Effects of felodipine on systemic and coronary haemodynamics in patients with angina pectoris.
In order to study the systemic and coronary haemodynamic effects of felodipine, a new dihydropyridine derivative, 10 patients with coronary artery disease were studied during cardiac catheterization. Measurements were performed at rest and during pacing-induced angina pectoris. At rest, the heart rate rose from 70 +/- 20 to 78 +/- 20 (P less than 0.05), the systemic arterial pressure decreased by about 20% (P less than 0.01) and the cardiac index rose from 2.9 +/- 1.2 to 4.0 +/- 1.0 (P less than 0.05). The coronary sinus flow (CSF) increased about 50% (P less than 0.01). During pacing to the same heart rate as in the control measurements, felodipine induced similar changes in systemic haemodynamic values as in the resting position. Myocardial lactate extraction and ST segment depression were not significantly altered. After felodipine, the pacing rate could be further increased in 7 patients as compared with the control value. Both systemic and coronary effects were then very similar compared with those during the lower pacing rate. In conclusion, felodipine is a very potent systemic and coronary vasodilator with potential value in the treatment of hypertension and cardiac failure. The drug may also be of value in the treatment of ischaemic heart disease, but further studies with titration of optimal doses are needed in that respect.


Arsenic biotransformation by a cyanobacterium Nostoc sp. PCC 7120.
Nostoc sp. PCC 7120 (Nostoc), a typical filamentous cyanobacterium ubiquitous in aquatic system, is recognized as a model organism to study prokaryotic cell differentiation and nitrogen fixation. In this study, Nostoc cells incubated with arsenite (As(III)) for two weeks were extracted with dichloromethane/methanol (DCM/MeOH) and the extract was partitioned between water and DCM. Arsenic species in aqueous and DCM layers were determined using high performance liquid chromatography - inductively coupled plasma mass spectrometer/electrospray tandem mass spectrometry (HPLC-ICPMS/ESIMSMS). In addition to inorganic arsenic (iAs), the aqueous layer also contained monomethylarsonate (MAs(V)), dimethylarsinate (DMAs(V)), and the two arsenosugars, namely a glycerol arsenosugar (Oxo-Gly) and a phosphate arsenosugar (Oxo-PO4). Two major arsenosugar phospholipids (AsSugPL982 and AsSugPL984) were detected in DCM fraction. Arsenic in the growth medium was also investigated by HPLC/ICPMS and shown to be present mainly as the inorganic forms As(III) and As(V) accounting for 29%-38% and 29%-57% of the total arsenic respectively. The total arsenic of methylated arsenic, arsenosugars, and arsenosugar phospholipids in Nostoc cells with increasing As(III) exposure were not markedly different, indicating that the transformation to organoarsenic in Nostoc was not dependent on As(III) concentration in the medium. Our results provide new insights into the role of cyanobacteria in the biogeochemical cycling of arsenic.


Medical evaluation of the sexually abused child.
Clearly, there are numerous troubling variations in the medical diagnosis of child sexual abuse. These variations include delays in disclosure; rapid healing; maturational changes; variations in normal congenital findings; the technique of the examiner; patient position, relaxation, and cooperation; and additional medical conditions that mimic abuse. For these reasons, physical evidence is often inconclusive and can be an unreliable source of information in child sexual abuse cases. The reader is logically cautioned against attempts to diagnose child sexual abuse based on a single finding, particularly that of the diameter of the hymenal orifice. Emphasis on the child's history in documenting the abuse is increasing. As physicians, we must develop interviewing techniques that will assist in child protection, and we must listen and believe the comments made by our patients.


