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Effect of sleep quality on memory, executive function, and language performance in patients with refractory focal epilepsy and controlled epilepsy versus healthy controls - A prospective study. We aimed to evaluate the effect of sleep quality on memory, executive function, and language performance in patients with refractory focal epilepsy and controlled epilepsy and compare these with healthy individuals. We prospectively enrolled 37 adolescent and adult patients with refractory focal epilepsy (Group 1) and controlled epilepsy (Group 2) in each group. History pertaining to epilepsy and sleep were recorded, and all patients underwent overnight polysomnography. Language, memory, and executive function assessments were done using Western Aphasia Battery, Post Graduate Institute (PGI) memory scale, and battery of four executive function tests (Trail Making Test A & B, Digit symbol test, Stroop Task, and Verbal Fluency Test), respectively. Forty age- and sex-matched controls were also included in the study. Significant differences were noted in both objective and subjective sleep parameters among all the groups. On polysomnography, parameters like total sleep time, sleep efficiency, sleep latency, and rapid eye movement (REM) latency were found to be significantly worse in Group 1 as compared with Group 2. Cognitive and executive parameters were significantly impaired in Group 1. Shorter total sleep time, poorer sleep efficiency, and prolonged sleep latencies were observed to be associated with poor memory and executive function in patients with refractory epilepsy. Our study strongly suggests that sleep disturbances, mainly shorter total sleep time, poor sleep efficiency, and prolonged sleep latencies, are associated with impaired memory and executive function in patients with refractory focal epilepsy and to a lesser extent, among those with medically controlled epilepsy.

Fluorescent labeling of both GABAergic and glycinergic neurons in vesicular GABA transporter (VGAT)-venus transgenic mouse. Inhibitory neurons play important roles in a number of brain functions. They are composed of GABAergic neurons and glycinergic neurons, and vesicular GABA transporter (VGAT) is specifically expressed in these neurons. Since the inhibitory neurons are scattered around in the CNS, it is difficult to identify these cells in living brain preparations. The glutamate decarboxylase (GAD) 67-GFP knock-in mouse has been widely used for the identification of GABAergic neurons, but their GAD67 expression was decreased compared to the wild-type mice. To overcome such a problem and to highlight the function and morphology of inhibitory neurons, we generated four lines of VGAT-Venus transgenic mice (lines #04, #29, #39 and #49) expressing Venus fluorescent protein under the control of mouse VGAT promoter. We found higher expression level of Venus transcripts and proteins as well as brighter fluorescent signal in line #39 mouse brains, compared to brains of other lines examined. By Western blots and spectrofluorometric measurements of forebrain, the line #39 mouse showed stronger GFP immunoreactivity and brighter fluorescent intensity than the GAD67-GFP knock-in mouse. In addition, Venus was present not only in somata, but also in neurites in the line #39 mouse by histological studies. In situ hybridization analysis showed that the expression pattern of Venus in the line #39 mouse was similar to that of endogenous VGAT. Double immunostaining analysis in line #39 mouse showed that Venus-expressing cells are primarily immunoreactive for GABA in cerebral cortex, hippocampus and cerebellar cortex and for GABA or glycine in dorsal cochlear nucleus. These results demonstrate that the VGAT-Venus line #39 mouse should be useful for studies on function and morphology of inhibitory neurons in the CNS.

Carotid endarterectomy: operative risks, recurrent stenosis, and long-term stroke rates in a modern series. To determine whether carotid endarterectomy (CEA) safely and effectively maintained a durable reduction in stroke complications over an extended period, we reviewed our data on 478 consecutive patients who underwent 544 CEA's since 1976. Follow-up was complete in 83% of patients (mean 44 months). There were 7 early deaths (1.3%), only 1 stroke related (0.2%). Perioperative stroke rates (overall 2.9%) varied according to operative indications: asymptomatic, 1.4%; transient ischemic attacks (TIA)/amaurosis fugax (AF), 1.3%; nonhemispheric symptoms (NH), 4.9%; and prior stroke (CVA), 7.1%. Five and 10-year stroke-free rates were 96% and 92% in the asymptomatic group, 93% and 87% in the TIA/AF group, 92% and 92% in the NH group, and 80% and 73% in the CVA group. Late ipsilateral strokes occurred infrequently (8 patients, 1.7%). Late deaths were primarily cardiac related (51.3%). Stroke-free rates were significantly (p less than 0.0001) greater than stroke-free survival rates, confirming a non-stroke related cause for late death. Restenoses greater than 50% according to duplex scanning developed in 13%, most (67%) within 2 years after CEA. Most of these (77%) were asymptomatic, and only 0.3% (1 patient) presented with a permanent neurologic deficit. The results of carotid endarterectomy are superior to those of optimal medical management in symptomatic and asymptomatic patients in terms of long-term stroke prevention. When low perioperative stroke mortality/morbidity rates are achieved, carotid endarterectomy is justified for treatment of patients with carotid bifurcation disease.

Regulation of the anaerobic metabolism in Bacillus subtilis. The Gram-positive soil bacterium Bacillus subtilis encounters changing environmental conditions in its habitat. The access to oxygen determines the mode of energy generation. A complex regulatory network is employed to switch from oxygen respiration to nitrate respiration and various fermentative processes. During adaptation, oxygen depletion is sensed by the [4Fe-4S](2+) cluster containing Fnr and the two-component regulatory system ResDE consisting of the membrane-bound histidine kinase ResE and the cytoplasmic ResD regulator. Nitric oxide is the signal recognized by NsrR. Acetate formation and decreasing pH are measured via AlsR. Finally, Rex is responding to changes in the cellular NAD(+)/NADH ration. The fine-tuned interplay of these regulators at approximately 400 target gene promoters ensures efficient adaptation of the B. subtilis physiology.

Early and long-term outcomes after manual and remote magnetic navigation-guided catheter ablation for ventricular tachycardia. Remote magnetic navigation (RMN) is a safe and effective means of performing ventricular tachycardia (VT) ablation. It may have advantages over manual catheter ablation due to ease of manoeuvrability and catheter stability. We sought to compare the safety and efficacy of RMN vs. manual VT ablation. Retrospective study of procedural outcomes of 139 consecutive VT ablation procedures (69 RMN, 70 manual ablation) in 113 patients between 2009 and 2015 was performed. Remote magnetic navigation was associated with overall higher acute procedural success (80% vs. 60%, P = 0.01), with a trend to fewer major complications (3% vs. 9% P = 0.09). Seventy-nine patients were followed up for a median of 17.0 [interquartile range (IQR) 3.0-41.0] months for the RMN group and 15.5 (IQR 6.5-30.0) months for manual ablation group. In the ischaemic cardiomyopathy subgroup, RMN was associated with longer survival from the composite endpoint of VT recurrence leading to defibrillator shock, re-hospitalization or repeat catheter ablation and all-cause mortality; single-procedure adjusted hazard ratio (HR) 0.240 (95% CI 0.070-0.821) P = 0.023, multi-procedure HR 0.170 (95% CI 0.046-0.632) P = 0.002. In patients with implanted defibrillators, multi-procedure VT-free survival was superior with RMN, HR 0.199 (95% CI 0.060-0.657) P = 0.003. Remote magnetic navigation may improve clinical outcomes after catheter ablation of VT in patients with ischaemic cardiomyopathy. Further prospective clinical studies are required to confirm these findings.

Effect of Cardiac Rehabilitation on Sexual Satisfaction Among Patients After Coronary Artery Bypass Graft Surgery. After coronary artery bypass graft (CABG) surgery, many patients experience diminished sexual function and satisfaction. The present study aimed to investigate the effect of outpatient cardiac rehabilitation (OCR) on the level of sexual satisfaction among post-CABG patients. A clinical trial was performed at the Al-Zahra Hospital, Shiraz, Iran, from July 2017 to January 2018. Based on the inclusion criteria, 104 post-CABG patients were recruited into the study. The participants were randomly assigned to the intervention (OCR) group (n = 52) or the usual care group (n = 52). The intervention group received 20 sessions of OCR, whereas the usual care group received the routine hospital care and education. Data were collected using the Index of Sexual Satisfaction and a demographic data sheet. The data were analyzed using the SPSS software, v23.0 (IBM) and the independent sample t test, paired-samples t test, and χ test. There was no statistically significant difference in the mean pre-intervention score for sexual satisfaction between the groups. However, a statistically significant difference in the mean post-intervention score for sexual satisfaction was observed between the groups (P < .001). The difference in the mean pre- and post-intervention scores for sexual satisfaction in the intervention group was statistically significant (P < .001), whereas there was no significant difference in the usual care group. Post-CABG patients who completed the OCR program experienced an increased level of sexual satisfaction. It is, therefore, recommended to include an OCR program as part of the patient treatment and aftercare following CABG surgery.

[Chronic intestinal pseudo-obstruction. Clinical symptomatology and course]. Chronic intestinal pseudoobstruction (CIP) is a motility disorder clinically characterized by recurrent symptoms of small intestinal or large bowel obstruction without organic stenosis. The aim of the present study was to assess the clinical presentation and course of the disease. During a four year period all available data including the symptoms as assessed by the bowel disease questionnaire (BDQ) of all patients with newly established diagnosis of CIP were analyzed including duration of symptoms and previous surgical interventions due to the abdominal symptoms. Data of nine patients (five females, four males, age 20 - 64 years) with newly diagnosed CIP were available for analysis. Median age at initial onset of symptoms were 24 years. The final diagnosis of CIP was established after a median of 7 years (range 1 - 20). Initially, the majority of patients suffered from uncharacteristic symptoms such as abdominal fullness and abdominal pain. All patients had undergone repeated abdominal surgical interventions for suspected mechanical bowel obstruction. On average, the first surgical intervention was performed 5 years after the onset of symptoms and there was a median number of 10 treatments as in-patients. Suspected acute bowel obstruction occurred between 1 and 14 times and laparotomies were performed in 50 % of these events. The diagnosis of CIP is usually preceded by several years with uncharacteristic abdominal symptoms. During this time, most patients undergo multiple surgical interventions. Thus, in patients with repeated suspected acute bowel obstruction without definite proof of mechanical obstruction, CIP has to be taken into consideration as differential diagnosis. In this context, small bowel manometry is an important diagnostic tool.

Posterior only versus combined anterior and posterior approaches to lumbar scoliosis in adults: a radiographic analysis. Retrospective study. To compare the radiographic lumbar curve correction between a posterior only and combined anterior-posterior approach in patients with adult spinal deformity. In adolescent idiopathic scoliosis correction, posterior only has been compared with the combined anterior-posterior approach; however, there have been no corollary studies in adult scoliosis. Traditionally, rigid lumbar curves have been treated with a combined anterior and posterior approach; however, the absolute indications for this approach are unclear. A total of 180 patients with degenerative or adult idiopathic spinal deformity and curves measuring between 40 degrees and 70 degrees who underwent reconstructive spinal fusion. The minimum follow-up period was 28 months and average follow-up was 53 months. Of the 155 patients who underwent surgery, 80 underwent posterior only (35 with idiopathic and 45 with degenerative scoliosis) while 75 patients (30 with idiopathic and 35 with degenerative scoliosis) underwent combined anterior-posterior surgery. The groups were compared by age at operation, preoperative deformity, levels operated and postoperative correction and balance. There were no significant differences in sagittal and coronal plane curve and balance correction between the posterior only and the combined anterior-posterior groups. When the patients were subdivided into degenerative adult scoliosis and idiopathic adult scoliosis, there were again no significant differences in the sagittal and coronal curves or balance between the posterior only and combined anterior and posterior approaches. While the posterior only group and the same-day anterior and posterior surgery group had a similar major complication rate of 24% and 23%, respectively, patients who underwent staged anterior and posterior surgery had a major complication rate of 45%. When combined with extensive posterior releases, posterior only approach is just as effective as combined anterior and posterior surgery for adult lumbar scoliosis measuring between 40 degrees and 70 degrees .

The pathophysiology of neurofibromatosis. I. Resistance in vitro to 3-nitrotyrosine as an expression of the mutation. The in vitro expression of the autosomal dominant mutation responsible for neurofibromatosis was probed using the amino acid analogue 3-nitrotyrosine as a cell culture selective agent. The presence of 3-nitrotyrosine in culture medium led to inhibition of growth and cell death among normal skin fibroblasts in log phase growth, whereas cell strains derived from six different patients' neurofibromas or skin cells, or both, exhibited a consistently enhanced ability to survive under the same conditions. At 0.8 mM 3-nitrotyrosine, four patient-derived skin fibroblast strains could be differentiated from five strains of control skin fibroblasts with a high level of confidence (P < 0.0000). In the same way four neurofibroma-derived fibroblast strains were differentiated from control skin fibroblasts (P < 0.0022). Neurofibroma-derived cells were not different from control cells when treated with 5-fluorotryptophan or p-fluorophenylalanine.

[A sociomedical geriatric assessment in the emergency units: an alternative to the hospitalization of aged patients?]. Elderly patients admitted to the emergency unit are usually hospitalized in medical units. Could a gerontologic evaluation in the emergency room lead to another solution than hospitalization? Since January 1993, a sociomedical geriatric reception has been operating in the emergency unit of the university hospital in Brest, France, every day from 10 AM. to 6 PM. Patients older than 75 years, dependent or at risk of dependence are examined by a geriatrician. The medical situation is evaluated. The nutrition status, the cognitive functions, the thymic functions, the gait, and the functional abilities are systematically studied. In the same time the social evaluation is realised by a social worker. From January 1993 to December 1996, 1,514 patients have been cared for by the social medical team. Once the assessment of each patient was made only 49% of them actually had to be hospitalized in a medical department. The outcome of 100 patients discharged between January 1994 and June 1994 was evaluated one year after their discharge at home, 11 patients were rehospitalized. The reason for rehospitalization were different from the reasons for the first hospitalization. A gerontologic assessment in the emergency room permits to avoid hospitalization in 50% of the cases. One year after discharge at home only 11% of the patients were rehospitalized.

Assessment of dynamical properties of mercaptopurine on the peptide-based metal-organic framework in response to experience of external electrical fields: a molecular dynamics simulation. In this work, the effect of the external electric field (EF) on the drug delivery performance of peptide-based metal-organic framework (MPF) for 6-mercaptopurine (6-MP) drug is investigated by means of the molecular dynamics (MD) simulations. It is found that the strength interaction of drug molecule with MPF is decreased under the influence of the electric field. In other words, the adsorbed drug molecules have more tendencies for the interaction with the porous nanostructure in the absence of EF. According to the radial distribution function (RDF) patterns, the probability of finding drug molecules in terms of the intermolecular distance with respect to the MPF surface is lowest during the high field strength. As the EF strength increases, the spread of drug molecules around MPF results in high dynamics movement and further more diffusion coefficient of drug molecule in the simulation system. This result emphasizes the weak intermolecular interaction of drug molecules with MPF with the application of EF. Assessment of dynamical properties of 6-mercaptopurine in the presence of EF with various strengths reveals that the applied electric field can act as a trigger on liberation behavior of drug from the porous nanostructure.

