Modeling brain adaptation to focal damage.
Determining how feature maps in the cerebral cortex adapt to sudden, focal damage is important for gaining a deeper understanding of neurological illnesses such as stroke. In this paper we describe a neural model of the region of primary sensory cortex related to upper extremity proprioception, and show how the feature map there reorganizes following a simulated lesion. A perilesion zone with decreased activity appears and then gradually expands with time. These results differ from those seen with previous models of cortical lesions, and offer an alternative mechanism to the "ischemic penumbra" seen in certain types of stroke.


De Garengeot hernia: an uncommon presentation of acute appendicitis.
We present a case of a 78-year-old female patient with an uncommon presentation of acute appendicitis. She was found to have a perforated appendicitis which developed in a femoral hernia sack. An appendix present in a femoral hernia is called a De Garengeot Hernia, which is a rare form of femoral hernia. Clinical presentation, diagnosis and management are discussed.


Regulation of blood-screening in vitro diagnostics in sub-Saharan African countries remains a challenge.
According to the World Health Organization, blood must be screened for major transmitted infections before transfusion to prevent the possibility of passing an infection to the recipient. For accurate detection of infectious disease pathogens in the blood of donors, in-vitro diagnostic medical devices (IVDs) of high specificity and sensitivity should be used. In mature healthcare systems, the regulatory authorities authorize the usage of devices with the highest performance capabilities, which are also controlled through active market oversight. However, in Sub-Saharan African countries, the regulation of IVDs is often poorly developed. With the lack of stringent regulatory oversight, IVDs of poor quality can be put on the market and used for blood donor screening, which, ultimately, poses a great public health threat. The BloodTrain is a humanitarian project from the Germany Federal Ministry of Health that aims to help strengthen the regulatory authorities in Sub-Saharan partner countries. Here, we present the status of IVD regulation in the partner countries and the objectives that the BloodTrain project aims to achieve in the region toward regulating IVDs.


Protonation and coordination properties towards Zn(II), Cd(II) and Hg(II) of a phenanthroline-containing macrocycle with an ethylamino pendant arm.
Protonation and Zn(II), Cd(II) and Hg(II) coordination with the ligand 5-aminoethyl-2,5,8-triaza-[9]-10,23-phenanthrolinophane (L2), which contains an aminoethyl pendant attached to a phenanthroline-containing macrocycle, have been investigated by means of potentiometric, 1H NMR and spectrofluorimetric titrations in aqueous solutions. The coordination properties of L2 are compared with those of the ligand 2,5,8-triaza-[9]-10,23-phenanthrolinophane (L1). Ligand protonation occurs on the aliphatic amine groups and does not involve directly the heteroaromatic nitrogens. The fluorescence emission properties of L2 are controlled by the protonation state of the benzylic nitrogens: when not protonated, their lone pairs are available for an electron transfer process to the excited phenanthroline, quenching the emission. As a consequence, the ligand is emissive only in the highly charged [H3L2]3+ and [H4L2]4+ species, where the benzylic nitrogens are protonated. Considering metal complexation, both [ML1]2+ and [ML2]2+ complexes (M = Zn(II) and Cd(II)) are not emissive, since the benzylic nitrogens are weakly involved in metal coordination, and, once again, they are available for quenching the fluorescence emission. Protonation of the L2 complexes to give [MHL2]3+ species, instead, leads to a recovery of the fluorescence emission. Complex protonation, in fact, occurs on the ethylamino group and gives a marked change of the coordination sphere of the metals, with a stronger involvement in metal coordination of the benzylic nitrogens; consequently, their lone pairs are not available for the process of emission quenching.


Should the presence of congenital para-ureteral diverticulum affect the management of vesicoureteral reflux?
The presence of congenital para-ureteral diverticulum (PUD) has been presumed to lower the resolution rate of vesicoureteral reflux (VUR). PUD is considered an important cause of distortion of the vesicoureteral junction and persistence of VUR. Early surgery has been recommended based on this assumption. However, the scientific evidence supporting this approach is weak. We have been managing this group of patients more conservatively in the last 7 to 8 years on the premise that the presence of PUD is not per se an indication for surgery. To test this hypothesis, we performed a retrospective cohort study to compare the outcome of VUR in children with and without PUD. We identified 141 consecutive patients with VUR associated with PUD between 1990 and 2004. Of the patients 57 with duplication, ureterocele, neurogenic bladder or outlet obstruction were excluded from study. Median age of the remaining 84 patients at diagnosis was 2.9 years and 56 (69%) were males. Reflux was bilateral in 4 patients, and low (I to II), intermediate (III) and high (IV to V) grade in 39%, 35% and 26%, respectively. Followup was 3 to 168 months (median 47). The outcome was compared to a control group of 95 patients (150 units) with primary VUR and no PUD. The baseline parameters and followup were comparable in both groups. Overall, VUR resolved in 43%, persisted in 27% and was surgically corrected in 30% of the units with PUD. In the 25 patients (26 units) who underwent surgical intervention breakthrough urinary tract infection or new renal scars were the indication in only 5. The remainder were operated on because of persistent VUR and the presence of PUD, mainly before 1997. The incidence of breakthrough urinary tract infection or new renal scar was similar in the controls (6% in PUD group vs 10% in controls, p = 0.7). The resolution rate was 60% for low grade, 39% for intermediate grade and 22% for high grade VUR. These figures were not significantly different from those of the control group in which the resolution rates were 52%, 28% and 33% for comparable grades (p = 0.9). Kaplan-Meier analysis and log rank test did not show any difference in resolution of VUR in the 2 groups (p = 0.84). Multivariate analysis identified grade as the only variable affecting resolution (p = 0.028). The size of PUD did not affect the likelihood of resolution. The outcome of VUR is similar in children with or without PUD. Therefore, treatment of these patients should not differ. Surgery should be reserved for patients with breakthrough infection or renal scar progression.


