[Extent of tuberculin skin testing spot in bacteriologically verified tuberculosis].
Tuberculin skin test was evaluated in patients with bacteriologically verified tuberculosis notified in the Czech Republic during 2003 and 2004. Out of 1172 patients with bacteriologically verified tuberculosis altogether 28.8% were tuberculin-negative. The average value of tuberculin reaction in this cohort was 11.6 mm. Among 30-year-old patients with bacteriologically verified tuberculosis the number of tuberculin-negative individuals was statistically lower (14 %) in comparison with 70-year-old and older patients, where the prevalence of tuberculin-negative individuals was 42 %. Higher rate of tuberculin-negative individuals with bacteriologically verified tuberculosis was found among patients who were diagnosed with liver disease (42 % of tuberculin-negative) or malignant tumor (47 % of tuberculin-negative). Presented results show that in circumstances of the Czech Republic the tuberculin skin test can be used to follow up the spreading of tuberculosis infection in younger age groups without accompanying serious disease only. The improvement of the diagnostics of latent tuberculosis infection can bring the routine introduction of new tests, e.g. Quantiferon-TB Gold or other methods.


B7 as a supergroup of crystal and quasicrystal symmetries.
In sharp contrast to the generation of a finite group that includes all the 14 types of Bravais lattices as its subgroups [Hosoya (2000). Acta Cryst. A56, 259-263; Hosoya (2002). Acta Cryst. A58, 208], it was proved that a signed permutation group Bk may be interpreted as the supergroup of both crystal and quasicrystal symmetries. Minimal dimension k = 6 is adequate for lattices referred to their three non-coplanar shortest vectors, or for symmetry groups of most quasicrystal types. If one prefers complete, well defined semi-reduced lattice descriptions or needs a dodecagonal group, the B7 supergroup is necessary. All considered matrix groups correspond to isometric transformations in extended k-bases and may be easily derived from B7 and projected onto three-dimensional crystallographic space. Three models of extended bases are proposed: semi-reduced, cyclic and axial. In all cases additional basis vectors are strictly (functionally) related to three original basis vectors.


Central metal determines pharmacokinetics of chlorophyll-derived xenobiotics.
Chlorophyll derivatives are potentially dangerous xenobiotics of dietary origin. The interactions of water-soluble derivatives of chlorophyll a with the animal organism were investigated using chlorophyllide a and its Zn-substituted analogue as model xenobiotics. The chlorophyllides were administered to tumor-bearing mice and their uptake, distribution, and clearance were compared. The centrally bound metal determines important aspects of the in vivo behavior of metallochlorophyllides as xenobiotics. The uptake and clearance of chlorophyllide a were significantly faster than those of [Zn]-chlorophyllide a. Chlorophyllide a showed some tissue selectivity, while [Zn]-chlorophyllide a was uniformly distributed among tissues. Interestingly, the tissue levels of the latter compound were ten times higher than those of the Mg-derivative. These differences indicate that [Zn]-chlorophyllide a, in contrast to chlorophyllide a, is only weakly recognized by the system of active transport of xenobiotics and by enzymes involved in chlorophyll metabolism. The dependence of chlorophyllide pharmacokinetics on the central metal is of great relevance to chlorophyll-based phototherapy.


Physiological consequences of multiple-target regulation by the small RNA SgrS in Escherichia coli.
Cells use complex mechanisms to regulate glucose transport and metabolism to achieve optimal energy and biomass production while avoiding accumulation of toxic metabolites. Glucose transport and glycolytic metabolism carry the risk of the buildup of phosphosugars, which can inhibit growth at high concentrations. Many enteric bacteria cope with phosphosugar accumulation and associated stress (i.e., sugar-phosphate stress) by producing a small RNA (sRNA) regulator, SgrS, which decreases phosphosugar accumulation in part by repressing translation of sugar transporter mRNAs (ptsG and manXYZ) and enhancing translation of a sugar phosphatase mRNA (yigL). Despite a molecular understanding of individual target regulation by SgrS, previously little was known about how coordinated regulation of these multiple targets contributes to the rescue of cell growth during sugar-phosphate stress. This study examines how SgrS regulation of different targets impacts growth under different nutritional conditions when sugar-phosphate stress is induced. The severity of stress-associated growth inhibition depended on nutrient availability. Stress in nutrient-rich media necessitated SgrS regulation of only sugar transporter mRNAs (ptsG or manXYZ). However, repression of transporter mRNAs was insufficient for growth rescue during stress in nutrient-poor media; here SgrS regulation of the phosphatase (yigL) and as-yet-undefined targets also contributed to growth rescue. The results of this study imply that regulation of only a subset of an sRNA's targets may be important in a given environment. Further, the results suggest that SgrS and perhaps other sRNAs are flexible regulators that modulate expression of multigene regulons to allow cells to adapt to an array of stress conditions.


Antiviral therapy: hepatitis B.
Antiviral therapy for chronic hepatitis B virus infection can result in clearance of replicating virus from the liver and prevention of progression to cirrhosis in a substantial proportion of patients. Adenosine arabinoside monophosphate, a potent inhibitor of HBV replication, is of limited usefulness because it causes significant neuromuscular toxicity. Acyclovir alone is relatively nontoxic, but is clinically ineffective in eliminating HBV from the liver. Lymphoblastoid or recombinant alpha-interferons are the best option at present and offer up to a 50% chance of long-term inhibition of HBV replication (with only minor side-effects) in patients who acquire the infection in adulthood. However alpha-interferon therapy alone is not effective when infection is acquired from birth. In this latter group of patients, prednisolone pre-treatment followed by alpha-interferon is currently under evaluation.


Bioactivity-Protected Electrochemiluminescence Biosensor Using Gold Nanoclusters as the Low-Potential Luminophor and Cu2S Snowflake as Co-reaction Accelerator for Procalcitonin Analysis.
The expansion of electrochemiluminescence (ECL) technology to immunoassay at the core of care emphasizes all immune molecules will not be inactivated in the analysis process. That poses a major challenge to ECL-based biosensors due to the deoxynucleotide sequences of an antigen or antibody could be oxidized through a route of excessive cyclic potential. Herein, an ultrasensitive ECL biosensor was developed based on a novel bioactivity-protected sensing strategy utilizing Au nanoclusters (Au NCs) as low-potential luminophor for detection of procalcitonin (PCT). Bovine serum albumin (BSA)-templated Au NCs exhibited a low-potential anodic ECL signal in triethylamine (TEA) solution at 0.87 V, where it is suitable for the survival of immune molecules. Taking advantage of good conductivity and high surface area, a Cu2S snowflake not only functions as a satisfying substrate for connecting immune molecules but also acts as co-reaction accelerator to produce more cationic radicals TEA•+, which could improve the ECL intensity needed to meet the requirements of trace analysis. Otherwise, HWRGWVC (HC-7) heptapeptide as specific antibody immobilizer for site-oriented fixation was introduced to further maintain the bioactivity of an antibody. In view of the preceding discussion, the obtained biosensor exhibited ultrahigh immune recognition to targets so that the detection limit was as low as an unprecedented value of 2.36 fg/mL, which will be of great significance to the application and development of a biosensor in the future.


Impaired vascular smooth muscle nitric oxide-dependent relaxation in human coronary arteries from "transplanted heart vasculopathy".
The long-term prognosis after heart transplant is mainly determined by the development of transplant vasculopathy. The pathogenic mechanism of transplant vasculopathy remain uncertain, although endothelial dysfunction has been postulated. The objective of this work is to evaluate the smooth muscle and endothelium nitric oxide relaxing mechanisms in coronary arteries from patients with transplant vasculopathy. We studied human coronary arteries obtained from heart transplant surgery specimens of patients with heart transplant vasculopathy, ischaemic cardiopathy or dilated cardiomyopathy. Rings from the coronary arteries were mounted on stainless steel hooks in 40 ml organ bath. The tissues were contracted with phenylephrine (approx. ED 80-90) and concentration-response curves were performed with glyceryltrinitrate and acetylcholine. Glyceryltrinitrate relaxed arterial rings from patients with dilated cardiomyopathy and ischaemic cardiopathy. Arterial rings from patients with heart transplant vasculopathy showed a lower response to glyceryltrinitrate. Acetylcholine induced dilatation of coronary arteries from dilated cardiomyopathy but increased the tension in coronary rings from heart transplant vasculopathy and inschaemic cardiopathy. In conclusion, there is a lower response to glyceryltrinitrate and a paradoxical response to acetylcholine in arteries from patients with transplant vasculopathy. The response to glyceryltrinitrate may be a meaningful tool in the early diagnosis of transplant vasculopathy.


Temperature-sensitive herpes simplex virus type 1 mutants defective in the shutoff of cellular DNA synthesis and host polypeptide synthesis.
Two temperature-sensitive herpes simplex virus type 1 mutants, ts 1-8 and ts 199, belonging to different complementation groups, were isolated. Both mutants were defective in the shutoff of host DNA synthesis at 39.5 degrees C (nonpermissive temperature). ts 1-8 exhibited intermediate levels of viral DNA synthesis at 39.5 degrees C, while ts 199 was completely deficient in viral DNA synthesis at 39.5 degrees C. Comparative polyacrylamide gel electrophoresis of the ts 1-8, ts 199 and wild-type viral-coded polypeptides and cellular proteins produced in vivo at 34 degrees C and 39.5 degrees C during various periods post infection was performed. The results indicated that ts 1-8 and ts 199 were temperature-sensitive for the secondary suppression of host polypeptide synthesis. Production of the beta (early) and gamma (late) viral polypeptides was slightly delayed in the mutant-infected cells at early times post infection at both 34 degrees C and 39.5 degrees C. This delayed protein production was not evident at later times post-infection. The ts 1-8 and ts 199 mutants were distinct from the HSV-1 viron-associated host shutoff (vhs) mutants of Read and Frenkel (J. Virol. 46 (1983) 498).