Common allelic variants of exons 10, 12, and 33 of the thyroglobulin gene are not associated with autoimmune thyroid disease in the United Kingdom. Thyroglobulin (Tg) is a major autoantigen for autoimmune thyroid disease (AITD). The Tg gene (Tg) has been mapped to chromosome 8q24, which has recently been linked in two independent studies to AITD. Association of specific alleles of microsatellite markers within Tg itself supports a role for Tg as a good candidate susceptibility locus for AITD. Resequencing of the Tg exons has led to the identification of a number of novel single nucleotide polymorphisms, four of which have been reported to be associated with AITD. Resequencing of Tg in Caucasian subjects in the United Kingdom (UK) has confirmed the presence of four single nucleotide polymorphisms in exons 10, 12, and 33. However, in the largest case-control association study to date with adequate power to detect the reported effect if present, we found no evidence for association of the Tg DNA variants with AITD in the UK. These data suggest that the recently identified single nucleotide polymorphisms do not have a causal role for AITD in the UK. At this stage, we cannot exclude the Tg region as harboring a susceptibility locus for AITD, and only large scale sequencing and fine mapping of the region, including neighboring genes, will allow us to identify any potential causal variants within this region.

Molecular dynamics simulations of the acyl-enzyme and the tetrahedral intermediate in the deacylation step of serine proteases. Despite the availability of many experimental data and some modeling studies, questions remain as to the precise mechanism of the serine proteases. Here we report molecular dynamics simulations on the acyl-enzyme complex and the tetrahedral intermediate during the deacylation step in elastase catalyzed hydrolysis of a simple peptide. The models are based on recent crystallographic data for an acyl-enzyme intermediate at pH 5 and a time-resolved study on the deacylation step. Simulations were carried out on the acyl enzyme complex with His-57 in protonated (as for the pH 5 crystallographic work) and deprotonated forms. In both cases, a water molecule that could provide the nucleophilic hydroxide ion to attack the ester carbonyl was located between the imidazole ring of His-57 and the carbonyl carbon, close to the hydrolytic position assigned in the crystal structure. In the "neutral pH" simulations of the acyl-enzyme complex, the hydrolytic water oxygen was hydrogen bonded to the imidazole ring and the side chain of Arg-61. Alternative stable locations for water in the active site were also observed. Movement of the His-57 side-chain from that observed in the crystal structure allowed more solvent waters to enter the active site, suggesting that an alternative hydrolytic process directly involving two water molecules may be possible. At the acyl-enzyme stage, the ester carbonyl was found to flip easily in and out of the oxyanion hole. In contrast, simulations on the tetrahedral intermediate showed no significant movement of His-57 and the ester carbonyl was constantly located in the oxyanion hole. A comparison between the simulated tetrahedral intermediate and a time-resolved crystallographic structure assigned as predominantly reflecting the tetrahedral intermediate suggests that the experimental structure may not precisely represent an optimal arrangement for catalysis in solution. Movement of loop residues 216-223 and P3 residue, seen both in the tetrahedral simulation and the experimental analysis, could be related to product release. Furthermore, an analysis of the geometric data obtained from the simulations and the pH 5 crystal structure of the acyl-enzyme suggests that since His-57 is protonated, in some aspects, this crystal structure resembles the tetrahedral intermediate.

Chemical induction of presumed dominant-lethal mutations in postcopulation germ cells and zygotes of mice. II. Sensitivity of different postcopulation-precleavage stages to three alkylating chemicals. The relative sensitivities of various postcopulation-precleabage and pronuclear stages to dominant-lethal effects of isopropyl methanesulfonate (IMS), ethyl methanesulfonate (EMS), and triethylenemelamine (TEM) were investigated. The pattern of sensitivity differed with the chemical. IMS was most effective when pronuclear formation was already completed and the majority of the zygotes were presumably undergoing DNA synthesis. EMS, on the other hand, induced its most pronounced effects when eggs in the course of second meiotic division and zygotes in early pronuclear stages were treated. The greatest effect of TEM was observed when zygotes were treated at the early pronuclear stage. EMS and TEM, in contrast to IMS, are similar to radiations in that zygotes undergoing DNA synthesis are more resistant to them than are the early pronuclear stages. In the case of IMS, effects induced in the most sensitive postcopulation-precleavage stage were 6 to 9 times greater than in the most sensitive precopulatory dictyate oocytes or male germ cells. On the other hand, in the case of EMS and TEM, the most sensitive precopulatory male germ cells, but not the dictyate oocytes, were more sensitive than the most sensitive postcopulation stages.

Seroprevalence study of Toxocara canis in selected Egyptian patients. This study was conducted in order to reveal the seroprevalence of T. canis infection in selected 150 Egyptian patients with presumptive clinical syndromes. They were children (128) with respiratory symptoms or pyrexia of unknown origin (PUO)and adults (22) with PUO. Anti-Toxocara antibodies (IgG) were detected in sera by ELISA. The results showed 6.2% positivity in children. The frequency increased in male gender, those in rural residence and in 6-12 years group versus 1-6 years, and 4% & 13.3% positivity in those with respiratory symptoms and PUO respectively. Adults positivity was 18%. So, male gender and residence in rural regions could be considered as risk factors for transmission of toxocariasis in children.

Spatial expression of the alternatively spliced EIIIB and EIIIA segments of fibronectin in the early chicken embryo. Using domain-specific antibodies, we have analyzed the tissue distribution of fibronectins (FNs) containing the alternatively spliced EIIIB and EIIIA segments relative to total FN in early chicken embryos. The results show a selective loss of EIIIA+ FN staining in the notochordal sheath and in cartilaginous structures between 4.5 and 7.0 days of development. In other regions, EIIIB+ and EIIIA+ FNs are extensively codistributed in and around mesoderm-derived structures (somites, notochord, heart, and blood vessels), in basal laminae of endoderm and ectoderm-derived structures, as well as within the vicinity of neural crest formation and migration. We also noted that EIIIA staining overlaps with spatial patterns of distribution that have previously been described for the alpha4 integrin subunit, a component of the EIIIA receptor alpha4beta1.

Developmental characteristics of vessel density in the human fetal and infant brains. We demonstrated the developmental characteristics of vessel density in the human brain, using an antibody against CD31, which specifically reacts with endothelium. In the cerebral cortex and subcortical white matter, the vessel density was low at 16-28 weeks of gestation (GW), and then increased after 36 GW. In the deep white matter, the vessel density was high in the middle fetal period (16-24 GW), and then transiently decreased at 28-36 GW, and increasing after 39 GW. In the putamen, the vessel density was high at 20-21 GW, remained high throughout the fetal period, and then rapidly increased after birth. In the basis pontis, the number of vessels increased after 28 GW, and after 32 GW was greater than in the pontine tegmentum. These alterations in vessel density may correlate with the pathogenesis of perinatal brain injury. Thus, the transient decrease of vessel density in the deep white matter may predispose to periventricular leukomalacia in cerebral hypoperfusion. Similarly, the well-developed vascularity in the basis pontis may predispose its relatively immature neurons to neuron necrosis produced by free radical injury.

bcl-xL and RAG genes are induced and the response to IL-2 enhanced in EmuEBNA-1 transgenic mouse lymphocytes. We have described transgenic mice expressing Epstein-Barr virus (EBV) nuclear antigen-1 (EBNA-1) in B-cells which show a predisposition to lymphoma. To investigate the underlying oncogenic mechanisms, we have cross bred transgenic strains of mice, examined the pre-tumour B-cell phenotype and investigated the expression levels of selected cellular genes as a response to EBNA-1 expression. We have found that bcl-xL and the recombination activating genes (RAG) 1 and 2 are induced in pre-neoplastic samples of EBNA-1 expressing mice. Induction of bcl-xL may explain the observed redundancy in lymphomagenesis between transgenic EBNA-1 and bcl-2. In addition, bone marrow cells derived from the EmuEBNA-1 mice show a greater capacity for cultured growth compared to controls, particularly in the presence of IL-2. Notably, bcl-xL expression is responsive to IL-2. These data shed new light on the potential contribution of EBNA-1 to EBV associated tumorigenicity as well as to the viral life cycle and open a potential avenue for therapeutic intervention.

Riverine regime shifts through reservoir dams reveal options for ecological management. Worldwide, dams are a main threat reducing river ecological functioning and biodiversity by severely altering water temperature, flow, and sediment regimes up- and downstream. Sustainable dam management therefore has a key role in achieving ecological targets. Here, we present an analysis of the effects of reservoir dams and resulting regime shifts on community structure and function of lotic macroinvertebrates. Our study derived management options to improve ecological integrity of affected streams. To do this, we contrasted time series data for water temperature (15-min intervals over one year), discharge (daily means over 10 yr), and records of deposited fine sediments against macroinvertebrate samples from pairs of river reaches downstream of dams and of comparable tributaries not affected by dams in the German low mountain range. We observed a decline in the density and diversity of disturbance-sensitive macroinvertebrates (Ephemeroptera, Plecoptera, and Trichoptera) and a correlation between hydrologic metrics and macroinvertebrate deterioration downstream of the dams. Typical "rhithral" (flow-adapted) species changed to "littoral" (flow-avoiding) species below dams, thus indicating a hydrologic regime shift. Increased fine sediment accumulations and deficits of pebbles and small cobbles below dams indicated a severe habitat loss below dams. Additional comparison with undisturbed reference streams allowed us to derive management options that could mitigate the negative impact of hydrologic alterations and accumulations of fine sediments downstream of dams. These options are conditional on the season and in particular address the frequency and duration of low and high flow events.

Continuous infusion of a local anesthetic versus interscalene block for postoperative pain control after arthroscopic shoulder surgery. The purpose of this investigation was to evaluate the efficacy, complication rate, and cost of a 1-time interscalene block compared with a continuous infusion of a local anesthetic for postoperative pain relief in patients having arthroscopic shoulder surgery. After prospective power analysis and institutional review board approval, 56 consecutive patients having arthroscopic shoulder surgery under general anesthesia performed by a single surgeon were randomly assigned to 1 of 2 groups to evaluate postoperative pain control. Group 1 patients received a preoperative interscalene block, and group 2 patients received a subacromial continuous infusion of a local anesthetic (0.5% bupivacaine) via a pain pump for 48 hours postoperatively. Pain was evaluated at 12, 24, 36, and 48 hours and then daily on postoperative days 3 through 7 by use of a visual analog scale included in a patient diary. Patients were provided with 2 "rescue" medication options: ibuprofen and Percocet (Endo Pharmaceuticals, Chadds Ford, PA). The total number of tablets ingested was also evaluated over these same intervals. Total hospital outpatient surgical costs for each group were calculated by dividing total hospital charges by the ratio of annual hospital cost to charges. No statistically significant differences were identified between the 2 groups with regard to visual analog scale pain scores, medication intake, or cost. Complications did not occur in either group. One patient inadvertently removed the pain pump catheter. Our results support the null hypothesis. We found no difference between interscalene block versus continuous subacromial infusion of a local anesthetic with regard to efficacy, complication rate, or cost. Level I, prospective, randomized controlled trial.

Orthodromic study of the sensory fibers innervating the fourth finger. Fourth finger stimulation has been used to obtain the compound nerve action potential (CNAP) of the median and ulnar nerves by a single cutaneous bipolar recording electrode placed in some specific sites of the upper limb. In normal subjects, the response was a combination of both action potentials which could be seen as separated peaks only when the recording was made at midarm with the elbow flexed at 90 degrees. This finding is mainly attributed to the longitudinal sliding of nerves according to the joint movements. In patients with a carpal tunnel syndrome, there were a striking separation between the responses of both nerves in wrist recording. This finding allows this technique to be applied in the clinical inspection of median nerve entrapment at wrist, demonstrating graphically the delay on the median nerve action potential with regard to that of the ulnar nerve.

From piecemeal to configurational representation of faces. Unlike older children and adults, children of less than about 10 years of age remember photographs of faces presented upside down almost as well as those shown upright and are easily fooled by simple disguises. The development at age 10 of the ability to encode orientation-specific configurational aspects of a face may reflect completion of certain maturational changes in the right cerebral hemisphere.

Long-term post-liver transplant complications of renal impairment and diabetes mellitus: data from Singapore. Patients who survive the initial post-liver transplantation period face the development of chronic diseases in the long run. We studied two important complications of liver transplantation, namely: renal impairment and diabetes mellitus. We analysed adult patients followed-up for more than one year using data from our liver transplant clinical records. Long-term post-transplant renal impairment (RI) was defined as glomerular filtration rate (GFR) less than 60 ml/min/1.73 square metres and long-term post-transplant diabetes mellitus (DM) was defined as fasting blood glucose more than 7.8 mmol/L, that existed at least one year after liver transplantation. Pre- and post-transplant factors that could be associated with these conditions were examined. Altogether, 35 patients were evaluated. Mean age at transplant was 50 years. Mean duration of follow-up was 58.4 months. There was 11.4 percent of pre-transplant RI and 17.0 percent of pre-transplant DM. Prevalence of post-transplant RI was 43.5 percent at one year and 45.0 percent at four years. Long-term post-transplant RI was associated with renal impairment at six months post-transplant (p-value is 0.033). Prevalence of severe post-transplant RI (GFR is less than 30 ml/min/1.73 square metres) at four years was 5.7 percent. Prevalence of post-transplant DM was 45.5 percent at two years but declined to 5.3 percent at four years. Post-transplant renal impairment appears to be a potential long-term problem while post-transplant diabetes mellitus appears to improve with time.

A novel illegitimate recombination event: precise excision and reintegration with the Mu gem mutant prophage. The bacteriophage Mu is known to insert its DNA more or less randomly within the Escherichia coli chromosome, as do transposable elements, but unlike the latter, precise excision of the prophage, thereby restoring the original sequence, is not observed with wild-type Mu, although it has been reported with certain defective mutants. We show here that the mutant prophage Mu gem2ts can excise precisely from at least three separate loci -- malT, lac and thyA (selected as Mal+, Lac+ and Thy+, respectively). This excision occurs under permissive conditions for phage development, is observed in fully immune (c+) lysogens, and is independent of RecA and of Mu transposase. Mu gemts2 excision is invariably accompanied by reintegration of a Mu gem2ts prophage elsewhere in the chromosome. In the case of Mal+ revertants, this prophage is systematically located at 94 min on the E. coli chromosome. Mu gem2ts excision therefore sheds some light on the long-standing paradox of the lack of precise Mu excision.