Prospective evaluation of patient-reported quality-of-life outcomes following SBRT ± cetuximab for locally-recurrent, previously-irradiated head and neck cancer.
Stereotactic body radiotherapy (SBRT) has emerged as a promising salvage strategy for unresectable, previously-irradiated recurrent squamous cell carcinomas of the head and neck (rSCCHN). Here-in, we report the first prospective evaluation of patient-reported quality-of-life (PR-QoL) following re-irradiation with SBRT±cetuximab for rSCCHN. From November 2004 to May 2011, 150 patients with unresectable, rSCCHN in a previously-irradiated field receiving >40 Gy were treated with SBRT to 40-50 Gy in 5 fractions ± concurrent cetuximab. PR-QoL was prospectively acquired using the University of Washington Quality-of-Life Revised (UW-QoL-R). Overall PR-QoL, health-related PR-QoL, and select domains commonly affected by re-irradiation progressively increase following an initial 1-month decline with statistically significant improvements noted in swallowing (p=0.025), speech (p=0.017), saliva (p=0.041), activity (p=0.032) and recreation (p=0.039). Especially for patients surviving >1-year, improved tumor control associated with SBRT re-irradiation may ameliorate decreased PR-QoL resulting from rSCCHN. These improvements in PR-QoL transcend all measured domains in a validated PR-QoL assessment tool independent of age, use of cetuximab, tumor volume, and interval since prior irradiation.


Caring for children with autism spectrum condition in paediatric emergency departments.
The needs of children with autism spectrum condition (ASC) in paediatric emergency departments (EDs) can often be overlooked. EDs are high-stress environments for children with ASC, which can result in meltdowns, making the diagnostic process challenging. There should be provision for children with ASC, who can have sensory, behavioural and communication needs, in the same way that analgesia is provided for children in pain. This article promotes a multi-strategy approach to making reasonable adjustments to help meet the needs of these children and provide them with a positive hospital experience.


[Investigation of the liver DNA methylation profile of rats under the influence of hepatotoxicants of different nature].
The functional importance of DNA methylation, which is a special case of epigenetic variation, is meant for regulation of many biological processes, ranged from tissue specific gene expression to remodeling of chromatin structure. Disorders of the DNA methylation can cause changes in the cell's phenotype, providing a significant impact on the development of pathology. Both exogenous and endogenous factors are able to cause disruption of DNA methylation, while epigenetic changes usually precede the emergence of clinical and morphological symptoms of pathological process development, consequently the parameters of DNA methylation can be used as sensitive biomarkers to detect adverse effects on the organism. The purpose of the study was to identify genes of the liver, the methylation profile of which changes under the influence of hepatotoxicants of different nature. The experiment was carried out on 60 male Wistar rats with initial body weight (b.w.) 83.3±1.5 g. Animals were randomly divided into 6 groups - 1 control and 5 test groups, with 10 rats in each group. During the first two weeks of the experiment the rats of the 1-5th test groups were administered to aflatoxin B1 (200 Mg/kg b.w.), cadmium chloride 2,5-hydrate (2 mg/kg), monosodium glutamate (1000 mg/kg), epigallocatechin gallate (EGCG) (1000 mg/kg), paracetamol (150 mg/kg), accordingly. Methylation of the liver genes in rats was determined by using high-performance methods, based on bisulfite sequencing of reduced representation. For each sample from 12 to 30 million pairs of reads were received, genes which demonstrated significant changes in methylation when exposed to toxic factors were identified: aflatoxin B1 caused changes in the methylation of 57 genes; cadmium - 54 genes; monosodium glutamate - 39 genes; EGCG -198 genes; paracetamol - 167 genes. The comparison of genes with altered methylation in the experimental groups revealed that none of the genes repeatedly occurred under the influence of each toxicant out of five, the highest number of repeats accounted 3. As a result of the present analysis 7 genes have been selected: methylation change in Fan1 gene was observed when exposed to cadmium, monosodium glutamate, EGCG; gene Lppr2 - under the influence of aflatoxin B1, EGCG, paracetamol; gene Mlh3 - under the influence of aflatoxin B1, cadmium, paracetamol; Sirt7 gene - under the influence of cadmium, EGCG, paracetamol; gene Fbxo15 - when exposed to cadmium, monosodium glutamate, paracetamol; gene E2f1 - when exposed to cadmium, EGCG, paracetamol; gene Mrps16 - when exposed to cadmium, EGCG, paracetamol. On the basis of the received data the project of the panel of genes-biomarkers of toxic effect, including genes Fan1, Lppr2, Mlh3, Sirt7, Fbxo15, E2f1, Mrps16 has been formed.