Elevation of growth hormone-releasing hormone receptor messenger ribonucleic acid expression in growth hormone-secreting pituitary adenoma with Gsalpha protein mutation.
Growth hormone-releasing hormone (GHRH) stimulates not only the synthesis and secretion of GH but also the proliferation of normal somatotrophs. The expression of GHRH receptor (GHRHR) is regulated by GHRH, both of which are known to be expressed in human GH-secreting pituitary adenoma cells. Somatic mutations in the subunit of Gsalpha protein (gsp), lead to the constitutive activation of adenylyl cyclase in pituitary adenomas that secrete GH. It has not been examined how gsp mutations influence GHRHR expression in GH-secreting adenomas. We therefore analyzed the expression levels of GHRHR messenger ribonucleic acid (mRNA) in GH-secreting pituitary adenomas focusing on a gsp mutation. Furthermore, we investigated the effect of GHRH on the expression of GHRHR mRNA in primary cultures of GH-secreting pituitary adenoma cells. GHRHR mRNA expression levels were significantly elevated in gsp mutation-positive GH-secreting adenomas compared with those in gsp mutation-negative ones. In primary-cultured GH-secreting adenoma cells, the increase of GH secretion in response to GHRH was shown in both gsp mutation-positive and -negative adenoma cells with a significantly higher response in the latter adenoma cells. GHRH increased GHRHR mRNA expression level in gsp mutation-negative adenoma cells while it was not influenced by GHRH in gsp mutation-positive adenoma cells. These results suggest that gsp mutations up-regulate GHRHR mRNA expression in GH-secreting pituitary adenoma cells, and that gsp mutations desensitize the adenoma cells to GHRH in terms of their GHRHR mRNA expression probably because of their saturation of GHRH signaling.


Scientific validation of the Chinese caterpillar medicinal mushroom, Ophiocordyceps sinensis (Ascomycetes) from India: immunomodulatory and antioxidant activity.
In the present study, we aimed to elucidate the antioxidant property and anti-inflammatory activity of the aqueous extract of the Indian species of Ophiocordyceps sinensis (AECS), which demonstrates medicinal activity against numerous diseases. The chemical composition of AECS was quantified using a colorimeteric technique to determine the total phenolic and flavonoid contents. Antioxidant activity was determined by assays for 2,2'-azinobis(3-ethylbenzothiazoline-6-sulphonic acid)diammonium salt (ABTS); 2,2-diphenyl-1-picryl-hydrazyl (DPPH); and ferric reducing antioxidant power (FRAP). Adenosine nucleoside and nitrogenous bases (adenine and uracil) were also quantified by high-performance thin layer chromatography (HPTLC). Furthermore, the aqueous extract was also analyzed for anti-inflammatory activity in vitro using THP1 cells. THP1 cells were treated with and without lipopolysaccharide (LPS) and AECS (at 25 µg/mL, 50 µg/mL and 100 µg/mL, respectively) for 24 h. After 24 h, supernatants were harvested and kept at -80°C until the cytokine assays were performed. Furthermore, nitric oxide (NO) content was also estimated in treated and untreated murine peritoneal macrophages using Griess reagent. AECS significantly suppressed LPS-induced release of TNF-α and IL-1β in THP1 cells and significantly suppressed NO release in macrophage cells without exerting any toxic effect. These results indicate the anti-inflammatory activity of AECS. Additionally, this extract also has an antioxidant property, as high contents of phenols and flavonoids are present in the extract with considerable reducing power. The results of this study clearly demonstrate the potent antioxidant property and anti-inflammatory activity of AECS. Therefore, consumption of AECS may be clinically useful to protect against inflammatory diseases.


Cost analysis of microtia treatment in the Netherlands.
Ear reconstruction for microtia is a challenging procedure. Although analyzing esthetic outcome is crucial, there is a paucity of information with regard to financial aspects of microtia reconstruction. This study was conducted to analyze the costs associated with ear reconstruction with costal cartilage in patients with microtia. Ten consecutive children with autologous ear reconstruction of a unilateral microtia were included in this analysis. All patients had completed their treatment protocol for ear reconstruction. Direct costs (admission to hospital, diagnostics, and surgery) and indirect cost (travel expenses and absence from work) were obtained retrospectively. The overall mean cumulative cost per patient was €14,753. Direct and indirect costs were €13,907 and €846, respectively. Hospital admission and surgery cover 55% and 32% of all the costs, respectively. This study analyzes the costs for autologous ear reconstruction. Hospital admission and surgery are the most important factors of the total costs. Total costs could be decreased by possibly decreasing admission days and surgical time. These data can be used for choosing and developing future treatment strategies.


The establishment of neuronal properties is controlled by Sox4 and Sox11.
The progression of neurogenesis relies on proneural basic helix-loop-helix (bHLH) transcription factors. These factors operate in undifferentiated neural stem cells and induce cell cycle exit and the initiation of a neurogenic program. However, the transient expression of proneural bHLH proteins in neural progenitors indicates that expression of neuronal traits must rely on previously unexplored mechanisms operating downstream from proneural bHLH proteins. Here we show that the HMG-box transcription factors Sox4 and Sox11 are of critical importance, downstream from proneural bHLH proteins, for the establishment of pan-neuronal protein expression. Examination of a neuronal gene promoter reveals that Sox4 and Sox11 exert their functions as transcriptional activators. Interestingly, the capacity of Sox4 and Sox11 to induce the expression of neuronal traits is independent of mechanisms regulating the exit of neural progenitors from the cell cycle. The transcriptional repressor protein REST/NRSF has been demonstrated to block neuronal gene expression in undifferentiated neural cells. We now show that REST/NRSF restricts the expression of Sox4 and Sox11, explaining how REST/NRSF can prevent precocious expression of neuronal proteins. Together, these findings demonstrate a central regulatory role of Sox4 and Sox11 during neuronal maturation and mechanistically separate cell cycle withdrawal from the establishment of neuronal properties.


Gingival overgrowth as secondary effect of calcium channel blockers administration. A case report.
Gingival overgrowth is, among other things, a side effect of the administration of dihydropyridine antihypertensives, generally associated with irritant factors of marginal periodontium. This case refers to a patient, female, who developed a large gingival enlargement that has a combined etiology: the systemic medication with lercanidipina and the presence of dental bridges, which are incorrectly adjusted to the dental cervix. The treatment for this case, involved a complex local treatment (antimicrobial, surgical, endodontic and prosthetic) and the collaboration with a specialist cardiologist. Maintaining the normal gingival parameters in time depends on the possibility of changing the antihypertensive medication, the accuracy of the new dental bridges and the periodic monitoring of the patient.


Reward related neurotransmitter changes in a model of depression: An in vivo microdialysis study.
The self-medication hypothesis assumes that symptoms related to potential monoaminergic deficits in depression may be relieved by drug abuse. The aim of this study was to elucidate the neurotransmitter changes in a rat model of depression by measuring their levels in the nucleus accumbens shell, which is typically involved in the drug of abuse acquisition mechanism. Depression was modelled by the olfactory bulbectomy (OBX) in Wistar male rats. In vivo microdialysis was performed, starting from the baseline and following after a single methamphetamine injection and behaviour was monitored. The determination of neurotransmitters and their metabolites was performed by high-performance liquid chromatography combined with mass spectrometry. OBX animals had lower basal levels of dopamine and serotonin and their metabolites. However, γ-aminobutyric acid (GABA) and glutamate levels were increased. The methamphetamine injection induced stronger dopamine and serotonin release in the OBX rats and lower release of glutamate in comparison with sham-operated rats; GABA levels did not differ significantly. This study provides an evidence of mesolimbic neurotransmitter changes in the rat model of depression which may elucidate mechanisms underlying intravenous self-administration studies in which OBX rats were demonstrated to have higher drug intake in comparison to intact controls.