Response of blood pressure and blood glucose to treatment with recombinant tissue-type plasminogen activator in acute ischemic stroke: evidence from the virtual international stroke trials archive. Elevations in blood pressure (BP) and blood glucose are common during stroke and may represent a stress response secondary to the acute neurological deficit. If so, they should settle more completely in recombinant tissue-type plasminogen activator (rtPA)-treated patients in association with improved neurological status. We performed a controlled comparison of 24-hour declines in BP and glucose in rtPA-treated and control patients from the Virtual Stroke International Stroke Trial Archive (VISTA) database. Twenty-four-hour falls in BP and glucose were compared using multiple regression to account for baseline imbalances. The logarithmic transformation of glucose was used and 24-hour differences expressed as ratios of 24 hours to admission geometric means. Two-way analysis of variance was used to test for interaction between rtPA and early improvement for 24-hour falls in BP and blood glucose. BP analysis included 5406 patients (rtPA=41%) and glucose analysis 4288 (rtPA=37%). rtPA-treated patients were younger, less likely to have a history of hypertension or diabetes, and had more severe strokes on admission. BP and glucose were lower at baseline in rtPA-treated patients than control subjects. On regression, rtPA predicted significantly greater 24-hour falls in systolic BP (β=3.9; 95% CI, 2.8-5.0), diastolic BP (β=3.1; 95% CI, 2.4-3.9), and glucose (β=0.97; 95% CI, 0.95-0.99). rtPA did not interact with early neurological improvement for 24-hour falls in systolic BP (P=0.72), diastolic BP (P=0.79), or blood glucose (P=0.51). A stress response does not appear to be the principal cause of elevations in BP and glucose during stroke.

Management of psoriasis with nutraceuticals: An update. Psoriasis is a chronic skin disorder that speeds up the life cycle of skin cells, typically on the surface of the skin. Additional skin cells form thick scales and red fixes which are awfully itchy and sometimes painful. Although there are many therapeutic systems available to get symptomatic relief, unfortunately replete cure for psoriasis is not yet reported. Moreover, poor treatment outcomes as well as high toxicity profile of drugs makes these therapies more inconvenient to treat psoriasis. In search of alternative and complementary therapy for this disease, the focus has been shifted to nutraceuticals, few of them were reported since ages. It includes vitamins, herbal extracts, phytochemicals and dietary supplements. In this review, the attempt has been made to highlight key nutraceuticals for better management of psoriasis. Supplementation of appropriate nutraceutical may improve the quality of patient's life and have positive impact on overall state of disease.

Drug interaction between valproic acid and meropenem: a case report. Valproic acid and meropenam is commonly co-administrated in neurosurgical patients. Meropenem potentially decreases the valproic acid level, which may cause perioperative seizure. There has been no previous report of drug interaction between valproic acid and meropenem in Thailand. The authors report a patient who faced uncontrolled seizure after co-administrated valproic acid and meropenem. The level of valproic acid was assessed in different times after the administration of meropenem. Rapid decrease of valproic level was detected. However due to the administration of other antiepileptic agents, seizure did not develop. It is important for the physicians to recognize drug interaction between valproic acid and meropenem. Avoiding co-administration of both agents, valproic acid level monitoring and additive of other antiepileptic agents seem to be the appropriate solution.

Biocompatibilities of organic solvents with Lactobacillus delbrueckii. In the search for biocompatible extractants for extractive fermentation of lactic acid, the effect of twelve organic solvents on the activity of L. delbrueckii were studied at different concentration levels. On this basis, the compatibilities of twelve solvents with L. delbrueckii were summarized into four classes: completely compatible, compatible at molecular level, partially compatible and non-compatible. The characteristics were described qualitatively for each class in terms of relative values between the solubility of organic solvent in water (Cs) and the toxicity of organic solvent, which is indicated by a newly defined concentration parameter (Cm). The classification was helpful for the selection of extractant in extractive fermentation.

[Perioperative prevention of thrombosis in cesarean section: results of a randomized prospective comparative study with 6% hydroxyethyl starch and 0.62 low dose heparin]. In 207 consecutive randomized women undergoing cesarean section, of whom 104 received 3 X 5000 IE unfractionated heparin and 103 3 X 500 ml hydroxyethylstarch 6% 0.62, the frequency of deep vein thrombosis was evaluated with a non-invasive diagnostic technique-impedance plethysmography. 5.9% of the patients in the hydroxyethylstarch group and 7.8% in the heparin-group developed deep vein thrombosis. Activation of blood coagulation at cesarean section results in an increasing of factor VIIIR:Ag, Fibrinogen and Reptilase clotting time. Hydroxyethylstarch 6% 0.62 produces minor abnormalities of coagulation test results. After 1500 ml infusions HES the following effects were noted: 1. Factor VIIIR:Ag fell by about 20%, a greater decrease than could be explained simply by hemodilution. 2. Reptilase clotting times shortened without a different increase in fibrin activation products (resulting in an increased lysability of the thrombus). 3. Plasma fibrinogen decreased by approximately 7% due to hemodilution caused by plasma volume expansion. For patients with a low risk of deep vein thrombosis (Cesarean section) HES has an excellent safety record in doses not exceeding 1500 ml/24 h.

Endoscopic resection of advanced and laterally spreading duodenal papillary tumors. Historically, neoplasia of the duodenal papilla has been managed surgically, which may be associated with substantial morbidity and mortality. In the absence of invasive cancer, even lesions with extensive lateral duodenal wall involvement, or limited intraductal extension may be cured endoscopically with a superior safety profile. Endoscopic papillectomy is associated with greater risks of adverse events such as bleeding than resection elsewhere in the gastrointestinal tract. Additionally site-specific complications such as pancreatitis exist. A structured approach to lesion assessment, adherence to technical aspects of resection, endoscopic management of complications and post-resection surveillance is required. Advances have been made in all facets of endoscopic papillary resection since its introduction in the 1980s; extending the boundaries of endoscopic cure, optimizing outcomes and enhancing patient safety. These will be the focus of the present review.

Total parenteral nutrition with and without fat as substrate for growth of rats and transplanted hepatocarcinoma. Differential effects of total parenteral nutrition (TPN) on host nutrition and growth of cancer are unclear. Growth of adult ACI-N rats bearing transplanted Morris hepatocarcinoma no. 3924A given TPN with or without fat was studied in comparison with Purina Chow-fed, fasting, and semifasting (either amino acid or dextrose alone) rats over 5 days. The isocaloric, isonitrogenous TPN regimens with or without fat maintained body weight and nitrogen balance of cancer-bearing rats equally well. When compared with Chow-fed rats, the volume of the cancer, its weight, doubling time, protein content, and incorporation of thymidine into DNA were similar in rats given TPN either with or without fat. Although the volume of the cancer decreased in fasting and semifasting rats, the nutritional status of the host was also impaired. Administration of TPN to cancer-bearing rats was associated with an abnormal increase in serum lactic acid level, which was not ameliorated by the use of fat to reduce the carbohydrate load. Although TPN with and without fat maintains the nutritional status, hepatomegaly and hepatic steatosis limit the administration of carbohydrate and fat as energy substrates in this system.

Preventive service utilisation as a predictor for emergency dental examinations. To quantify the relationship between receipt of routine dental care and the use of non-trauma related emergency dental services. A multiple logistic regression was run on administrative dental claim and encounter data. The model dependent variable was the use of non-trauma related emergency dental care. Predictors included previous year oral examinations, radiographs, dental cleanings and, as a control, member age. Administrative data were obtained from a dental health maintenance organisation located in the state of Texas. Claim and encounter data for 2,947 insured members were used, representing experience from 1995 through 1996. The outcome of interest was the use of non-trauma related emergency dental services. Results demonstrated empirically that those who availed themselves of preventive dental services were significantly less likely to use non-trauma related emergency services (P<0.01). The probability of needing non-trauma related dental services in 1996 was 42.7% lower among those who had an examination in 1995 when compared with those who did not. When analysed in a simple logistic regression, dental cleanings in 1995 were also significantly associated with a decreased probability of needing non-trauma related emergency services. However, this relationship did not hold in the controlled model, which was probably due to multicollinearity. This study provides evidence of the value of periodic preventive dental examinations and services. Those who receive such services are less likely to use non-trauma related emergency dental services.

Defunctioning loop ileostomy for pelvic anastomoses: predictors of morbidity and nonclosure. The aim of this study was to determine the morbidity of a defunctioning loop ileostomy and the subsequent closure rate, and to identify the predictors of complications and nonclosure of stoma. This study is a retrospective review of a single-institution experience. All patients who underwent a planned temporary defunctioning loop ileostomy performed synchronously with a pelvic anastomosis during a 6-year period were included. The primary outcome measures were the ileostomy complication rate for the entire spectrum of care, readmission and reoperation rates to treat ileostomy complications, and subsequent closure rate. Patient and treatment factors were evaluated for their independent effect on complications and closure rate with the use of multivariable logistic regression. One hundred twenty-three patients were identified (median age, 51 years). Of these patients, 64.2% developed ≥1 minor or major ileostomy complications (13.8% during index hospitalization, 52.8% as outpatient, and 23.4% after closure). Readmitted for dehydration following ileostomy formation were 11.4% of patients. The ileostomy was closed in 76.4% of patients with 8.6% requiring a midline laparotomy. The overall ileostomy-related reoperation rate was 10.4% (2.4% during index hospitalization, 1.6% at readmission, and 6.4% following ileostomy closure). Obesity (BMI ≥30 kg/m) was associated with a higher overall ileostomy complication rate (OR 8.56, 95% CI 1.64-44.74) and outpatient complication rate (OR 7.69, 95% CI 2.48-23.81). Age >65 years (OR 53.34, 95% CI 4.21-676.14) and hypertension (OR 8.36, 95% CI 1.09-64.43) increased the risks of high ileostomy output and dehydration. Obesity (OR 4.61, 95% CI 1.14-18.54) and smoking (4.47, 95% CI 1.43-13.98) decreased the likelihood of ileostomy closure. This study was limited by its retrospective nature. The morbidity of a defunctioning loop ileostomy remains significant. Obesity is an independent predictor of ileostomy complications. Older age and hypertension increase the risks of high-output stoma and dehydration. Almost one quarter of patients never have the ileostomy closed. Obesity and smoking are associated with less likelihood of a subsequent ileostomy closure.

Methylglyoxal bis(butylamidinohydrazone) exhibits antitumor effect on human malignant melanoma cells but reduces the antitumor action of cisplatin. The antitumor effect of a polyamine biosynthetic pathway inhibitor methylglyloxal bis(butylamidinohydrazone) (MGBB) on human malignant melanoma (HMG) cells and its combination effect with cisplatin were investigated. The growth of cultured HMG cells was inhibited in a dose dependent manner by either MGBB or cisplatin; complete inhibition of cell proliferation was attained with 5 micrograms/ml of MGBB or 50 micrograms/ml of cisplatin. Pretreatment of HMG cells with MGBB diminished the antitumor action of cisplatin. The cultured HMG cells were inoculated in nude mice and aliquots of the resulting solid tumors (HMG tumor) were transplanted. The growth of transplanted HMG tumors in mice was inhibited markedly by cisplatin (3.8 mg/kg) and moderately by MGBB (10 or 20 mg/kg). The in vivo antitumor effect of cisplatin was also reduced by combined treatment with MGBB.

A randomised control trial of physical activity in a perceived environment on self-esteem and mood in UK adolescents. This study assessed whether exercising whilst viewing natural or built scenes affected self-esteem (SE) and mood in adolescents. Twenty-five adolescents participated in three exercise tests on consecutive days. A graded exercise test established the work rate equivalent to 50% heart rate reserve for use in subsequent constant load tests (CLTs). Participants undertook two 15-min CLTs in random order viewing scenes of either natural or built environments. Participants completed Rosenberg's SE scale and the adolescent profile of mood states questionnaire pre- and post-exercise. There was a significant main effect for SE (F(1) = 6.10; P < 0.05) and mood (F(6) = 5.29; P < 0.001) due to exercise, but no effect of viewing different environmental scenes (P > 0.05). Short bouts of moderate physical activity can have a positive impact on SE and mood in adolescents. Future research should incorporate field studies to examine the psychological effects of contact with real environments.

Will a 5-ASA a day keep the cancer (and dysplasia) away? Prevention strategies for colorectal cancer in chronic ulcerative colitis (UC) are currently based on the identification of neoplasia by surveillance colonoscopy, but there is a great interest in the possibility of primary chemoprevention. 5-aminosalicylic acid (5-ASA) therapy is an attractive option for chemoprevention in UC due to the fact that it is a derivative of aspirin and has been shown to have a variety of other molecular and genetic targets of cancer prevention, but human studies in UC have been limited by observational design and limited data collection or follow-up. The recently performed metaanalysis of 5-ASA chemoprevention trials shows a favorable role of 5-ASA in the prevention of cancer and dysplasia in patients with UC, and adds to the available evidence favoring its use. This editorial discusses the substantial logistical and ethical challenges in designing a randomized double-blind trial to measure the effect of 5-ASA on cancer risk in UC. The authors conclude that the safety and current maintenance use of 5-ASA warrant its acceptance as a probable chemopreventive agent at this time.

The effect of xenoantisera on T-lymphocyte functions in the absence of complement. An attempt was made to determine whether xenoantisera can detect functional receptors on mouse T lymphocytes. Antisera were raised by immunizing rabbits with BALB/c thymus cells, boiled thymus homogenate, brain homogenate or bone marrow cells. Following heat inactivation these antisera were absorbed with mouse kidney and liver homogenates, and studied for their effect, in the absence of C', on the activity of murine T lymphocytes. Rabbit anti-bone marrow serum (RAB) had no effect on the mixed lymphocyte reaction (MLR) nor on cell-mediated lysis (CML). In contrast, rabbit anti-thymus serum (RAT) and anti-boiled thymus serum (RABT) inhibited strikingly, the MLR, CML, and the response to concanavalin A and phytohemagglutinin. Rabbit anti-brain serum (RABR) caused a marked increase of the proliferation of lymphocytes both in the presence or absence of various stimuli and had no effect on the CML. Absorption experiments indicated that a number of antigens are involved in the inhibitory activity of RAT. Antibodies to a T cell specific antigen interfere with the response of T lymphocytes to mitogenic stimuli, while the activity of cytotoxic T cells is inhibited by antibodies to a determinant shared by B and T lymphocytes.