Gastroprotection in patients prescribed non-selective NSAIDs, and the risk of related hospitalization.
To assess co-prescription of gastroprotective agents (GPAs) for non-selective NSAID (nsNSAID)-treated patients in UK primary care, and the rate of gastrointestinal (GI)-related hospitalizations occurring with varying levels of GPA use in patients at high Gl risk. A retrospective, observational study was conducted using the DIN-LINK UK primary care database, on patients prescribed nsNSAIDs alone or concomitantly with GPAs between September 2003 and August 2005. Patients were stratified by GI risk, frequency of nsNSAID use and level of GPA use. Rates and odds ratios of GI-related hospitalizations were calculated for high GI-risk patients. In August 2005, 26 371 patients with nsNSAID prescriptions were identified, of whom 55% were frequent users. In the overall and frequent nsNSAID-user populations, 74% and 71%, respectively, were co-prescribed none or few GPAs (0-19% level of use), and only 18% and 20%, respectively, received complete gastroprotection. GI risk factors were identified in 76% of all patients. Overall, 70% of patients with serious co-morbidity, 44% with GI event history, and 56% of aspirin users received little or no gastroprotection (0-19%). Data for previous months of the analysis period were similar. In patients with a GI-event history, based on data over the 2-year study period, hospitalization rates ranged from 2.4% (with full gastroprotection) to 8.0% (20-39% GPA use). Odds of a GI-related hospitalization were up to 3.5 times higher with low GPA use. This study revealed low levels of GPA co-prescription for nsNSAID users in UK primary care, even among high-risk patients. Lower levels of GPA co-therapy were associated with increasing rates of GI-related hospitalization.


Access to 5-fluoroalkylated trisubstituted oxazoles via copper-catalyzed cyclization of α-fluoroalkyl-α-diazoketones with amides.
A novel copper-catalyzed cyclization of α-fluoroalkyl-α-diazoketones with (thio)amides has been developed. This mechanistically distinct protocol provides a robust and straightforward approach to construct 5-fluoroalkylated trisubstituted oxazoles and thiazoles with high efficiency and excellent functional group compatibility. Experimental studies suggest a mechanism involving imidate ligand migratory insertion of a copper carbenoid as the key step.


Level 3: comprehensive assessment and management of urinary incontinence by continence nurse specialists.
An increasing number of NPs are specializing in the management of incontinent patients. These continence nurse specialists may be involved in collaborative practice arrangements with physicians or have their own independent practices. They practice in a variety of settings from home and ambulatory care to acute and long-term institutional care. This article describes the comprehensive assessment and management of urinary incontinence that may be provided by a continence nurse specialist.


The Role of Molecular Imaging in Drug Delivery.
The parallel development of molecular imaging and drug delivery allows the combination of therapeutic agents with imaging moieties, which facilitates visualisation of the drug delivery process and provides a realtime readout on the in vivo efficacy of a therapeutic agent. Although challenging, it is feasible to construct a highly versatile, multifunctional single 'theranostic' probe for quantitative molecular imaging, targeted drug delivery and controlled drug release to obtain an effective therapeutic response. Compared with conventional methods for the evaluation of pharmacokinetics/pharmacodynamics, molecular imaging has advantages such as substantially decreasing the workload and increasing the volume of more precise data with statistical relevance. More importantly, molecular imaging techniques bridge the gap between pre-clinical and clinical research to develop candidate drugs that have the optimal target specificity, pharmacodynamics and efficacy. With the advancement and integration of technology in various fields, diverse types of targeted imaging probe coupled with drug delivery potential have been developed. Preliminary data have demonstrated that it is feasible and promising to use these targeted carriers for simultaneous target imaging and drug delivery.


Structured Reporting versus Free-Text Reporting for Appendiceal Computed Tomography in Adolescents and Young Adults: Preference Survey of 594 Referring Physicians, Surgeons, and Radiologists from 20 Hospitals.
To survey care providers' preference between structured reporting (SR) and free-text reporting (FTR) for appendiceal computed tomography (CT) in adolescents and young adults. An ethical committee approved this prospective study. The requirement for participant consent was waived. We distributed the Likert scale-based SR form delivering the likelihood of appendicitis across 20 hospitals through a large clinical trial. In the final phase of the trial, we invited 706 potential care providers to participate in an online survey. The survey questions included usefulness in patient management, communicating the likelihood of appendicitis, convenience, style and format, and overall preference. Logistic regression analysis was performed for the overall preference. Three months after the completion of the trial, we checked if the use of the SR was sustained. Responses were analyzed from 594 participants (175 attendings and 419 trainees; 225 radiologists, 207 emergency physicians, and 162 surgeons). For each question, 47.3-64.8% of the participants preferred SR, 13.1-32.7% preferred FTR, and the remaining had no preference. The overall preference varied considerably across the hospitals, but slightly across the departments or job positions. The overall preference for SR over FTR was significantly associated with attendings, SR experience for appendiceal CT, hospitals with small appendectomy volume, and hospitals enrolling more patients in the trial. Five hospitals continued using the SR in usual care after the trial. Overall, the care providers preferred SR to FTR. Further investigation into the sustained use of the SR is needed.


Quality and reliability of routine coagulation testing: can we trust that sample?
Poor standardization of preanalytic variables exerts a strong influence on the reliability of coagulation testing, consuming valuable health care resources and compromising patient outcome. Most uncertainties emerge from patient misidentification and the procedures for specimen collection and handling. Location of unsuitable venous access or problematic phlebotomies may produce spurious activation of the hemostatic system and hemolytic specimens. Prolonged venous stasis is associated with hemoconcentration and spurious variations of most coagulation assays. Additional pitfalls can be introduced by inappropriate phlebotomy tools and small-gauge needles. Inappropriate filling and mixing of the tube, unsuitable procedures for centrifugation and storage of the specimens are additional aspects that need accurate standardization. Besides traditional preanalytic variables affecting routine coagulation testing, thrombin-generation assays require specific criteria to be accurately fulfilled. These aspects include the type of specimen (platelet-poor plasma, platelet-rich plasma or whole blood), blood collection tubes, storage conditions and the presence of residual platelets. Compliance with new international quality assessment programs, which will also involve coagulation laboratories, encompasses the adoption of suitable strategies for reducing undue variability throughout the whole testing process. Such strategies would not entail extraordinary costs and are affordable with a structured outlay of existing resources, educational policies and compliance with reliable guidelines.


Rough and tough. How does silicic acid protect horsetail from fungal infection?
Horsetail (Equisetum arvense) plants grew healthily for 10 weeks under both Si-deficient and Si-replete conditions. After 10 weeks, plants grown under Si-deficient conditions succumbed to fungal infection. We have used NanoSIMS and fluorescence microscopy to investigate silica deposition in the tissues of these plants. Horsetail grown under Si-deficient conditions did not deposit identifiable amounts of silica in their tissues. Plants grown under Si-replete conditions accumulated silica throughout their tissues and especially in the epidermis of the outer side of the leaf and the furrow region of the stem where it was continuous and often, as a double layer suggestive of a barrier function. We have previously shown, both in vivo (in horsetail and thale cress) and in vitro (using an undersaturated solution of Si(OH)4), that callose is a "catalyst" of plant silica deposition. Here we support this finding by comparing the deposition of silica to that of callose and by showing that they are co-localized. We propose the existence of a synergistic mechanical protection by callose and silica against pathogens in horsetail, whereby the induction of callose synthesis and deposition is the first, biochemical line of defence and callose-induced precipitation of silica is the second, adventitious mechanical barrier.


[Physiopathology and principles of intensive care in intestinal obstructions].
The physiopathology of intestinal obstruction consists of increased intestinal peristaltis, distension by gas and fluids, contraction of the extracellular fluid volumes (plasma and interstitial sectors) and bacterial proliferation. To this must be added, in obstruction by strangulation, the passage of bacteria and bacterial products into the general circulation and the peritoneal cavity through an ischaemic or necrotic intestinal wall. Metabolic disorders consist of water, sodium and potassium deficits and acid-base disturbances. Water and electrolyte replacement should take into account the deficits that existed at the beginning of treatment, the additional losses expected during treatment and the needs for daily maintenance of water and electrolyte balance. The therapeutic procedure is simple provided it is systematized.


Bronchial carcinoid tumor metastatic to the breast.
We report a case of bronchial carcinoid that initially manifested as metastatic tumor in the breast. An exhaustive search for the primary tumor yielded the finding of a large right lung mass. Subsequent histopathologic examination of the resected lung and breast tissues confirmed the lung cancer as a primary tumor and the breast tumor as metastatic disease.


Pulmonary hemorrhage associated with systemic lupus erythematosus in children.
Four children with systemic lupus erythematosus (SLE) and pulmonary hemorrhage are discussed. Radiologists should be aware of the possibility of such bleeding when confronted with diffuse parenchymal abnormalities in a child, particularly if there is (a) evidence of unexplained blood loss or (b) signs and symptoms of collagen vascular disease. Pulmonary hemorrhage may occur long before SLE is suspected and appear identical to idiopathic pulmonary hemosiderosis.


High-Efficiency Blue Phosphorescent Organic Light-Emitting Devices with Low Efficiency Roll-Off at Ultrahigh Luminance by the Reduction of Triplet-Polaron Quenching.
High-performance phosphorescent organic light-emitting devices (PhOLEDs) at high luminance are still a remaining problem that needs to be solved, especially blue PhOLEDs. Here, 5-(5-9 H-carbazol-9-yl)pyridin-2-yl)-8-(9 H-carbazol-9-yl)-5 H-pyrido[3,2- b]indole (p2PCB2CZ) with excellent characteristics as a host is designed to realize a novel host-guest system without hole trapping effect in blue PhOLEDs. The device in which p2PCB2CZ and bis(3,5-difluoro-2-(2-pyridyl)phenyl-(2-carboxypyridyl)iridium(III) (FIrpic) is used as host and guest, respectively, is proposed to improve the performances of blue PhOLEDs at high luminance, especially at ultrahigh luminance (>30000 cd/m2). The maximum external quantum efficiency (EQE) of this type of blue PhOLEDs is 19.2%, while the maximum EQE of the reference blue PhOLEDs is 18.7%. Nevertheless, the p2PCB2CZ-based devices exhibit significant advantages at high luminance, because its EQE still attains to 10.8% even when the luminance increases to 30000 cd/m2, which is 1.67 times that of the reference device. From measurements based on steady-state and time-resolved spectroscopies, the reduction of triplet-polaron quenching in p2PCB2CZ-based devices is proved to be the main reason for improving the performances of blue PhOLEDs at high luminance.


Effect of physicochemical parameters on skin permeability of antihypertensive.
Studies were carried out to establish a correlation of skin permeability with physicochemical parameters using five antihypertensive drugs. In vitro skin permeation was carried out in vertical type diffusion cells. When steady-state fluxes of the drugs were correlated with physicochemical properties, good correlation was obtained with the reciprocal of melting point. Weak correlation was obtained with partition coefficient, molecular weight and solubility. However skin permeability versus solubility profiles revealed an interesting trend. The initial permeation rates of the poorly water soluble drugs, prazosin hydrochloride and reserpine were higher than their steady-state fluxes and moderately water soluble drug atenolol showed more or less similar permeation throughout the entire span of the study. This trend changed gradually and reversed completely in the highly water soluble drug diltiazem hydrochloride. The study suggests that drug derivatives of low melting point and good aqueous solubility could be favorable candidates for transdermal delivery.