Characteristics of particulate constituents and gas precursors during the episode and non-episode periods.
Size-segregated distribution of ambient particulate matter (PM) was determined using a micro-orifice uniform deposition impactor (MOUDI) and a nano-MOUDI in southern Taiwan. Eleven water-soluble ionic species including six anions (NO3-, SO4(2-), Cl-, F-, NO2-, Br-) and five cations (NH4+, Na+, K+, Ca2+, Mg2+) for particulate inorganic ions and five gaseous pollutants (i.e., HNO2, HNO3, HCl, SO2, NH3) were analyzed during episode and non-episode periods. The particulate mass concentration was about 30 microg/ m3 higher at night than during the day, and it reached 162 microg/m3 during the episode periods. The difference was mainly attributable to the particle size of 0.1-2.5 microm. Nitrate, sulfate, ammonium, and chloride ions were the dominant inorganic ions in PM. HONO and NH3 concentrations were high at night; in contrast, HNO3, HCl, and SO2 were high during the day. The equivalent ratio of {[NO3-] + 2 [SO4(2-)}/[NH4+] was about 0.98 and revealed a high correlation between {[NO3-] + 2[SO4(2-)]} and [NH4+] that clearly pointed to ammonium neutralization or condensation of ammonium nitrate and ammonium sulfate in PM0.32. The precursor gases and ionic species in different particle sizes did not reveal a strong correlation, which could be attributed to the complex of source emissions, atmospheric reactions and meteorological parameters in the area. Size-segregated distribution and chemical compositions of atmospheric aerosols play important roles in their visibility reduction, health effects, and toxicity in urban areas. Inorganic ionic species are major constituents in particulate matter, except carbonaceous chemicals. In this work, the compositions of water-soluble ions in particulate matter and acid/base gaseous pollutants (such as HNO2, HNO3, HCl, SO2, NH3) were determined during the day and at night during episode and non-episode periods from 2006 to 2007 in southern Taiwan.


Differences in the determinants of eplerenone, spironolactone and aldosterone binding to the mineralocorticoid receptor.
The importance of mineralocorticoid receptor (MR) antagonists in the treatment of cardiovascular disease has been emphasised by two recent clinical trials, one using spironolactone and the other using a new selective MR antagonist, namely eplerenone. Eplerenone has a very low affinity for the glucocorticoid receptor (GR). Determinants of binding specificity of eplerenone to the MR were investigated using chimeras created between the ligand-binding domains (LBD) of the MR and the GR. These chimeras had been used previously to investigate aldosterone and spironolactone binding specificity to the MR. Eplerenone competed strongly for [(3)H]-dexamethasone binding to a MR/GR chimera containing amino acids 804-874 of the MR and weakly to a chimera containing amino acids 672-803 of the MR. Within the 804-874 region, eplerenone competed for [(3)H]-dexamethasone binding to a chimera containing amino acids 820-844 of the MR, although the calculated affinity was approximately 10-fold lower than for binding to the full-length MR LBD. Similar results were obtained using another MR antagonist, namely spironolactone. Modelling of eplerenone binding to the MR LBD, based on the GR LBD crystal structure, suggests that amino acids 820-844 affect the overall shape of the ligand-binding pocket and that eplerenone acts as an MR antagonist because it fails to stabilize the active conformation of the receptor. In contrast with results with the MR antagonists eplerenone and spironolactone, amino acids 820-844 are sufficient in themselves to confer high-affinity aldosterone binding to the MR, suggesting that the binding determinants of the two antagonists are similar to each other but differ from those of aldosterone.


The intrinsic cause of color fading in sliced cooked cured beef during chilled storage.
The relationship between color change and other physical and chemical characteristics of sliced cooked cured beef (SCCB) during chilled storage were investigated using principal components analysis (PCA) to determine the color fading causes. Samples were prepared and stored at 8°C for up to 35 days in a vacuum package to simulate a supermarket storage environment; related indicators were measured periodically every week. The results showed that the first PC explained 59.82% of the total variation, and the second explained 22.28%. PC1 was a concentrated reflection of color changes of SCCB during storage and PC2 was an environment factor causing the change of color. The change in apparent redness is mainly caused by redox reaction of the nitroso hemochromogen (NH) (eigenvectors of a*, C and NH in PC1 were all the maximum value of 0.28); a* was correlated with NH (0.96), free sulfhydryls (0.98), carbonyl derivatives (-0.95) formed during protein oxidation, and malondialdehyde (-0.98) and dienes (-0.92) formed by lipid oxidation. Color fading was significantly correlated with oxidizing and reducing power, existing forms of nitrogen and with the pH of the meat matrix. Changes in the internal environment of the sample initially influenced L* and b* values, and subsequently a*.


Impaired interdomain communication in mitochondrial Hsp70 results in the loss of inward-directed translocation force.
The essential mitochondrial Hsp70 (mtHsp70) is required for the import of mitochondrial preproteins into the matrix compartment. The translocation-specific activity of mtHsp70 is coordinated by its interaction with specific partner proteins, forming the import motor complex that provides the energy for unfolding and complete translocation of precursor polypeptide chains. A major biochemical characteristic of Hsp70-type chaperones is their nucleotide-regulated affinity to polypeptide substrates. To study the role of this allosteric regulation in the course of preprotein translocation, we have generated specific mtHsp70 mutations located within or close to the interface between the nucleotide-binding and the substrate-binding domains. Mitochondria isolated from the mtHsp70 mutants displayed severely reduced import efficiencies in vitro. Two of the mutants exhibited strong growth defects in vivo and were significantly impaired in the generation of an inward-directed, ATP-dependent import force on precursor proteins in transit. The biochemical properties of these two mutant proteins were consistent with defects in the transfer of conformational signals to the substrate-binding domain, resulting in a prolonged and enhanced interaction with imported substrate proteins. Furthermore, interference with the allosteric mechanism resulted in defects of translocation-specific partner protein interaction. We conclude that even a partial disruption of the interdomain communication in the mtHsp70 chaperone results in an almost complete breakdown of its translocation-driving properties.