Preparation of siloxy focal dendron-protected TiO2 nanoparticles and their photocatalysis. TiO2 nanoparticles were synthesized at approximately 0 degrees C by hydrolyzing [(CH3)2CHO]4Ti in 1-propanol solutions of poly(amido amine) dendrons with a siloxy focal point and long alkyl chain spacers. Transmission electron microscopic photographs showed that TiO2 nanoparticle was 1-5 nm in size and protected by dendrons, when prepared at a mixing ratio 1:10 of Ti ion and dendron. At higher contents of Ti ion, TiO2 nanoparticles aggregated up to a maximum size of 90 nm, depending on the dendron generation (first to third). It was confirmed from X-ray photoelectron spectroscopy that Si-O-Ti covalent bond was formed in dendron-protected TiO2 nanoparticles. The ability of dendron-protected TiO2 nanoparticles as a photocatalyst for the photodegradation of 2,4-dichlorophenoxyacetic acid was higher than that of nonprotected nanoparticle and superior at higher generation. It was suggested that the dendrons protecting TiO2 nanoparticle have enough void volume to conserve guest molecules and behave effectively as a reservoir of guest molecules.

New chemical cross-coupling between aryl halides and allylic acetates using a cobalt catalyst. [reaction: see text] The cobalt-catalyzed coupling reaction of aromatic halides and allylic acetates proceeds readily under mild conditions in the presence of the appropriate reducing agent to produce allylaromatic derivatives either in pure acetonitrile (aryl bromides) or in an acetonitrile/pyridine mixture (aryl chlorides).

[Protein-loosing enteropathy: report of four cases and review of etiology, diagnostic work-up and treatment]. The protein-loosing enteropathy (PLE) may result from a broad variety of underlying diseases. These conditions are of systemic nature or locally affecting the gastrointestinal tract. Major symptoms are oedema due to low plasma protein levels. Gastrointestinal symptoms are not necessarily present. The diagnosis is confirmed by the finding of increased faecal concentrations of Alpha-1-Antitrypsin (> 320 mg/L). In the majority of cases, in which underlying diseases are present, the etiology is obvious. In unclear cases the differentiation into inflammatory or circulatory disturbances or alterations of the architecture of the basal membrane is helpful. An economic, staged approach is presented. To localize the site of protein loss imaging is required (abdominal ultrasound, CT-scan, endoscopy and Technetium-Scan). If a circumscribed intestinal source of protein loss is suspected which may be amenable to surgery, intraoperative enteroscopy should be considered. If causal treatment is impossible; intravenous replacement of albumin and immunoglobulines in intervals from 1 to 4 weeks will be necessary. The prognosis in patients with isolated PLE is good. Otherwise it depends on the underlying disease.

[Fatal hemorrhage from an isolated scalp injury]. By means of 3 casuistics it is illustrated, that fatal bleeding from a single scalp injury can occur under special preconditions. Beside signs of massive loss of blood at the place of discovery and on the corpse, particularly chronic and acute alcohol intoxication with presumably impaired coagulation and prospective anemic history play a dominant role in these courses.

Compounded gabapentin for neuropathic pain: Stability and beyond-use date (BUD) in some commonly used bases. To investigate the stability and beyond-use date (BUD) of topical gabapentin in 3 commonly used bases. Lipoderm cream, Versabase gel, and Emollient cream were used to compound gabapentin (10%). The products were stored in Ecolojars, kept at 25°C, 4°C, and 40°C, and samples were collected on different days (days 0, 14, 28, and 90). Potency, stability, and organoleptic changes were monitored. At 25°C and 40°C, the potency of gabapentin in Lipoderm cream significantly increased (P < 0.05) after 28 and 90 days, respectively. In contrast, gabapentin degraded in Emollient cream (P < 0.05). At 25°C, the organoleptic properties of the drug compounded with Lipoderm cream (25°C) remained consistent for up to 28 days but showed signs of physical changes in other bases. Gabapentin recrystallized from Versabase gel and Emollient cream within 14 days. Gabapentin compounded with Lipoderm cream for topical use was stable in Ecolojars for 28 days at 25°C. Under the same conditions, the drug was not stable in Versabase gel and Emollient cream. Based on our stability and potency data, the beyond-use date of currently dispensed gabapentin (10%) formulations with Lipoderm cream should not be extended beyond the currently assigned 30-day mark, even when refrigerated. It is unclear whether the stability of these formulations is improved if stored in air-tight containers.

[Tactics in the surgical treatment of nodular formations in the thyroid gland in an endemic goiter region]. The extrafascial method of operation was used because of high risk of malignization of nodular endemic goiters. The extrafascial hemithyroidectomy with an isthmus is considered by the authors to be the major and minimum operation volume in patients with nodular goiters. The method was used in 76,8% of the patients. In patients with thyroid carcinoma the operation of this volume was fulfilled in 66,5% of cases.

[Clinical analysis of liver transplantation in treatment of liver metastatic cancer]. To evaluate the feasibility and outcome of liver transplantation in the treatment of liver metastatic cancer. Four patients with pathologically confirmed liver metastatic cancer underwent liver transplantation, including one of liver metastases from pancreatic endocrine tumor, one from rectal endocrine tumor, one from stomach stromal tumor and one from colorectal carcinoma. Classic surgical method was adopted, i. e. orthotopic liver transplantation for the recipients and transplants came from cadaveric donors. All the four patients had a smooth operation, an uneventful early postoperative recovery and good living quality. The patient with liver metastases from pancreatic endocrine tumor had liver tumor recurrence at four and a half years after the transplantation, and then underwent left lateral hepatic lobectomy, without any recurrence until now. The patient with liver metastases from rectal endocrine tumor had right renal and pelvic tumor metastasis at 16 months after the operation, and died of tumor recurrence 5 years after the liver transplantation. The patient with liver metastases from gastric stromal tumor had extensive pelvic metastases at five and a half months after the transplantation, and survived with tumor for 4 years and 6 months after the operation. The patient with liver metastases from colorectal carcinoma had extensive bilateral lung metastases at 3 months after the transplantation and died one and a half years after the operation. For well-differentiated unresectable metastatic liver cancers, liver transplantation may serve as a treatment option and better treatment results can be achieved for some highly selected patients.

Effect of switch to the highest dose of rosuvastatin versus add-on-statin fenofibrate versus add-on-statin nicotinic acid/laropiprant on oxidative stress markers in patients with mixed dyslipidemia. Oxidative stress plays an important role in atherosclerosis. Both F2-isoprostane (8-iso-PGF2a) and oxidized low-density lipoprotein (ox-LDL) have emerged as biomarkers of oxidative stress and have been proposed as useful biomarkers that could potentially be used as indicators of cardiovascular disease. This is a prespecified analysis of a prospective, randomized, open-label, blinded endpoint (PROBE) study (ClinicalTrials.gov identifier: NCT01010516). Patients (N = 100) with mixed dyslipidemia on a standard statin dose (10-40 mg simvastatin or 10-20 mg atorvastatin or 5-10 mg rosuvastatin) who had not achieved lipid targets were randomized to switch to the highest dose of rosuvastatin (40 mg/day) or to add-on-statin extended release nicotinic acid (ER-NA)/laropiprant (LRPT) (1000/20 mg/day for the first 4 weeks followed by 2000/40 mg/day for the next 8 weeks) or to add-on-statin micronized fenofibrate (200 mg/day) for a total of 3 months. Levels of plasma and urine F2-isoprostane and plasma ox-LDL were assessed at baseline and 3 months later. Plasma F2-isoprostane levels decreased similarly in all groups. On the other hand, both ox-LDL and urine F2-isoprostane levels decreased similarly in the add-on ER-NA/LRPT and rosuvastatin monotherapy group, while a less pronounced decrease was observed in the add-on fenofibrate group. All treatment interventions reduced the concentration of the assessed oxidative stress markers, but the reduction was more pronounced in the add-on ER-NA/LRPT and rosuvastatin monotherapy groups, compared with add-on fenofibrate. Specifically designed studies should address the abovementioned risk factors modulation in terms of cardiovascular risk.

Peripheral chemoreceptor insensitivity in chronic severe anaemia. Ventilatory response to central and peripheral chemoreceptor stimulation by carbon dioxide was assessed in 15 severely and chronically anaemic subjects before and after the correction of anaemia. Whereas the central CO2 responsiveness was found to be normal in the anaemic state, the peripheral response to CO2 was remarkably depressed. This blunted peripheral response to CO2 was restored to normal with the correction of anaemia.

Risk factors for Salmonella enterica subsp. enterica infection in senegalese broiler-chicken flocks. Our objective was to assess the association of managerial practices, general hygiene and Salmonella infection in Senegalese broiler flocks. Seventy broilers farms were studied from January 2000 to December 2001 around Dakar. A questionnaire was submitted to the farmers and samples of fresh broiler droppings were taken. A 28.6% of the flocks were infected by Salmonella (mainly Hadar and Brancaster serovars). Salmonella infection of the previous flock (OR = 6.82) and of day-old chicks (OR = 3.73), frequent poultry farmers' visits (OR = 5.38) and keeping sick birds inside the farm (OR = 5.32) increased the risk of Salmonella infection. But, using antibiotics on day-old chicks (OR = 0.17) and a detergent for cleaning (OR = 0.16) decreased the risk.

Relationship between Pd oxidation states on TiO(2) and the photocatalytic oxidation behaviors of nitric oxide. This study has been undertaken to investigate the relationship between Pd oxidation states on TiO(2) photocatalysts and their photocatalytic oxidation behaviors of NO. Three types of Pd-modified TiO(2) with different Pd oxidation states were prepared by wet impregnation method, neutralization method and photodeposition method, respectively. And these Pd-modified photocatalysts were characterized by X-ray diffraction analysis, X-ray photoelectron spectrum analysis (XPS), UV-Vis diffuse reflectance spectra and temperature programmed desorption (TPD). It was found from XPS results that the dominant oxidation states of Pd on these Pd-modified TiO(2) catalysts were Pd(2+), PdO, and Pd(0), respectively. NO-TPD results showed that the NO adsorption capacity was improved greatly by the modification of Pd(2+) ions. The activity tests showed that Pd-modified TiO(2) by a wet impregnation method increased photocatalytic activity compared to pure TiO(2) (Degussa P25). It was concluded that Pd(2+) ions on as-prepared TiO(2) catalysts provided key contributions to the improvement of photocatalytic activity. However, Pd(0) and PdO deposits on TiO(2) almost had no positive effect on NO oxidation. The mechanism of photocatalytic oxidation of NO in gas phase over Pd-modified TiO(2) was also proposed.

Silver nanoparticles affect on gene expression of inflammatory and neurodegenerative responses in mouse brain neural cells. Silver nanoparticles (AgNPs) have antibacterial characteristics, and currently are applied in Ag-containing products. This study found neural cells can uptake 3-5 nm AgNPs, and investigated the potential effects of AgNPs on gene expression of inflammation and neurodegenerative disorder in murine brain ALT astrocytes, microglial BV-2 cells and neuron N2a cells. After AgNPs (5, 10, 12.5 μg/ml) exposure, these neural cells had obviously increased IL-1β secretion, and induced gene expression of C-X-C motif chemokine 13 (CXCL13), macrophage receptor with collagenous structure (MARCO) and glutathione synthetase (GSS) for inflammatory response and oxidative stress neutralization. Additionally, this study found amyloid-β (Aβ) plaques for pathological feature of Alzheimer's disease (AD) deposited in neural cells after AgNPs treatment. After AgNPs exposure, the gene expression of amyloid precursor protein (APP) was induced, and otherwise, neprilysin (NEP) and low-density lipoprotein receptor (LDLR) were reduced in neural cells as well as protein level. These results suggested AgNPs could alter gene and protein expressions of Aβ deposition potentially to induce AD progress in neural cells. It's necessary to take notice of AgNPs distribution in the environment.

Translocation of deltaPKC to mitochondria during cardiac reperfusion enhances superoxide anion production and induces loss in mitochondrial function. Activation of the delta-isoform of protein kinase C (deltaPKC) by certain conditions of oxidative stress results in translocation of the kinase to the mitochondria leading to release of cytochrome c and the induction of apoptosis. In the current study, the effects of myocardial reperfusion-induced deltaPKC translocation on mitochondrial function were assessed. Mitochondria isolated from hearts that had undergone ischemia (30 min) followed by reperfusion (15 min) exhibited a significant increase in the rate of superoxide anion (O(2)(-)) generation. This was associated with the translocation of deltaPKC to the mitochondria within the first 5 min of reperfusion. deltaPKC translocation occurred exclusively during reperfusion and could be mimicked by infusion of intact hearts with H(2)O(2) suggesting redox-dependent activation during reperfusion. Infusion of a peptide inhibitor (deltaV(1-1)) specific to the delta-isoform of PKC significantly reduced reperfusion-induced increases in mitochondrial O(2)(-) generation. Finally, the decline in mitochondrial respiratory activity evident upon prolonged reperfusion (120min) was completely prevented by inhibition of deltaPKC translocation. Thus, deltaPKC represents a cytosolic redox-sensitive molecule that plays an important role in amplification of O(2)(-) production and subsequent declines in mitochondrial function during reperfusion.

Do yoga and aerobic exercise training have impact on functional capacity, fatigue, peripheral muscle strength, and quality of life in breast cancer survivors? The aim of the study was to compare the effects of aerobic exercise training and yoga on the functional capacity, peripheral muscle strength, quality of life (QOL), and fatigue in breast cancer survivors. A total of 52 patients with a diagnosis of breast cancer were included in the study. The patients were randomly assigned to 2 groups: aerobic exercise (n = 28) and yoga added to aerobic exercise (n = 24). Both groups participated in submaximal exercise 30 minutes/d, 3 d/wk for 6 weeks. The second group participated in a 1-hour yoga program in addition to aerobic exercise training. Functional capacity was assessed by the 6-Minute Walk Test (6MWT). Peripheral muscle strength was evaluated with a hand-held dynamometer. The fatigue severity level was assessed with the Fatigue Severity Scale (FSS). The QOL was determined by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire. There were statistically significant increases in peripheral muscle strength, the 6MWT distance, and the perception of QOL in both groups (P < .05). Additionally, the group with aerobic exercise and yoga showed marked improvement compared with the aerobic exercise group in fatigue perception (P < .05). According to the data from this study, aerobic exercise training and yoga improved the functional capacity and QOL of breast cancer patients. Aerobic exercise programs can be supported by body mind techniques, such as yoga, in the rehabilitation of cancer patients for improving functional recovery and psychosocial wellness.

