzymatic fingerprinting was performed using a combination of pectin lyase (PL) and endo-polygalacturonase. Detailed information about the structure and level of galacturonic acid oligomers released was obtained using LC-HILIC-MS/ELSD and HPAEC. Predominantly, unsaturated and methyl-esterified oligomers (DP 3-5) were released indicating that high proportions of methylesterified 'PL degradable' areas were present within the pectin. The data revealed that homogalacturonan is the main building block of the extracted pectin and consists of long methylesterified/acetylated GalA sequences interspersed with small blocks of non-methyl-esterified GalA units.


Three-Dimensional (3D) Vision: Does It Improve Laparoscopic Skills? An Assessment of a 3D Head-Mounted Visualization System.
Laparoscopic urologic procedures have become increasingly popular, but their widespread use has been limited by training issues. The use of 3-dimensional (3D) vision might aid in training and performance of laparoscopic tasks. The purpose of this study was to evaluate a 3D visual system used by novice laparoscopists. In this prospective, randomized study, 24 novice laparos-copists were evaluated on a validated and standardized laparoscopic task using both 2-dimensional (2D) and 3D visualization systems. The task was performed more rapidly with 3D visualization (108 vs. 127 seconds, P < .05). On subjective evaluations, participants believed the task was easier with the 3D system, and participants preferred the 3D system to the 2D system by a 2:1 margin. 3D visualization improves the learning curve for laparoscopic surgery. Surgeons should consider 3D systems when learning complex laparoscopic surgeries. Further evaluation of operative times and complications is needed in clinical studies.


Perception of Children's Productions of /l/: Acoustic Correlates and Effects of Listener Experience.
The aim of the current study was to examine the effect of listeners' experience with child speech and phonetic training on perceptual judgment of children's word-initial /l/ productions. The acoustic correlates of acceptable and misarticulated productions of /l/ and their relation to listeners' experience with child speech were explored. Three listener groups listened to children's word-initial /l/ productions embedded in monosyllabic words and judged the "/l/-likeness" of the productions using a Visual Analog Scale (VAS). Three listener groups included (a) speech-language pathologists with at least 10 years of experience (SLP group), (b) graduate students in speech-language pathology (GS group), and (c) naïve listeners with no clinical phonetics experience (NL group). Acoustic correlates (both static and dynamic measures) of listeners' perception of /l/ sounds were also investigated. While mean VAS ratings did not differ significantly by listener group, the SLP group used a wider range of the VAS than the GS and NL groups. Correlational analysis between the static measure (F2-F1 values) and mean listener ratings showed that listeners tend to perceive sounds with the highest F2-F1 values more as /j/ than /l/, while those with the lowest F2-F1 value were perceived more as /w/ than /l/, especially for sounds that are in between phonemic categories. Listener ratings were not highly correlated with dynamic measures. These results suggest that experienced listeners use the VAS more continuously than less experienced listeners to indicate perception of subphonemic features of children's productions of /l/, and that their ratings correlate with acoustic measures. Furthermore, listeners with experience with child speech and phonetic training are more sensitive to subphonemic features of children's productions of /l/, especially for misarticulated productions. This supports the clinical use of VAS for perceptual judgments of children's /l/ productions.


Asymptomatic and neurologically symptomatic HIV-seropositive subjects: results of long-term MR imaging and clinical follow-up.
Cranial magnetic resonance (MR) images were prospectively obtained in 74 human immunodeficiency virus (HIV)-seropositive subjects, all of whom had undergone MR imaging 24-42 months earlier. The images were interpreted by neuroradiologists blinded to the subject's clinical status and were compared with the initial MR images and clinical findings. Ten subjects had mild neurologic symptoms, with mildly abnormal unchanged images in five (50%). Sixty-four subjects were neurologically asymptomatic, with mildly abnormal images in 13 (20%), most of which remained unchanged. chi 2 analysis revealed a significant difference (P = .042) between the asymptomatic and symptomatic groups with regard to the number of subjects with abnormal follow-up images. The number of abnormal images in the asymptomatic subjects was significantly less than that in the symptomatic subjects. During follow-up of 2-3 1/2 years, most asymptomatic subjects had persistently normal MR images. When abnormal, the imaging abnormalities were usually static and minor.


Genomic analysis of the phosphotransferase system in Clostridium botulinum.
Clostridium botulinum is capable of fermenting carbohydrates, but there have been no detailed studies of the uptake of sugars and related substrates. In bacteria, a common and often predominant system of carbohydrate uptake is the phosphoenolpyruvate (PEP)-dependent phosphotransferase system (PTS). This multi-protein complex catalyses a group translocation involving both uptake and phosphorylation of carbohydrates, and is also known to play an important role in environmental sensing and metabolic regulation. The genome of C. botulinum encodes 15 PTSs which have a similar domain structure to the PTS in other bacteria. Based on phylogenetic relationships and analysis of gene clusters, the C. botulinum PTS appears to be involved in the uptake of hexoses, hexose derivatives and disaccharides. C. botulinum also contains the components of PTS-associated regulatory mechanisms which have been characterised in other bacteria. It therefore seems likely that the PTS plays a significant, and previously unrecognised, role in the physiology of this bacterium.


Erythrocyte pyruvate kinase deficiency in the Ohio Amish: origin and characterization of the mutant enzyme.
We have identified eight individuals in an Amish population in Geauga County, Ohio, who have a congenital hemolytic anemia and red cell pyruvate kinase (PK) deficiency. The mutant enzyme is a low Km phosphoenolpyruvate (PEP) variant associated with a slower (77.5% of normal) electrophoretic mobility in starch gel. Because of the high consanguinity in this population, we assume the affected individuals are homozygous for the mutant gene. Genealogical records allow us to trace all eight cases back to a common ancestor who lived in Mifflin County, Pennsylvania. His sister was a common ancestor to all cases of PK deficiency originally described in the Pennsylvania Amish isolate. Therefore, all cases of PK deficiency in the Amish arose from a common ancestral pair.


Campylobacter in waterfowl and aquatic environments: incidence and methods of detection.
Campylobacters are emerging as one of the most significant causes of human infections worldwide, and the role that waterfowl and the aquatic environment have in the spread of disease is beginning to be elucidated. On a world scale campylobacters are possibly the major cause of gastrointestinal infections. Campylobacters are common commensals in the intestinal tract of many species of wild birds, including waterfowl. They are also widely distributed in aquatic environments where their origins may include waterfowl as well as sewage effluents and agricultural runoff. Campylobacters have marked seasonal trends. In temperate aquatic environments they peak during winter, whereas spring-summer is the peak period for human infection. Campylobacter species may survive, and remain potentially pathogenic, for long periods in aquatic environments. The utility of bacterial fecal indicators in predicting the presence of campylobacters in natural waters is questionable. Viable but nonculturable Campylobacter cells may occur, but whether they have any role in the generation of outbreaks of campylobacteriosis is unclear. The routine detection of Campylobacter spp. in avian feces and environmental waters largely relies on conventional culture methods, while the recognition of a particular species or strain is based on serotyping and increasingly on molecular methods. Thus, PCR combined with selective enrichment enhances the detection of campylobacters in water and feces, while DNA sequencing facilitates recognition of particular species and strains.


Thyroid hormones as predictors of short- and long-term mortality in very old hospitalized patients.
Although extensively investigated, the prognostic role of thyroid hormone abnormalities in older participants remains uncertain. We investigated the relationship between thyroid hormones and mortality during hospitalization and in a prolonged follow-up in frail older patients. A nonconcurrent cohort study was conducted by enrolling 450 participants hospitalized for an acute disease, who were classified into four groups (euthyroidism, hypothyroidism, hyperthyroidism, and low triiodothyronine [T3] syndrome), according to clinical and laboratory data. Multidimensional geriatric assessment variables were considered in order to identify short- and long-term predictors of death. Participants were very old (mean age: 84 years) and frail, as indicated by severely impaired functional status, extensive comorbidity, high prevalence of dementia, and hospital mortality (8%). Prevalence of any thyroid dysfunction was 40.7%; 32% of participants had low T3 syndrome, which was associated with an excess hospital mortality risk (odds ratio: 2.7, 95% confidence interval [CI]: 1.1-6.5; p = .025), adjusted for demographic, clinical, functional, and laboratory data. Conversely, long-term mortality was unrelated to low T3 syndrome. In euthyroid participants, increasing levels of free thyroxine (FT4) were associated with a slightly greater mortality (hazard ratio, CI: 2.12, 0.99-4.54; p = .053) in adjusted Cox regression models. This observational study on a cohort of very old, frail hospitalized patients gives support to the independent prognostic short-term, but not long-term, role of low T3 syndrome. Moreover, in older euthyroid participants, increasing levels of FT4 are a weak marker of poorer long-term survival. Thyroid hormones may help monitor changes in general health status and predict short- and long-term clinical outcomes in very old, frail patients.


Exposure to common respiratory bacteria alters the airway epithelial response to subsequent viral infection.
Colonization of the airways with potential pathogenic bacteria is observed in a number of chronic respiratory diseases, such as COPD or cystic fibrosis. Infections with respiratory viruses are known triggers of exacerbations of these diseases. We here investigated if pre-exposure to bacteria alters the response of lung epithelial cells to subsequent viral infection. Bronchial epithelial cells (BEAS-2B cells and primary bronchial epithelial cells) were exposed to heat-inactivated Haemophilus influenzae, Pseudomonas aeruginosa or Streptococcus pneumoniae and subsequently infected with respiratory syncytial virus (RSV), type 2 human adenovirus or influenza B. Levels of pro-inflammatory cytokines, viral replication and expression of pattern recognition receptors were determined in culture supernatants and/or cell lysates. Exposure of BEAS-2B cells to H. influenzae before and during RSV-infection synergistically increased the release of IL-6 (increase above calculated additive effect at 72 h: 56 % ± 3 %, mean ± SEM) and IL-8 (53 % ± 12 %). This effect was sustained even when bacteria were washed away before viral infection and was neither associated with enhanced viral replication, nor linked to increased expression of key pattern recognition receptors. P. aeruginosa enhanced the release of inflammatory cytokines to a similar extent, yet only if bacteria were also present during viral infection. S. pneumoniae did not enhance RSV-induced cytokine release. Surprisingly, adenovirus infection significantly reduced IL-6 release in cells exposed to either of the three tested bacterial strains by on average more than 50 %. Infection with influenza B on the other hand did not affect cytokine production in BEAS-2B cells exposed to the different bacterial strains. Pre-exposure of epithelial cells to bacteria alters the response to subsequent viral infection depending on the types of pathogen involved. These findings highlight the complexity of microbiome interactions in the airways, possibly contributing to the susceptibility to exacerbations and the natural course of airway diseases.