Fatigue life estimation of dental implants using a combination of the finite element method and traditional fatigue criteria.
Failure by fatigue can be sudden and catastrophic. Therefore, ensuring that dental implants, which are under constant cyclic loading, do not fail to fatigue is imperative. The majority of the studies about the topic only performed in vitro tests, which are expensive and time-consuming. The Finite Element (FE) method is less costly and it allows the simulation of several different loading scenarios. Nonetheless, there are only a few studies analysing fatigue in dental prostheses using FE models, and the few available did not include all the relevant parameters, such as geometry effect, surface finishing, etc. Therefore, this study aimed to analyse the fatigue behaviour of a single-unit dental implant with two screws using a combination of the numerical results and the traditional fatigue criteria - a combination that was not yet fully and correctly explored. A finite element model comprising a single implant, one abutment, one abutment screw, one fixation screw and one prosthetic crown was developed. Material properties were assigned based on literature data. A 100 N load was applied to mimic the mastication forces and fatigue analysis was conducted using the Gerber, Goodman and Soderberg fatigue criteria. The fatigue analysis demonstrated that the abutment screw could fail in less than 1 year, depending on the criteria, while the fixation screw exhibits an infinite life. The results illustrated the importance of analysing the fatigue behaviour of dental implants and highlighted the potential of finite element models to simulate the biomechanical behaviour of dental implants.


[A case of gastric carcinoid associated with multiple early gastric cancers and atypical epithelium].
A 69-year-old man was admitted to our hospital complaining of the sensation of abdominal fullness and tarry stool. X-ray and endoscopic examination revealed a gastric tumor measuring 6.5 X 7.5 cm in the antrum along the greater curvature. Histologically, the tumor was diagnosed as carcinoid; five lesions of early gastric cancer and one lesion of atypical epithelium were also detected. Through 1982, 24 Japanese patients with gastric carcinoid associated with gastric cancer have been reported.


Structure emerges faster during cultural transmission in children than in adults.
How does children's limited processing capacity affect cultural transmission of complex information? We show that over the course of iterated reproduction of two-dimensional random dot patterns transmission accuracy increased to a similar extent in 5- to 8-year-old children and adults whereas algorithmic complexity decreased faster in children. Thus, children require more structure to render complex inputs learnable. In line with the Less-Is-More hypothesis, we interpret this as evidence that children's processing limitations affecting working memory capacity and executive control constrain the ability to represent and generate complexity, which, in turn, facilitates emergence of structure. This underscores the importance of investigating the role of children in the transmission of complex cultural traits.


Hypokalemia from intercostal nerve block.
Hypokalemia may arise from adrenergic stimulation during regional anesthesia. The authors studied the effects of adding epinephrine to the local anesthetic solution and of upper abdominal surgery on the hypokalemia following intercostal nerve block. Intercostal block was induced with bupivacaine 0.5% in 10 female volunteers. Bupivacaine 0.5% with epinephrine 1:200,000 was used for another intercostal nerve block in the same volunteers and in eight women who had just undergone cholecystectomy. Plasma concentrations of potassium, epinephrine, glucose, and bupivacaine were measured and the ECG was recorded. The decrease in the plasma potassium level during the experiment with plain bupivacaine was 0.10 +/- 0.09 mmol/L (mean +/- SEM). With bupivacaine and epinephrine, the decrease was 0.26 +/- 0.06 mmol/L in the volunteers and 0.58 +/- 0.07 mmol/L in the patients. After surgery the drug absorption was facilitated and the concentration-response relationship between epinephrine and potassium was maintained. The epinephrine-containing local anesthetic was associated with minor ECG changes. The hypokalemic effect of intercostal nerve block with bupivacaine 0.5% and epinephrine 1:200,000 is doubled after upper abdominal surgery performed under general anesthesia.


The Metal or the Ligand? The Preferred Locus for Redox Changes in Oxygen Atom Transfer Reactions of Rhenium Amidodiphenoxides.
The rhenium(V) oxo complex oxo(triphenylphosphine) (bis(3,5-di-tert-butyl-2-phenoxo)amido)rhenium(V), (ONOCat)ReO(PPh3), reacts with molecular oxygen to give triphenylphosphine oxide and the dimeric rhenium(VII) complex fac,anti-(ONOCat)Re(O)(μ-O)2Re(O)(ONOCat). The ONO ligand adopts an unusual fac geometry, presumably to maximize π donation to rhenium; strong π donation is substantiated by the intraligand bond distances (metrical oxidation state = -2.24(9)). Addition of the N-heterocyclic carbene ligand IMes to fac,anti-(ONOCat)Re(O)(μ-O)2Re(O)(ONOCat) cleaves the dimer into monomeric C1-symmetric fac-(ONOCat)ReO2(IMes). The monorhenium(VII) complex is deoxygenated by PMe2Ph to give the rhenium(V) compound (ONOCat)ReO(IMes), which can be independently prepared by ligand substitution of (ONOCat)ReO(PPh3). The degree of stereochemical rigidity exhibited by the dioxo compound, as established by dynamic NMR spectroscopy, excludes the intermediacy of mer-(ONOQ)ReVO2(IMes) in this oxygen atom transfer reaction. Thus, oxygen atom transfer takes place preferentially by direct reduction of the oxorhenium(VII) moiety (classical oxygen atom transfer) rather than through initial internal electron transfer and ligand-centered reduction of an oxorhenium(V)-iminoquinone.


The effect of an H2-receptor antagonist on small-bowel colonization and bacterial translocation in newborn rats.
Bacterial translocation (BT) is defined as the passage of enteric bacteria from the gastrointestinal tract to extraintestinal tissues. Bacterial overgrowth is one of the main promoting factors of BT, which is thought to play an important role in the pathogenesis of sepsis and necrotizing enterocolitis. It is believed that small-bowel colonization is established by bacterial spread through the rectum. Gastric acid is also involved in this process. An experimental study was designed for investigating the effect of gastric acid inhibition with the use of an H2-receptor antagonist on intestinal colonization and BT in newborn rats. Animals were divided into two groups: the ranitidine group (n = 20) received ranitidine 10 mg/kg per day intramuscularly for 5 days; the control group (n = 30) received saline solution. Mesenteric lymph node, spleen, liver, stomach, small bowel/cecum, and large bowel specimens were obtained from each rat 5 days later and gram-negative and -positive aerobic bacteria identified by the use of chocolate and Endo agar. It is concluded that: (1) there was a strong correlation between gastric and small-bowel bacterial colonization in the ranitidine group; (2) no correlation between large-and small-bowel colonization could be demonstrated; and (3) BT occurred only in the ranitidine group.