Stable 5,5'-Substituted 2,2'-Bipyrroles: Building Blocks for Macrocyclic and Materials Chemistry. The preparation and characterization of a family of stable 2,2'-bipyrroles substituted at positions 5 and 5' with thienyl, phenyl, TMS-ethynyl, and vinyl groups is reported herein. The synthesis of these new bipyrroles comprises three steps: formation of the corresponding 5,5'-unsubstituted bipyrrole, bromination, and Stille or Suzuki coupling. The best results in the coupling are obtained using the Stille reaction under microwave irradiation. The new compounds have been fully characterized by UV-vis absorption, fluorescence, and IR spectroscopies and cyclic voltammetry. X-ray single-crystal analysis of four of the synthesized bipyrroles indicates a trans coplanar geometry of the pyrrole rings. Furthermore, the substituents at positions 5,5' remain coplanar to the central rings. This particular geometry extends the π-conjugation of the systems, which is in agreement with a red-shifting observed for the λmax of the substituted molecules compared to the unsubstituted bipyrrole. All of these new compounds display a moderate fluorescence. In contrast with unsubstituted bipyrroles, these bipyrroles are endowed with a high chemical and thermal stability and solubility in organic solvents.

Increased production of ADAMTS13 in hepatic stellate cells contributes to enhanced plasma ADAMTS13 activity in rat models of cholestasis and steatohepatitis. Although hepatic stellate cells, endothelial cells, glomerular podocytes and plateles were reported to be a source of ADAMTS13, it is not clarified which source is involved in the regulation of plasma ADAMTS13 activity. It was demonstrated previously that selective hepatic stellate cell damage in rats caused decreased plasma ADAMTS13 activity. To further elucidate the potential contribution of hepatic stellate cells to the regulation of plasma ADAMTS13 activity, this study examined plasma ADAMTS13 activity when hepatic stellate cells proliferate during the process of liver fibrosis by employing rat models of liver fibrosis due to cholestasis, bile duct ligation, and steatohepatitis, a choline-deficient L-amino acid-defined-diet. ADAMTS13 expression was increased with co-localisation with smooth muscle alpha-actin, a marker of hepatic stellate cells, in bile duct-ligated livers up to four weeks, in which a close correlation between ADAMTS13 and smooth muscle alpha-actin mRNA expressions was determined. Plasma ADAMTS13 activity, measured by a sandwich ELISA involving a specific substrate to ADAMTS13, was increased in bile duct-ligated rats with a significant correlation with ADAMTS13 mRNA expression levels in the liver. Furthermore, ADAMTS13 mRNA expression was increased with enhanced mRNA expression in smooth muscle alpha-actin in the livers of rats fed a choline-deficient L-amino acid-defined-diet for 16 weeks, in which increased plasma ADAMTS13 activity was determined. Thus, increased plasma ADAMTS13 activity in cholestasis and steatohepatitis in rats may be due, at least in part, to enhanced ADAMTS13 production in the liver, suggesting a significant role of hepatic stellate cells in the regulation of plasma ADAMTS13 activity.

Pre-therapeutic evaluation of laryngeal carcinomas using computed tomography and magnetic resonance imaging. A prospective and comparative computed tomography (CT)/magnetic resonance imaging (MRI) study on 90 patients with endoscopically examined and histologically proven laryngeal malignancy is presented. Post-operative pathological and intra-radiological (CT vs. MRI) correlations are established. We conclude that MRI is the method of choice for staging laryngeal malignancies.

Dependence of induced transmembrane potential on cell density, arrangement, and cell position inside a cell system. A nonuniform transmembrane potential (TMP) is induced on a cell membrane exposed to external electric field. If the induced TMP is above the threshold value, cell membrane becomes permeabilized in a reversible process called electropermeabilization. Studying electric potential distribution on the cell membrane gives us an insight into the effects of the electric field on cells and tissues. Since cells are always surrounded by other cells, we studied how their interactions influence the induced TMP. In the first part of our study, we studied dependence of potential distribution on cell arrangement and density in infinite cell suspensions where cells were organized into simple-cubic, body-centered cubic, and face-centered cubic lattice. In the second part of the study, we examined how induced TMP on a cell membrane is dependent on its position inside a three-dimensional cell cluster. Finally, the results for cells inside the cluster were compared to those in infinite lattice. We used numerical analysis for the study, specifically the finite-element method (FEM). The results for infinite cell suspensions show that the induced TMP depends on both: cell volume fraction and cell arrangement. We established from the results for finite volume cell clusters and layers, that there is no radial dependence of induced TMP for cells inside the cluster.

Cell membrane topology analysis by RICM enables marker-free adhesion strength quantification. Reflection interference contrast microscopy (RICM) allows the visualization of the cell's adhesion topology on substrates. Here it is applied as a new label-free method to measure adhesion forces between tumor cells and their substrate without any external manipulation, i.e., the application of force or adjustments in the substrate elasticity. Malignant cancer transformation is closely associated with the down-regulation of adhesion proteins and the consequent reduction of adhesion forces. By analyzing the size and distribution of adhesion patches from a benign and a malignant human pancreatic tumor cell line, we established a model for calculating the adhesion strength based on RICM images. Further, we could show that the cell's spread area does not necessarily scale with adhesion strength. Despite the larger projected cell area of the malignant cell line, adhesion strength was clearly reduced. This underscores the importance of adhesion patch analysis. The calculated force values were verified by microfluidic detachment assays. Static and dynamic RICM measurements produce numerous adhesion-related parameters from which characteristic cell signatures can be derived. Such a cellular fingerprint can refine the process of categorizing cell lines according to their grade of differentiation.

Alpha1-antichymotrypsin/Alzheimer's peptide Abeta(1-42) complex perturbs lipid metabolism and activates transcription factors PPARgamma and NFkappaB in human neuroblastoma (Kelly) cells. Amyloid-beta peptide (Abeta) and the serpin proteinase inhibitor alpha1-antichymotrypsin (ACT) are components of the amyloid plaques associated with Alzheimer's disease (AD). Abeta exists in soluble monomeric and oligomeric forms and in an insoluble polymerised fibrillar form, but it is not clear which of these plays the most important role in the etiology of AD. In vitro, Abeta(1-42) interacts with ACT, and as a result of this, ACT loses its proteinase inhibitor activity and polymerisation of Abeta(1-42) is promoted. Here we provide evidence that new molecular forms resulting from incubation of ACT with Abeta(1-42) have multiple cellular level effects on neuronal cells. The mixture of soluble Abeta and an ACT/Abeta complex formed by 2 hr incubation at a 10:1 molar ratio of Abeta:ACT strongly induce cellular proliferation and expression of transcription factors peroxisome proliferator-activated receptor-gamma (PPARgamma) and NFkappaB, and also increase uptake and depress degradation of native and oxidised low-density lipoprotein (LDL) by cells. Similar but less pronounced effects are seen when cells are exposed to the Abeta peptide alone preincubated for 2 hr. Abeta(1-42) and to a lesser extent ACT/Abeta(1-42) complex mixture prepared by 2 hr incubation both inhibit association of native LDL with cells. Neither ACT alone nor the Abeta(1-42) and ACT/Abeta(1-42) forms prepared by 24-hr incubation show any significant effects in these assays. We propose that specific molecular forms of Abeta(1-42) and ACT/Abeta(1-42) complex mixture, both dependent on the abundances of Abeta(1-42) and ACT/Abeta(1-42) in vivo and on their time of exposure to each other, have cellular effects which are important for the initiation and progression of the pathologies associated with AD.

Anterior vaginal wall prolapse and voiding dysfunction in urogynecology patients. We investigated whether women with and without anterior vaginal wall prolapse have voiding differences. Women (n=109) who presented to a urogynecology practice were categorized into two groups based on anterior vaginal wall prolapse: stages 0 and 1 and stages 2, 3, and 4. Women with prolapse were older than the women without prolapse but the groups were otherwise similar demographically. There was a higher rate of activity-related urine loss and use of wetness protection amongst women without prolapse. There was no significant difference for urgency symptoms or urge incontinence. Urodynamic testing found no significant differences for maximal flow rate or maximal urethral closing pressures. Postvoid residual volume and detrusor overactivity were not different but approached significance. Anterior vaginal wall prolapse of stage 2 or greater was not associated with urge incontinence or voiding function in this population. Women without prolapse were more likely to report stress incontinence.

Self-generated identification codes in longitudinal prevention research with adolescents: a pilot study of matched and unmatched subjects. Self-generated identification codes (SGICs) are an increasingly utilized methodological feature of longitudinal prevention research among adolescents. This study sought to test the differences between the matched and unmatched groups at baseline on a number of background, health, and well-being and risk behavior measures in a prevention study among 13- to 16-year-old Icelandic adolescents where a SGIC was constructed and used to link individual-level respondent data over two data collection points one year apart. We use pilot data from two Reykjavik city secondary schools collected as part of the population study Youth in Iceland in February 2010 and 2011 (N = 366, SGIC matching rate 61%). Baseline results for the matched and unmatched participants are compared. Findings indicate that the unmatched subjects are both more likely to be substance users than their matched counterparts as well as being more likely to be boys and/or from disrupted families. Five out of the seven scaled measures for risk and protective factors and personality indicators reveal no difference between the matched and unmatched subjects and the significantly different measures reveal small effect sizes between the two groups. However, the effect sizes for substance use are significantly different between the matched and unmatched groups for all seven substance use measures with effect sizes from 0.52 to 1.32. These findings therefore indicate that the measurement validity of adolescent risk behaviors such as substance use may be put in jeopardy when using SGIC and that unmatched subjects may be more likely to distrust the SGIC process.

Six monoclonal antibodies to the CD59 antigen. CD59 defines an N-glycosylated glycoprotein expressed on various hemopoietic cells. It is anchored to the cell membrane by a glycosylpbospbatidylinositol linkage and restricts the action of homologous complement. Monoclonal antibodies 2/24, 182, Fib75.1, BRIC 229, MEM-43, and YTH 53.1 were compared by immunoblotting against normal erythrocyte ghosts. All six stained a diffuse band of 17-25 kDa, but BRIC 229 also detected bands at 35 and 80 kDa. 2/24 reacts with all red blood cells (RBCs) tested, including Rhnull; Ob; ii; Ko; FY:-1,-2,-3; JK:-1,-2,-3; S-s-U-; p; CO:-1,-2; Yt(a-); Jr(a-); Vel-; At(a-); Cr(a-); GE:-2,-3; Wr(a+b+ MkMk; Jo(a-); and Lan-. 2-aminoethylisotbiouronium bromide treatment of erythrocytes destroyed blotting and serologic reactivity of all six antibodies. Pronase treatment reduced serologic reactivity and blotting ability of all antibodies except BRlC 229. Reactivity of all six antibodies was reduced with RBCs from paroxysmal nocturnal hemoglobinuria patients. Flow cytometric analysis was used to demonstrate that 182, Fib75.1, BRIC 229, YTH 53.1, and MEM-43 competitively inhibited the binding of 2/24 to RBCs, thus demonstrating that all six antibodies detect epitopes on the same molecule.

Impaired enteric degradation of pancreatic endopeptidases in antibiotic-treated rats. Conventional Sprague-Dawley rats were fed by gastric tube for 5 days with either benzylpenicillin, ampicillin, doxycycline, or clindamycin. In contrast to the pretreatment period fibrinolytic activity and active and immunoreactive trypsin and immunoreactive elastase were present in fecal extracts after 4 days of antibiotic administration. This is consistent with findings in germfree rats and represents an alteration in the intestinal microflora. The germfree characteristics persisted until a suspension of cecal contents from normal rats was administered by enema on the 26th day. In fecal extracts from the clindamycin-treated rats considerable amounts of active and immunoreactive enzymes were, however, still found 10 days after the enema. A possible explanation is that clindamycin or a metabolite remains in the intestinal tract for a long time. The pathophysiological significance of this finding is unknown.

[A study of developmental order of secondary sexual characteristics in Beijing girls]. A six-year (1980-1986) study of the developmental status of the secondary sexual characteristics was made among 937 girls in Beijing. The mean age of the first appearance of the secondary sexual characteristics was breast 11.84 +/- 0.95 years, pubic hair 13.29 +/- 1.11 years, axillary hair 13.71 +/- 1.21 years; the average age of developmental maturation was breast 13.95 +/- 1.16 years, pubic hair 14.85 +/- 1.29 years, axillary hair 15.14 +/- 1.24 years. Their developmental order, as measured by the mean values of the groups, was breast, the first menarche (12.88 years), pubic hair, axillary hair. But when the individuals were examined only 22.85% was found to be in accord with the above order. The individual variation was very great. The course of development took about 3.5 years, but some needed one year to develop others six years. Some girls developed and finished at the same time, some finished earlier or later. Only a few girls have had no development of pubic hair and axillary hair until 18 years old.

Single port VATS resection of a sessile solitary fibrous tumour of the visceral pleura. A case report. The solitary fibrous tumour of the visceral pleura is a rare neoplasm that derives from mesenchymal cells adjacent to the mesothelial tissue of pleura. Surgical resection is the treatment of choice in benign lesions and healing resulting in half of malignant. Local recurrence can occur in malignant cases, but it is very rare in solitary benign tumors. It may be a result of an incomplete or conservative surgery, lack of identification of a tumor during the operation or a growth of a synchronous neoplasm independent from that removed. Surgical resection is also burdened with some difficulty as the size of the tumor, the relationship with the adjacent structures and identification of the vascular peduncle. We report a case of 72 years-old male with a sessile left solitary fibrous tumour of the visceral pleura. The mass of 10 x 7 x 5 cm was attached, thanks to large planting base, to lateral basal segment of left lower lobe. The patient was treated by single port video assisted approach with a 4 cm skin incision. This case, in our knowledge, represents the first resection by single port VATS of a sessile SFTP with a large plating base and, more generally, the third SFTP resection treated by single portal access. Solitary fibrous tumour, Uniportal VATS.

Acute Stimulant Treatment and Reinforcement Increase the Speed of Information Accumulation in Children with ADHD. The current studies utilized drift diffusion modeling (DDM) to examine how reinforcement and stimulant medication affect cognitive task performance in children with ADHD. In Study 1, children with (n = 25; 88 % male) and without ADHD (n = 33; 82 % male) completed a 2-choice discrimination task at baseline (100 trials) and again a week later under alternating reinforcement and no-reinforcement contingencies (400 trials total). In Study 2, participants with ADHD (n = 29; 72 % male) completed a double-blind, placebo-controlled trial of 0.3 and 0.6 mg/kg methylphenidate and completed the same task utilized in Study 1 at baseline (100 trials). Children with ADHD accumulated information at a much slower rate than controls, as evidenced by a lower drift rate. Groups were similar in nondecision time and boundary separation. Both reinforcement and stimulant medication markedly improved drift rate in children with ADHD (ds = 0.70 and 0.95 for reinforcement and methylphenidate, respectively); both treatments also reduced boundary separation (ds = 0.70 and 0.39). Reinforcement, which emphasized speeded accuracy, reduced nondecision time (d = 0.37), whereas stimulant medication increased nondecision time (d = 0.38). These studies provide initial evidence that frontline treatments for ADHD primarily impact cognitive performance in youth with ADHD by improving the speed/efficiency of information accumulation. Treatment effects on other DDM parameters may vary between treatments or interact with task parameters (number of trials, task difficulty). DDM, in conjunction with other approaches, may be helpful in clarifying the specific cognitive processes that are disrupted in ADHD, as well as the basic mechanisms that underlie the efficacy of ADHD treatments.