Early Homo and the role of the genus in paleoanthropology.
The history of the discovery of early fossils attributed to the genus Homo has been contentious, with scholars disagreeing over the generic assignment of fossils proposed as members of our genus. In this manuscript I review the history of discovery and debate over early Homo and evaluate the various taxonomic hypotheses for the genus. To get a sense of how hominin taxonomy compares to taxonomic practice outside paleoanthropology, I compare the diversity of Homo to genera in other vertebrate clades. Finally, I propose a taxonomic model that hews closely to current models for hominin phylogeny and is consistent with taxonomic practice across evolutionary biology.


cis-Acting elements and trans-acting factors in the transcriptional regulation of raf kinase inhibitory protein expression.
The Raf kinase inhibitory protein (RKIP) is down-regulated in multiple types of human cancers. Decreased RKIP transcription activity may be one of the major mechanisms responsible for the downregulation of RKIP expression in human diseases. To test this hypothesis, we need to gain basic knowledge of the transcriptional regulation of RKIP. To achieve this objective, we made a systematic effort to identify cis-acting elements and trans-acting factors that control RKIP promoter activity. We found that full RKIP promoter activity requires the region -56 to +261 relative to the transcription start site. Within the full promoter region, there are two motifs rich in G/C that responded to transcription factor Sp1, one cAMP-responsive element that responded to the transcription factor CREB, and one docking site for the histone acetylase p300. In human melanoma A375 cells and human cervical cancer HeLa cells, mutation or deletion of each of these cis-acting elements decreased promoter activity. In A375 cells, knockdown of the corresponding transcription factors Sp1, CREB, or p300 decreased RKIP promoter activity, whereas overexpression of CREB and p300 increased RKIP promoter activity. The results obtained with HeLa cells also supported the idea that Sp1 and CREB play positive roles in the regulation of RKIP transcription. These findings suggest that regulators of the expression or activity of Sp1, CREB, and p300 are involved in regulating RKIP transcription.


Communication: Non-Newtonian rheology of inorganic glass-forming liquids: Universal patterns and outstanding questions.
All families of inorganic glass-forming liquids display non-Newtonian rheological behavior in the form of shear thinning at high shear rates. Experimental evidence is presented to demonstrate the existence of remarkable universality in this behavior, irrespective of chemical composition, structure, topology, and viscosity. However, contrary to intuition, in all cases the characteristic shear rates that mark the onset of shear thinning in these liquids are orders of magnitude slower than the global shear relaxation rates. Attempt is made to reconcile such differences within the framework of the cooperative structural relaxation model of glass-forming liquids.


Revisits within 48 Hours to a Thai Emergency Department.
Objective. Emergency department (ED) revisits are a common ED quality measure. This study was undertaken to ascertain the contributing factors of revisits within 48 hours to a Thai ED and to explore physician-related, illness-related, and patient-related factors behind those revisits. Methods. This study was a chart review from one tertiary care, urban Thai hospital from October 1, 2009, to September 31, 2010. We identified patients who returned to the ED within 48 hours for the same or related complaints after their initial discharge. Three physicians classified revisit as physician-related, illness-related, and patient-related factors. Results. Our study included 172 ED patients' charts. 86/172 (50%) were male and the mean age was 38 ± 5.6 (SD) years. The ED revisits contributing factors were physician-related factors [86/172 (50.0%)], illness-related factors [61/172 (35.5%)], and patient-related factor [25/172 (14.5%)], respectively. Among revisits classified as physician-related factors, 40/86 (46.5%) revisits were due to misdiagnosis and 36/86 (41.9%) were due to suboptimal management. Abdominal pain [27/86 (31.4%)] was the majority of physician-related chief complaints, followed by fever [16/86 (18.6%)] and dyspnea [15/86 (17.4%)]. Conclusion. Misdiagnosis and suboptimal management contributed to half of the 48-hour repeat ED visits in this Thai hospital.


Clinical management of multiple sclerosis: the treatment paradigm and issues of patient management.
To summarize the conclusions of an expert panel of neurologists specializing in multiple sclerosis (MS) convened for the purpose of creating a treatment algorithm with regard to the clinical management of MS. The panel was sponsored by the Health Science Center for Continuing Medical Education and the University of Medicine and Dentistry of New Jersey and supported by an educational grant from Biogen Idec, Inc. MS is a chronic demyelinating disease characterized by a variable clinical course. Currently, there is no cure for MS, and the management of MS requires lifelong treatment with disease-modifying agents. Some patients respond well to therapy for many years, whereas others may have aggressive disease that is more difficult to manage. Hence, given the variable nature in the course of MS and patients. response to treatment, neurologists must individualize care for their patients. An MS treatment algorithm was recently developed by a panel of neurologists who are MS experts to provide community neurologists with best-practice protocols for treating and managing their MS patients. The panel of experts categorized MS into 3 different stages, with patients transitioning between the stages based on their response to therapy and disease progression. Stage I represents MS early in the progression of the disease, during which platform drug therapy is recommended (i.e., interferon beta-1b [IFNbeta-1b], IFNbeta-1a, or glatiramer acetate). The results of randomized, controlled clinical trials suggest that IFNbeta is the optimal choice for platform therapy. Despite treatment with platform therapy, it is common for patients to experience some ongoing symptoms and periodic exacerbations of the disease (annual relapse rate of 0.59 to 0.84 on treatment); such relapses should not be considered treatment failures and are best managed with steroids. Stage II represents acute breakthrough disease (i.e., when the clinical activity becomes more frequent or severe). This stage is best managed by the addition of pulse corticosteroids to the platform drug. Stage III represents continued breakthrough disease and is best managed by the addition of immunosuppressants to the platform drug. The MS treatment algorithm provides an educational resource for physicians. It should assist all health care professionals involved in the management of MS patients and enhance their ability to improve quality of life for these patients over the course of the disease.


Evaluation of the influence of peritoneal dialysis on cellular immunity by the E-rosette inhibition test.
Sera of patients on peritoneal dialysis and regular hemodialysis were analyzed over a follow-up period of 8 months for the capacity of normal lymphocytes to inhibit E-rosette formation. The percentage of inhibition in sera from peritoneal dialysis patients was significantly reduced (p less than 0.02) only 1 month after treatment was started, whereas in hemodialysis patients the percentage of inhibition remained unchanged. No difference was observed between sera collected before and after the hemodialysis sessions. There was no significant positive correlation between the percentage of E-rosette inhibition and p-urea, p-creatinine, s-albumin, and s-proteins, respectively. Statistical analysis of the E-rosette inhibition test by uremic serum and spontaneous E-rosettes in these patients showed a significant regression coefficient (p less than 0.01) in both groups. The fact that, unlike ultrafiltrate from hemodialysis, peritoneal dialysate significantly (p less than 0.05) inhibits the E-rosette formation capacity of normal lymphocytes, confirms these findings, suggesting an inhibitory activity of serum factors on lymphocyte function.


Depletion of cardiac noradrenaline stores by the calcium-channel blocker D-600.
The actions of the calcium-channel blocker D-600 on cardiac noradrenaline stores were investigated by giving rats the drug systemically and then using a high-performance liquid chromatograph equipped with an electrochemical detector to determine the noradrenaline content of their hearts. A single 5-mg/kg dose of D-600 caused a significant depletion of noradrenaline content of the ventricles (approximately 31%) but not of the auricles. However, when multiple doses of D-600 were given at 12-h intervals, the depletion of cardiac noradrenaline content was more marked and both the auricular and ventricular contents were significantly decreased. Depletion of noradrenaline content was maximal 4 h after administration of D-600. A partial recovery of noradrenaline content occurred 16 h after administration of D-600, indicating that this effect of D-600 is reversible. In in vitro studies, D-600 (10(-7) to 10(-3) M) evoked a dose-related increase in the basal outflow of tritium from the rat isolated atria preloaded with [3H]noradrenaline ([3H]NA), indicating that depletion of cardiac noradrenaline stores by D-600 may be due to a direct action on sympathetic nerves rather than to increased reflex sympathetic activity secondary to profound vasodilation caused by the drug. The metabolic profile of tissue 3H content and of D-600-evoked 3H overflow was also examined. Whereas greater than 90% of tissue 3H content consisted of unchanged [3H]NA, 60-70% of the D-600-evoked overflow consisted of [3,4-3H]dihydroxyphenylglycol, and approximately 5% was unchanged NA, thus indicating that D-600 causes release of [3H]NA intraneuronally.(ABSTRACT TRUNCATED AT 250 WORDS)


Terahertz time-domain spectroscopy and quantitative analysis of metal gluconates.
A series of metal gluconates (Na(+), K(+), Mg(2+), Ca(2+), Fe(2+), Cu(2+), and Zn(2+)) were investigated by terahertz (THz) time-domain spectroscopy. The absorption coefficients and refractive indices of the samples were obtained in the frequency range of 0.5-2.6 THz. The gluconates showed distinct THz characteristic fingerprints, and the dissimilarities reflect their different structures, hydrogen-bond networks, and molecular interactions. In addition, some common features were observed among these gluconates, and the similarities probably come from the similar carbohydrate anion group. The X-ray powder diffraction measurements of these metal gluconates were performed, and the copper(II) gluconate was found to be amorphous, corresponding to the monotonic increase feature in the THz absorption spectrum. The results suggest that THz spectroscopy is sensitive to molecular structure and physical form. Binary and ternary mixtures of different gluconates were quantitatively analyzed based on the Beer-Lambert law. A chemical map of a tablet containing calcium D-gluconate monohydrate and α-lactose in the polyethylene host was obtained by THz imaging. The study shows that THz technology is a useful tool in pharmaceutical research and quality control applications.


Visible infrared spin-scan radiometer atmospheric sounder radiometric calibration: an inflight evaluation from intercomparisons with HIRS and radiosonde measurements.
The Visible IR spin-scan radiometer Atmospheric Sounder (VAS) is the first sounding instrument placed in geostationary orbit. The calibration procedure for determining VAS radiances requires modeling the contributions of the telescope foreoptics components to the background radiation. A simple relation between target radiance and detector output voltage is derived. The calibration procedure is successfully tested by comparisons with HIRS and radiosonde data. After removing a negative offset of up to 3 degrees C in three of the upper atmospheric CO(2) bands of VAS, the capability to produce accurate soundings (within 2 degrees C of radiosonde) was demonstrated.