Novel method for high-throughput phenotyping of sleep in mice.
Assessment of sleep in mice currently requires initial implantation of chronic electrodes for assessment of electroencephalogram (EEG) and electromyogram (EMG) followed by time to recover from surgery. Hence, it is not ideal for high-throughput screening. To address this deficiency, a method of assessment of sleep and wakefulness in mice has been developed based on assessment of activity/inactivity either by digital video analysis or by breaking infrared beams in the mouse cage. It is based on the algorithm that any episode of continuous inactivity of > or =40 s is predicted to be sleep. The method gives excellent agreement in C57BL/6J male mice with simultaneous assessment of sleep by EEG/EMG recording. The average agreement over 8,640 10-s epochs in 24 h is 92% (n = 7 mice) with agreement in individual mice being 88-94%. Average EEG/EMG determined sleep per 2-h interval across the day was 59.4 min. The estimated mean difference (bias) per 2-h interval between inactivity-defined sleep and EEG/EMG-defined sleep was only 1.0 min (95% confidence interval for mean bias -0.06 to +2.6 min). The standard deviation of differences (precision) was 7.5 min per 2-h interval with 95% limits of agreement ranging from -13.7 to +15.7 min. Although bias significantly varied by time of day (P = 0.0007), the magnitude of time-of-day differences was not large (average bias during lights on and lights off was +5.0 and -3.0 min per 2-h interval, respectively). This method has applications in chemical mutagenesis and for studies of molecular changes in brain with sleep/wakefulness.


Characterization of a novel potency endpoint for the evaluation of immune checkpoint blockade in humanized mice.
Humanized mice are emerging as valuable models to experimentally evaluate the impact of different immunotherapeutics on the human immune system. These immunodeficient mice are engrafted with human cells or tissues, that then mimic the human immune system, offering an alternative and potentially more predictive preclinical model. Immunodeficient NSG mice engrafted with human CD34+ cord blood stem cells develop human T cells educated against murine MHC. However, autoimmune graft versus host disease (GvHD), mediated by T cells, typically develops 1 year post engraftment. Here, we have used the development of GvHD in NSG mice, using donors with HLA alleles predisposed to autoimmunity (psoriasis) to weight in favor of GvHD, as an endpoint to evaluate the relative potency of monoclonal and BiSpecific antibodies targeting PD-1 and CTLA-4 to break immune tolerance. We found that treatment with either a combination of anti-PD-1 & anti-CTLA-4 mAbs or a quadrivalent anti-PD-1/CTLA-4 BiSpecific (MEDI8500), had enhanced potency compared to treatment with anti-PD-1 or anti-CTLA-4 monotherapies, increasing T cell activity both in vitro and in vivo. This resulted in accelerated development of GvHD and shorter survival of the humanized mice in these treatment groups commensurate with their on target activity. Our findings demonstrate the potential of humanized mouse models for preclinical evaluation of different immunotherapies and combinations, using acceleration of GvHD development as a surrogate of aggravated antigenic T-cell response against host.


Multi-Function of the Ni Interlayer in the Design of a BiVO4-Based Photoanode for Photoelectrochemical Water Splitting.
BiVO4 with an appropriate band structure is considered to be an ideal candidate for photoanodes. However, slow water oxidation kinetics and low charge separation efficiency seriously restrict its application. To address these issues, an NF/N/BVO photoanode with a hierarchical network structure was successfully constructed by direct-current magnetron sputtering of Ni followed by electrochemical deposition of nickel-iron layered double hydroxide (NiFe-LDH) on BiVO4. A photocurrent density of 4.50 mA/cm2 was obtained for NF/N/BVO, which was 2.4 times that for pristine BiVO4. The introduction of the Ni layer contributed to the following growth of NiFe-LDH nanosheets with larger size, which acted as active sites and speeded up water oxidation kinetics. Furthermore, surface photovoltage microscopy revealed that Ni and NiFe-LDH acted as the electron collector and hole reservoir, respectively. The co-existence of the two components constituted a highly efficient surface charge separation structure, which was one of the important issues for the excellent water oxidation activity.


Levetiracetam-Induced Psychosis in the Setting of Intracranial Cavernomas.
Levetiracetam is a commonly used antiepileptic medication that has been associated with the development of psychosis. Cavernomas are vascular malformations that have been associated with psychosis as well, especially in the setting of hemorrhagic transformation. This case report describes a patient with cavernomas who developed psychotic symptoms after restarting her levetiracetam at a high dose (2000 mg twice a day) without gradual uptitration. Her symptoms improved upon the reduction of the levetiracetam as well as the initiation of paliperidone. This case highlights the importance of considering the biologic and medication-related factors for the development of psychosis, as well as the importance of gradual medication adjustments.


Intimate connections: Inositol pyrophosphates at the interface of metabolic regulation and cell signaling.
Inositol pyrophosphates are small, diffusible signaling molecules that possess the most concentrated three-dimensional array of phosphate groups in Nature; up to eight phosphates are crammed around a six-carbon inositol ring. This review discusses the physico-chemical properties of these unique molecules, and their mechanisms of action. Also provided is information on the enzymes that regulate the levels and hence the signaling properties of these molecules. This review pursues the idea that many of the biological effects of inositol pyrophosphates can be rationalized by their actions at the interface of cell signaling and metabolism that is essential to cellular and organismal homeostasis.


The relationship between inflammatory response markers and the prognosis of non-muscle invasive bladder cancer and the development of a nomogram model.
Patients with non-muscle invasive bladder cancer (NMIBC) have a high possibility of recurrence after surgery. We aimed to assess the factors associated with tumor recurrence and to construct a nomogram model that can contribute to personalized treatment plans of each patient. 496 patients with primary bladder cancer (BC) from 2 centers were retrospectively analyzed. Preoperative neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and traditional clinical parameters were collected, then using univariate and multivariate Cox regression analysis to find out the independent risk factors associated with tumor recurrence among them, and then these independent factors were incorporated into the nomogram model. The internal calibration curves and the external calibration curves were used to verify their usefulness. In the training cohort, 150 patients (43.1%) experienced recurrence. After Cox regression analysis, the independent risk factors affecting recurrence-free survival (RFS) were tumor grade, immediate postoperative instillation therapy (IPPIT), NLR, and SII. These factors were used to construct a model to predict RFS 1, 2, 3, and 5 years of NMIBC patients after surgery. And then, we found that the constructed model outperforms the conventional model in terms of accuracy and predictability, the results were verified by statistical tests. Preoperative inflammatory response markers have a predictive value for postoperative recurrence in patients with NMIBC. The constructed nomogram model can be helpful in guiding personalized clinical evaluation and subsequent treatment.