A conserved mechanism for replication origin recognition and binding in archaea. To date, methanogens are the only group within the archaea where firing DNA replication origins have not been demonstrated in vivo. In the present study we show that a previously identified cluster of ORB (origin recognition box) sequences do indeed function as an origin of replication in vivo in the archaeon Methanothermobacter thermautotrophicus. Although the consensus sequence of ORBs in M. thermautotrophicus is somewhat conserved when compared with ORB sequences in other archaea, the Cdc6-1 protein from M. thermautotrophicus (termed MthCdc6-1) displays sequence-specific binding that is selective for the MthORB sequence and does not recognize ORBs from other archaeal species. Stabilization of in vitro MthORB DNA binding by MthCdc6-1 requires additional conserved sequences 3' to those originally described for M. thermautotrophicus. By testing synthetic sequences bearing mutations in the MthORB consensus sequence, we show that Cdc6/ORB binding is critically dependent on the presence of an invariant guanine found in all archaeal ORB sequences. Mutation of a universally conserved arginine residue in the recognition helix of the winged helix domain of archaeal Cdc6-1 shows that specific origin sequence recognition is dependent on the interaction of this arginine residue with the invariant guanine. Recognition of a mutated origin sequence can be achieved by mutation of the conserved arginine residue to a lysine or glutamine residue. Thus despite a number of differences in protein and DNA sequences between species, the mechanism of origin recognition and binding appears to be conserved throughout the archaea.

Spontaneously occurring arrhythmogenic right ventricular cardiomyopathy in the domestic cat: A new animal model similar to the human disease. Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a primary myocardial disease of incompletely resolved pathogenesis and is a largely unappreciated cause of sudden death in the young. Clinical features of 12 domestic cats with ARVC (7 male; 1 to 20 years old, mean 7.3+/-5.2 years) were right-sided congestive heart failure (n=8), supraventricular tachyarrhythmias (n=5), ventricular tachycardia (n=3), polymorphic ventricular arrhythmias (n=6), and right bundle-branch block (n=5). ARVC was suspected in all 8 cats examined with echocardiography by marked enlargement of the right ventricle (RV) and right atrium and tricuspid regurgitation. Eight died of cardiovascular disease and 4 died of noncardiac conditions. At autopsy, hearts of ARVC cats were characterized grossly by moderate-to-severe RV cavity enlargement and wall thinning (n=12) and apical aneurysm formation (n=6). Histology demonstrated pronounced RV lesions in all 12 ARVC cats, including marked myocardial injury (myocyte death and atrophy) and repair (fibrous and/or fatty replacement). Injury and repair were also evident in the left ventricle (LV) in 10 cats, and 2 had involvement of both atria. Myocarditis was present in 10 of the 12 ARVC cats. Apoptosis was detected in 9 ARVC cats (mean apoptotic index, 28+/-23% RV, 21+/-19% LV, and 17+/-15% ventricular septum) but not in controls. In the common domestic cat, we identified a clinically relevant cardiomyopathy that closely mimics ARVC in humans. This unique feline model of human disease will be relevant to defining pathogenesis and investigating mechanisms responsible for disease progression in ARVC.

Extracorporeal shock-wave lithotripsy in horseshoe kidneys. Using the Dornier HM-3 lithotriptor, 10 patients (11 renal units) with calculi in horseshoe kidneys were treated with extracorporeal shock-wave lithotripsy (ESWL) and ancillary procedures. Six renal units (55%) underwent pre-ESWL manipulation consisting of a Double J stent, ureteral catheter, or percutaneous nephrostomy. The "blast path" was employed to treat five renal units which could not be positioned at F2. Good initial stone fragmentation was obtained in eight renal units (73%). There were two episodes of post-ESWL obstruction requiring intervention; both occurred in the same patient. A total of seven post-ESWL procedures were performed on two renal units. After all procedures, eight renal units (73%) were rendered stone-free, six (55%) with ESWL alone. The average follow-up interval was twelve months (range 1-28 months). ESWL can be used effectively to treat some patients with calculi in horseshoe kidneys. The ectopic location of these renal units may make it difficult to position calculi at F2, thus necessitating treatment on the blast path or placement of the patient in prone position. Multiple ancillary procedures may be necessary.

Are current body mass index referenced pedometer step-count recommendations applicable to US youth? The purpose of this study was to cross-validate international BMI-referenced steps/d cut points for US girls (12,000 steps/d) and boys (15,000 steps/d) 6 to 12 years of age. Secondary pedometer-determined physical activity data from US children (N=1067; 633 girls and 434 boys, 6 to 12 years) were analyzed. Using international BMI classifications, cross-validation of the 12,000 and 15,000 steps/d cut points was examined by the classification precision, sensitivity, and specificity for each age-sex stratum. For girls (boys) 6 to 12 years, the 12,000 (15,000) steps/d cut points correctly classified 42% to 60% (38% to 67%) as meeting (achieved steps/d cut point and healthy weight) and failing (did not achieve steps/d cut point and overweight). Sensitivity ranged from 55% to 85% (64% to 100%); specificity ranged from 23% to 62% (19% to 50%). The utility of pedometer steps/d cut points was minimal in this sample given their inability to differentiate among children who failed to achieve the recommended steps/d and exhibited an unhealthy weight. Caution, therefore, should be used in applying previous steps/d cut points to US children.

[Infections in the elderly]. SPECIFIC EPIDEMIOLOGY: Respiratory infections predominate in the elderly; community acquired infections can be quite severe. In hospital, urinary infections predominate. Antibiotics must be prescribed without delay due to the less active immune response and the severe and rapid effect infection has on underlying diseases. Monitor renal function in order to adapt dosage and administration intervals to pharmacokinetic variations, notably concerning urinary excretion of many antibiotics; watch for drug interactions; beware of intolerance, more frequent than in younger patients. Wide interindividual variability suggests the need for clinical trials to study drug behavior, efficacy and tolerance in the elderly and to search for specific interaction or unexpected complications. The result would be better therapeutic options and dosages.

Modulation by IBMX, fasting and experimental diabetes of glibenclamide-induced islet hormone release from the perfused rat pancreas. The impact of increased c-AMP levels, short-term fasting as well as experimental diabetes on glibenclamide-induced secretion of somatostatin, insulin and glucagon was studied in the isolated perfused rat pancreas. Dose-response curves revealed that 1 microgram/ml of glibenclamide (in the presence of 3.3 mmol/l of glucose) induced maximal stimulation of insulin and near maximal stimulation of somatostatin release, but did not significantly affect glucagon release. A combination of glibenclamide and the phosphodiesterase inhibitor IBMX synergistically and equally increased both B- and D-cell secretion. Fasting the rats for 24 h significantly suppressed the insulin and glucagon responses to glibenclamide while the concomitant somatostatin response was slightly enhanced. Rats injected with alloxan 3 days prior to perfusion were rendered either moderately diabetic or severely ill with ketoacidosis. Their insulin responses were poor or absent, respectively. In the moderately diabetic rats glibenclamide-induced somatostatin release was blunted while it was abolished in the ketotic rats. The results indicate that glibenclamide-induced B- and D-cell secretion are both modulated by c-AMP, that short-term fasting differentially affects B- and D-cell secretion and that D-cell secretion is inhibited in alloxan diabetes of short duration. It is concluded that the balance of effects by glibenclamide on hormones of the endocrine pancreas may depend on the nutritional and metabolic environment.

Leptomeningeal metastasis with urological presentation. The incidence of clinical leptomeningeal metastases from non-neurologic solid tumour is generally increasing as a result of better survival of systemic cancer with chemotherapy. Their presentation varies according to the neurological involvement. A case of leptomeningeal metastasis from an unknown primary source presenting with urinary incontinence as the sole complaint is reported. While urinary incontinence is common in the community and is often functional, neurogenic causes must also be considered. Urodynamic study and electrophysiological assessment are useful investigations in the exclusion of a neurogenic cause. An MRI of the spine will be required to define any anatomic lesion.

[Modified technique of the Ivanissevich operation for varicocele in children]. On the basis of the results of rheotesticulographic studies in 38 children with left-sided II-III degree varicocele, the impairment in hemodynamics in the testicle at the involved side was established. No suppression of androgen function of the organ was revealed. The expediency to perform in patients of pediatric and young age the Ivanissevich operation, the effectiveness of which is increased in use of intraoperative phlebotesticulography was noted. The effective method for varicocele treatment in children has been suggested. The testicular vein is ligated near the deep inguinal ring as well as at the level of the upper third, then it is excised between the ligatures together with the deviating branches. The method was used in treatment of 120 patients with II-III degree varicocele. No disease recurrence is noted during 1.5 years.

Effect of wheat leaf ribonuclease on tumor cells and tissues. The antiproliferative and antitumor effect of wheat leaf ribonuclease was tested in vitro on the human ML-2 cell line and in vivo on athymic nude mice bearing human melanoma tumors. The antiproliferative activity of this plant ribonuclease was negligible in comparison with bovine seminal ribonuclease. In the experiments in vivo, a significant decrease of the tumor size, however, was observed in the mice treated with wheat leaf ribonuclease (27 kDa) compared with the control RNase A and polyethylene glycol. In nude mice injected intratumoraly with wheat leaf ribonuclease, the tumor size decreased from 100% in the control mice to 39% in treated mice. In the mice treated with polyethylene glycol-conjugated wheat leaf ribonuclease, the tumor reduction was observed from 100 to 28%, whereas in counterparts treated with polyethylene glycol-conjugated bovine seminal ribonuclease the tumor inhibition was reduced from 100 to 33%. Certain aspermatogenic and embryotoxic activity of wheat leaf ribonuclease and bovine seminal ribonuclease also appeared, but was lower in comparison with the effect of onconase. Mutual immunological cross-reactivity between wheat leaf ribonuclease antigens on one side and animal RNases (bovine seminal ribonuclease, RNase A, human HP-RNase and onconase) on the other side proved a certain structural similarity between animal and plant ribonucleases. Immunogenicity of wheat leaf ribonuclease was weaker in comparison with bovine seminal ribonuclease (titer of antibodies 160-320 against 1280-2560 in bovine seminal ribonuclease). Interestingly, immunosuppressive effect of wheat leaf ribonuclease tested on mixed lymphocyte culture-stimulated human lymphocytes reached the same level as that of bovine seminal RNase. The antibodies against wheat leaf ribonuclease produced in the injected mice did not inactivate the biological effect of this plant RNase in vivo. This is probably the first paper in which plant ribonuclease was used as antiproliferative and antitumor drug against animal and human normal and tumor cells and tissues in comparison with animal ribonucleases.

Elevated plasma-free cortisol concentrations and ratios are associated with increased mortality even in the presence of statin therapy in patients with severe sepsis. Dissociation between plasma-free cortisol and total cortisol profiles exists in critical illness. Data on plasma-free cortisol are based on either calculated values or immunoassay-based measurements. Both have significant limitations. Statins have been advocated as a therapy in sepsis. Whether they impact on plasma cortisol through inhibition of cholesterol synthesis is unclear. In patients enrolled into a randomized trial of statins in sepsis (n = 250), we examined the association of mass spectrometry measured plasma-free cortisol, plasma-free cortisol/plasma total cortisol ratios, and outcome and the impact of concomitant statin therapy on cortisol profiles in 80 steroid naïve patients. Two hundred twenty serial measurements of plasma-free cortisol, plasma total cortisol, and interleukin-6 were collected from 80 patients (43 placebo and 37 statins). Data from 10 volunteers were used as controls. Data are presented as median and interquartile range. Compared with controls, in severe sepsis, baseline plasma total cortisol was elevated two-fold (463 nmol/L [284-742 nmol/L] vs 245 nmol/L [200-299 nmol/L], p < 0.001), plasma-free cortisol 20-fold (75 nmol/L [20-151 nmol/L] vs 5 nmol/L [5-7 nmol/L], p < 0.001), and plasma-free cortisol/plasma total cortisol ratio six-fold (0.15 vs 0.02, p = 0.058). Baseline interleukin-6 was elevated at 121 pg/mL (65-611 pg/mL). In severe sepsis, there were no differences in plasma total cortisol (p = 0.66), plasma-free cortisol (p = 0.77), and interleukin-6 (p = 0.29) between statins and placebo groups. Plasma-free cortisol, plasma total cortisol, and plasma-free cortisol/plasma total cortisol were positively correlated with interleukin-6 (p = 0.0001, p < 0.0004, and p < 0.001, respectively) and day 90 mortality (p = 0.03, p = 0.03, and p = 0.058, respectively). Elevated plasma-free cortisol/plasma total cortisol ratios were associated with increased length of stay (p = 0.04). Baseline plasma-free cortisol, plasma total cortisol, and plasma-free cortisol/plasma total cortisol ratios were higher in nonsurvivors as compared with survivors (174 nmol/L [77-329 nmol/L] vs 57 nmol/L [17-122 nmol/L], p = 0.016; 890 nmol/L [333-1,430 nmol/L] vs 408 nmol/L [269-681 nmol/L], p = 0.035; and 0.19 [0.13-0.29] vs 0.14 [0.07-0.20]; p = 0.054, respectively). In severe sepsis, plasma-free cortisol increase is 10-fold greater than that of plasma total cortisol. Both are similarly associated with inflammatory response and mortality. Elevated plasma-free cortisol/plasma total cortisol ratios were associated with increased length of stay. Statin therapy does not influence the plasma cortisol profiles in patients with severe sepsis.