Endoscopic retrograde cholangiopancreatography (ERCP) in biliary tract disease of infants less than one year old.
We performed a total of 75 examinations with endoscopic retrograde chlangiopancreatography (ERCP) in 73 infants aged from 8 days to 300 days (mean 71 days) between 1977 and 1995. ERCP examination was performed with a prototype duodenoscope and was successful in 47 of 52 examinations in biliary atresia, 9 of 11 in neonatal hepatitis, all 4 in paucity of intra-hepatic bile duct, 4 of 5 in congenital biliary dilatation, 1 of 2 in duodenal stricture, and 1 case of in postoperative jaundice of hepatoblastoma. In 46 infants with biliary atresia, excluding one in whom the findings could not be evaluated due to poor x-ray image quality, we distinguished the following four patterns of ERCP findings: Pattern 1, only the pancreatic duct could be demonstrated and no bile duct was visualized (76%); Pattern 2, only a part of the distal common bile duct with the pancreatic duct was visualized (2%); Pattern 3, the entire length of the common bile duct with the pancreatic duct was visualized without the gallbladder and the common hepatic duct (4%); and Pattern 4, the common bile duct and the gallbladder with the pancreatic duct were visualized without the common hepatic duct (18%). In all of these 46 patients, laparotomy, an operative cholangiogram, and histological evaluation of the biliary duct were performed. In 9 neonates with neonatal hepatitis, the biliary tract was opacified and biliary atresia was excluded. Laparotomy was thus avoided in these neonates. There was no complication caused by either ERCP or by anesthesia.


Bacterial diversity of cosmopolitan Culex pipiens and invasive Aedes japonicus from Germany.
Symbiotic bacteria have gained significant attention in recent years. For example, microbiota of some mosquito species seems to influence the development and transmission of pathogens. Furthermore, several attempts using bacteria as a paratransgenetic tool have been made in order to assist the control of mosquito-borne diseases. In this study, we examined the bacterial diversity of wild-caught adult Culex (Cx.) pipiens and laboratory-reared adult Aedes japonicus (Ae. japonicus) in Germany using a culture-independent method. Genomic DNA was extracted from each specimen and submitted to PCR amplification of eubacterial 16S rDNA. After the cloning reaction, 28 bacterial transformants per sample containing the 16S rDNA inserts were selected per each sample for sequencing. The analysed specimens of Cx. pipiens as well as of Ae. japonicus showed a diverse bacterial community including some common bacterial genera. Blast analysis allowed to identify 21 bacterial genera belonging to 2 phyla among the 23 specimens of Cx. pipiens. The 14 analysed Ae. japonicus revealed 11 bacterial genera belonging to 3 phyla. In both mosquito species, identified isolates were mainly Proteobacteria. Only 4 of the bacterial genera were found in both mosquito species, with the most prevalent genera Sphingomonas and Rahnella in Cx. pipiens and in Ae. japonicus respectively. Most of the bacterial genera found in our study have been identified in other mosquito species before. Due to the currently scarce data situation, ongoing examinations on the very abundant bacterial genera or species are strongly required to determine their relevance for the biology and adaptiveness of mosquitoes including pathogen-host relationship.


GRP78 Impairs Production of Lipopolysaccharide-Induced Cytokines by Interaction with CD14.
The 78-kDa glucose-regulated protein (GRP78) is a stress-inducible chaperone that resides primarily in the endoplasmic reticulum. GRP78 has been described to be released at times of cellular stress and as having extracellular properties that are anti-inflammatory or favor the resolution of inflammation. In the current study, we confirmed that GRP78 impaired the production of lipopolysaccharide-induced pro-inflammatory cytokines in GRP78-treated bone-marrow-derived dendritic cells (DCs). To explore the underlying mechanism, first of all, GRP78 was checked to be bound to the plasma membrane. Interestingly, such binding promoted endocytosis of toll-like receptor (TLR) 4 and reduction in TLR4 on the plasma surface had a key role in desensitization of GRP78-treated DCs to lipopolysaccharide. Given that cluster of differentiation (CD)14 is a crucial regulator of TLR4 endocytosis, interaction of GRP78 with CD14 was investigated next. Data showed that GRP78 co-localized with CD14 on the plasma membrane and glutathione-S-transferase-GRP78 precipitated CD14. In CD14 knockout mice, down-regulation of tumor necrosis factor-α and reduction in TLR4 on the plasma surface were abrogated in GRP78-treated DCs. Overall, these data suggested that GRP78 mediates endocytosis of TLR4 by targeting CD14 to favor the resolution of inflammation.


Preclinical Studies and Translational Applications of Intracerebral Hemorrhage.
Intracerebral hemorrhage (ICH) which refers to bleeding in the brain is a very deleterious condition with high mortality and disability rate. Surgery or conservative therapy remains the treatment option. Various studies have divided the disease process of ICH into primary and secondary injury, for which knowledge into these processes has yielded many preclinical and clinical treatment options. The aim of this review is to highlight some of the new experimental drugs as well as other treatment options like stem cell therapy, rehabilitation, and nanomedicine and mention some translational clinical applications that have been done with these treatment options.


Influence of the subarachnoid position of microcatheters on onset of analgesia and dose of plain bupivacaine 0.5% in continuous spinal anesthesia.
Many factors have an impact on the outcome of continuous spinal anesthesia (CSA) with small-bore catheters. Recent publications of neurologic complications after CSA suggest that the local anesthetic as well as the microspinal catheter influence the analgesic effect in CSA. This prospective study was designed to evaluate the influence of the subarachnoid position of 28-gauge spinal catheters on the speed of onset of analgesia and on the dose of plain bupivacaine 0.5% required for a block at the level of T-10 in CSA. Sixty-eight patients (mean age 61.7 +/- 6.4 years) received CSA using a 22-gauge Quincke needle (Kendall, Mansfield, MA) and a 28-gauge spinal catheter. After initial injection of 2.5 mL (minimum) up to a maximum of 5 mL of supplemental doses of plain bupivacaine 0.5%, the time of onset of analgesia at the level of T-10 and the dose of local anesthetics required for this block were determined. The subarachnoid catheter position was examined radiographically by a dye supported conventional anteroposterior roentgenogram of the lumbar spine on the first day after the operation. The onset time of analgesia and the dose of plain bupivacaine 0.5% required for the block at the level of T-10 were significantly dependent on the subarachnoid position of the microcatheters (P < .01), but not on the level of the lumbar dural puncture (P = .29, P = .69). In patients with cranially running catheters or catheters with the tip at the level of the puncture site, analgesia onset was faster and required doses of bupivacaine were smaller than in patients with caudally running catheters. The subarachnoid position of a 28-gauge microcatheter is an important factor with regard to the effectiveness (e.g., onset time of analgesia and dose requirement) of CSA using plain bupivacaine 0.5%.


Random Serum Cortisol as a Predictor for Survival of Terminally Ill Patients With Cancer: A Preliminary Study.
Although previous research found that serum cortisol levels were associated with cancer prognosis, it is unclear whether this association remains robust even at the very end of life of patients with cancer. We conducted a retrospective chart review of 125 patients with terminal cancer to investigate the role of random serum cortisol levels in predicting the remaining life expectancy. The high random cortisol group had a significantly shorter survival time than the low random cortisol group (7.5 vs 26 days). After adjusting for potential confounders, key factors such as poor performance status, hypoalbuminemia, and high random cortisol level are associated with poor survival. Our results suggest that the random serum cortisol level is an independent predictor of survival time of patients with terminally ill cancer.


The Mark Coventry Award: white blood cell gene expression: a new approach toward the study and diagnosis of infection.
We introduce a new genomic approach toward the study and diagnosis of infection. Our purpose is to show that synovial fluid white blood cells express a gene expression "signature" that differentiates septic from aseptic inflammation. Synovial fluid was aspirated from patients with acute Staphylococcus aureus infections or acute gout of the knee. Differential cell counts included predominantly neutrophils in all aspirates. Ribonucleic acid was isolated from the synovial-fluid white blood cells and was analyzed on the Affymetrix U133A GeneChip. The neutrophils from a patient whose knee is infected with Staphylococcus aureus can be distinguished from the neutrophils found in gout by nature of their differential gene expression. There are 1615 genes that have an expression level that is significantly different between the groups. The 124 most significant differences are in genes from immune pathways including the interleukin pathway, the tumor necrosis factor pathway, and the antibacterial response. The neutrophils at a site of infection (Staphylococcus aureus) express different genes than the neutrophils at a site of aseptic inflammation (gout). To our knowledge, this is the first in vivo demonstration of this principle. The differences in neutrophil gene expression may be used to develop simple laboratory tests that distinguish the causes of inflammation in a total joint arthroplasty. Diagnostic study, Level II-1. See the Guidelines for Authors for a complete description of levels of evidence.


Clinical and molecular prognostic and predictive biomarkers in clear cell renal cell cancer.
The natural history of clear cell renal cell cancer is highly unpredictable with various progressors and with populations where small renal masses may be accompanied by metastatic disease. Currently, there is a critical need to determine patient risk and optimize treatment regimes. For these patients, molecular markers may offer significant information in terms of prognostic and predictive values, as well as determination of valid therapeutic targets. Until now, only a few of the many identified clear cell renal cell cancer biomarkers have been clinically validated in large cohorts. And only several biomarkers are integrated in predictive or prognostic models. Therefore, a large cohesive effort is required to advance the field of clear cell renal cell cancer prognostic biomarkers through systematic discovery, verification, validation and clinical implementation.