Acyclic diene metathesis polymerization and heck polymer-polymer conjugation for the synthesis of star-shaped block copolymers.
Three- and four-arm star shaped polymers, as well as diblock copolymers, are synthesized via acyclic diene metathesis (ADMET) polymerization. This is accomplished by using an asymmetric α,ω-diene containing a terminal double bond and an acrylate, which is polymerized in the presence of multifunctional acrylates as selective and irreversible chain transfer agents using Hoveyda-Grubbs second generation catalyst. High cross-metathesis selectivities are achieved at low temperatures enabling good control over molecular weights. Furthermore, additional polyethyleneglycol (PEG) blocks are attached to these polymers via Heck coupling of the acrylate end-groups of these polymers with aryl iodide functionalized PEG, obtaining three- and four-arm star shaped di- and triblock copolymers with molecular weights up to 31 kDa.


Trimipramine and duodenal ulcer.
The gastric acid secretion, fasting serum gastrin and serum concentration of trimipramine were studied in 20 patients with duodenal ulcer during a 6 weeks treatment with trimipramine. Ulcer healing was examined endoscopically. In the group of 11 patients with healed ulcers the gastric acid secretion decreased significantly at 3 and 6 weeks in contrast to the 9 patients in whom ulcers did not heal, indicating a different antisecretory response in the two groups. The serum concentration of trimipramine was similar in both groups during treatment. Possible mechanisms of action of trimipramine in peptic ulcer disease and problems concerning clinical response and dose are discussed.


The Extraction and Characterization of Pseudorange Multipath Based on BDS-3 Multi-Frequency Observations.
Global Navigation Satellite System (GNSS) observations are subject to various errors during their propagation process. A reasonable correction of these errors can improve the positioning, navigation, and timing (PNT) service capability. The impact of multipaths on pseudorange observations can reach a decimeters or even meters level. However, their mechanism is complex and there is currently no universally accepted high-precision correction model. The correlation between the pseudorange multipaths (MP) of BDS-2 satellites and satellite elevation has been confirmed, while there have been fewer analyses of the MP characteristics for different frequencies of BDS-3 satellites. The broadcasting of multi-frequency observations in BDS-3 should theoretically make the extracted MP more accurate compared to traditional methods. Based on this, in this contribution, a multi-frequency MP extraction algorithm based on the least squares principle is proposed, which can simultaneously eliminate the influence of higher-order ionospheric delay. The analytical expression for only eliminating first-order ionospheric delay is successfully derived. Subsequently, the characteristics of the MPs extracted from different frequency combinations and the impact of combination noise on the extraction accuracy are discussed. The influence of second-order ionospheric delay on the MPs for each frequency under different combination noises, as well as the periodic behavior exhibited in long-term observations of the BDS-3 medium earth orbit (MEO) and inclined geosynchronous orbit (IGSO) satellites, are also analyzed. Finally, the correlations between the MPs of each frequency of BDS satellite and elevation are quantitatively analyzed based on observations from 35 stations. Overall, this work has positive implications for the study of the MP characteristics of BDS-3 and subsequent modeling efforts.


Comparing Relative Value Units among Shoulder Arthroplasty, Hemiarthroplasty, and ORIF for Proximal Humerus Fractures in the Elderly: Which is Most Worth Your Time?
Relative value units (RVUs) are assigned to Current Procedural Technology (CPT) codes and give relative economic values to the services physicians provide. This study compared the RVU reimbursements for the surgical options of proximal humerus fractures in the elderly, which include arthroplasty (reverse [RSA] and total [TSA]), hemiarthroplasty (HA), and open reduction and internal fixation (ORIF). Using the National Surgical Quality Improvement Program, a total of 1,437 patients of at least 65 years of age with proximal humerus fractures between 2008 and 2016 were identified. Of those, 259 underwent RSA/TSA (CPT code 23472), 418 underwent HA (CPT codes 23470 and 23616), and 760 underwent ORIF (CPT code 23615). Univariate analysis compared RVU per minute, reimbursement rate, and the average annual revenue across cohorts based on respective operative times. RSA/TSA generated a mean RVU per minute of 0.197 (SD 0.078; 95%CI [0.188, 0.207]), which was significantly greater than the mean RVU per minute for 23470 HA (0.156; SD 0.057; 95%CI [0.148, 0.163]), 23616 HA (0.166; SD 0.065; 95%CI [0.005, 0.156]), and ORIF (0.135; SD 0.048; 95%CI [0.132, 0.138]; P<0.001). This converted to respective reimbursement rates of $6.97/min (SD 2.78; 95%CI [6.63, 7.31]), $5.48/min (SD 2.05; 95%CI [5.22, 5.74]), $5.83/min (SD 2.28; 95%CI [5.49, 6.16]) and $4.74/min (SD 1.69; 95%CI [4.62, 4.87]). After extrapolation, respective average annual revenues were $580,386, $456,633, $475,077, and $395,608. RSA/TSA provides significantly greater reimbursement rates compared to HA and ORIF. Orthopaedic surgeons can use this information to optimize daily procedural cost-effectiveness in their practices.


LATIN AS A LANGUAGE OF INTERNATIONAL COMMUNICATIVE STATUS: MEDICINE OF THE 16TH-17TH CENTURIES.
The research paper is of interdisciplinary nature, written at the crossroads of the history of medicine, functional stylistics and terminology science. The choice of the 16th century as a starting point of the study is due to the fact that quality changes in book and manuscript writing that took place during this period led to unprecedented development and dissemination of scientific knowledge, including biomedical. The 16th century embraces the life and work of such prominent figures in the history of medicine, as Andreas Vesalius, Gabriele Fallopian, Bartolomeo Eustachi, and Girolamo Fracastoro. The 17th century, which is called the century of "scientific revolution", left not less honourable names in the history of medicine - William Harvey, Marcello Malpighi, Thomas Willis, Jean Pecquet, Francis Glisson, Thomas Sydenham. In the context of this study, these prominent figures are interesting due to the fact that their works were written in Latin and constitute the prototypes of modern scientific style, in particular of such genres as thesis, monograph, scientific article, scientific report, polemic presentation, textbook. On the basis of extensive factual material, it has been demonstrated that during 16th-17th centuries, Latin acted as a fully developed language with a clearly oriented international status. As one of basic tools in scientific knowledge, Latin not only performed the epistemological function which was the priority for the development of medicine, but also served as a means of accumulation, reception, transmission and popularization of achievements in various areas of medical science.