Informed consent: client participation in childbirth decisions.
In recent years, there has been a tremendous rise in public consciousness concerning patients' rights. Previously, patients relied upon the expertise of health-care providers, but now it is more common for patients to seek active involvement in the decision-making process affecting their care. The patient's right to self-determination is central to the decision-making process between the client and the provider. A patient's right to autonomy, therefore, imposes an obligation upon the health-care provider to obtain informed consent from the obstetric client.


A topographic gradient of molecules in retina can be used to identify neuron position.
A monoclonal antibody was obtained that binds to cell membrane molecules distributed in a topographic gradient in avian retina. Thirty-five-fold more antigen was detected in dorsoposterior retina that in ventroanterior retina. Most of the antigen was associated with the synaptic layers of the retina. Less antigen was detected in cerebrum, thalamus, cerebellum, and optic tectum, but little or none was found in non-neural tissues tested. The antigen was found on most or all cell types in retina, and the concentration of antigen found is a function of the square of the circumferential distance from the ventroanterior pole of the gradient toward the dorsoposterior pole. Thus, the antigen can be used as a marker of cell position along the ventroanterior-dorsoposterior axis of the retina.


Bacterial contamination of intraocular lens surgery.
One hundred sterile intraocular lenses were placed on the external eye of 50 patients during cataract surgery. Half of the specimens were cultured for bacteria, the other half were examined under the light microscope after fixing and staining. A bacterial contamination rate of 26% was recorded. This is significantly higher than that found in conjunctival swabs (6%) or irrigation specimens (8%) taken at the same time, and higher than that recorded in a group of control lenses (15.2%) exposed to operating theatre air alone. We propose that intraocular lenses contaminated with viable bacteria may be implanted into the eye and thereby account for some cases of postoperative uveitis in the pseudophakic eye.


Redox state changes in density-dependent regulation of proliferation.
The ability of certain transcription factors to bind to DNA has been demonstrated to be influenced by the redox environment. Therefore, fluctuations in the redox state of the cell may regulate the transcription of genes which control proliferation. To assess whether changes in the redox state may be related to proliferation, levels of oxidized (GSSG) and reduced (GSH) glutathione, the primary modulators of the redox state, were measured in cultures of varying densities of normal human fibroblasts which exhibit contact inhibition of proliferation, as well as fibrosarcoma cells, which lack this mechanism of growth control. Redox potentials calculated from normal, proliferating fibroblasts were found to be -34 mV more reducing than confluent, contact-inhibited cells. However, fibrosarcoma cells did not demonstrate this modulation in redox state. Further, to delineate whether these redox changes were the consequence or the cause of contact inhibition, cultures of subconfluent proliferating fibroblasts were treated with modulators of glutathione synthesis. Buthionine sulfoximine, an inhibitor of GSH synthesis, induced a less reducing redox state and decreased proliferation. In contrast, GSH synthesis precursors caused a more reduced redox state and increased proliferation. Collectively, these results suggest an interrelationship between redox state and growth control.


A Rare Case of Anaplastic Large Cell Lymphoma of the Knee Joint.
Anaplastic large cell lymphoma (ALCL), which makes up only 2-5% of instances of NHL, is a rare and aggressive form of the disease. Anaplastic Lymphoma Kinase (ALK)-positive ALCL is a variant of the illness that is identified by the presence of an ALK gene fusion. The disease is most commonly confined to the nodes, but extranodal spread has been reported. Skin and soft tissue are the most frequently identified locations for extranodal involvement, while joints are extremely rare. We describe a rare case of ALCL affecting the knee joint that is ALK -positive. A 51-year-old female presented with pain in her right knee. It was diagnosed as synovitis and treated accordingly. The symptoms did not relieve and a magnetic resonance imaging (MRI) scan was performed that indicated a meniscus tear. She was treated for it; however, the symptoms worsened. She underwent two more scans (1 MRI and 1 PET) that indicated an enhancing polypoidal mass in the knee joint, and two arthroscopic procedures. The histopathology report indicated an ALK-positive ALCL. She was treated with Brentuximab vedotin + CHP followed by involved-site radiotherapy to the postoperative region with margins. The patient has had a complete clinical and pathological response which was assessed after 1 year from the start of the treatment. This is the first instance of primary ALK-positive ALCL affecting the knee joint that has been documented, to the best of our knowledge. The case emphasizes the significance of taking ALCL into account when determining the differential diagnosis of knee joint tumors as well as the requirement for a thorough assessment of extranodal involvement.