Self-retaining intraurethral stent: an alternative to long-term indwelling catheters or surgery in the treatment of prostatism.
The self-retaining intraurethral coil is a device to stent the urethra in men who have severe urethral obstruction. It allows them to empty their bladders and still remain continent and sexually active. The device can be used in place of long-term indwelling catheters or as an alternative to surgery. During 1 year, we inserted the stent in 26 men who were poor operative risks. The treatment was successful in 20 (77%). All 20 were able to void satisfactorily. Four of the 20 resumed sexual activity, which previously had been prevented by indwelling catheters. Two patients who had delayed prostatic surgery because of fear of impotence were able to empty their bladders properly and to remain sexually active. Three patients subsequently had surgery, two after anticoagulant therapy could be stopped and one after renal function improved. No difficulties caused by the stent were encountered during surgery. Follow-up was for 2-12 months. Four patients who had had the stent in place for 12 months had no difficulties. In 16 of the 18 patients who had indwelling catheters and infected urine before insertion of the stent, sterilization of the urine was obtained after relatively short courses of antibiotic treatment. Short-term complications associated with the stent were incontinence or urinary retention. These were treated by repositioning the stent. Frequency of urination after insertion of the stent either disappeared spontaneously or was treated with anticholinergic drugs. In six patients, frequency was so severe that removal of the stent and insertion of an indwelling catheter were necessary. Slight to mild dysuria occurred immediately after surgery in all patients but eventually disappeared. Our experience suggests that the self-retaining intraurethral stent has considerable promise for the treatment of prostatic obstruction of the urethra.


Amino acid residues in subsites e and f responsible for the characteristic enzymatic activity of duck egg-white lysozyme.
We analyzed the enzymatic properties of duck egg-white lysozyme II (DEL), which differs from hen egg-white lysozyme (HEL) in nineteen amino acid substitutions. A substrate binding study showed that DEL binds to the substrate analog at subsites A-C in the same manner as HEL. However, the experimental time-courses of DEL against the substrate N-acetylglucosamine pentamer, (GlcNAc)(5), revealed remarkably enhanced production of (GlcNAc)(2) and reduced production of (GlcNAc)(1) as compared to in the case of HEL. Computer simulation of the DEL-catalyzed reaction suggested that the amino acid substitutions at subsites E and F (Phe34 to Tyr and Asn37 to Ser) caused the great alteration in the time-courses of DEL. Subsequently, the enzymatic reactions of mutants, in which Phe34 and Asn37 in HEL were converted to Tyr and Ser, respectively, were characterized. The time-courses of the F34Y mutant exhibited profiles similar to those of HEL. In contrast, the characteristics of the N37S mutant were different from those of HEL and rather similar to those of DEL; the order of the amounts of (GlcNAc)(1) and (GlcNAc)(2) was reversed in comparison with in the case of HEL. Enhanced production of (GlcNAc)(2) was also observed for the mutant protein, F34Y/N37S, with two substitutions. These results indicated that the substitution of Asn37 with Ser can account, at least in part, for the characteristic time-courses of DEL. Moreover, replacement of Asn37 with Ser reduced the rate constant of transglycosylation. The substitution of the Asn37 residue may affect the transglycosylation activity of HEL.


[Genetic analysis of a pedigree with primary hypertrophic osteoarthropathy].
Objective: To analyze the clinical and genetic features of primary hypertrophic osteoarthropathy (PHO). Methods: The clinical data of one Chinese pedigree of PHO, namely pachydermoperiostosis (PDP) were collected.Blood samples were drawn from the propositus and other family members.DNA was extracted and genetic analysis was performed by Sanger method after PCR.The sequencing data of HPGD gene exons were analyzed by alignment with sequences from National Center for Biotechnology Information (NCBI). Results: (1)The propositus represented symptoms in childhood including clubbing fingers, sweating, seborrhea, joint swelling and so on.Periosteal thickening and bone hyperplasia were found by X-ray. (2)The homozygous mutation named c. 310_311delCT in propositus, which located in the third exon of HPGD, was identified.His parents carried the same heterozygous mutation, while his sister did not inherit any mutation of this gene. (3)The prediction of spatial structure of proteins revealed that the mutant proteins had about 60% discrepancy compared with wild-type protein, losing a lot of motifs responsible for combining with coenzyms and prostaglandin E(2), as well as active sites of enzymes. Conclusions: The clinical manifestations and imaging findings are helpful to diagnose PDP. Moreover gene mutation analysis ensures the diagnosis.The structure and function of HPGD gene mutation induce 15-hydroxy prostaglandin dehydrogenase mutation, contributing to the occurrence of PDP.


Role of Sphingosine-1-Phosphate in Mast Cell Functions and Asthma and Its Regulation by Non-Coding RNA.
Sphingolipid metabolites are emerging as important signaling molecules in allergic diseases specifically asthma. One of the sphingolipid metabolite, sphingosine-1-phosphate (S1P), is involved in cell differentiation, proliferation, survival, migration, and angiogenesis. In the allergic diseases, alteration of S1P levels influences the differentiation and responsiveness of mast cells (MCs). S1P is synthesized by two sphingosine kinases (SphKs), sphingosine kinase 1, and sphingosine kinase 2. Engagement of IgE to the FcεRI receptor induces the activation of both the SphKs and generates S1P. Furthermore, SphKs are also essential to FcεRI-mediated MC activation. Activated MCs export S1P into the extracellular space and causes inflammatory response and tissue remodeling. S1P signaling has dual role in allergic responses. Activation of SphKs and secretion of S1P are required for MC activation; however, S1P signaling plays a vital role in the recovery from anaphylaxis. Several non-coding RNAs have been shown to play a crucial role in controlling the MC-associated inflammatory and allergic responses. Thus, S1P signaling pathway and its regulation by non-coding RNA could be explored as an exciting potential therapeutic target for asthma and other MC-associated diseases.


Dynamic light scattering arising from flowing Brownian particles: analytical model in optical coherence tomography conditions.
The statistical model of scattered by flowing Brownian particles coherent radiation is suggested. The model includes the random Doppler shifts caused by particle Brownian motion and the speckle fluctuations caused primarily by the flow motion of particles. Analytical expressions are obtained for the correlation function, power spectrum, and spectral width of scattered radiation in the imaging geometry typically used in optical coherence tomography (OCT). It is shown that the spectral density has the Voigt shape, a well-known spectral profile from atomic and molecular spectroscopy. The approach enables the choice of the experimental regimes for the measurement of Brownian particle motion parameters even in the presence of flow. These regimes are characterized by the dominant contribution of Brownian motion in the spectral width of the flow-caused Doppler shift component. Further, the new formalism suggests that prior attempts to extract transverse flow velocity are only valid at near-perpendicular geometry. The impact of the small scattering volume contributing to the OCT signal is also discussed.


Disseminated intravascular coagulation in cats.
The purpose of this study was to describe the clinical characteristics of cats with disseminated intravascular coagulation (DIC), including associated diseases and hemostatic abnormalities, and to identify risk factors for death and treatments that potentially altered outcome. Medical records for cats with DIC from 1990-2004 were evaluated retrospectively. Inclusion criteria were the presence of an underlying disorder associated with DIC and either postmortem examination findings of intravascular fibrin deposition or thrombosis, or both of 2 or more organs or coagulation profiles that meet 3 of 5 criteria: prolonged prothrombin time (PT), activated partial thromboplastin time (aPTT), presence of fibrin degradation products (FDP), low plasma fibrinogen (FIB) concentration, and thrombocytopenia (<160,000 platelets/microL). Signalment, historical data, clinical findings, clinicopathologic data, underlying disorders, management, and outcome were recorded. Forty-six cats fulfilled the criteria for DIC. Cats ranged in age from 7 weeks to 17 years (median, 9 years). Hemorrhage was noted in 7 of 46 cats (15%). Three of 46 cats (7%) survived, whereas 43 of 46 (93%) died or were euthanized. The most common underlying disorders were lymphoma, other forms of neoplasia, pancreatitis, and sepsis. There was no association detected between outcome and signalment; underlying disease; hemorrhage; abnormalities in aPTT, FIB, FDPs, platelet count; transfusion of blood products; and heparin therapy. However, the median PT of nonsurvivors was more prolonged than in survivors (P < .005). DIC in cats can result from a variety of neoplastic, infectious, and inflammatory disorders, and is associated with a high case fatality rate.


Temporal variation of RAPD-PCR phenotype composition of the grain aphid Sitobion avenae (Hemiptera: Aphididae) on wheat: the role of hydroxamic acids.
Hydroxamic acids (Hx) contained in wheat are active mutagens which play an important role in the defence of the plant against aphids. Random amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR) dominant markers were used to assess genetic variability in the aphid Sitobion avenae (Fabricius) in relation to hydroxamic acid levels in their host-plants. Colonies of aphids belonging to a single RAPD-PCR profile were grown on different host-plants differing in their Hx content under greenhouse conditions. The RAPD-PCR phenotypic pattern showed the appearance of two new RAPD-PCR variants after four to five generations of exposure to wheat cv. Chagual (high Hx levels), one after exposure to wheat cv. Huayún (low Hx levels), and none after exposure to oat (lacking Hx). Differential appearance of new RAPD-PCR aphid phenotypes also occurred on field-grown wheat. While the overall phenotypic 'richness' diminished during the season, the number of RAPD-PCR phenotypes decreased on cv. Huayún and increased on cv. Chagual. The preferential appearance in the field and in the greenhouse of new RAPD-PCR phenotypes of S. avenae on cv. Chagual is discussed on the basis of mutagenesis induced by hydroxamic acids and by the products of their transformation within the aphid. Aphid abundance is interpreted in terms of antixenosis and antibiosis by hydroxamic acids. The appearance on cv. Chagual of phenotypes first detected on cv. Huayún was accounted for by intercrop migrations.


Water Dynamics at Protein-Protein Interfaces: Molecular Dynamics Study of Virus-Host Receptor Complexes.
The dynamical properties of water at protein-water interfaces are unlike those in the bulk. Here we utilize molecular dynamics simulations to study water dynamics in interstitial regions between two proteins. We consider two natural protein-protein complexes, one in which the Nipah virus G protein binds to cellular ephrin B2 and the other in which the same G protein binds to ephrin B3. While the two complexes are structurally similar, the two ephrins share only a modest sequence identity of ∼50%. X-ray crystallography also suggests that these interfaces are fairly extensive and contain exceptionally large amounts of waters. We find that while the interstitial waters tend to occupy crystallographic sites, almost all waters exhibit residence times of less than hundred picoseconds in the interstitial region. We also find that while the differences in the sequence of the two ephrins result in quantitative differences in the dynamics of interstitial waters, the trends in the shifts with respect to bulk values are similar. Despite the high wetness of the protein-protein interfaces, the dynamics of interstitial waters are considerably slower compared to the bulk-the interstitial waters diffuse an order of magnitude slower and have 2-3 fold longer hydrogen bond lifetimes and 2-1000 fold slower dipole relaxation rates. To understand the role of interstitial waters, we examine how implicit solvent models compare against explicit solvent models in producing ephrin-induced shifts in the G conformational density. Ephrin-induced shifts in the G conformational density are critical to the allosteric activation of another viral protein that mediates fusion. We find that in comparison with the explicit solvent model, the implicit solvent model predicts a more compact G-B2 interface, presumably because of the absence of discrete waters at the G-B2 interface. Simultaneously, we find that the two models yield strikingly different induced changes in the G conformational density, even for those residues whose conformational densities in the apo state are unaffected by the treatment of the bulk solvent. Together, these results show that the explicit treatment of interstitial water molecules is necessary for a proper description of allosteric transitions.