Evaporative water loss in seven species of fossorial rodents: Does effect of degree of fossoriality and sociality exist?
In terrestrial endotherms, evaporation is a significant mechanism of water loss in hot environments. Although water is passively lost by evaporation, individuals can regulate it at different levels. Inhabiting a relatively stable environment characterized by mild ambient temperature (Ta) and high humidity can ensure a balanced water budget. Many fossorial rodents are well adapted to live in such conditions. In this study, evaporative water loss (EWL) of fossorial rodent species with different degree of adaptations to underground life (from strictly subterranean to those with regular surface activity) was evaluated. By measuring EWL, the specific contribution of either evaporative or non-evaporative components of heat loss can be determined. With the exception of the silvery mole-rat (Heliophobius argenteocinereus), in all tested rodents EWL is relatively stable below and within the thermoneutral zone (TNZ). As Tas increase above TNZ, EWL increases as does total thermal conductance, but conductance increases several times more than EWL. In addition, non-evaporative routes seem to be more important than evaporative heat loss in the analyzed species. No clear pattern of EWL in relation to a species degree of fossoriality or sociality was detected. In this context, atmosphere of burrows could affect EWL, since the high humidity found inside tunnels can establish limits on evaporation to favor water rather than thermal balance.


Mediating Short-Term Plasticity in an Artificial Memristive Synapse by the Orientation of Silica Mesopores.
Memristive synapses based on resistive switching are promising electronic devices that emulate the synaptic plasticity in neural systems. Short-term plasticity (STP), reflecting a temporal strengthening of the synaptic connection, allows artificial synapses to perform critical computational functions, such as fast response and information filtering. To mediate this fundamental property in memristive electronic devices, the regulation of the dynamic resistive change is necessary for an artificial synapse. Here, it is demonstrated that the orientation of mesopores in the dielectric silica layer can be used to modulate the STP of an artificial memristive synapse. The dielectric silica layer with vertical mesopores can facilitate the formation of a conductive pathway, which underlies a lower set voltage (≈1.0 V) compared to these with parallel mesopores (≈1.2 V) and dense amorphous silica (≈2.0 V). Also, the artificial memristive synapses with vertical mesopores exhibit the fastest current increase by successive voltage pulses. Finally, oriented silica mesopores are designed for varying the relaxation time of memory, and thus the successful mediation of STP is achieved. The implementation of mesoporous orientation provides a new perspective for engineering artificial synapses with multilevel learning and forgetting capability, which is essential for neuromorphic computing.


Shock in an infant with bullous mastocytosis.
A 6-month-old infant had bullous lesions on his posterior neck, upper trunk, and extremities for two months prior to admission for fever and shock. He had an elevated white blood cell count with left shift and normal platelet count, but abnormal coagulation studies. He was treated with intravenous antibiotics, crystalloids, fresh-frozen plasma, and pressor agents. A histamine H2 receptor antagonist was started for guaiac-positive nasogastric tube drainage. The patient recovered after four days of treatment. A skin biopsy confirmed mastocytosis. A week later the child passed grossly bloody stools with blood clots. No source of gastrointestinal bleeding was identified by extensive work-up. Blood histamine level measured one day before gastrointestinal bleeding was 16,400 pg/ml (normal 263 +/- 202 pg/ml). The bleeding resolved spontaneously. The patient was maintained on cimetidine. Results of a subsequent bone scan were normal. Shock or gastrointestinal bleeding associated with unusual skin lesions should alert the pediatrician to the possibility of mastocytosis.


Grazing resistance of Pseudomonas aeruginosa biofilms depends on type of protective mechanism, developmental stage and protozoan feeding mode.
In a previous study we identified microcolony formation and inhibitor production as the major protective mechanisms of Pseudomonas aeruginosa biofilms against flagellate grazing. Here we compared the efficacy of these two key protective mechanisms by exposing biofilms of the non-toxic alginate overproducing strain PDO300 and the wild-type toxic strain PAO1 to a range of feeding types commonly found in the succession of protozoans associated with natural biofilms. Alginate-mediated microcolony formation conferred effective protection for strain PDO300 against the suspension feeding flagellate Bodo saltans and, as reported earlier, the surface feeding flagellate Rhynchomonas nasuta, both of which are considered as early biofilm colonizers. However, microcolonies of mature PDO300 biofilms were highly susceptible to late biofilm colonizers, the surface-feeding amoeba Acanthamoeba polyphaga and the planktonic ciliate Tetrahymena sp., resulting in a significant reduction of biofilm biomass. Mature biofilms of strain PAO1 inhibited growth of flagellates and A. polyphaga while the grazing activity of Tetrahymena sp. remained unaffected. Our findings suggest that inhibitor production of mature P. aeruginosa biofilms is effective against a wider range of biofilm-feeding predators while microcolony-mediated protection is only beneficial in the early stages of biofilm formation.


Tandem domain structure determination based on a systematic enumeration of conformations.
Protein structure determination is undergoing a change of perspective due to the larger importance taken in biology by the disordered regions of biomolecules. In such cases, the convergence criterion is more difficult to set up and the size of the conformational space is a obstacle to exhaustive exploration. A pipeline is proposed here to exhaustively sample protein conformations using backbone angle limits obtained by nuclear magnetic resonance (NMR), and then to determine the populations of conformations. The pipeline is applied to a tandem domain of the protein whirlin. An original approach, derived from a reformulation of the Distance Geometry Problem is used to enumerate the conformations of the linker connecting the two domains. Specifically designed procedure then permit to assemble the domains to the linker conformations and to optimize the tandem domain conformations with respect to two sets of NMR measurements: residual dipolar couplings and paramagnetic resonance enhancements. The relative populations of optimized conformations are finally determined by fitting small angle X-ray scattering (SAXS) data. The most populated conformation of the tandem domain is a semi-closed one, fully closed and more extended conformations being in minority, in agreement with previous observations. The SAXS and NMR data show different influences on the determination of populations.


Comparison of Dolichos biflorus lectin and other lectin-horseradish peroxidase conjugates in staining of cutaneous blood vessels in the hairless mini-pig.
Angiogenesis is necessary for normal growth, wound healing, and plays a key role in many pathologic processes. A variety of endothelial markers have been used to investigate angiogenesis. Unfortunately, excellent markers for vascular endothelium in human tissues exhibit little or no staining of endothelia in tissues of other animal species, including the pig. We are interested in the hairless Yucatan strain of mini-pig as an animal model for studying cutaneous wound healing because its skin is histologically and functionally very similar to that of man. Hoping to find a specific marker to identify vascular endothelium in the mini-pig, we therefore screened a battery of 11 different lectin-horseradish peroxidase conjugates. Based on specificity and staining intensity, Dolichos biflorus agglutinin (DBA) was chosen from this battery to investigate vascular changes in the healing of cutaneous wounds in the mini-pig. When compared with routine histologic sections stained with hematoxylin and eosin, blood vessels were much easier to identify in sections stained histochemically with DBA. Lectin histochemistry was particularly useful in investigations of early events in angiogenesis during wound healing when newly derived capillary buds and minute blood vessels were obscured in normal histologic sections by an inflammatory cell infiltrate associated with the healing wound. Ultrastructural lectin cytochemistry revealed staining along the luminal surface and the basolateral plasmalemma of endothelial cells. Histochemical staining with DBA promises to provide a useful method for further investigation of angiogenesis and other vascular phenomena in a variety of normal and pathologic processes using the hairless Yucatan strain of mini-pig as the animal model.