Prolonged daytime exercise repeated over 4 days increases sleeping heart rate and metabolic rate. The aim of this study was to determine the influence of prolonged exercise repeated for 4 days on sleeping heart rate (SHR) and metabolic rate (SMR). Eleven young untrained men exercised at moderate intensity 5 hrs daily for 4 days, alternately on a cycle ergometer (57.0 +/- 1.3% .VO2max) and a treadmill (64.7 +/- 1.6% .VO2max). They spent the night prior to the exercise period (control, C) and the 4 nights following exercise days (N1 to N4) in room calorimeters for the measurement of SHR, SMR, and respiratory quotient (RQ) from midnight until 6 a.m. Every morning, before the exercise bouts, plasma-free epinephrine (E) and norepinephrine (NE) levels were measured. After exercise, all SHR values were significantly higher than at C level (52 +/- 1 bpm, p < 0.001) and the highest value was observed on N2 (61 +/- 2 bpm). SMR increased by 11.2 +/- 1.5% from C to N1, p < 0.001, and then plateaued up to N4, whereas RQ decreased from C (0.833 +/- 0.009) to N2 (0.798 +/- 0.005) and then plateaued. Plasma NE levels were higher the morning after each day of exercise and peaked on N2, whereas no significant variations were found for E. Variations of SHR between C and N2, and N3 and N4 were correlated with changes of SMR. No significant relationships were found between morning plasma NE, and either SMR or SHR variations. To conclude, prolonged exercise repeated for 4 days was associated with increases in SHR and SMR during the night following each day of exercise concomitantly with an enhanced lipid oxidation. The sustained stimulation of the sympathetic nervous system may be partly responsible for these effects.

Interaction of the periplasmic PratA factor and the PsbA (D1) protein during biogenesis of photosystem II in Synechocystis sp. PCC 6803. The biogenesis of photosynthetic complexes is assisted by a growing number of trans-acting factors in both chloroplasts and cyanobacteria. We have previously shown that the periplasmic PratA factor from Synechocystis sp. PCC 6803 (Synechocystis 6803) is required for adequate C-terminal processing of the PsbA (D1) subunit of photosystem II (PSII) supporting the idea that the early steps of PSII assembly occur at the plasma membrane. Here we report on the molecular analysis of the interaction between PratA and the D1 protein. Both yeast two-hybrid and glutathione S-transferase pulldown assays revealed that PratA binds to the soluble forms of both mature and precursor D1 C-terminal regions. In agreement with that finding, the binding region was mapped to amino acid positions 314-328 of D1 by applying a peptide-scanning approach. Approximately 10-20% of the soluble PratA factor was found to be associated with membranes in a D1-dependent manner. Sucrose density gradient centrifugations allowed the identification of a specific membrane subfraction that contains both PratA and D1 and which might represent a transfer and/or connecting region between plasma and thylakoid membrane. Imaging data obtained with enhanced cyan fluorescent protein-labeled D1 protein in wild-type and pratA mutant backgrounds further supported this notion.

Shared and Subject-Specific Dictionary Learning (ShSSDL) Algorithm for Multisubject fMRI Data Analysis. Analysis of functional magnetic resonance imaging (fMRI) data from multiple subjects is at the heart of many medical imaging studies, and approaches based on dictionary learning (DL) are recently noted as promising solutions to the problem. However, the DL-based methods for fMRI analysis proposed to date do not naturally extend to multisubject analysis. In this paper, we propose a DL algorithm for multisubject fMRI data analysis. The proposed algorithm [named shared and subject-specific dictionary learning (ShSSDL)] is derived based on a temporal concatenation, which is particularly attractive for the analysis of multisubject task-related fMRI datasets. It differs from existing DL algorithms in both its sparse coding and dictionary update stages and has the advantage of learning a dictionary shared by all subjects as well as a set of subject-specific dictionaries. The performance of the proposed DL algorithm is illustrated using simulated and real fMRI datasets. The results show that it can successfully extract shared as well as subject-specific latent components. In addition to offering a new DL approach, when applied on multisubject fMRI data analysis, the proposed algorithm generates a group level as well as a set of subject-specific spatial maps. The proposed algorithm has the advantage of learning simultaneously multiple dictionaries providing us with a shared as well discriminative source of information about the analyzed fMRI datasets.

Implicit semantic perception in object substitution masking. Decades of research on visual perception has uncovered many phenomena, such as binocular rivalry, backward masking, and the attentional blink, that reflect 'failures of consciousness'. Although stimuli do not reach awareness in these paradigms, there is evidence that they nevertheless undergo semantic processing. Object substitution masking (OSM), however, appears to be the exception to this rule. In OSM, a temporally-trailing four-dot mask interferes with target perception, even though it has different contours from and does not spatially overlap with the target. Previous research suggests that OSM has an early locus, blocking the extraction of semantic information. Here, we refute this claim, showing implicit semantic perception in OSM using a target-mask priming paradigm. We conclude that semantic information suppressed via OSM can nevertheless guide behavior.

Remote astrocytic response as demonstrated by glial fibrillary acidic protein immunohistochemistry in the visual cortex of dorsal lateral geniculate nucleus lesioned rats. The reaction of astroglia was investigated after unilateral destruction of the dorsal lateral geniculate nucleus in the primary visual cortex of adult albino rats. The destruction of the dorsal lateral geniculate nucleus was performed by stereotaxic injections of ibotenic acid, and the location was verified in Nissl stained sections in each animal. Electron microscopic observations demonstrated the presence of degenerating axon terminals surrounded by hypertrophic astroglial processes mainly in layers III and IV of the ipsilateral primary visual cortex. The ipsilateral (impaired) and contralateral (control) sides of the primary visual cortex showed light microscopically a clearly differing appearance and distribution of glial fibrillary acidic protein (GFAP) immunoreactivity 7 to 11 days after the unilateral injection of ibotenic acid into the dorsal lateral geniculate nucleus. Whereas the control side of the primary visual cortex showed GFAP staining only in the subpial zone of layer I and close to the white matter, all layers of the impaired cortex showed an intense GFAP immunoreactivity. The increase in immunoreactivity was confined to the primary visual cortex. The extent of and increase in immunoreactivity was corroborated by image analysis. These findings were interpreted as a localized hypertrophy of astroglia caused by the anterograde degeneration of geniculocortical terminals. This hypertrophy is accompanied by an increase in GFAP, which may represent the stabilization of the cytoskeleton of newly formed glial processes involved in the rearrangement of the impaired neuropil.

Atrial natriuretic peptide in brain preoptic areas: implications for fluid and salt homeostasis. The influence of adrenalectomy and mineralocorticoid and glucocorticoid treatment on atrial natriuretic peptide (ANP) concentration of 18 microdissected rat brain nuclei was investigated. Adrenalectomy increased ANP levels highly in those brain areas that control water intake (the subfornical organ and supraoptic nucleus) and in the drinking center (the perifornical nucleus and the lateral hypothalamus). In all of these brain regions, aldosterone elevated ANP levels in intact animals. Adrenalectomy decreased ANP levels markedly in the OVLT and preoptic periventricular nucleus, which constitute the so-called AV3V region. The ANP level of these two brain areas was nearly restored to baseline levels both after administration of sodium chloride and after replacement of aldosterone, whereas dexamethasone treatment failed to have any effect.

Spectroscopic study on the enzymatic degradation of a biodegradable composite periodontal membrane. The enzymatic in vitro degradation of a commercial biodegradable hydroxyapatite (HA)-polymer (poly(epsilon-caprolactone)-poly(oxyethylene)(POE)-poly(epsilon-caprolactone) block copolymer) composite membrane was investigated by Raman and IR spectroscopies in two enzymatic solutions at 37 degrees C: esterase and alpha-chymotrypsin in saline phosphate buffer (SPB, pH 7.4). The degradation was found to be faster in the enzymatic medium than in SPB and alkaline solutions. The fastest degradation rate was observed in esterase solution. The trend of properly chosen Raman and IR intensity ratios was evaluated to go deeper inside the degradation mechanism: both polymeric and apatitic components were found to be involved in degradation. The former underwent preferential degradation of POE blocks, while HA is removed by the degradation medium faster than the polymer. Vibrational spectroscopy proved a valid tool for investigating the degradation of the membrane.

Depletion of plasma vitamin C but not of vitamin E in response to cardiac operations. The whole-body inflammatory response produced by cardiopulmonary bypass is an important cause of perioperative morbidity after cardiac operations. This inflammatory response produces reactive oxygen species and other cytotoxic substances, such as the cytokines. The generation of reactive oxygen species might deplete principal antioxidant micronutrients, that is, vitamins C and E and the carotenoids. Therefore, we have investigated the time course of the plasma concentrations of vitamins C and E and the carotenoids in 18 patients undergoing coronary bypass operations after randomization for previous vitamin E supplementation (300 mg dl-alpha-acetyl-tocopherol 3 times daily for 4 weeks) or placebo. Supplementation with alpha-tocopherol doubled the lipid-standardized plasma vitamin E concentration to 63.7 +/- 14.5 mumol/L when compared with that of the control subjects (31.2 +/- 9.0 mumol/L) before the operation. The plasma concentrations of vitamin C (36.0 +/- 19.0 mumol/L and 44.0 +/- 21.7 mumol/L, respectively) and of the carotenoids were not statistically different between the two groups at baseline. The absolute plasma concentrations of both vitamin E and the carotenoids decreased during and after cardiopulmonary bypass, but after correction for hemodilution the plasma concentrations of vitamin E and the carotenoids showed no decrease. The vitamin E concentrations in the erythrocytes did not change either. In contrast, the plasma concentration of vitamin C decreased in all subjects within 24 hours after the operation by roughly 70%. Correction for hemodilution still revealed a significant decrease in plasma vitamin C that persisted in most patients up to 2 weeks. In conclusion, the vitamin E and the carotenoid plasma concentrations are of no major concern during and after cardiac operations. In contrast, the serious depletion of vitamin C may deteriorate the defense against reactive oxygen species-induced injury during cardiac operations.

Mucocutaneous manifestations in human immunodeficiency virus (HIV)-infected patients in Nouakchott, Mauritania. Mucocutaneous manifestations are one of the first clinical signs in patients infected with human immunodeficiency virus (HIV). To the best of our knowledge, there has been no previous study describing dermatologic manifestations in Mauritanians infected with HIV. The aim of the present study was to determine the profiles of mucocutaneous manifestations in relation to CD4 T cell count in HIV-positive Mauritanian patients. A total of 86 adult patients aged > 18 years old attending the Ambulatory Treatment Center of the National Hospital of Nouakchott, Mauritania, with newly diagnosed HIV and who were not under antiretroviral treatment were included in the study in 2015. Dermatologic manifestations were documented before initiating antiretroviral treatment. Most of the included patients were in clinical stage 3 of the World Health Organization classification at initial diagnosis, with the mean CD4 T cell count (± SD) of 514 ± 319 cells/mm3 (range, 2-1328 cells/mm3 ), and 19 of 86 (22.1%) patients had CD4 T cell counts below 200 cells/mm3 . More than half (64%) of newly diagnosed HIV-infected patients had dermatoses, including the following: pruritic papular eruption (44.2%), seborrheic dermatitis (4.7%), Kaposi's sarcoma (3.5%), extensive xerosis cutis (2.3%), drug-induced skin reactions (1.2%), and various infectious dermatoses (dermatophyte infections [16.3%], oral candidiasis [11.6%], herpes zoster [8.1%], and scabies [2.3%]). A low CD4 T cell count (< 200 cells/mm3 ) was significantly correlated (P < 0.05) with the presence of following dermatoses: dermatophytosis, oral candidiasis, Kaposi's sarcoma, seborrheic dermatitis, and extensive xerosis cutis. Mucocutaneous lesions occur throughout the course of HIV infection, and dermatologic findings in Mauritanian HIV-positive patients are similar to those of patients in other countries. Early detection of skin disorders in some patients may help establish the diagnosis of HIV and management of HIV-associated diseases, limiting the cost of care in low-resource countries.

Intrahepatic cholestasis due to systemic mastocytosis: a case report and review of literature. A 35-yr-old female presented with symptoms of obstructive jaundice. Liver biopsy, bone marrow aspiration, and biopsy revealed systemic mastocytosis and acute myeloid leukemia. The liver biopsy specimen showed infiltration of mast cells within portal tracts with periductal and portal edema, irregularity of interlobular duct epithelium, and centrizonal cholestasis. Endoscopic retrograde cholangiography was normal. Following chemotherapy treatment with idarubicin and cytarabine for seven days for AML, the bilirubin levels continued to increase for two weeks and then decreased, reaching normal levels in two months. Infiltration of mast cells in the liver leads to hepatomegaly, liver function abnormality and rarely portal hypertension. Intrahepatic cholestasis due to systemic mastocytosis has never been reported. We report a rare case of systemic mastocytosis causing intrahepatic cholestasis that resolved with remission of AML following chemotherapy.

Effect of a Structured Pharmaceutical Care Intervention Versus Usual Care on Cardiovascular Risk in HIV Patients on Antiretroviral Therapy: INFAMERICA Study. HIV+ patients have increased their life expectancy with a parallel increase in age-associated comorbidities. To determine the effectiveness of an intensive pharmaceutical care follow-up program in comparison to a traditional model among HIV-infected patients with moderate/high cardiovascular risk. This was a multicenter, prospective, randomized study of a structured health intervention conducted between January-2014 and June-2015 with 12 months of follow-up at outpatient pharmacy services. The selected patients were randomized to a control group (usual care) or intervention group (intensive pharmaceutical care). The interventional program included follow-up of all medication taken by the patient to detect and work toward the achievement of pharmacotherapeutic objectives related to cardiovascular risk and making recommendations for improving diet, exercising, and smoking cessation. Individual motivational interview and periodic contact by text messages about health promotion were used. The primary end point was the percentage of patients who had reduced the cardiovascular risk index, according to the Framingham-score. A total of 53 patients were included. As regards the main variable, 20.7% of patients reduced their Framingham-score from high/very high to moderate/low cardiovascular risk versus 12.5% in the control group ( P=0.016). In the intervention group, the number of patients with controlled blood pressure increased by 32.1% ( P=0.012); 37.9% of patients overall stopped smoking ( P=0.001), and concomitant medication adherence increased by 39.4% at the 48-week follow-up ( P=0.002). Conclusion and Relevance: Tailored pharmaceutical care based on risk stratification, motivational interviewing, and new technologies might lead to improved health outcomes in HIV+ patients at greater cardiovascular risk.

Comparative pharmacokinetics of doramectin and ivermectin in cattle. Plasma pharmacokinetics were compared for 40 cattle dosed by subcutaneous injection with doramectin or ivermectin (200 micrograms kg-1), commercial formulations of doramectin or ivermectin, 20 cattle per product). Doramectin exhibited a similar peak plasma concentration to ivermectin (about 32 ng ml-1), but the time to Cmax was longer for doramectin (5.3 +/- 0.35 days) than for ivermectin (4.0 +/- 0.28 days). The area under the curve from time 0 to infinity post-injection was significantly higher (p < 0.001) for doramectin (511 +/- 16 ng day ml-1) than for ivermectin (361 +/- 17 ng day ml-1). This was explained by a lower clearance, a lower volume of distribution and, probably, a higher bioavailability of doramectin over ivermectin. It is concluded that the pharmacokinetic differences between doramectin and ivermectin may explain the longer duration of preventive efficacy of doramectin.