A case of anterior mediastinum paraganglioma presented with pericardial effusion two years before symptoms of catecholamine excess: first case report in Thailand.
Pheochromocytoma (PCC) and paraganglioma (PGL) are uncommon tumors. Clinical manifestations are mass effect or hormone secretion. The initial manifestation with pericardial effusion is rare. The author presented a case of anterior mediastinum paraganglioma presenting with pericardial effusion two years before symptoms of catecholamine excess. This is the first case reported in Thailand. A 34 year-old female patient presented with dyspnea. There was pericardial effusion from echocardiography was diagnosed with no definite causes of pericardial effusion. After treatment with ibuprofen, pericardial effusion was absolutely resolved from repeated echocardiography. Two years later she had headache and hypertension. Chest X-ray, there was an anterior mediastinal mass. Her 24 hours urine metanephrine was very high. By imaging, an anterior mediastinal mass was observed from CT chest without adrenal mass from CT abdomen. The result of metaiodobenzylguanidine (MIBG) scan was compatible with paraganglioma. Symptoms of headache and hypertension disappeared after surgical removal of the mass. Pericardial effusion may be the first manifestation of paraganglioma especially if the patient had hypertension or could not find the etiology. Thus, pericardial effusion should be investigated for paraganglioma. Due to long term follow-up, this indolent growing tumor may respond to NSAIDs or regress spontaneously.


Beta-carotene metabolites enhance inflammation-induced oxidative DNA damage in lung epithelial cells.
beta-Carotene (BC) intake has been shown to enhance lung cancer risk in smokers and asbestos-exposed subjects (according to the ATBC and CARET studies), but the mechanism behind this procarcinogenic effect of BC is unclear. Both smoking and asbestos exposure induce an influx of inflammatory neutrophils into the airways, which results in an increased production of reactive oxygen species and formation of promutagenic DNA lesions. Therefore, the aim of our study was to investigate the effects of BC and its metabolites (BCM) on neutrophil-induced genotoxicity. We observed that the BCM vitamin A (Vit A) and retinoic acid (RA) inhibited the H(2)O(2)-utilizing enzyme myeloperoxidase (MPO), which is released by neutrophils, thereby reducing H(2)O(2) conversion. Moreover, BC and BCM were able to increase (.)OH formation from H(2)O(2) in the Fenton reaction (determined by electron spin resonance spectroscopy). Addition of Vit A and RA to lung epithelial cells that were co-incubated with activated neutrophils resulted in a significant increase in the level of oxidized purines assessed by the formamidopyrimidine DNA glycosylase-modified comet assay. These data indicate that BCM can enhance neutrophil-induced genotoxicity by inhibition of MPO in combination with subsequent increased formation of hydroxyl radicals.


Technical aspects of lymphoma immunohistology.
Immunohistological techniques (i.e., based on tissue sections) for the study of human lymphoma have been developed in recent years as alternatives to immunocytochemical methods (based on cell suspensions). These techniques not only allow the important architectural features of the lymphoma sample to be preserved, but are also more convenient to use in that tissues can be processed rapidly and studied at leisure. The relative advantages and disadvantages of frozen versus fixed embedded tissue, and of immunofluorescence versus immunoenzymatic methods are reviewed, and technical aspects of proteolytic digestion (as a technique for enhancing immunohistochemical labeling) are discussed. This review concludes with a consideration of the problems encountered in the interpretation of immunohistochemical labeling for lymphoma cell immunoglobulin in paraffin sections.


Non-Hodgkin's lymphoma arising in bone in children and adolescents is associated with an excellent outcome: a Children's Cancer Group report.
Non-Hodgkin's lymphoma (NHL) arising in bone is a heterogeneous histologic type of NHL that includes large-cell lymphoma, lymphoblastic lymphoma, and small noncleaved-cell lymphoma. NHL arising in bone is well recognized in adults but is less well characterized and infrequent in children and adolescents. We performed a retrospective review of Children's Cancer Group (CCG) studies treating children and adolescents with NHL over a 20-year period (CCG-551, CCG-501, CCG-502, CCG-503, CCG-552, CCG-5911, and CCG-5941) and determined the response and event-free survival (EFS) rates in 31 patients with NHL arising in bone. The patients ranged in age from 3 to 17 years (median, 11 years; mean, 11 years), and 64.5% were male. All 31 (100%) patients achieved complete response. For 31 patients with NHL arising in bone, the product-limit estimated 5-year EFS was 83.8% +/- 6.7%. EFS in 17 patients with localized disease (Murphy stages I and II) was 94.1% +/- 5.7%, and EFS in 14 patients with disseminated disease (Murphy stage III) was 70.7% +/- 12.4% (log-rank P =.10). EFS in 17 patients treated with chemotherapy and radiation was 70.1% +/- 11.2%, and EFS in 14 patients treated with chemotherapy without radiation was 100% (P =.03). EFS in 26 patients with histology-directed treatment (LSA2-L2 or ADCOMP for lymphoblastic, other therapy for nonlymphoblastic) was 92.2% +/- 5.3%, and in five patients with nonhistology-directed treatment it was 40.0% +/- 21.9% (P <.001). NHL arising in bone is a heterogeneous type of NHL that makes up approximately 2.0% of NHL in children and adolescents on CCG studies. Response and survival in this young age group seem superb, with histology-directed treatment protocols without radiation in both localized and disseminated disease.


Cholera toxin and cholera toxin B subunit induce IgA switching through the action of TGF-beta 1.
Cholera toxin (CT) and its B subunit (CTB) are potent immunogens and adjuvants that, either alone or linked to protein Ags, can stimulate mucosal immune responses, modulate the induction of oral tolerance, and stimulate IgA isotype switching. The present studies addressed the mechanisms by which CT and CTB promote IgA switching. CT and rCTB, in the presence of IL-2, significantly increased IgA isotype switching at the clonal level in populations of purified and LPS-activated murine surface IgA- spleen B cells, as determined by ELISA, enzyme linked immunospot assays, and limiting dilution analysis. The IgA stimulatory effects of CT and CTB were independent of the A subunit of CT. CTB and CT did not increase the secretory rate of IgA-producing cells or the clonal burst size of IgA clones, and did inhibit B cell growth. Because TGF-beta 1 also inhibits B cell growth and promotes IgA switching, further studies tested whether the activity of CTB and CT on IgA isotype switching was mediated through TGF-beta 1. Anti-TGF-beta Ab and soluble TGF-beta 1 type IIR inhibited CTB- and CT-stimulated IgA isotype switching. Furthermore, increased TGF-beta 1 mRNA levels and bioactive TGF-beta 1, within a range shown to induce IgA isotype switching, were detected in cultures of surface IgA- B cells stimulated with CT or CTB and IL-2. These data indicate that CTB- and CT-stimulated IgA isotype switching are mediated through TGF-beta 1. The finding that CTB up-regulates TGF-beta 1 activity has important implications for understanding the mechanisms by which CTB promotes both IgA mucosal immunity and oral tolerance.


Self-Assembly of Tetraphenylalanine Peptides.
Three different tetraphenylalanine (FFFF) based peptides that differ at the N- and C-termini have been synthesized by using standard procedures to study their ability to form different nanoassemblies under a variety of conditions. The FFFF peptide assembles into nanotubes that show more structural imperfections at the surface than those formed by the diphenylalanine (FF) peptide under the same conditions. Periodic DFT calculations (M06L functional) were used to propose a model that consists of three FFFF molecules defining a ring through head-to-tail NH3(+)⋅⋅⋅(-)OOC interactions, which in turn stack to produce deformed channels with internal diameters between 12 and 16 Å. Depending on the experimental conditions used for the peptide incubation, N-fluorenylmethoxycarbonyl (Fmoc) protected FFFF self-assembles into a variety of polymorphs: ultra-thin nanoplates, fibrils, and star-like submicrometric aggregates. DFT calculations indicate that Fmoc-FFFF prefers a parallel rather than an antiparallel β-sheet assembly. Finally, coexisting multiple assemblies (up to three) were observed for Fmoc-FFFF-OBzl (OBzl = benzyl ester), which incorporates aromatic protecting groups at the two peptide terminals. This unusual and noticeable feature is attributed to the fact that the assemblies obtained by combining the Fmoc and OBzl groups contained in the peptide are isoenergetic.


Lurasidone for major depressive disorder with mixed features and irritability: a post-hoc analysis.
The aim of this post-hoc analysis was to evaluate the efficacy of lurasidone in treating major depressive disorder (MDD) with mixed features including irritability. The data in this analysis were derived from a study of patients meeting DSM-IV-TR criteria for unipolar MDD, with a Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≥26, presenting with two or three protocol-defined manic symptoms, and who were randomized to 6 weeks of double-blind treatment with either lurasidone 20-60 mg/d (n=109) or placebo (n=100). We defined "irritability" as a score ≥2 on both the Young Mania Rating Scale (YMRS) irritability item (#5) and the disruptive-aggressive item (#9). Endpoint change in the MADRS and YMRS items 5 and 9 were analyzed using a mixed model for repeated measures for patients with and without irritability. Some 20.7% of patients met the criteria for irritability. Treatment with lurasidone was associated with a significant week 6 change vs. placebo in MADRS score in both patients with (-22.6 vs. -9.5, p<0.0001, effect size [ES]=1.4) and without (-19.9 vs. -13.8, p<0.0001, ES=0.7) irritability. In patients with irritable features, treatment with lurasidone was associated with significant week 6 changes vs. placebo in both the YMRS irritability item (-1.4 vs. -0.3, p=0.0012, ES=1.0) and the YMRS disruptive-aggressive item (-1.0 vs. -0.3, p=0.0002, ES=1.2). In our post-hoc analysis of a randomized, placebo-controlled, 6-week trial, treatment with lurasidone significantly improved depressive symptoms in MDD patients with mixed features including irritability. In addition, irritability symptoms significantly improved in patients treated with lurasidone.