Empowering Staff Nurses With Essential Skills: Training Strategies for Success.
Nurse leaders in the mental health field are challenged to ensure the mental health environment is safe and therapeutic. They must also continually evaluate whether nurses are effectively engaging therapeutically with patients in their care. Undergraduate nursing students and practicing nurses usually receive little or no training in facilitating nurse-led groups. Nurses who are trained and capable of facilitating groups may enhance therapeutic relationships and engage patients to improve treatment outcomes. Training staff and disseminating educational materials in an efficient manner are often challenges for nurse leaders. The Veterans Health Administration (VHA) Office of Nursing Services (ONS) Mental Health Field Advisory Committee (MH-FAC) developed a nursing guide for conducting psychoeducation groups. This was followed up with a complementary live virtual training with "on-demand" features that included discussion and demonstration of nurse-led group implementation strategies. Both products were disseminated to nurse leaders throughout the VHA ONS Web site. Responses to both the guide and video were overwhelmingly positive. This article discusses the importance of nurse-led psychoeducational groups and describes a project implemented by the ONS MH-FAC, which helped provide an essential training to more than 1100 RNs within the Veterans Affairs Health System nationally.


Robot-assisted Therapy in Stroke Rehabilitation.
Research into rehabilitation robotics has grown rapidly and the number of therapeutic rehabilitation robots has expanded dramatically during the last two decades. Robotic rehabilitation therapy can deliver high-dosage and high-intensity training, making it useful for patients with motor disorders caused by stroke or spinal cord disease. Robotic devices used for motor rehabilitation include end-effector and exoskeleton types; herein, we review the clinical use of both types. One application of robot-assisted therapy is improvement of gait function in patients with stroke. Both end-effector and the exoskeleton devices have proven to be effective complements to conventional physiotherapy in patients with subacute stroke, but there is no clear evidence that robotic gait training is superior to conventional physiotherapy in patients with chronic stroke or when delivered alone. In another application, upper limb motor function training in patients recovering from stroke, robot-assisted therapy was comparable or superior to conventional therapy in patients with subacute stroke. With end-effector devices, the intensity of therapy was the most important determinant of upper limb motor recovery. However, there is insufficient evidence for the use of exoskeleton devices for upper limb motor function in patients with stroke. For rehabilitation of hand motor function, either end-effector and exoskeleton devices showed similar or additive effects relative to conventional therapy in patients with chronic stroke. The present evidence supports the use of robot-assisted therapy for improving motor function in stroke patients as an additional therapeutic intervention in combination with the conventional rehabilitation therapies. Nevertheless, there will be substantial opportunities for technical development in near future.


Serological levels of zinc, copper and iron elements among Giardia lamblia infected children in Turkey.
Giardiasis, an intestinal protozoan infection caused by Giardia lamblia, is common in Turkey, especially among children aged between 2- and 14-years-old. Effects of giardiasis on serological levels of zinc, copper and iron elements were assessed in this study. A total of 45 children, aged between 2- and 14-years-old, who were admitted to the Pediatrics Department of Celal Bayar University Medical School with gastrointestinal complaints and diagnosed as having giardiasis by stool examinations in the Parasitology Department, were enrolled as the study group (SG). The control group (CG) consisted of 45 age-matched healthy children. Serological levels of zinc, copper and iron were measured by atomic absorption spectrophotometer in all samples. As a result of the study, serum zinc levels were 67.43 +/- 17.72 microg/dL and 145.20 +/- 9.13 microg/dL, copper levels were 198.45 +/- 39.14 microg/dL and 150 +/- 21.14 microg/dL and iron levels were 87.98 +/- 18.31 microg/dL and 160.45 +/- 45.40 microg/dL, in SG and CG, respectively. When compared separately as SG and CG, there was a statistically significant difference between the serological levels of all these elements. These results revealed that giardiasis increased the serological levels of copper, like other infectious agents. However, zinc and iron levels decreased during giardiasis due to malabsorption.


[Gait analysis after anterior cruciate ligament reconstruction with different methods].
To examine and compare the gait patterns of subjects with hamstring and patellar tendon graft reconstructions of anterior cruciate ligament (ACL). Three groups were compared: 19 patellar tendon anterior cruciate ligament reconstruction patients (a mean of 11.8 weeks after injury), 19 hamstring tendon anterior cruciate ligament reconstruction patients (a mean of 10.4 weeks after injury) and 19 matched controls. Gait analysis was performed using the DorealSoft DVMC-8801 three-dimensional motion capture system. Kinematic data were recorded for the lower limb prior to and 3, 6, 9 and 12 months after ACL reconstructive surgery. Each subject was asked to walk on a motorized treadmill with different slopes and perform-after 6 minutes of familiarization time- at least 2 minutes of walking at a constant speed of 1.9 km/h. All the ACL-deficient patients exhibited a quadriceps avoidance pattern prior to and 3 months post-operation. In the operated individuals, the spatial-temporal parameters and the knee angle had already regained a normal pattern for the ACL-deficient limb during gait at 6 months post-operation. However, the angular acceleration showed no significant statistical difference with the values of healthy control group at just 9 months post-operation. The flexion angular acceleration at 15 degrees treadmill was significantly smaller than that in the hamstring tendon group and the extension angular acceleration was significantly smaller than that in the patellar tendon group at 6 months post-operation. ACL surgical repair significantly alters the lower-extremity gait patterns and the establishment of pre-injury gait patterns takes at least 9 months to occur. The graft-specific differences in knee biomechanics after anterior cruciate ligament reconstruction appear to be related with the donor site.


[Retrospect and prospect of pollution ecology].
Since 1970s, pollution ecology has gone through several historical stages including the natal, growing and developing and expanding stage with the rise in environmental sciences and the development of applied ecology. The theoretical system and researching methods with special characteristic of the subject has taken shape. So far pollution ecology has become an independent discipline to probe into interactions between biological systems and polluted environment and to control and remedy polluted environment using ecological principles, is an important component part of applied ecology and derives from amalgamation and intersection between ecology is faced with challenges and opportunities. A breakthrough and good progresses will be made in its branches and frontal fields such as ecology of combined pollution, contaminant ecotoxicology, ecological processes of pollutants and ecological remediation of contaminated environment.


Entry of extracellular calcium mediates dopamine D1-stimulated growth hormone release from goldfish pituitary cells.
Unlike mammals, the goldfish is unique in having dopamine (DA) D1 receptors in the anterior pituitary. In this species, DA stimulates growth hormone (GH) release via D1 receptors coupled to the cAMP-dependent pathway. To further examine the postreceptor mechanisms of this novel pituitary DA D1 system, the role of extracellular Ca2+ ([Ca2+]e] in mediating DA D1-stimulated GH release was studied using dispersed goldfish pituitary cells. The GH responses to DA (1 nM-10 microM), the D1 agonist SKF38393 (1 microM), and the Ca2+ ionophore A23187 (10 microM) were abolished by incubation with Ca(2+)-deficient medium. Incubation with depolarizing doses of KCl (10-25 mM), which activate voltage-sensitive Ca2+ channels (VSCC), induced GH release in a dose-dependent manner. In contrast, the VSCC blockers nifedipine (10 microM), nicardipine (10 microM), and verapamil (10 microM) and the inorganic competitor of Ca2+ entry CoCl2 (5 mM) blocked the GH responses to DA (1 microM) as well as SKF38393 (1 microM). These results strongly indicate that the entry of [Ca2+]e via VSCC is an essential part of the signal transduction mechanisms mediating DA D1-stimulated GH release in the goldfish. In this study, the possible interactions between the Ca(2+)- and cAMP-dependent pathways in DA-induced GH secretion were also investigated. The membrane-permeant cAMP analogue 8Br.cAMP (1 mM) and the adenylate cyclase activator forskolin (10 microM) stimulated GH release from goldfish pituitary cells. These GH responses were suppressed by incubation with Ca(2+)-deficient medium or with the VSCC blocker nifedipine (10 microM). Furthermore, the GH responses to forskolin (10 microM) and the nonselective DA agonist apomorphine (1 microM) were not additive to that of the Ca2+ ionophore A23187 (10 microM). These results suggest that [Ca2+]e entry induced by DA D1 stimulation occur at steps after activation of the cAMP-dependent pathway.


Relationship of limited joint mobility and foot deformities with neurological examination in patients with diabetes.
The aim is to define the association of forefoot deformity and limited joint mobility in the ankle and hallux joints in patients with diabetes mellitus subject to different diagnostic tests for diabetic neuropathy. Prospective study with 118 type 2 diabetic patients (68 men, mean age of 65.6±9.9 years) enrolled consecutively from the Diabetic Foot Unit of the Complutense University of Madrid subject to evaluation of plantar surface sensitivity by 10-g Semmes-Weinstein Monofilament, vibratory threshold by biothesiometer, and sudomotor dysfunction by Neuropad®. The patients presented with limited joint mobility of the ankle and the first metatarsophalangeal joints, and forefoot deformities were registered. Statistical analysis was done through a univariate model to test the association between neurological and biomechanical alteration. There was an association of abnormal Monofilament (p=0.01; OR=3.9) and biothesiometer tests (p=0.01; OR=2.6) with the presence of forefoot deformity. Furthermore, a relation was found between abnormal Monofilament (p=0.02; OR=4.8) and biothesiometer (p<0.00; OR=12.8) tests with limited mobility of the first metatarsophalangeal joint both in loading and off-loading. Abnormal sudomotor function test was related with limited joint mobility of the ankle joint with the knee flexed (p=0.04; OR=2.8). The results of this study show discordance between biomechanical abnormalities and neuropathy depending on the diagnostic test used. Tests that assess large myelinated nerve fibers are associated with the presence of deformities. Abnormal sudomotor function test is associated with limited joint mobility and this test has a greater capacity for selecting patients at risk.


[The capture-recapture applied to epidemiology: principles, limits and application].
By matching several sources of information coming from the same population, the capture-recapture method allows, if matches between sources can be identified, to estimate the number of cases not identified by any of the sources, the total number (N) of cases in the population and the sensitivity of each source. Used first in zoology and demography, this technique has been increasingly applied to epidemiology in the last two decades. However, six conditions need to be satisfied: all cases identified by each source are true cases; occurred during the time and the geographical area studied; the study population is closed; all matches are true matches; sources are independent and there is no heterogeneous catchability within sources. It is possible to assess and take into account dependence between sources when 3 or more sources are used, in particular by log linear modelling. However interactions of maximal order cannot be adjusted for. In case of a biased estimation because of the non respect of the conditions, it is recommended to apply a method of correction. The complete application of the methods is illustrated in the study of estimating the number of Salmonella infectious foodborne outbreak. As capture-recapture studies often use data collected for other purposes, this technique should be regarded as exploratory or be used to validate an estimate of a number of cases obtained by another method. It should not replace population sampling methods only because of its low cost. Otherwise it is a very informative approach to evaluate the sensitivity and representativeness of surveillance systems and registries.