N-acetyl-L-cysteine modulates the metabolism of cis-platin in human plasma in vitro.
Cis-Platin (CP) is a remarkably effective Pt-based anticancer drug, but it also exhibits severe toxic side-effects, including nephrotoxicity and ototoxicity. Previous studies conducted with mammalian model organisms have clearly demonstrated that the intravenous administration of N-acetyl-L-cysteine (NAC) or sodium thiosulfate (STS) along with CP can significantly reduce these toxic side effects. A molecular understanding of the biochemical events that unfold in the bloodstream when these 'ameliorating agents' and CP are co-administered, therefore, constitutes an important first step in devising novel strategies to ultimately improve the quality of life of patients undergoing treatment with CP. We have employed size exclusion chromatography (SEC) coupled on-line to an inductively coupled plasma atomic emission spectrometer (ICP-AES) to visualize how NAC affects the metabolism of CP in human plasma (obtained from healthy male volunteers) in vitro. Clinically relevant doses of CP and NAC were added to plasma at various NAC : CP molar ratios and the Pt-distribution was determined after 10 and 50 min. The results revealed that a putative Pt-NAC complex was formed in plasma with NAC : CP molar ratios ≥ 50 : 1 and that plasma protein binding of CP-derived Pt-species was marginally affected by NAC. In addition, the anti-tumor active CP remained in plasma for more than 50 min. Furthermore, NAC (but not CP) adversely affected the integrity of Fe and Zn plasma metalloproteins in a dose and a time dependent manner. Based on these in vitro data, NAC appears to be a less ideal ameliorating agent to mitigate CP toxicity compared to STS.


Abscisic acid induced changes in production of primary and secondary metabolites, photosynthetic capacity, antioxidant capability, antioxidant enzymes and lipoxygenase inhibitory activity of Orthosiphon stamineus Benth.
An experiment was conducted to investigate and distinguish the relationships in the production of total phenolics, total flavonoids, soluble sugars, H2O2, O2-, phenylalanine ammonia lyase (PAL) activity, leaf gas exchange, antioxidant activity, antioxidant enzyme activity [ascorbate peroxidase (APX), catalase (CAT), superoxide dismutase (SOD) and Lipoxygenase inhibitory activity (LOX)] under four levels of foliar abscisic acid (ABA) application (0, 2, 4, 6 µM) for 15 weeks in Orthosiphon stamineus Benth. It was found that the production of plant secondary metabolites, soluble sugars, antioxidant activity, PAL activity and LOX inhibitory activity was influenced by foliar application of ABA. As the concentration of ABA was increased from 0 to 6 µM the production of total phenolics, flavonoids, sucrose, H2O2, O2-, PAL activity and LOX inhibitory activity was enhanced. It was also observed that the antioxidant capabilities (DPPH and ORAC) were increased. This was followed by increases in production of antioxidant enzymes APX, CAT and SOD. Under high application rates of ABA the net photosynthesis and stomatal conductance was found to be reduced. The production of primary and secondary metabolites displayed a significant positive relationship with H2O2 (total phenolics, r2 = 0.877; total flavonoids, r2 = 0.812; p ≤ 0.05) and O2- (total phenolics, r2 = 0.778; total flavonoids, r2 = 0.912; p ≤ 0.05). This indicated that increased oxidative stress at high application rates of ABA, improved the production of phytochemicals.