Dendritic keratitis caused by an acyclovir-resistant herpes simplex virus with frameshift mutation.
To report a case of acyclovir-resistant herpes simplex virus (HSV) keratitis after long-term, inconsistent use of topical acyclovir and fluorometholone. A 70-year-old man with dendritic keratitis caused by an acyclovir-resistant HSV strain was examined. The 50% inhibitory concentration of different antiviral agents against the isolated virus and the DNA sequence of viral thymidine kinase were determined. The 50% inhibitory concentration of acyclovir and trifluorothymidine for the isolated HSV strain was 13.75 and 0.28 microg/mL, respectively, indicating that the virus was resistant to acyclovir. DNA sequencing of the viral thymidine kinase revealed that this virus had a frameshift mutant with a G insertion in the 7Gs homopolymer. Topical trifluorothymidine was effective, and the epithelial lesion was completely resolved within 2 weeks. A typical form of dendritic keratitis was caused by an acyclovir-resistant HSV with frameshift mutation in a 7Gs homopolymer region.


Ab initio potential energy surfaces for both the ground (X (1)A') and excited (A (1)A") electronic states of HGeCl and the absorption and emission spectra of HGeCl/DGeCl.
Potential energy surfaces for the ground (X (1)A(')) and excited (A (1)A(")) electronic states of HGeCl and the transition dipole moment surface were obtained using an internally contracted multireference configuration interaction method with the Davidson correction and an augmented correlation-consistent polarized valence quadruple zeta basis set. Calculated vibrational energy levels of HGeCl and DGeCl on both the ground and excited electronic states are in excellent agreement with available experimental data. In addition, the absorption and emission spectra of both HGeCl and DGeCl were obtained using an efficient single Lanczos propagation method and the agreement with experimental spectra is also excellent.


Response, thermal regulatory threshold and thermal breakdown threshold of restrained RF-exposed mice at 905 MHz.
The objective of this study was the determination of the thermal regulatory and the thermal breakdown thresholds for in-tube restrained B6C3F1 and NMRI mice exposed to radiofrequency electromagnetic fields at 905 MHz. Different levels of the whole-body averaged specific absorption rate (SAR = 0, 2, 5, 7.2, 10, 12.6 and 20 W kg(-1)) have been applied to the mice inside the 'Ferris Wheel' exposure setup at 22 +/- 2 degrees C and 30-70% humidity. The thermal responses were assessed by measurement of the rectal temperature prior, during and after the 2 h exposure session. For B6C3F1 mice, the thermal response was examined for three different weight groups (20 g, 24 g, 29 g), both genders and for pregnant mice. Additionally, NMRI mice with a weight of 36 g were investigated for an interstrain comparison. The thermal regulatory threshold of in-tube restrained mice was found at SAR levels between 2 W kg(-1) and 5 W kg(-1), whereas the breakdown of regulation was determined at 10.1 +/- 4.0 W kg(-1)(K = 2) for B6C3F1 mice and 7.7 +/- 1.6 W kg(-1)(K = 2) for NMRI mice. Based on a simplified power balance equation, the thresholds show a clear dependence upon the metabolic rate and weight. NMRI mice were more sensitive to thermal stress and respond at lower SAR values with regulation and breakdown. The presented data suggest that the thermal breakdown for in-tube restrained mice, whole-body exposed to radiofrequency fields, may occur at SAR levels of 6 W kg(-1)(K = 2) at laboratory conditions.


Polarity governed selective amplification of through plane proton shuttling in proton exchange membrane fuel cells.
Graphene oxide (GO) anisotropically conducts protons with directional dominance of in plane ionic transport (σ IP) over the through plane (σ TP). In a typical H2-O2 fuel cell, since the proton conduction occurs through the plane during its generation at the fuel electrode, it is indeed inevitable to selectively accelerate GO's σ TP for advancement towards a potential fuel cell membrane. We successfully achieved ∼7 times selective amplification of GO's σ TP by tuning the polarity of the dopant molecule in its nanoporous matrix. The coexistence of strongly non-polar and polar domains in the dopant demonstrated a synergistic effect towards σ TP with the former decreasing the number of water molecules coordinated to protons by ∼3 times, diminishing the effects of electroosmotic drag exerted on ionic movements, and the latter selectively accelerating σ TP across the catalytic layers by bridging the individual GO planes via extensive host guest H-bonding interactions. When they are decoupled, the dopant with mainly non-polar or polar features only marginally enhances the σ TP, revealing that polarity factors contribute to fuel cell relevant transport properties of GO membranes only when they coexist. Fuel cell polarization and kinetic analyses revealed that these multitask dopants increased the fuel cell performance metrics of the power and current densities by ∼3 times compared to the pure GO membranes, suggesting that the functional group factors of the dopants are of utmost importance in GO-based proton exchange membrane fuel cells.


Testicular failure in patients with extragonadal germ cell tumors.
Eight patients with mediastinal or retroperitoneal germ cell tumors who had undergone testicular biopsy or orchiectomy were retrospectively analyzed for primary testicular abnormalities, subfertility, and abnormal sex hormone levels. Testicular tissue was abnormal in all patients, revealing peritubular fibrosis (six), decreased spermatogenesis (eight), interstitial edema (five), Sertoli cells only (one), and Leydig cell hyperplasia (two). Detailed hormone analysis in five patients revealed elevations of luteinizing hormone in four, decreased serum testosterone in two, elevations of estradiol in two, and elevation of human chorionic gonadotropin in one patient. A history of infertility was documented 2 months to 13 years before presentation in four patients and suspected in another. Extragonadal germ cell tumors, like their testicular counterparts are associated with primary germ cell defects, some of which seem to be independent of gonadotropin production by the tumor. In addition, the rather high incidence of antecedent infertility suggests that either a congenital or acquired primary germ cell defect contributes to defective spermatogenesis and the development of cancer in incompletely migrated germ cells.


Cationic Carbon Dots for Modification-Free Detection of Hyaluronidase via an Electrostatic-Controlled Ratiometric Fluorescence Assay.
Carbon dots (CDs) emerge as excellent fluorescent nanomaterials, but the full exploitation and application of their exceptional properties in the development of fluorescence assay are still rare. In this work, cationic carbon dots (C-CDs) covered with plenty of positive charges on the surface were synthesized through a facile ultrasonic method. Negatively charged hyaluronic acid (HA) caused the aggregation of positively charged C-CDs and neutral red (NR) along its linear chain via electrostatic adsorption, leading to a remarkable Förster resonance energy transfer (FRET) from C-CDs to NR. However, the presence of hyaluronidase (HAase) resulted in the enzymolysis of HA, as well as the liberation of C-CDs and NR. The corresponding change of fluorescence color from red to green-yellow afforded a reliable ratiometric assay for HAase. Also the ratio of fluorescence intensity for C-CDs (I525) to that for NR (I630) was used for quantitative detection of HAase. The proposed sensing system was easily operated in aqueous media with a detection limit of 0.05 U/mL. This strategy provides a new approach for the wider application of some special CDs in detecting biomolecules.


Single-centre experience of allogeneic haemopoietic stem cell transplant in paediatric patients in Cape Town, South Africa.
Allogeneic haemopoietic stem cell transplant (Allo-HSCT) is a specialised and costly intervention, associated with significant morbidity and mortality. It is used to treat a broad range of paediatric conditions. South Africa (SA) is an upper middle-income country with limitations on healthcare spending. The role of paediatric Allo-HSCT in this setting is reviewed. To review paediatric patients who underwent Allo-HSCT at the Groote Schuur Hospital/University of Cape Town Private Academic Hospital transplant unit in Cape Town, South Africa, and received post-transplant care at Red Cross War Memorial Children's Hospital, over the period January 2006 - December 2014 in respect of indications for the transplant, donor sources, conditioning regimens, treatment-related morbidity and overall survival (OS). A retrospective analysis of patient records was performed and a database was created in Microsoft Access. Descriptive analyses of relevant demographic, clinical and laboratory data were performed. Summary statistics of demographic and clinical parameters were derived with Excel. OS was calculated from the date of transplant to the date of an event (death) or last follow-up using the Kaplan-Meier method in Statistica. A total of 48 children received Allo-HSCT: 24 for haematological malignancies, 20 for non-oncological haematological conditions, 3 for immune disorders and 1 for adrenoleukodystrophy. There were 28 boys (median age 7.5 years) and 20 girls (8.5 years). There were 31 sibling matched peripheral-blood stem cell (PBSC) transplants and 1 maternal haploidentical PBSC transplant. Stem cells were mobilised from bone marrow into peripheral blood by administering granulocyte-colony stimulating factor to donors. PBSCs were harvested by apheresis. Eight patients received 10/10 HLA-matched grafts from unrelated donors. Six were PBSC grafts and 2 were bone marrow grafts. Three of the unrelated PBSC grafts were from SA donors. Eight transplants used umbilical cord blood from international registries. OS for patients with non-oncological disorders was 91.3% (median follow-up 3.9 years), while that for oncology patients was 56.8% (1.9 years). Two of the survivors developed chronic graft-versus-host disease. OS for non-oncological conditions was excellent, while outcomes for oncological disorders were on par with those in high-income settings. Transplantation offers many patients the opportunity for long-term survival and has been shown to be both feasible and rewarding in a less well-resourced environment servicing an economically diverse population.


Analysis of backbone dynamics in cytochrome b5 using 15N-NMR relaxation measurements.
Determination of 15N-NMR relaxation rates has allowed the characterisation of the dynamic properties of 55 1H-15N bond vectors in a soluble haem-binding domain of bovine microsomal ferricytochrome b5 consisting of the first 104 amino acid residues. Measurements of heteronuclear [1H]-15N-NMR nuclear Overhauser effects, and 15N-NMR longitudinal and transverse relaxation rates have been analysed using both model-free and reduced spectral density mapping approaches, demonstrating the application of these methods to a paramagnetic system. Analysis reveals that, for those regions which have been assessed, the polypeptide backbone of ferricytochrome b5 is largely rigid (average S2 = 0.80), and that minimal internal backbone motion occurs on the sub-nanosecond timescale. In contrast, motions on the microsecond to millisecond timescale, especially pronounced for the loop region extending from residues 28 to 31, and which may be of biological relevance, are indicated.