Predominant intracellular expression of CXCR4 and CCR5 in purified primary trophoblast cells from first trimester and term human placentae. The aim of the present study was to define the expression of CXCR4 and CCR5 on non-cultured non-stimulated primary human trophoblast cells (TCs) immediately after their immunopurification. We have evaluated by flow cytometric analysis and immunofluorescence, highly purified primary TCs prepared from first trimester (8.2 +/- 0.3 weeks, n = 15) and term (Caesarean section, n = 10) placentae for the cell surface and intracellular expression of CXCR4 and CCR5. There was a high level of individual variability for CXCR4 and CCR5 expression between trophoblast batches. In first trimester and term placentae TCs, we found a greater number of TCs preparations expressing intracellular CXCR4 than CCR5 (P < 0.05). Both receptors were predominantly localized in the intracellular compartment of TCs, whatever if isolated from first trimester or term placentae. The functional consequences of the predominance of CXCR4 expression and of cellular addressing are briefly discussed.

Carcinoid syndrome misdiagnosed as a malabsorptive syndrome after biliopancreatic diversion. A case is reported of a woman who developed untreatable diarrhea after a prior biliopancreatic diversion (BPD), attributed to the malabsorptive component. Abdominal ultrasound incidentally found focal liver lesions. On fine needle aspiration biopsy, atypia was found, and these hepatic lesions were resected with free margins. The specimen showed liver metastases of an aggressive malignant neuroendocrine neoplasm. The primary site was subsequently identified to be in the pancreas. The physician and surgeon must realize that non-related diseases can develop after bariatric surgery, as in the general population.

The use of laboratory biomarkers for surveillance, diagnosis and prediction of clinical outcomes in neonatal sepsis and necrotising enterocolitis. Biomarkers have been used to differentiate systemic neonatal infection and necrotising enterocolitis (NEC) from other non-infective neonatal conditions that share similar clinical features. With increasing understanding in biochemical characteristics of different categories of biomarkers, a specific mediator or a panel of mediators have been used in different aspects of clinical management in neonatal sepsis/NEC. This review focuses on how these biomarkers can be used in real-life clinical settings for daily surveillance, bedside point-of-care testing, early diagnosis and predicting the severity and prognosis of neonatal sepsis/NEC. In addition, with recent development of 'multi-omic' approaches and rapid advancement in knowledge of bioinformatics, more novel biomarkers and unique signatures of mediators would be discovered for diagnosis of specific diseases and organ injuries.

Local structural plasticity of the prion protein. Analysis of NMR relaxation dynamics. A template-assisted conformational change of the cellular prion protein (PrP(C)) from a predominantly helical structure to an amyloid-type structure with a higher proportion of beta-sheet is thought to be the causative factor in prion diseases. Since flexibility of the polypeptide is likely to contribute to the ability of PrP(C) to undergo the conformational change that leads to the infective state, we have undertaken a comprehensive examination of the dynamics of two recombinant Syrian hamster PrP fragments, PrP(29-231) and PrP(90-231), using (15)N NMR relaxation measurements. The molecular motions of these PrP fragments have been studied in solution using (15)N longitudinal (T(1)) and transverse relaxation (T(2)) measurements as well as [(1)H]-(15)N nuclear Overhauser effects (NOE). These data have been analyzed using both reduced spectral density mapping and the Lipari-Szabo model free formalism. The relaxation properties of the common regions of PrP(29-231) and PrP(90-231) are very similar; both have a relatively inflexible globular domain (residues 128-227) with a highly flexible and largely unstructured N-terminal domain. Residues 29-89 of PrP(29-231), which include the copper-binding octarepeat sequences, are also highly flexible. Analysis of the spectral densities at each residue indicates that even within the structured core of PrP(C), a markedly diverse range of motions is observed, consistent with the inherent plasticity of the protein. The central portions of helices B and C form a relatively rigid core, which is stabilized by the presence of an interhelix disulfide bond. Of the remainder of the globular domain, the parts that are not in direct contact with the rigid region, including helix A, are more flexible. Most significantly, slow conformational fluctuations on a millisecond to microsecond time scale are observed for the small beta-sheet. These results are consistent with the hypothesis that the infectious, scrapie form of the protein PrP(Sc) could contain a helical core consisting of helices B and C, similar in structure to the cellular form PrP(C). Our results indicate that residues 90-140, which are required for prion infectivity, are relatively flexible in PrP(C), consistent with a lowered thermodynamic barrier to a template-assisted conformational change to the infectious beta-sheet-rich scrapie isoform.

[Preparation and characterization of transfersomes of three drugs in vitro]. To investigate the influence of drug properties on the encapsulation effiency (EE) and drug release of transfersomes for a proper transfersome preparation. To prepare the transfersomes of colchicines (CLC), vincristine sulfate (VCR) and mitoxantrone hydrochloride (DHAD) with the same materials and methods, and then measure their EE. To find out the relationship between drug properties like solubility, molecular weight and charges, and EE. To performe the drug release experiments of various types of transfersomes in vitro, and compare their differences. VCR and DHAD are lipophilic or hydrophilic, owing positive charges and large molecular weight, as a result, their EE are high, while CLC is amphipathic, neutral, and of small molecular weight, its EE is very low. As DHAD can insert into the membrane of transfersome, the drug release of DHAD-T in vitro is much slower than that of VCR-T. To prepare transfersomes with high EE, drugs that are lipophilic or hydrophilic, high molecular weight and opposite charges to the membrane should be chosen. Interaction between drugs and membrane will influnce the rate of drug release.

[Evaluation of the level of students' knowledge about psychoactive drugs]. The aim of the paper is to evaluate the level of knowledge about addictions. The research was conducted among a group of 158 people, with 85 of whom studying physiotherapy and 73--physical education at the Academy of Physical Education in Krakow. Students of both disciplines had compulsory health promotion classes. The level of knowledge is insufficient and comparable in both cases. The vast majority of the surveyed know the definition of psychical and physical addiction. Students are not capable of listing the consequences of smoking for health. A relatively high percentage claims that beer is not addictive. Not all students know that marijuana smoking leads to addiction as well.

The Doctor Patient Relationship; what if Communication Skills are not used? A Maltese Story. The doctor patient relationship is fundamental to the practice of medicine. In the UK, much work has been carried out to develop taining in communication skills for both doctors and medical students. Whereas it is true that controled trials of communication skills are now beginning to emerge in the primary care literature, it is also true that there is need for studies of communication skills on the hospital ward. One alternative form of evidence for the need of communication skills is that of anthropological studies of hospital wards. We here summarise the observations made in one such anthropological study which was carried out in a renal unit in Malta. The conclusion of these observations is that the inability of the doctors to utilise communication skills is that patients develop meaningful relationships with other groups of professionals, to the extent that they consider them as part of an extended family. Doctors remain isolated from all these relationships and only relate to patients from a position of power.

CT of intracranial metastases with skull and scalp involvement. Twenty-eight persons with contiguous intracranial skull, and often extracranial metastatic disease are reported. These lesions comprised 7.6% of a series of 250 consecutive patients with intracranial metastatic disease. Only three of 28 patients had other intracranial lesions and only seven of 28 patients has other skull lesions demonstrable on computed tomography (CT). Carcinoma of the prostate and breast, multiple myeloma, and neuroblastoma are especially likely to appear in this manner. All metastases enhanced. The bone destruction was so pervasive that in 19 of the patients it was obvious at routine CT settings. In the nine other patients, it could be clearly seen only at bone settings (high window and level). The CT demonstration of an enhancing intracranial mass involving the skull and often the scalp is highly suggestive but not diagnostic of a metastatic lesion.

Evolution at a different pace: distinctive phylogenetic patterns of cone snails from two ancient oceanic archipelagos. Ancient oceanic archipelagos of similar geological age are expected to accrue comparable numbers of endemic lineages with identical life history strategies, especially if the islands exhibit analogous habitats. We tested this hypothesis using marine snails of the genus Conus from the Atlantic archipelagos of Cape Verde and Canary Islands. Together with Azores and Madeira, these archipelagos comprise the Macaronesia biogeographic region and differ remarkably in the diversity of this group. More than 50 endemic Conus species have been described from Cape Verde, whereas prior to this study, only two nonendemic species, including a putative species complex, were thought to occur in the Canary Islands. We combined molecular phylogenetic data and geometric morphometrics with bathymetric and paleoclimatic reconstructions to understand the contrasting diversification patterns found in these regions. Our results suggest that species diversity is even lower than previously thought in the Canary Islands, with the putative species complex corresponding to a single species, Conus guanche. One explanation for the enormous disparity in Conus diversity is that the amount of available habitat may differ, or may have differed in the past due to eustatic (global) sea level changes. Historical bathymetric data, however, indicated that sea level fluctuations since the Miocene have had a similar impact on the available habitat area in both Cape Verde and Canary archipelagos and therefore do not explain this disparity. We suggest that recurrent gene flow between the Canary Islands and West Africa, habitat losses due to intense volcanic activity in combination with unsuccessful colonization of new Conus species from more diverse regions, were all determinant in shaping diversity patterns within the Canarian archipelago. Worldwide Conus species diversity follows the well-established pattern of latitudinal increase of species richness from the poles towards the tropics. However, the eastern Atlantic revealed a striking pattern with two main peaks of Conus species richness in the subtropical area and decreasing diversities toward the tropical western African coast. A Random Forests model using 12 oceanographic variables suggested that sea surface temperature is the main determinant of Conus diversity either at continental scales (eastern Atlantic coast) or in a broader context (worldwide). Other factors such as availability of suitable habitat and reduced salinity due to the influx of large rivers in the tropical area also play an important role in shaping Conus diversity patterns in the western coast of Africa.

Effects of endurance training on body-consciousness in women. The Body Consciousness Questionnaire by Miller, Murphy, and Buss in 1981 was employed to assess the effects of intensive endurance training on changes in self-perception in 13 women volunteers aged 20 to 30 yr. The participants engaged in an intensive progressive running program for 6 to 8 wk. Additional moderate exercise (softball or volleyball) was engaged in for 3 1/2 hr. per day. Before and after the training subjects completed the questionnaire on self-perceived attributes of internal body consciousness, public body consciousness, and body competence. Aerobic fitness, measured pre- and posttraining, significantly increased while body fat and weight significantly decreased. In consonance with these physiological changes, rated self-perception of internal body consciousness and body competence increased significantly while public body consciousness remained unchanged. Self-report of internal body consciousness tended to increase in proportion to changes in fitness (r = 0.53). These results suggest that endurance and moderate exercise training contribute to increased self-perception specifically with regard to perceived internal and body competence.

Predictors of progression in hypertensive renal disease in children. In hypertensive renal disease in children, several risk factors influence the development and the rate of progression of renal damage, including blood pressure levels, proteinuria, lipid disorders, and genetic differences. The impact of blood pressure on renal structures, the most important of the factors, depends not only on blood pressure levels, but also on the persistence of the blood pressure levels over time, mainly during the hours when the patient is resting or sleeping. Abnormal circadian variability is frequently observed in patients with renal damage, and nocturnal blood pressure reduction should be a major therapeutic objective to protect against a decline in renal function. Proteinuria is a guide for establishing targets and for monitoring treatment. It should be reduced as much as possible to obtain maximal renoprotective effect. The role of the other factors, such as lipid disorders and genetics, remains elusive.

Taking stock of pay-for-performance: a candid assessment from the front lines. Pay-for-performance (P4P) has been widely adopted, but it remains unclear how providers are responding and whether results are meeting expectations. Physician organizations involved in the California Integrated Healthcare Association's (IHA) P4P program reported having increased physician-level performance feedback and accountability, speeded up information technology adoption, and sharpened their organizational focus and support for improvement in response to P4P; however, after three years of investment, these changes had not translated into breakthrough quality improvements. Continued monitoring is required to determine whether early investments made by physician organizations provide a basis for greater improvements in the future.

Four-year follow-up of mycophenolate mofetil for graft rescue in liver allograft recipients. Mycophenolate mofetil (MMF) has been shown to have promise in short-term liver transplantation graft rescue studies. The purpose of this study was to evaluate the long-term efficacy and safety of MMF in liver transplant patients who had failed cyclosporine (CsA)-based conventional immunosuppression. Nineteen orthotopic liver allograft recipients were converted from azathioprine to MMF in combination with CsA and prednisone in this prospective, open-labeled, single-center, graft rescue, pilot study. Six patients were taken off CsA when MMF was initiated. A 4-year patient follow-up is reported here. Patients were considered to have failed CsA-based immunosuppression either for refractory rejection, chronic rejection, or severe CsA neurologic toxicity. Twelve patients had complete histologic resolution, two had partial resolution, and three had worsening of their rejection. Thirteen patients had a complete biochemical response; one had a partial response and four had worsening of their rejection. Two patients had no histologic and one no biochemical follow-up. Of the six patients treated with MMF and prednisone alone, four had complete resolution of rejection without recurrence. The majority of adverse reactions were gastrointestinal [nausea and/or vomiting (n=5); diarrhea (n=8); gastritis, duodenitis, or esophagitis (n=4); and ulcers (n=2)] or bone marrow suppressive [leukopenia (n=9), anemia (n=6), and thrombocytopenia (n=5)]. MMF seems to be an effective alternative immunosuppressive in patients failing CsA-based conventional therapy. MMF may be of particular benefit in patients who do not tolerate CsA or tacrolimus. The long-term safety profile is similar to that of other immunosuppressives.

Multi-terminal transport measurements of MoS2 using a van der Waals heterostructure device platform. Atomically thin two-dimensional semiconductors such as MoS2 hold great promise for electrical, optical and mechanical devices and display novel physical phenomena. However, the electron mobility of mono- and few-layer MoS2 has so far been substantially below theoretically predicted limits, which has hampered efforts to observe its intrinsic quantum transport behaviours. Potential sources of disorder and scattering include defects such as sulphur vacancies in the MoS2 itself as well as extrinsic sources such as charged impurities and remote optical phonons from oxide dielectrics. To reduce extrinsic scattering, we have developed here a van der Waals heterostructure device platform where MoS2 layers are fully encapsulated within hexagonal boron nitride and electrically contacted in a multi-terminal geometry using gate-tunable graphene electrodes. Magneto-transport measurements show dramatic improvements in performance, including a record-high Hall mobility reaching 34,000 cm(2) V(-1) s(-1) for six-layer MoS2 at low temperature, confirming that low-temperature performance in previous studies was limited by extrinsic interfacial impurities rather than bulk defects in the MoS2. We also observed Shubnikov-de Haas oscillations in high-mobility monolayer and few-layer MoS2. Modelling of potential scattering sources and quantum lifetime analysis indicate that a combination of short-range and long-range interfacial scattering limits the low-temperature mobility of MoS2.