Intestinal helminths and schistosomiasis among school children in a rural district in Kenya.
To determine the extent of intestinal schistosomiasis, ascariasis, trichuriasis and hookworm infections among school children of Usigu and Bondo divisions of Bondo District. A cross sectional study. Fifty out of 130 primary schools in Usigu and Bondo divisions, Bondo District. Randomly selected school children (n= 3158) aged five to 20 years, were examined for intestinal helminths and schistosomiasis using Kato thick smear technique. The overall prevalence and geometric mean egg counts per gram/faeces for Schistosoma mansoni were 31.6% and 3.1; hookworm 36.8% and 4.1; Trichuris trichiura 21.8% and 1.5, and Ascaris lumbricoides 16.5% and 2.5. More girls (34.9%) than boys (28.6%) were infected with S. mansoni whereas more boys (39.0%) than girls (34.5%) were infected with hookworm. The prevalence of S. mansoni and hookworm infections increased with age but Ascaris and Trichuris infections decreased with age without any sex differences. Children under ten years of age tended to be more heavily infected with ascariasis, trichuriasis and hookworm than the older ones, while the intensity of S. mansoni increased gradually with age. There were positive relationships between different infections except for a significant negative correlation between Schistosoma mansoni and hookworm infections. Only four cases out of 789 had S. haematobium infection. CONCLUSION. Schistosoma mansoni and geohelminths were endemic in Bondo District, where two thirds of the school children suffered from these parasites. Polyparasitism was also common. There was a little overlap in the distribution of Schistosoma mansoni and hookworm, whereas ascariasis and trichuriasis were fairly distributed in the district.


[Low vision in Madagascar and education in ethics].
In this contribution, we analyze four clinical cases relating to low vision in Madagascar while insisting on the raised ethical questions. We identify several factors worsening the disabilities, including the low vision, by showing the importance of the environment in this field. In Madagascar, like elsewhere, laws and rules are dedicated to the alleviation of the difficulties lived by persons with disabilities, but the gap is huge between the intentions displayed by the public authorities and the measures taken concretely on the ground. A change of perception is necessary with regard to people with low vision while insisting on the value of solidarity. An education in ethics could contribute to such a change. Although concentrated on the Malagasy situation and the low vision, our analysis is applicable to other contexts and other disabilities.


Burkitt's Lymphoma.
Endemic Burkitt's lymphoma (BL) remains the most prevalent pediatric cancer in sub-Saharan Africa even though it was the first human cancer with a viral etiology described over 50 years ago. Epstein-Barr virus (EBV) was discovered in a BL tumor in 1964 and has since been implicated in other malignancies. The etiology of endemic BL has been linked to EBV and Plasmodium falciparum malaria co-infection. While epidemiologic studies have yielded insight into EBV infection and the etiology of endemic BL, the modulation of viral persistence in children by malaria and deficits in EBV immunosurveillance has more recently been reified. Renewed efforts to design prophylactic and therapeutic EBV vaccines provide hope of preventing EBV-associated BL as well as increasing the ability to cure this cancer.


[Femoral Derotation in Children with Cerebral Palsy - Does the Result Depend on the Age at Operation and the Kind of Surgery?].
Patients with spastic cerebral palsy GMFCS I-III often develop gait dysfunctions. One of the most prevalent gait dysfunctions is the intoeing gait. Femoral derotation osteotomy is the common treatment for internal rotation gait in cerebral palsy. We now present 3D-gait analysis data of the hip rotation in gait before and after femoral derotation osteotomy. We analysed the influence of the age at the index operation on the risk of recurrence and the surgical technique. We included 48 patients treated with femoral derotation osteotomy during a single event of multi-level surgery. Mean hip rotation in standing was measured before and after femoral derotation osteotomy (FDO). The patients were divided into two groups of different age and in a second analysis into two groups with the osteotomy in different locations, either inter-trochanteric (DO proximal) or supracondylar (DO distal). Age at FDO and surgical technique had no influence on the results. However, the variance of the results was very high. Differences were found in the walking speed between the DO proximal and DO distal groups. The walking speed in the group of distal femoral osteotomy was higher. This difference was not significant, but there was a trend to proximal osteotomy in slower walkers. Significant improvements in IRG after FDO were found in our investigation. Our results indicate that FDO as a part of single-event multilevel surgery SEMLS provides a satisfactory mean overall correction of IRG. The results were independent of the age at the index operation and the location of the osteotomy.


Changing nursing practice: Implementation challenges of intentional rounding on three rehabilitation units.
The purpose of this article is to critically examine the process and results of a participatory action study designed to implement intentional rounding on a rehabilitation inpatient service. As a change initiative, this brief case study highlights the successes and challenges of implementing a practice intervention. Intentional rounding is a nursing intervention whereby hourly contact and support is provided to patients and families to strengthen the therapeutic relationship and proactively address their needs. Three units implemented rounding, and pre- and post-data were collected on four indicators: patient falls, call bell frequencies, satisfaction with care, and the nurses' practice environment. The results demonstrated small, positive changes in all indicators, but the level of rounding was lower than expected. Focus groups revealed the complexities of integrating rounding into established routines. Three factors were identified that contributed to the findings.


Hybrid laser diode with ultrawide wavelength-tunable range using curved directional couplers.
Wavelength-tunable laser diode with a wide tuning range is required for optical communication systems and optical sensing. External cavity laser diodes with silicon-photonic wire waveguides and ring resonators have small footprint because of high refractive index contrast between Si. However, power coupling efficiency κ of conventional straight directional coupler between ring and bus waveguides have large wavelength dependence, which lowers tunable range. In this study, we demonstrate a hybrid wavelength-tunable laser diode using curved directional couplers, whose wavelength dependence on κ is low. The wavelength-tunable range record of 120.9 nm has been achieved. In addition, curved directional couplers are tolerant of waveguide width fabrication error.


Impact on the nutritional attributes of rice bran following various stabilization procedures.
Rice bran, a valuable byproduct of the rice milling process, has limitations in food industrial applications due to its instability during storage. This review summaries the methodology for stabilization and its impact on the nutritional properties of rice bran. A variety of treatments have been used and these include heat treatment, low-temperature storage, biological and chemical approaches and these will be discussed in terms of their ability to destroy/inhibit enzyme activity and improve storage performance of rice bran. More importantly, changes in the nutritional value of rice bran in terms of vitamins, polyphenols, tocopherols, flavonoids, free fatty acids caused by stabilization of rice bran will also be discussed. This review highlights the importance of appropriate design of processes for stabilization and controlling storage conditions to ensure quality of the rice bran and enhancing levels of phytochemicals in the bran for novel applications in functional foods.


Changes in bioactive components related to the harvest time from the spicas of Prunella vulgaris.
Prunella vulgaris L. (Labiatae) is a perennial plant common in China and Europe and is rich in rosmarinic acid (RA), ursolic acid (UA), and oleanolic acid (OA). The dried spica of P. vulgaris has been used as traditional medicine in China for over a hundred years. To our best knowledge, no study has been conducted to determine the influence of harvesting time on concentrations of bioactive compounds of P. vulgaris. In the current study, changes in the bioactive compounds present in spicas were investigated at five harvest times over 2 months. Plant material were collected at five fixed dates: 5th May, 20th May, 7th June, 15th June, and 25th June and assayed for chemical contents by high-performance liquid chromatography (HPLC). Among the different harvest times, the highest levels of RA (56.81 mg·g⁻¹), UA (2.77 mg·g⁻¹), and OA (0.91 mg·g⁻¹) were found on 5th May, whereas the lowest levels of RA (1.66 mg·g⁻¹), UA (2.27 mg·g⁻¹), and OA (0.43 mg·g⁻¹) were observed on 25th June. As each medicinal product has its own content requirement for different bioactive components, the optimum harvest time might be determined according to the accumulation dynamics of target compound in dried spicas of P. vulgaris. These results may be useful for determining the optimal harvest time when bioactive components are at the maximum level, which is in early May.


Magnetic reasonance imaging of the surgically repaired meniscus: a 13-year follow-up study of 13 knees.
This study was initiated to evaluate the long-term outcome of meniscal sutures and to correlate clinical findings with MRI findings. We were interested to see if a clinically healed meniscus also showed as such on MRI and if degenerative changes were present We studied prospectively 13 patients (7 men) aged between 29 and 50 years, who had undergone closed meniscus repair between 1985 and 1988 using an inside-out technique, clinically and with MRI, with a mean follow-up time of 13 years. Meniscal suture gave good clinical long-term results: all patients got a Hospital for Special Surgery score of more than 75%. In all patients the site of the previous suture was still visible on MRI, mainly from small metal artefacts in the meniscus. 4 of 7 patients with an unrepaired ACL lesion had signs of arthrosis and cartilage degeneration. MRI showed signs of mucoid degeneration or scar tissue in 6/13 of the patients. We believe that asymptomatic meniscal tears produce abnormal MR signals even though they have stable unions, and that MR signals at the site of repair represent edematous scar tissue, not true nonunions.


Update on the assessment of magnesium status.
Magnesium (Mg) is the fourth most abundant mineral in the body and the most abundant intracellular divalent cation, with essential roles in many physiological functions. Consequently, the assessment of Mg status is important for the study of diseases associated with chronic deficiency. In spite of intense research activities there is still no simple, rapid, and accurate laboratory test to determine total body Mg status in humans. However, serum Mg < 0.75 mmol/l is a useful measurement for severe deficiency, and for values between 0.75 and 0.85 mmol/l a loading test can identify deficient subjects. The loading test seems to be the gold standard for Mg status, but is unsuitable in patients with disturbed kidney and intestinal functions when administered orally. There is also a need to reach a consensus on a standardized protocol in order to compare results obtained in different clinical units. Other cellular Mg measurements, such as total or ionized Mg, frequently disagree and more research and systematic evaluations are needed. Muscle Mg appears to be a good marker, but biopsies limit its usefulness, as is the case with bone Mg, the most important but heterogeneous Mg compartment. The development of new and non invasive techniques such as nuclear magnetic resonance (NMR) may provide valuable tools for routinely analysing ionized Mg in tissues. With the development of molecular genetics techniques, the recent discovery of Transient Receptor Potential Melastatin channels offers new possibilities for the sensitive and rapid evaluation of Mg status in humans.