Effects of San'o-shashin-to and the constituent herbal medicines on theophylline-induced increase in arterial blood pressure of rats.
San'o-shashin-to, composed of Scutellariae Radix, Coptidis Rhizoma and Rhei Rhizoma (volume ratio = 1:1:1), reduced an increase in arterial blood pressure of anesthetized rats induced by theophylline (5 mg/kg, i.v.). The hypotensive effect of San'o-shashin-to was produced in a dose dependent manner and was maximum at its 0.5 g/kg. Then the constituent herbal medicines were examined for their possible hypotensive effect. Scutellariae Radix of 0.2 g/kg slightly decreased in the blood presure. Rhei Rhizoma of 0.2 g/kg decreased in the blood pressure and the hypotensive effect was significantly produced even at the dose of 0.05 g/kg, while Coptidis Rhizoma had little effect. Among fractions of San'o-shashin-to separated by Diaion HP-20 column chromatography, the 50% methanol-eluted fraction had a large hypotensive effect. The 50% methanol-eluted fraction of Scutellariae Radix and Rhei Rhizoma were also effective and, especially, that of Rhei Rhizoma had a large hypotensive effect. In isometric tension study, Scutellariae Radix and Rhei Rhizoma (10-30 microg/ml) slightly exerted contractile and relaxant effects, respectively, on the phenylephrine-contracted endothelium-intact rat thoracic aorta. Coptidis Rhizoma (1-10 microg/ml) caused both endothelium-dependent and -independent relaxantion. These results suggest that the hypotensive effect of San'o-shashin-to is not mediated by the direct action on blood vessel but by other actions. Some components in Scutellariae Radix and Rhei Rhizoma, especially in the latter may play a main role in the hypotensive effect.


Six food diet for childhood atopic dermatitis.
Sixty-three children with severe atopic dermatitis aged 0.4 to 14.8 years, were treated with a diet eliminating all but six foods for a 6-week period. Nine (14%) abandoned the diet before 6 weeks had elapsed. Twenty-one (33%) completed the diet but did not benefit. Thirty-three (52%) patients obtained greater than or equal to 20% improvement in the disease severity score at 6 weeks, and for these patients, foods were reintroduced singly at weekly intervals. The outcome at 12 months was the same for the group who responded to the diet, the group who failed to respond, and the group who failed to comply, because of the tendency for dermatitis to improve markedly in all three groups. Although dietary elimination of this type may be associated with immediate improvement, the long term outcome appears to be unaffected by dietary success or failure.


Muscle structure and function before and after surgery for primary hyperparathyroidism.
In 23 unselected cases of primary hyperparathyroidism (pHPT), muscle strength, morphology and enzymatic activities were studied and electromyography (EMG) performed before and 6 months after surgical treatment. Hypercalcemia was mostly mild or moderate. Nine women undergoing surgery for benign thyroid conditions served as controls regarding muscle strength, while muscle morphologic and enzymatic data were compared with findings in healthy persons of similar age. Only three pHPT patients reported muscle weakness preoperatively, and two were subjectively improved after surgery. Muscle strength did not differ significantly before or after operation between patients and controls: After surgery both groups showed increased isokinetic muscle strength at higher angular velocities. Nor did muscle morphology differ between pHPT patients and controls. No conclusive EMG changes were found before or after surgery for pHPT but postoperatively the pHPT patients showed significant increase in glycolytic but not oxidative muscle enzymes, possibly reflecting early effect of pHPT on especially type II fibers, which previously were shown to be most extensively involved in pHPT. Otherwise no measurable negative effects of mild or moderate pHPT were found on muscle strength or function.


Modular domain swapping among the bacterial cytotoxic necrotizing factor (CNF) family for efficient cargo delivery into mammalian cells.
Modular AB-type bacterial protein toxins target mammalian host cells with high specificity and deliver their toxic cargo into the cytosol. Hence, these toxins are being explored as agents for targeted cytosolic delivery in biomedical and research applications. The cytotoxic necrotizing factor (CNF) family is unique among these toxins in that their homologous sequences are found in a wide array of bacteria, and their activity domains are packaged in various delivery systems. Here, to study how CNF cargo and delivery modules can be assembled for efficient cytosolic delivery, we generated chimeric toxins by swapping functional domains among CNF1, CNF2, CNF3, and CNFy. Chimeras with a CNFy delivery vehicle were more stably expressed, but were less efficient at cargo delivery into HEK293-T cells. We also found that CNFy cargo is the most universally compatible and that CNF3 delivery vehicle is the most flexible and efficient at delivering cargo. These findings suggest that domains within proteins can be swapped and accommodate each other for efficient function and that an individual domain could be engineered for compatibility with multiple partner domains. We anticipate that our insights could help inform chemical biology approaches to develop toxin-based cargo-delivery platforms for cytosolic cargo delivery of therapeutics or molecular probes into mammalian cells.


Preoperative T and N Restaging of Rectal Cancer After Neoadjuvant Chemoradiotherapy: An Accuracy Comparison Between MSCT and MRI.
It is well established that magnetic resonance imaging (MRI) is better than multi-slice computed tomography (MSCT) for the accurate diagnosis of pretreatment tumor (T) and node (N) staging of rectal cancer. However, the diagnostic value of MRI and MSCT in local restaging of rectal cancer after neoadjuvant chemoradiotherapy (NCRT) is controversial. The aim of this study is to investigate the performance of the two imaging exams in restaging of patients with rectal cancer. Patients with rectal cancer from April 2015 to April 2021 were analyzed retrospectively. The inclusion criteria are as follows: 1) diagnosis of rectal cancer through pathology; 2) NCRT had been performed; 3) all patients had undergone both MSCT and MRI examination before the surgery. Exclusion criteria are as follows: 1) incomplete clinical and imaging data; 2) previous history of pelvic surgery. Two radiologists performed T and N staging of patient images. Diagnostic accuracy, consistency analysis, and error restaging distribution of the two imaging exams for T and N restaging of rectal cancer were assessed using postoperative pathological staging as the gold standard. A total of 62 patients (49 men; mean age: 59 years; age range 29-83 years) were included in the study. The diagnostic accuracy of MSCT and MRI for T restaging was 51.6% (95% CI 39.3%-63.9%) and 41.9% (95% CI 29.6%-54.2%), respectively, and no statistical difference was found between them (p > 0.05). The diagnostic accuracy of MSCT and MRI for N restaging was 56.5% (95% CI 44.2%-68.8%) and 53.2% (95% CI 40.8%-65.6%), respectively, and no statistical difference was found between them (p > 0.05). The consistency analysis showed that T restaging (κ = 0.583, p < 0.001) and N restaging (κ = 0.644, p < 0.001) were similar between MSCT and MRI. There was no significant difference in the distribution of over, accurate, or low staging in T restaging (p > 0.05) and N restaging (p > 0.05) between MSCT and MRI. MSCT and MRI have similarly poor performance in the diagnosis of preoperative T and N restaging of rectal cancer after NCRT. Neither of them cannot effectively stage the ypT0-1 of rectal cancer. These findings may be of clinical relevance for planning less imaging exam.


Improving combination antiretroviral therapy by targeting HIV-1 gene transcription.
Combination Antiretroviral Therapy (cART) has not allowed the cure of HIV. The main obstacle to HIV eradication is the existence of quiescent reservoirs. Several other limitations of cART have been described, such as strict life-long treatment and high costs, restricting it to Western countries, as well as the development of multidrug resistance. Given these limitations and the impetus to find a cure, the development of new treatments is necessary. Areas covered: In this review, we discuss the current status of several efficient molecules able to suppress HIV gene transcription, including NF-kB and Tat inhibitors. We also assess the potential of new proteins belonging to the intriguing DING family, which have been reported to have potential anti-HIV-1 activity by inhibiting HIV gene transcription. Expert opinion: Targeting HIV-1 gene transcription is an alternative approach, which could overcome cART-related issues, such as the emergence of multidrug resistance. Improving cART will rely on the identification and characterization of new actors inhibiting HIV-1 transcription. Combining such efforts with the use of new technologies, the development of new models for preclinical studies, and improvement in drug delivery will considerably reduce drug toxicity and thus increase patient adherence.


Pharmacoeconomic analysis of hypertriglyceridemia treatment at medical institutions.
It has been demonstrated that HMG-CoA reductase inhibitors effectively decrease low density lipoprotein and total cholesterol levels, and presently, HMG-CoA reductase inhibitors are most widely used in hyperlipidemia treatment. On the other hand, it has been demonstrated that fibrate agents decrease triglyceride levels more effectively compared to HMG-CoA reductase inhibitors. A cost-effectiveness study comparing fenofibrate, a fibrate agent, and atorvastatin was therefore conducted in hypertriglyceridemia patients. Referring to an analytical method published in the UK, the percentage of patients received fenofibrate and atorvastatin treatments at each dose level was estimated from prescription records at the medical institutions investigated. Changes in the total cholesterol and triglyceride values after the drug administration were investigated examining published reports. Based on the said data, the treatment effectiveness was measured by the percentage of patients who achieved the target lipid levels. The treatment costs were estimated based on the number of patients investigated and reimbursement prices of the drugs. The incremental cost-effectiveness ratio of fenofibrate in decreasing triglyceride levels was dominant over atorvastatin. The incremental cost-effectiveness ratio of atorvastatin in decreasing low density lipoprotein cholesterol levels was JPY 69911. This provides a model for choosing drug treatments that reflects clinical practices at medical institutions by substituting figures for individual cases.


Continent urinary diversion using a Modified Indiana Pouch in elderly patients.
A total of 25 patients at least 75 years old underwent continent urinary diversion via a modified Indiana Pouch during a 68-month period, 21 of these with simultaneous radical cystectomy or anterior exenteration. The preoperative medical conditions as well as the early and late operative morbidity and mortality are reviewed with a mean follow up of 27 months. Average age of patients was 78.5 years, and the mean age of survivors is 81 years. There were two early mortalities attributed to ileal gangrene with secondary sepsis and aspiration pneumonia. Postoperative complications (superficial wound infection, middle colic vein bleed, right ureteral leak, ileus) occurred in five patients, two of whom required re-operation. Mean hospital stay was 12.4 days and ranged from 9-20. There were only six late complications [ureteral stricture (3), small bowel obstruction (1), incontinence (1)] necessitating re-hospitalization and surgical intervention. Late infectious complications included recurrent urinary tract infections (3), pyelonephritis (2), and C. Difficile enterocolitis (2) all managed medically. In addition, 10 other patients have died, 9 from metastatic disease and 1 from intercurrent medical problems. Of the 13 remaining patients, 11 are disease free and all are continent with a mean follow-up time of 33 months. We conclude that continent urinary diversion via a modified Indiana pouch with radical cystectomy or anterior exenteration can be performed with minimal morbidity or mortality, even in an elderly population.