[A case report of monitoring neuromuscular blockade during anesthesia in a patient with facioscapulohumeral muscle dystrophy].
Facioscapulohumeral muscle dystrophy (FSHMD) is characterized by slowly progressive wasting of facial, pectoral and shoulder-girdle muscles that begins in adolescence. A 31 year-old man with FSHMD had dystrophic changes in the deltoid, anterior serratus and pectoralis major muscles but not in the distal muscle of his arms and legs. He underwent an operation for thoraco-scapula fixation under enflurane-nitrous oxide anesthesia with vecuronium 6 mg. At the end of the surgical procedure, the train-of-four (TOF) responses of a thumb and a toe, as measured by using an acceleration transducer, were recorded simultaneously. TOF stimulation in an arm demonstrated an apparent fade phenomenon (TOF; 0.54), while a TOF test in the leg showed complete recovery of the TOF ratio (TOF; 1.0). The patient revealed no clinical signs of residual neuromuscular blockade. It was clear that there was a difference in the degree of neuromuscular block between the arm and the leg in a FSHMD patient. Use of the peripheral nerve stimulator only in the arm may be an unreliable guide to assess neuromuscular block in FSHMD patients. Therefore, two sites should be chosen for monitoring neuromuscular blockade in a FSHMD patient.


Enhanced Carbon Dioxide Electroreduction to Carbon Monoxide over Defect-Rich Plasma-Activated Silver Catalysts.
Efficient, stable catalysts with high selectivity for a single product are essential if electroreduction of CO2 is to become a viable route to the synthesis of industrial feedstocks and fuels. A plasma oxidation pre-treatment of silver foil enhances the number of low-coordinated catalytically active sites, which dramatically lowers the overpotential and increases the activity of CO2 electroreduction to CO. At -0.6 V versus RHE more than 90 % Faradaic efficiency towards CO was achieved on a pre-oxidized silver foil. While transmission electron microscopy (TEM) and operando X-ray absorption spectroscopy showed that oxygen species can survive in the bulk of the catalyst during the reaction, quasi in situ X-ray photoelectron spectroscopy showed that the surface is metallic under reaction conditions. DFT calculations reveal that the defect-rich surface of the plasma-oxidized silver foils in the presence of local electric fields drastically decrease the overpotential of CO2 electroreduction.


An in vitro Comparison of Accuracy Between Three Different Face Scanning Modalities.
A mannequin head was digitized using a reference scanner (Scan in a Box) to acquire the reference mesh. Subsequently it was scanned with a structured light scanner (Einscan Pro HD), a stereophotogrammetry scanner (RayFace100) and a laser scanner (Proface 3D Mid) to acquire test meshes.Resulting meshes were delineated in four horizontal areas and discrepancies calculated for the complete face and different facial partitions. One-way Anova and pairwise comparisons tests were used to compare trueness and precision between scanners across different areas. Significant differences were detected among scanners for complete face (F (3, 27) =776, P ⟨ 0.01)) and for delineated face areas (F (11, 99) =200.1, P ⟨ 0.01)). Einscan had significantly higher accuracy for the complete face (P⟨0.01) and significantly higher trueness for each facial partition compared to other scanners. RayFace had significantly higher trueness when scanning the middle part of face compared to other facial parts. Proface had significantly lower upper facial third trueness compared to other facial parts. All scanners had accuracy levels below the 2.00mm threshold. Facial scanning accuracy was influenced per scanner used. Scanning trueness per device was influenced by location of surface area. All scanners had accuracy levels within the acceptable accuracy threshold.


Gene vaccination for the induction of immune tolerance.
DNA vaccination is a strategy of immunization based on the injection of a gene encoding for a target protein with the goal of eliciting a potentially protective immune response in the host. Compared to traditional immunization procedures, DNA vaccination offers several advantages: increased availability of antigenic peptides because of the endogenous and long-term synthesis of the gene product, improved antigen processing and presentation, possibility of antigen structure modeling through molecular engineering, coexpression of immunologically relevant agents, and low cost of vaccine production. Although the choice of the most appropriate vector for gene transfer may still be controversial, the application of DNA vaccination to the treatment of autoimmune diseases in different experimental animal models has demonstrated the great potential of this procedure for therapeutic purposes. DNA vaccination has been successful in protecting mice from the development of organ-specific autoimmunity (experimental allergic encephalomyelitis (EAE), autoimmune diabetes, experimental arthritis, experimental uveitis) as well as systemic autoimmune disease (systemic lupus erythematosus (SLE), antiphospholipid syndrome). The protection appears to be highly influenced by the capacity of DNA vaccination to modulate immune responses affecting the Th1, Th2 and, importantly, the T cell immunoregulatory arms. We review here the experimental evidence and most recent data supporting the use of DNA vaccination in the induction of immune tolerance.


Sonographic diagnosis of urethral anomalies in infants: value of perineal sonography.
To assess the value of urethral sonography including a perineal approach in evaluating urethral anomalies in infants. A radiology database review identified 88 patients (mean age +/- SD, 64 +/- 84 days) who underwent voiding cystourethrography (VCUG) and urethral sonography as part of extended sonography of the urinary tract. Sonographic and VCUG images and reports were reviewed to assess agreement between both modalities for detection of urethral anomalies. Sonography facilitated the correct diagnosis of all 3 posterior urethral valves. The only urethral diverticulum, the only ectopic ureteric insertion into the urethra, the only urogenital sinus, and the only urethrovaginal fistula were also shown on sonography. In 73 (94%) of 78 cases, sonography correctly showed the absence of anomalies. In 5 infants, sonography could not reliably assess the urethra and showed indirect signs of urethral anomalies; however, these patients had normal urethras on VCUG. Our data show that sonography of the urethra is a valuable tool for diagnosis of urethral anomalies. Especially, negative findings on sonography are highly suggestive of the absence of urethral anomalies. Positive or equivocal sonographic findings should indicate VCUG.