Development and Implementation of an HTS-Compatible Assay for the Discovery of Selective Small-Molecule Ligands for Pre-microRNAs.
microRNAs (miRNAs) are small gene regulatory RNAs, and their expression has been found to be dysregulated in a number of human diseases. To facilitate the discovery of small molecules capable of selectively modulating the activity of a specific miRNA, we have utilized new high-throughput screening technology targeting Dicer-mediated pre-miRNA maturation. Pilot screening of ~50,000 small molecules and ~33,000 natural product extract libraries against pre-miR-21 processing indicated the potential of our assay for this goal, yielding a campaign Z' factor of 0.52 and an average plate signal-to-background (S/B) ratio of 13. Using two-dimensional screening against a second pre-miRNA, pre-let-7d, we evaluated the selectivity of confirmed hits. The results presented demonstrate how high-throughput screening can be used to identify selective small molecules for a target RNA.


Spodoptera littoralis oral secretions inhibit the activity of Phaseolus lunatus plasma membrane H+-ATPase.
Biotic stresses induced by herbivores result in diverse physiological changes in plants. In the interaction between the Lima bean (Phaseolus lunatus) and the herbivore Spodoptera littoralis, the earliest event induced by feeding on leaves is the depolarization of the plasma membrane potential (Vm), which is the results of both mechanical damage and insect oral secretions (OS). Although this herbivore-induced Vm depolarization depends on a calcium-dependent opening of potassium channels, the attacked leaf remains depolarized for an extended period, which cannot be explained by the sole action of potassium channels. Here we show that the plasma membrane H+-ATPase of P. lunatus leaves is strongly inhibited by S. littoralis OS. Inhibition of the H+-ATPase was also found in plasma membranes purified from leaf sections located distally from the application zone of OS, thus suggesting a long-distance transport of a signaling molecule(s). S. littoralis' OS did not influence the amount of the plasma membrane H+-ATPase, whereas the levels of membrane-bound 14-3-3 proteins were significantly decreased in membranes purified from treated leaves. Furthermore, OS strongly reduced the in vitro interaction between P. lunatus H+-ATPase and 14-3-3 proteins. The results of this work demonstrate that inhibition of the plasma membrane H+-ATPase is a key component of the S. littoralis OS mechanism leading to an enduring Vm depolarization in P. lunatus wounded leaves.


Postoperative complications in gastrointestinal surgery: A "hidden" basic quality indicator.
Postoperative complications represent a basic quality indicator for measuring outcomes at surgical units. At present, however, they are not systematically measured in all surgical procedures. A more accurate assessment of their impact could help to evaluate the real morbidity associated with different surgical interventions, establish measures for improvement, increase efficiency and identify benchmarking services. The Clavien-Dindo Classification is the most widely used system worldwide for assessing postoperative complications. However, the postoperative period is summarized by the most serious complication without taking into account others of lesser magnitude. Recently, two new scoring systems have emerged, the Comprehensive Complication Index and the Complication Severity Score, which include all postoperative complications and quantify them from 0 (no complications) to 100 (patient's death), These allow the comparison of results. It is important to train surgical staff to report and classify complications and to record 90-d morbidity rates in all patients. Comparisons with other services must take into account patient comorbidities and the complexity of the particular surgical procedure. To avoid subjectivity and bias, external audits are necessary. In addition, ensuring transparency in the reporting of the results is an urgent obligation.


6,7,8,9-Tetrahydro-N,N-di-n-propyl-3H-benzindol-8-amines. Derivatives as potent and orally active serotonin 5-HT1A receptor agonists.
Derivatives and isosteric derivatives of the potent 5-HT1A agonist 8-(di-n-propylamino)-6,7,8,9- tetrahydro-3H-benz[e]indole-1-carbaldehyde (5) were prepared and evaluated in vivo and in vitro for serotonergic and dopaminergic activity. The 1-cyano analog 8 was found to be almost equipotent to 5 and the previously described 2-cyano derivative 6, while a 1-chloro and 1-(1,1,1-trifluoroethyl) substituent (9 and 10, respectively) formed less potent derivatives. The isosteric 6,7,8,9-tetrahydro-1H-benz[g]indoles 4 and 12-15 showed surprisingly low affinity or activity at both serotonergic and dopaminergic systems. The interpretations of these results by means of drug-receptor interactions at the 5-HT1A subtype are discussed. Compounds 6 and 8 were found to have high oral bioavailability in the rat (63% and 54%, respectively).


[Effect of concentration of chlorhexidine on bonding durability of dentine and resin].
To evaluate the effect of concentration of chlorhexidine on bonding durability of dentine and resin. Forty extracted third molars were randomly allocated into five groups, which include one control group and four test groups. Teeth dentin surfaces in each group were treated with one of the following solution, 1.5 microl water (control), 0.02%, 0.2%, 2% and 20% chlorhexidine. Single Bond 2 adhesive was applied to the dentin surface according to manufacturer's recommendations. Then 5 mm thickness of composite (Z250) was built up on the dentin of each molar. The teeth were sectioned into microtensile samples and subdivided into two subgroups, 16 samples each. Samples in subgroup II and I were tested after being stored in distilled water for 24 h and 6 month respectively. Each fractured sample was examined with SEM. No significant differences of 24 h bonding strength were found among the five groups. There were significant difference in bonding strength between 0.2%, 2% chlorhexidine groups [(24.68 ± 5.26) and (23.19 ± 5.26) MPa] and the control group [(19.10 ± 4.67) MPa] after 6 month (P = 0.007,0.045), and significant differences were also found between 0.2%, 2% and 0.02% chlorhexidine group [(19.01 ± 6.87) MPa, P = 0.006, 0.041). Most of the fractured modes were mixed or interface failures after 24 h of water storage, and the mixed failure increased after six month of water storage. In the 0.2%, 2% and 20% chlorhexidine treated group, most of the failure was found at the top of hybrid layer, while in the 0.02% group, it was found in the base part of hybrid layer. Chlorhexidine could increase the bonding durability of resin and dentine. Higher than 0.2%, concentration of chlorhexidine couldn't improve bonding durability.


Rate dependent influence of arterial desaturation on self-selected exercise intensity during cycling.
The purpose of this study was to clarify if Ratings of Perceived Exertion (RPE) and self-selected exercise intensity are sensitive not only to alterations in the absolute level of arterial saturation (SPO2) but also the rate of change in SPO2. Twelve healthy participants (31.6 ± 3.9 y, 175.5 ± 7.7 cm, 73.3 ± 10.3 kg, 51 ± 7 mL·kg-1·min-1 [Formula: see text]) exercised four times on a cycle ergometer, freely adjusting power output (PO) to maintain RPE at 5 on Borg's 10-point scale with no external feedback to indicate their exercise intensity. The fraction of inspired oxygen (FIO2) was reduced during three of those trials such that SPO2 decreased during exercise from starting values (>98%) to 70%. These trials were differentiated by the time over which the desaturation occurred: 3.9 ± 1.4 min, -8.7 ± 4.2%•min-1 (FAST), 11.0 ± 3.7 min, -2.8 ± 1.3%•min-1 (MED), and 19.5 ± 5.8 min, -1.5 ± 0.8%•min-1 (SLOW) (P < 0.001). Compared to stable PO throughout the control condition (no SPO2 manipulation), PO significantly decreased across the experimental conditions (FAST = 2.8 ± 2.1 W•% SPO2-1; MED = 2.5 ± 1.8 W•% SPO2-1; SLOW = 1.8 ± 1.6 W•% SPO2-1; P < 0.001). The rates of decline in PO during FAST and MED were similar, with both greater than SLOW. Our results confirm that decreases in absolute SPO2 impair exercise performance and that a faster rate of oxygen desaturation magnifies that impairment.


Reciprocal Interference Between Audition and Touch in the Perception of Duration.
Audition and touch interact with one another and share a number of similarities; however, little is known about their interplay in the perception of temporal duration. The present study intended to investigate whether the temporal duration of an irrelevant auditory or tactile stimulus could modulate the perceived duration of a target stimulus presented in the other modality (i.e., tactile or auditory) adopting both a between-participants (Experiment 1) and a within-participants (Experiment 2) experimental design. In a two-alternative forced-choice task, participants decided which of two events in a target modality was longer. The simultaneously distractor stimuli were presented with a duration that was either congruent or incongruent to the target's. Results showed that both the auditory and tactile modalities affected duration judgments in the incongruent condition, decreasing performance in both experiments. Moreover, in Experiment 1, the tactile modality enhanced the perception of auditory stimuli in the congruent condition, but audition did not facilitate performance for the congruent condition in the tactile modality; this tactile enhancement of audition was not found in Experiment 2. To the best of our knowledge, this is the first study documenting audiotactile interactions in the perception of duration, and suggests that audition and touch might modulate one another in a more balanced manner, in contrast to audiovisual pairings. The findings support previous evidence as to the shared links and reciprocal influences when audition and touch interact with one another.


Elevated levels of antibodies against phosphatidylserine/prothrombin complex and/or cardiolipin associated with infection and recurrent purpura in a child: a forme fruste of antiphospholipid syndrome?
Antiphospholipid syndrome is an autoimmune disorder characterized by the occurrence of venous and arterial thrombosis, as well as morbidity in pregnancy, in the presence of anti-phospholipid antibodies. The diagnosis of antiphospholipid syndrome is usually established based on clinical and laboratory findings by strictly following the 2006 Sapporo classification. However, the diagnosis remains challenging owing to the ongoing debates on the serological criteria. We report a case we describe as forme fruste antiphospholipid syndrome in which these criteria were not fulfilled. Purpura appeared repeatedly in a female infant starting from the age of 6 months and following episodes of upper respiratory infections and vaccinations. The levels of anti-cardiolipin IgG antibodies and anti-phosphatidylserine/prothrombin complex antibodies were elevated in accordance with these events. Histopathological evaluation revealed multiple small vessel thrombi in the dermis and adipose tissue. After 2 weeks of treatment with aspirin and heparin, the cutaneous symptoms subsided. Infection has long been associated with antiphospholipid syndrome, and anti-phosphatidylserine/prothrombin antibodies are considered a new marker for the diagnosis of antiphospholipid syndrome. Forme fruste antiphospholipid syndrome should be considered even if the antiphospholipid syndrome diagnostic criteria are not completely fulfilled, especially in the presence of elevated levels of anti-phosphatidylserine/prothrombin antibodies and known preceding infections.