Using syringe drivers in palliative care within a rural, community setting: capturing the whole experience.
The aim of this research was to understand how the introduction of a syringe driver, which is considered routine practice in many palliative care settings, impacted on patients, carers and community nurses within a rural, community setting. A phenomenological study was conducted exploring the experiences from the perspective of patients (n=4), carers (n=9) and community nurses (n=12) when syringe drivers are used at home. We interviewed patients and carers in their own homes and conducted two focus groups with community nurses who had an interest in palliative care but were not specialists. Despite the wide use of syringe drivers within palliative care, our study found their use among community nurses, particularly in rural areas can be variable with frequent time lapses between a nurse's exposure, impacting on both their technical abilities and knowledge. In-depth interviews with patients revealed few barriers to their use, but carers clearly identified areas where their expectations and experiences differed and where more information setting realistic goals of care would have been helpful. The authors conclude that although nurses require competencies related to syringe drivers, they also need an in-depth knowledge of the actions of the drugs and the likely changes which occur physiologically as patients approach the end of their life. This will ensure accurate information is delivered, and facilitate meaningful dialogue.


Relative abundance of deformed wing virus, Varroa destructor virus 1, and their recombinants in honey bees (Apis mellifera) assessed by kmer analysis of public RNA-Seq data.
Deformed wing virus (DWV) is a major pathogen of concern to apiculture, and recent reports have indicated the local predominance and potential virulence of recombinants between DWV and a related virus, Varroa destructor virus 1 (VDV). However, little is known about the frequency and titer of VDV and recombinants relative to DWV generally. In this study, I assessed the relative occurrence and titer of DWV and VDV in public RNA-seq accessions of honey bee using a rapid, kmer-based approach. Three recombinant types were detectable graphically and corroborated by de novo assembly. Recombination breakpoints did not disrupt the capsid-encoding region, consistent with previous reports, and both VDV- and DWV-derived capsids were observed in recombinant backgrounds. High abundance of VDV kmers was largely restricted to recombinant forms. Non-metric multidimensional scaling identified genotypic clusters among DWV isolates, which was corroborated by read mapping and consensus generation. The recently described DWV-C lineage was not detected in the searched accessions. The data further highlight the utility of high-throughput sequencing to monitor viral polymorphisms and statistically test biological predictors of titer, and point to the need for consistent methodologies and sampling schemes.


Identification of the small heat shock protein, HSP21, of shrimp Penaeus monodon and the gene expression of HSP21 is inactivated after white spot syndrome virus (WSSV) infection.
The white spot syndrome virus (WSSV) is the causative agent of a severe disease in cultivated shrimp. The virus causes high mortality and leads to heavy stress on shrimps. In response to a variety of stresses, living organisms express particular sets of genes such as HSPs. In this study, a HSP21 gene, categorized into the small heat shock protein (smHSP) family, of shrimp Penaeus monodon was identified by annotating the EST databases established from WSSV-infected and WSSV-uninfected shrimp. The shrimp HSP21 gene was 555 bp in length. The thermal aggregation assay showed that the HSP21 had chaperone activity. The result of real-time PCR indicated that HSP21 was constitutive and inducible and was highly expressed in almost all organs such as the epithelium, gill, stomach, midgut, lymphoid organ, hepatopancreas, nervous tissue and heart, but less expressed in haemolymph. However, HSP21 gene showed down-regulation after WSSV infection. It suggests that gene regulation of HSP21 was seriously affected by WSSV.


Utility of Anterior Segment Optical Coherence Tomography in Muscle Aplasia.
Congenital absence of the extraocular muscles is a relatively rare entity that is diagnosed by magnetic resonance imaging and is usually associated with craniofacial syndromes, microcornea, microphthalmos, and coloboma. The authors describe anterior segment optical coherence tomography as a quick and valuable modality in this setting before subjecting the patient to magnetic resonance imaging or computed tomography. [J Pediatr Ophthalmol Strabismus. 2022;59(2):e20-e22.].


Maternal cocaine use: estimated effects on mother-child play interactions in the preschool period.
The study objective was to evaluate the quality of parent-child interactions in preschool-aged children exposed prenatally to cocaine. African-American mothers and their full-term newborns (n = 343) were enrolled prospectively at birth and classified as either prenatally cocaine-exposed (n = 157) or non-cocaine-exposed (n = 186) on the basis of maternal self-report and bioassays. Follow-up evaluations at 3 years of age (mean age, 40 mo) included a videotaped dyadic play session and maternal interviews to assess ongoing drug use and maternal psychological distress. Play interactions were coded using a modified version of Egeland et al's Teaching Task coding scheme. Regression analyses indicated cocaine-associated deficits in mother-child interaction, even with statistical adjustment for multiple suspected influences on interaction dynamics. Mother-child interactions were most impaired in cocaine-exposed dyads when the mother continued to report cocaine use at the 3-year follow-up. Multivariate profile analysis of the Egeland interaction subscales indicated greater maternal intrusiveness and hostility, poorer quality of instruction, lower maternal confidence, and diminished child persistence in the cocaine-exposed dyads.


The capybara eye: clinical tests, anatomic and biometric features.
To carry out a descriptive investigation of the capybara (Hydrochaeris hydrochaeris) eye and to perform selected ophthalmic diagnostic tests with the aim of establishing normal physiological reference values for this species. A total of 22 healthy, capybaras were used to test most of the parameters in this investigation. Ages varied from 2 to 4 years of age. Selected diagnostic ocular tests were performed including Schirmer tear test, tonometry using an applanation tonometer (Tonopen), central corneal thickness using an ultrasonic pachymeter (Sonomed, Micropach, Model 200P +), axial globe length and culture of the normal conjunctival bacterial flora. Capybara's normal ocular features include: dorsal and ventral puncta, vestigial third eyelid, true cilia only at the upper eyelid margins. The bulbar conjunctiva is noticeably densely pigmented with a brown to bronze color. The capybara's pupil is oval in shape and vertical in position No tapetum lucidum is present in this species and the retinal blood vessels are almost absent. Results for selected ocular diagnostic tests investigated were: Intraocular pressure: 18.4 +/- 3.8 mmHg; Schirmer tear test: 14.9 +/- 5.1 mm/min; Central corneal thickness: 0.46 +/- 0.03 mm; Axial globe length: 22.20 +/- 1.71 mm. No statistically significant differences between ages or genders were found for any of the results. Corynebacterium sp., Micrococcus sp., Bacillus sp. and Staphylococcus sp. were isolated from healthy conjunctiva, suggesting they are normal constituents of the conjunctival flora of the capybara eye. The corneal epithelium of the capybara possesses a thin and discrete Bowman's layer. Results and parameters obtained in this investigation exposed unique anatomic features of the capybara eye and will help veterinary ophthalmologists to more accurately diagnose discrete or unusual pathological changes of the capybara eye. Furthermore, corneal thickness and axial length of the capybara are similar to that of human beings, revealing that the world's largest living rodent might be an excellent biological model for ophthalmic studies.


Conjugates of dopamine and serotonin in ventriculocisternal perfusates of the cat.
The in vivo formation of acid-hydrolyzable conjugates of dopamine and of serotonin (presumably dopamine-O-sulfate and serotonin-O-sulfate) in ventriculocisternal perfusions of the cat is described. Small amounts of these amine conjugates were detected under quiescent conditions and during evoked release of the parent amines. The amounts of conjugated dopamine in perfusate were increased during and immediately after the period in which release of dopamine was evoked, but were not affected by inhibition of monoamine oxidase. In contrast, the efflux of serotonin conjugate during the evoked release of serotonin was not increased unless monoamine oxidase was inhibited. The data suggest that conjugation of amines in the CNS may be of functional importance in their disposition either under conditions of augmented release or during inhibition of oxidative deamination.


Adaptive Door Opening Control Algorithm of Bio-Inspired Mobile Manipulator Based on Synchronous Sensing.
At present, the research of robot door opening method is basically realized by identifying the door handle through the synchronous sensing system on the premise that the bio-inspired mobile manipulator is located in front of the door. An adaptive door opening strategy of a bio-inspired mobile manipulator based on a synchronous sensing system is proposed. Firstly, the random delay distribution in clock synchronization technology is analyzed in detail, and its distribution is verified on the experimental platform of adjacent nodes. Based on the Gaussian distribution of random delay, the relative frequency offset and relative phase offset of adjacent nodes are calculated. The clock synchronization of network cable sensor nodes is realized. Secondly, based on the information data of synchronous sensing system, this article realizes target detection and tracking based on depth network. In addition, based on the sliding mode control theory, the dynamic model of the nonholonomic bio-inspired mobile manipulator is applied. Finally, a robust adaptive sliding mode control method for nonlinear systems with input gain uncertainty and unmatched uncertainty is proposed by combining adaptive backstepping with sliding mode control. By adding sliding mode control in the last step of adaptive backstepping, the uncertainty of the system is compensated, and the system trajectory is maintained on the specified sliding mode manifold. The tracking control and stability control of the nonholonomic bio-inspired mobile manipulator are simulated. The experimental and simulation results show that the control method proposed in this article is effective and feasible.


[Various aspects of the morphology of granular cell tumors].
Histology and ultrastructure of human granular cell tumors (GCT) are studied. Apart from "granular" cells which are the main component of the tumor, GCT contain the cells of ordinary structure with signs of neurogenic differentiation, cell processus typical for the nervous tissue and peripheral nervous tissue tumors (these processus are in a close space connection with "granular" cells) as well as structurally transitional cells. This implies that "granular" cells are likely to originate from the ordinary lemmocytes as a result of disturbance and hypertrophy of intracellular processus. Preoperative diagnosis of this rare peculiar neurogenic tumor is difficult and the diagnosis is possible only after the operative material examination. If other signs of malignancy are lacking, infiltrative growth typical for these tumors allows one to consider them locally-destructive neoplasms.