[Family centered evaluation of treatment outcome in schizophrenia: Marmara Family Interview for the Assesment of Psychiatric Treatment].
Assessment of psychiatric treatment has been a central issue in psychiatric research. Most assessment tools are based on the patient's account and mainly focus on clinical agendas. Assessment tools, which gather the perspective of attached daily needs are limited. The purpose of our study was to evaluate the inter-rater reliability and internal consistency of the Marmara Family Interview for the Assessment of Psychiatric Treatment (MFIPT) in a clinical sample. The study also aimed to explore a possible association between the investigated assessment tool and the Brief Psychiatric Rating Scale. Thirty patients were followed over a period of 6 months. The inter-rater reliability for the interview subscales were self care/hygiene: kappa= 0.77; social participation: kappa= 0.84; boundaries in daily life: kappa= 0.76; academic/work activities: r= 0.81, clinical condition/symptom severity: kappa= 0.72; attitude towards treatment: kappa=0.82; participation in family crisis/emotional support: kappa= 0.77; participation in daily routines/household activities: kappa= 0.63; use of psychiatric services: kappa= 0.62. Cronbach's alpha was found to be 0.90 for the overall internal consistency of the assessment tool. The strongest correlation between the Brief Psychiatric Rating Scale and Marmara Family Interview for the Assessment of Psychiatric Treatment was the depression subscale and the participation in family crisis/emotional support item (r= 0.151; P > 0.05). Marmara Family Interview for the Assessment of Psychiatric Treatment is a reliable instrument for the assessment of daily results of the treatment and daily functioning by the caregivers. Although, it has some limitations in assessing the clinical course.


Quantitation of biomarkers of exposure to nitrogen mustards in urine from rats dosed with nitrogen mustards and from an unexposed human population.
The nitrogen mustards bis(2-chloroethyl)ethylamine (HN1), bis(2-chloroethyl)methylamine (HN2), and tris(2-chloroethyl)amine (HN3) have the potential to be used as chemical terrorism agents because of their extreme vesicant properties. We modified a previously reported method to incorporate automated solid-phase extraction, improve chromatography, and include the urinary metabolite for HN3. The improved method was used to measure levels of the urinary metabolites N-ethyldiethanolamine (EDEA), N-methyldiethanolamine (MDEA), and triethanolamine (TEA) in rats dosed with HN1, HN2, and HN3, respectively, and to establish background levels of EDEA, MDEA, and TEA in human urine samples from a population with no known exposure to nitrogen mustards. Rat dosing experiments confirmed that EDEA, MDEA, and TEA could be detected in urine for at least 48 h after exposure to HN1, HN2, and HN3, respectively. Substantial amounts of EDEA (89 ng/mL), MDEA (170 ng/mL), and TEA (1105 ng/mL) were measured in the urine of rats exposed to 10 mg HN1, HN2, and HN3, respectively, 48 h after exposure. The background concentrations for TEA in the human population ranged from below the limit of detection (LOD 3 ng/mL) to approximately 6500 ng/mL. Neither EDEA (LOD 0.4 ng/mL) nor MDEA (LOD 0.8 ng/mL) was detected above the LOD in the human samples.


Comparative in vitro study of temocillin (BRL 17421), a new penicillin.
The activity of temocillin (BRL 17421), a new penicillin, was tested in vitro against 653 isolates of gram-negative bacilli and gram-positive cocci. The drug was compared with other beta-lactam antibiotics and tobramycin. It inhibited the majority of gram-negative bacilli tested except for Pseudomonas aeruginosa and Acinetobacter calcoaceticus, which were highly resistant. It was active against more than 50% of the multiresistant strains tested. Temocillin was more active than mezlocillin against most gram-negative bacilli and more active than moxalactam, ceftriaxone, and ceftazidime against Enterobacter spp. In general, it was slightly less active than the other drugs tested and had no activity against the gram-positive cocci. There was no significant change in drug activity when pH and medium were varied, and the effect of serum binding was minimal. There was no significant inoculum effect when the size of the inoculum was increased from 10(4) to 10(6) organisms per ml.


A light and electron microscope study of the interaction of soil bacteria with Phytophthora cinnamomi Rands.
Light- and electron-microscopic examination showed that bacteria became associated with the hyphae and asexual reproductive structures of P. cinnamomi in soil. In suppressive soils this association appears to be correlated with hyphal lysis, inhibition of zoospore production, and sporangial breakdown. One notable feature of the microbial association between P. cinnamomi and soil bacteria is the formation of extensive slime material. Many of the bacteria isolated from the fungal hyphosphere display antagonism to the growth of P. cinnamomi in vitro. The bacteria are morphologically varied and include Pseudomonas, Bacillus, and Streptomyces spp. These observations suggest that the appropriate manipulation of the antagonistic bacteria may provide a means of biological control of P. cinnamomi.


Progesterone receptor antagonist provides palliative effects for uterine leiomyoma through a Bcl-2/Beclin1-dependent mechanism.
Uterine leiomyoma is the most common benign smooth muscle tumor of uterus in women of reproductive age, with a high lifetime incidence. Nowadays, the exploration on the pharmacotherapies, such as progesterone receptor antagonist (PRA) requires more attention. Hence, the current study aimed to examine whether mifepristone, a PRA, influences the autophagy and apoptosis of uterine leiomyoma cells. Primary uterine leiomyoma cells were collected from 36 patients diagnosed with uterine leiomyoma to establish PR-M-positive (PR-M[+]) cells. The lentiviral vector overexpressing or silencing PR-M was subsequently delivered into one part of PR-M(+) cells in order to evaluate the role of PR-M in PR-M(+) cells. The results obtained revealed that cell viability was increased, while cell autophagy and apoptosis were diminished in the PR-M(+) cells treated with overexpressed PR-M, whereby the Bcl-2 level was elevated and the level of Beclin1 was reduced. An opposite trends were identified following treatment with knockdown of PR-M. Mifepristone at different concentrations (low, moderate, or high) was then applied to treat another part of the PR-M(+) cells. Mifepristone was identified to promote cell autophagy and apoptosis, decrease Bcl-2 level and increase Beclin1 level, accompanied by weakened interaction between Bcl-2 and Beclin1. Moreover, these effects of mifepristone on PR-M(+) cells were enhanced with increasing of the concentration. Taken together, the present study present evidence indicates the ability of PRA to regulate the Bcl-2/Beclin1 axis, ultimately promoting the autophagy and apoptosis of uterine leiomyoma cells, highlighting that PRA serves as a promising therapeutic target for the treatment of uterine leiomyoma.


Metabolic Mechanism for l-Leucine-Induced Metabolome To Eliminate Streptococcus iniae.
Crucial metabolites that modulate hosts' metabolome to eliminate bacterial pathogens have been documented, but the metabolic mechanisms are largely unknown. The present study explores the metabolic mechanism for l-leucine-induced metabolome to eliminate Streptococcus iniae in tilapia. GC-MS-based metabolomics was used to investigate the tilapia liver metabolic profile in the presence of exogenous l-leucine. Thirty-seven metabolites of differential abundance were determined, and 11 metabolic pathways were enriched. Pattern recognition analysis identified serine and proline as crucial metabolites, which are the two metabolites identified in survived tilapias during S. iniae infection, suggesting that the two metabolites play crucial roles in l-leucine-induced elimination of the pathogen by the host. Exogenous l-serine reduces the mortality of tilapias infected by S. iniae, providing a robust proof supporting the conclusion. Furthermore, exogenous l-serine elevates expression of genes IL-1β and IL-8 in tilapia spleen, but not TNFα, CXCR4 and Mx, suggesting that the metabolite promotes a phagocytosis role of macrophages, which is consistent with the finding that l-leucine promotes macrophages to kill both Gram-positive and Gram-negative bacterial pathogens. Therefore, the ability of phagocytosis enhanced by exogenous l-leucine is partly attributed to elevation of l-serine. These results demonstrate a metabolic mechanism by which exogenous l-leucine modulates tilapias' metabolome to enhance innate immunity and eliminate pathogens.


Designing a fully automated multi-bioreactor plant for fast DoE optimization of pharmaceutical protein production.
The identification of optimal expression conditions for state-of-the-art production of pharmaceutical proteins is a very time-consuming and expensive process. In this report a method for rapid and reproducible optimization of protein expression in an in-house designed small-scale BIOSTAT® multi-bioreactor plant is described. A newly developed BioPAT® MFCS/win Design of Experiments (DoE) module (Sartorius Stedim Systems, Germany) connects the process control system MFCS/win and the DoE software MODDE® (Umetrics AB, Sweden) and enables therefore the implementation of fully automated optimization procedures. As a proof of concept, a commercial Pichia pastoris strain KM71H has been transformed for the expression of potential malaria vaccines. This approach has allowed a doubling of intact protein secretion productivity due to the DoE optimization procedure compared to initial cultivation results. In a next step, robustness regarding the sensitivity to process parameter variability has been proven around the determined optimum. Thereby, a pharmaceutical production process that is significantly improved within seven 24-hour cultivation cycles was established. Specifically, regarding the regulatory demands pointed out in the process analytical technology (PAT) initiative of the United States Food and Drug Administration (FDA), the combination of a highly instrumented, fully automated multi-bioreactor platform with proper cultivation strategies and extended DoE software solutions opens up promising benefits and opportunities for pharmaceutical protein production.


Technetium pyrophosphate muscle scans in inflammatory muscle disease.
Technetium-99M pyrophosphate (TcPYP) nuclear scans of extremities were performed on 15 patients at 10 minutes and 2 hours after isotope injection. Scans were carried out both to confirm the diagnosis of myositis and to direct subsequent muscle biopsy. Five of six patients with clinical features strongly suggestive of inflammatory muscle disease had positive scans. All muscle biopsies performed at areas of increased isotope uptake showed inflammatory muscle disease. All nine patients not suspected of active inflammatory muscle disease had negative scans. Two of these underwent muscle biopsy with negative results. Our observations suggest that TcPYP muscle scans may be useful both to confirm the clinical suspicion of inflammatory muscle disease and in directing the choice of site for muscle biopsy.


Non-natural olefin cyclopropanation catalyzed by diverse cytochrome P450s and other hemoproteins.
Recent work has shown that engineered variants of cytochrome P450BM3 (CYP102A1) efficiently catalyze non-natural reactions, including carbene and nitrene transfer reactions. Given the broad substrate range of natural P450 enzymes, we set out to explore if this diversity could be leveraged to generate a broad panel of new catalysts for olefin cyclopropanation (i.e., carbene transfer). Here, we took a step towards this goal by characterizing the carbene transfer activities of four new wild-type P450s that have different native substrates. All four were active and exhibited a range of product selectivities in the model reaction: cyclopropanation of styrene by using ethyl diazoacetate (EDA). Previous work on P450BM3 demonstrated that mutation of the axial coordinating cysteine, universally conserved among P450 enzymes, to a serine residue, increased activity for this non-natural reaction. The equivalent mutation in the selected P450s was found to activate carbene transfer chemistry both in vitro and in vivo. Furthermore, serum albumins complexed with hemin were also found to be efficient in vitro cyclopropanation catalysts.


A metal-organic-framework approach to engineer hollow bimetal oxide microspheres towards enhanced electrochemical performances of lithium storage.
Nanosized electrode materials with a hollow structure, larger specific surface area, and lower energy density as well as more void space are widely adopted for high-performance lithium-ion batteries. In this work, we obtained bimetal-organic frameworks of Fe/Mn-MOF-74 with a hollow microsphere morphology via a facile one-step microwave method and further used it to fabricate hollow Fe-Mn-O/C microspheres. Endowed with the metal-organic-framework-derived carbon-coated nanoparticle-assembled hollow structure with hierarchical porous characteristics and synergistic effects between two different metal species, the Fe-Mn-O/C electrode exhibits outstanding electrochemical performances as the anode of lithium-ion batteries. It achieves improved cycling performance (1294 mA h g-1 after 200 cycles at 0.1 A g-1) and good rate capability (722, 604, and 521 mA h g-1 at 0.2, 0.5 and 1 A g-1). The smart design of a hollow morphology with uniform two metal species can promote the synthesis of multimetal oxides and their carbon composites, as well as their further potential application for energy-storage.


Rifaximin: recent advances in gastroenterology and hepatology.
Rifaximin was initially developed for the treatment of bacteria-related diarrhea, but appreciation of its potentially broader use has increased as understanding of the importance of enteric bacteria in many organic and functional gastrointestinal diseases has advanced. This article reviews data that have been presented at medical meetings or published in medical journals since the publication of a 2006 rifaximin review in this journal. The data presented expand previous research, suggesting that rifaximin may be considered as monotherapy or combination therapy for a variety of enteric conditions, including Clostridium difficile-associated diarrhea, cryptosporidial diarrhea, Helicobacter pylori-associated gastritis, inflammatory bowel disease, pouchitis, diverticular disease, hepatic encephalopathy, small intestinal bacterial overgrowth, and irritable bowel syndrome. Although most of the new data come from small, uncontrolled studies, results are encouraging. Together, these studies suggest the efficacy of rifaximin and provide a foundation for further research that will help to better define the potential benefits of rifaximin in gastroenterology and hepatology.


CT findings in pulmonary venoocclusive disease.
We report a case of pulmonary venoocclusive disease in which chest radiography, when supplemented with computed tomography after contrast medium administration, was specific enough to make the diagnosis without resorting to more invasive, potentially dangerous procedures. A brief review of the literature, with emphasis on etiology, pathogenesis, and possible therapeutic approaches, emphasizes the importance of early diagnosis of this rare and usually fatal disease.


Warming deferentially altered multidimensional soil legacy induced by past land use history.
The legacy effects of previous land use and climate history may affect current soil function. However, the manner in which these legacy effects of land use are modulated by the subsequent climate remains unclear. For this reason, we investigated how the legacies of soil multiple functions left by conversion of grassland to agricultural management were mediated by climate warming with a reciprocal transplant approach. The overall legacy was further separated into the contributions by changes in the abiotic properties of the soil (abiotic process) and microbial community (biotic process). We here hypothesized that warming may mediate the legacy effects of previous land use, mainly by changing biotic processes. Results indicated that warming significantly influenced the total legacies of soil respiration and three exoenzyme activities representing recalcitrant carbon, nitrogen, and phosphorus cycling, but did not affect the total legacy of β-1,4-glucosidase activity, which is involved in labile carbon cycling. The relative contributions of abiotic and biotic processes to the warming effects on the total legacy depended on the type of soil function. The effects of warming on land use change legacies were derived from altered bacterial community structure. The results of the present study suggest that climate conditions could interact with land use legacy to determine the ecosystem functions in a process-specific way.


Population pharmacokinetic analysis of colistin in burn patients.
Colistin is increasingly used as a salvage therapy for nosocomial infections caused by multidrug-resistant Gram-negative bacteria such as Pseudomonas aeruginosa and Acinetobacter baumannii. However, the available pharmacokinetic (PK) data for colistin are limited to guide dosing. The aim of this study was to develop a population PK model of colistin and to identify the optimal dosage regimens for burn patients. Fifty patients with burns ranging from 4% to 85% of total body surface area who had been treated with colistimethate sodium (CMS) were studied. CMS, which is hydrolyzed in vivo to an active metabolite, was intravenously administered every 12 h. Blood samples were collected at 0, 1, 2, 4, 6, and 8 h after more than five infusions to measure the colistin concentration using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) system. The population PK model was developed using nonlinear mixed effect modeling (NONMEM, v. 6.2). A one-compartment linear PK model for colistin best described the data. The covariates included in the final model were creatinine clearance for the relative fraction of CMS converted into colistin and the presence of edema for the turnover rate constant of CMS converted into colistin. A steady-state 24-h area under the concentration-time curve was simulated from 1,000 virtual patients receiving 150 mg colistin base activity every 12 h using the final model. Relative to previous studies with critically ill patients, the elimination half-life of colistin (6.6 h) was much shorter, and continuous renal replacement therapy was not a significant covariate for any PK parameters.


Relationship between adenylate cyclase sensitivity to follitropin and FSH receptor mRNA expression in the ovary of the lizard Podarcis sicula.
In mammals, gonadal functions are regulated by two pituitary gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), that interact with gonadal membrane receptors to activate adenylate cyclase. In comparison to mammalian systems, in squamate reptiles a reduced amount of information exists on gonadotropins and their related receptors. This study is aimed at clarifying if, in the lizard Podarcis sicula, the ovarian sensitivity to FSH is correlated to the reproductive cycle and to the expression of membrane receptors involved in the hormone recognition. The results demonstrate that the ovarian adenylate cyclase responsiveness to FSH parallels ovarian functions, being maximal during the ovulatory period. The ovarian sensitivity to FSH is also related to oocyte growth and vitellogenesis. Northern blot analyses reveal that the FSH receptor mRNA is maximally expressed in vitellogenic oocytes during the reproductive period. These results suggest that, in lizard ovary, hormone activation of adenylate cyclase is mediated by de novo synthesis of receptors specifically involved in FSH recognition. In lizards treated in vivo with FSH during the pre-ovulatory period, adenylate cyclase becomes refractory to further FSH stimulation 2 hr after treatment, but sensitivity to the hormone is restored after 2 weeks. Nevertheless, while the restored level of activity never exceeds that observed during the nonreproductive period, the expression level of FSH receptor mRNAs is significantly enhanced in these animals. These results suggest that in lizard the processes that regulate ovarian growth, vitellogenesis, and ovulation are controlled by a complex network of signals including gonadotropin, FSH receptor expression, and adenylate cyclase.


Stability of unstimulated and stimulated whole saliva flow rates in children.
To analyze the stability of the unstimulated saliva flow rate (USFR) and the stimulated saliva flow rate (SSFR) in children followed from age 7 to 12 years old. Longitudinal study. Whole saliva samples were collected from school children (50 girls and 50 boys). Forty-four girls and 32 boys remained in this cohort for 6 years (dropout rate 24%). Variables that could influence USFR or SSFR patterns were analyzed in a repeated-measures manova. Over a 6-year follow-up, the children's USFR ranged from 0.41 to 0.46 mL/min in the initial and final observation, respectively, and showed no significant differences (P = 0.4455) during the follow-up. The children consistently belonged to one of three distinct SSFR groups (P < 0.0001). A repeated-measures manova model showed that USFR and SSFR were not associated with sex, body mass index, or indoor temperature during sampling. These results indicate that USFR and SSFR patterns were stable from 7 to 12 years old. This finding may be useful in oral health prevention or treatment and in the search for biomarkers in saliva for screening or diagnostic purposes.


Chondrosarcoma of the nasal septum.
Chondrosarcoma of the nasal septum is a rare malignancy. When it occurs, early diagnosis is difficult because patients generally present with common, non-specific sinonasal complaints. This is the report of a 62-year-old woman who presented with a 1-month history of nasal obstruction, headache and anosmia. Nasal endoscopy showed a nasal mass obstructing both nasal cavities not separable from the septum. A wedge biopsy of the nasal mass was taken. Histopathology was suggestive of chondrosarcoma. The tumour was removed by an endoscopic approach. The clinical presentation, diagnosis and treatment of this case as well as a review of the literature are discussed.


Updated foxtail millet genome assembly and gene mapping of nine key agronomic traits by resequencing a RIL population.
Foxtail millet (Setaria italica) provides food and fodder in semi-arid regions and infertile land. Resequencing of 184 foxtail millet recombinant inbred lines (RILs) was carried out to aid essential research on foxtail millet improvement. A total 483 414 single nucleotide polymorphisms were determined. Bin maps were constructed based on the RILs' recombination data. Based on the high-density bin map, we updated Zhanggu reference with 416 Mb after adding 16 Mb unanchored scaffolds and Yugu reference with some assembly error correction and 3158 gaps filled. Quantitative trait loci (QTL) mapping of nine agronomic traits was done based on this RIL population, five of which were controlled by a single gene. Meanwhile, two QTLs were found for plant height, and a candidate gene showed 89% identity to the known rice gibberellin-synthesis gene sd1. Three QTLs were found for the trait of heading date. The whole genome resequencing and QTL mapping provided important tools for foxtail millet research and breeding. Resequencing of the RILs could also provide an effective way for high-quality genome assembly and gene identification.


A direct effect of the autonomic nervous system on somatic stem cell proliferation?
Regulation of somatic stem cell proliferation is critical for the maintenance of tissue and organ function throughout the body. Modulators of this process include nutrients and peptides, but the role of an autonomic neural influence on stem cell proliferation has been neglected. This article describes the literature in support of autonomic nervous system (ANS) influence on somatic stem cells, with emphasis on intestinal epithelial stem cells (IESCs) as a representative somatic stem cell. Based on the current available data, models for the direct influence of both branches of the ANS (the sympathetic and parasympathetic nervous systems) on IESCs are outlined. Finally, the prospect of treatments derived from ANS influence on somatic stem cells is explored.