Facial speech gestures: the relation between visual speech processing, phonological awareness, and developmental dyslexia in 10-year-olds.
Successful communication in everyday life crucially involves the processing of auditory and visual components of speech. Viewing our interlocutor and processing visual components of speech facilitates speech processing by triggering auditory processing. Auditory phoneme processing, analyzed by event-related brain potentials (ERP), has been shown to be associated with impairments in reading and spelling (i.e. developmental dyslexia), but visual aspects of phoneme processing have not been investigated in individuals with such deficits. The present study analyzed the passive visual Mismatch Response (vMMR) in school children with and without developmental dyslexia in response to video-recorded mouth movements pronouncing syllables silently. Our results reveal that both groups of children showed processing of visual speech stimuli, but with different scalp distribution. Children without developmental dyslexia showed a vMMR with typical posterior distribution. In contrast, children with developmental dyslexia showed a vMMR with anterior distribution, which was even more pronounced in children with severe phonological deficits and very low spelling abilities. As anterior scalp distributions are typically reported for auditory speech processing, the anterior vMMR of children with developmental dyslexia might suggest an attempt to anticipate potentially upcoming auditory speech information in order to support phonological processing, which has been shown to be deficient in children with developmental dyslexia.


Efficacy of transcranial direct-current stimulation in women with provoked vestibulodynia.
Provoked vestibulodynia is a highly prevalent condition characterized by acute recurrent pain located at the vaginal entrance in response to pressure application or attempted vaginal penetration. Despite a wide variety of treatments offered to women with provoked vestibulodynia, a high proportion of women are refractory to conventional treatment. Transcranial direct-current stimulation is a noninvasive brain stimulation technique that has been shown effective for improving various chronic pain conditions. Growing evidence suggests that the central nervous system could play a key role in provoked vestibulodynia. Targeting the central nervous system could therefore be a promising treatment for women with provoked vestibulodynia. The purpose of this study was to evaluate and compare the efficacy of active and sham transcranial direct-current stimulation in reducing pain intensity during intercourse in patients with provoked vestibulodynia. We conducted a triple-blind, parallel-group, randomized controlled trial. Women aged 17-45 years diagnosed with provoked vestibulodynia by a gynecologist using a validated protocol were randomized to 10 sessions of either active transcranial direct-current stimulation (intensity = 2 mA) or 10 sessions of sham transcranial direct-current stimulation, over a 2-week period. Both active and sham transcranial direct-current stimulation were applied for 20 minutes, with the anode positioned over the primary motor cortex, and the cathode over the contralateral supraorbital area. Outcome measures were collected at baseline, 2 weeks after treatment, and at 3-month follow-up by an evaluator blinded to group assignment. The primary objective was to assess pain intensity during intercourse, using a numerical rating scale. Secondary outcomes focused on sexual function and distress, vestibular sensitivity, psychological distress, treatment satisfaction, and patient impression of change. Statistical analyses were conducted on the intention-to-treat basis, and treatment effects were evaluated using a mixed linear model for repeated measures. A total of 40 patients were randomly assigned to receive either active (n = 20) or sham (n = 20) transcranial direct-current stimulation treatments from November 2014 through February 2016. Baseline characteristics were similar between the active and sham transcranial direct-current stimulation groups. In full compliance with the study protocol, every participant followed all courses of the study treatment, including assessments at 2-week and 3-month follow-up. Pain during sexual intercourse was not significantly different between active and sham treatment groups 2 weeks after treatment (P = .84) and at follow-up (P = .09). Mean baseline and 2-week assessment pain intensity were, respectively, 6.8 (95% confidence interval, 5.9-7.7) and 5.6 (95% confidence interval, 4.7-6.5) for active transcranial direct-current stimulation (P = .03) vs 7.5 (95% confidence interval, 6.6-8.4) and 5.7 (95% confidence interval, 4.8-6.6) for sham transcranial direct-current stimulation (P = .001). Nonsignificant differences between the 2 groups were also found in their sexual function and distress after treatment (P > .20) and at follow-up (P > .10). Overall, at 2-week assessment 68% assigned to active transcranial direct-current stimulation reported being very much, much, or slightly improved compared to 65% assigned to sham transcranial direct-current stimulation (P = .82), and still comparable at follow-up: 42% vs 65%, respectively (P = .15). Findings suggest that active transcranial direct-current stimulation is not more effective than sham transcranial direct-current stimulation for reducing pain in women with provoked vestibulodynia. Likewise, no significant effects were found on sexual function, vestibular sensitivity, or psychological distress.


Bacterial outer membrane vesicle biogenesis: a new mechanism and its implications.
Outer membrane vesicle (OMV) release by Gram-negative bacteria has been observed and studied for decades. First considered as a by-product of cell lysis, it soon became evident that OMVs are actively secreted from the outer membrane (OM) of Gram-negative bacteria. Accordingly, these small particles (~ 10-300 nm in diameter) consist mainly of OM components like phospholipids (PLs), OM proteins, and lipopolysaccharides or lipooligosaccharides. However, OMVs may also comprise periplasmic, inner membrane, or cytoplasmic components. Since the shedding of substantial amounts of OM material represents a significant energy cost to the bacterial cell, OMV production must have some vital biological functions for Gram-negative bacteria. Indeed, intense research on that topic revealed that OMVs play important roles in bacterial physiology and pathogenesis, ranging from secretion and delivery of biomolecules (for example, toxins, DNA, or quorum sensing molecules) over stress response and biofilm formation to immunomodulation and adherence to host cells. Only recently researchers have begun to elucidate the mechanistic aspects of OMV formation, but a general mechanism for the biogenesis of these vesicles is still lacking. Here we review the findings and implications of our recent study published in Nature Communications (Roier S, et al. (2016) Nat. Commun. 7:10515), where we propose a novel and highly conserved bacterial OMV biogenesis mechanism based on PL accumulation in the outer leaflet of the OM. This mechanism might not only have important pathophysiological roles in vivo, but also represents the first general mechanism of OMV formation applicable to all Gram-negative bacteria.


Dipyridamole enhancement of toxicity to L1210 cells by deoxyadenosine and deoxycoformycin combinations in vitro.
The combination of 2'-deoxyadenosine and deoxycoformycin is known to be markedly toxic to T-lymphocyte cell lines relative to B-cell lines, and this difference appears to be related to the capacity of the cells to accumulate deoxyadenosine triphosphate (dATP). In the presence of dipyridamole and 2'-deoxyadenosine and when adenosine deaminase was inhibited with deoxycoformycin, the L1210 leukemia cell which is a non-T-, non-B-cell type accumulated dATP like a T-cell type. The intracellular L1210 concentration of dATP using the triple combination (1.1 microM deoxycoformycin-40 microM deoxyadenosine-10 microM dipyridamole) reached 400 microM at which concentration ribonucleotide reductase specific activity was reduced by 80%. While this degree of enzyme may be significant, complete inhibition might have been expected, since 400 microM dATP is approximately 40 times the concentration to give 50% inhibition in some purified systems.


Nifedipine in ulnar artery occlusion.
With the introduction of the calcium channel blocker, Nifedipine, potent peripheral vasodilatation has been demonstrated. Its main action is on the peripheral arterioles and venules with decreased peripheral resistance. Calcium affects most smooth muscle cells of the peripheral arteries and arterioles. Any small increase in the radius of a peripheral vessel or collateral increases the blood flow by an increment of four square. It is not surprising, therefore, that the calcium entry blocker exerts a vasodilatory effect. That effect varies with the intensity of the disease in the vascular bed in the different patients.


Lower Limb Biomechanical Analysis of Healthy Participants.
Biomechanical analysis techniques are useful in the study of human movement. The aim of this study was to introduce a technique for the lower limb biomechanical assessment in healthy participants using commercially available systems. Separate protocols were introduced for the gait analysis and muscle strength testing systems. To ensure maximum accuracy for gait assessment, attention should be given to the marker placements and self-paced treadmill acclimatization time. Similarly, participant positioning, a practice trial, and verbal encouragement are three critical stages in muscle strength testing. The current evidence suggests that the methodology outlined in this article may be effective for the assessment of lower limb biomechanics.


Effects of Donor Breastmilk Feeding on Growth and Early Neurodevelopmental Outcomes in Preterm Infants: An Observational Study.
Donor breastmilk (DBM) has gained popularity as an alternative to formula when mother's own milk (MOM) is unavailable. The objective of this study was to evaluate the effects of a predominantly DBM diet on growth and subsequent neurodevelopment in preterm infants at a level 3 neonatal intensive care unit (NICU). This single-center, observational cohort study compared data from preterm infants supplemented with predominantly (>50%) DBM to those from age- and weight-matched infants fed only MOM or supplemented with predominantly (>50%) preterm formula (PF). The primary outcome was in-hospital weight gain, and the secondary outcome was neurodevelopment, as assessed by the Bayley III scale at 1 and 2 years' corrected age. Exclusion criteria were major congenital defects, death prior to discharge from the NICU, or supplementation volumes of <50% over the first month of life. We compared the outcomes among the 3 feeding groups with the χ2 test, ANOVA, and ANCOVA, with post hoc pairwise comparisons after adjustment for the following confounders: bronchopulmonary dysplasia, multiple births, and social work involvement. In the entire cohort, the mean gestational age was 27.1 weeks and the mean birthweight was 914 g. The DBM (n = 27) and PF (n = 25) groups were similar with regard to socioeconomic characteristics. DBM infants regained birthweight more slowly over the first month of life compared with infants fed MOM (n = 29) or PF (mean [SD], 17.9 [5.7], 22.0 [6.8], and 20.3 [5.7] g/kg/d, respectively; P = 0.05); however, this growth difference was attenuated at later time points. In a fully adjusted model, the DBM group scored significantly lower in cognition at both 1 year (P = 0.005) and 2 years (P = 0.03) of age compared with the infants fed non-DBM diets. The findings from this study suggest that in this NICU, preterm infants supplemented with predominantly DBM had compromised early in-hospital weight gain and, possibly, early cognitive delays compared with infants fed only MOM or infants supplemented with predominantly PF. These findings reinforce the need for further research on the optimal use of DBM in the preterm population and a continued need for promoting breastfeeding efforts to supply MOM.