Construction of a one-step multiplex real-time PCR assay for the detection of serogroups A, B, and E of Pasteurella multocida associated with bovine pasteurellosis.
Bovine pasteurellosis, caused by serogroups A, B, and E of Pasteurella multocida (Pm), is mainly manifested as bovine respiratory disease (BRD) and hemorrhagic septicemia (HS). The disease has caused a great economic loss for the cattle industry globally. Therefore, identifying the Pm serogroups is critical for optimal diagnosis and subsequent clinical treatment and even epidemiological studies. In this study, a one-step multiplex real-time PCR assay was established. Three pairs of specific primers were prepared to detect the highly conserved genomic regions of serogroups A (HyaD), B (bcbD), and E (ecbJ) of Pm, respectively. The results depicted that the method had no cross-reaction with other bovine pathogens (Mannheimia hemolytica, Escherichia coli, Listeria monocytogenes, Staphylococcus aureus, Salmonella Dublin, Mycobacterium paratuberculosis, infectious bovine rhinotracheitis virus, and Mycoplasma bovis). The linear range (107 to 102 copies/μL) showed the R2 values for serogroups A, B, and E of Pm as 0.9975, 0.9964, and 0.996, respectively. The multiplex real-time PCR efficiency was 90.30%, 90.72%, and 90.57% for CartA, CartB, and CartE, respectively. The sensitivity result showed that the serogroups A, B, and E of Pm could be detected to be as low as 10 copies/μL. The repeatability result clarified that an intra-assay and an inter-assay coefficient of variation of serogroups A, B, and E of Pm was < 2%. For the clinical samples, the detection rate was higher than the OIE-recommended ordinary PCR. Overall, the established one-step multiplex real-time PCR assay may be a valuable tool for the rapid and early detection of the serogroups A, B, and E of Pm with high specificity and sensitivity.


Plasma levels of beta 2-microglobulin in rheumatoid arthritis.
A simple and inexpensive method is described for the determination of beta 2-microglobulin (beta 2-MG) by enzyme-amplified single radial immunodiffusion. The values obtained with this method correlate well with those determined by means of a commerical RIA kit. Using the immunodiffusion method we have measured the plasma levels of beta 2-MG in 135 patients with rheumatoid arthritis (RA) and normal serum creatinine levels. 33% of the patients had increased concentrations of beta 2 MG, but the levels were found to correlate poorly with the values of several variables generally used as indices of the degree inflammatory activity in RA. Furthermore, in contrast to earlier claims to the contrary, beta 2-MG correlated positively with age. The value of beta 2-MG in plasma as an index of inflammatory activity in RA is questioned.


Accumulation of γ-aminobutyric acid in nodulated soybean in response to drought stress.
Nitrogen fixation and nodule permeability to O2 diffusion are decreased by drought stress. Since γ-aminobutyric acid (GABA) synthesis is rapidly stimulated by a variety of stress conditions including hypoxia, it was hypothesized that decreased O2 availability in nodules stimulates glutamate decarboxylase (GAD) activity (EC 22.214.171.124), thereby resulting in GABA accumulation. First, the amino acid composition of xylem sap was determined in plants subjected to soil water deficits. While the xylem sap concentration of several amino acids increased when the plant was subjected to a water deficit, the greatest increase was in GABA. GABA accumulation was examined in response to stress induced by hypoxia or the addition of polyethylene glycol (PEG) to the nutrient solution. The exposure of soybean nodules to hypoxia for 6 h enhanced the GABA concentration by 6-fold, but there was no change in GABA concentration in response to the PEG treatment. No major changes in the in vitro GAD activity were measured in nodule cytosol or bacteroids. The present data do not support the hypothesis that decreased nodule O2 permeability and a resulting O2 deprivation inside nodules may stimulate in vitro GAD activity and thus GABA accumulation. However, the data could indicate a possible effect of hypoxia and drought stress on the in vivo activity of GAD.


Hospitals' compliance with prophylaxis guidelines for venous thromboembolism.
A study was conducted to evaluate compliance with the Sixth American College of Chest Physicians (ACCP) Consensus Conference on Antithrombotic Therapy guidelines for the prevention of venous thromboembolism (VTE) in hospitals. Using the HealthFacts database, hospitalized patients, age 40 years or more, with medical conditions at risk for VTE (surgical, trauma, and acute spinal injury patients) were identified. Hospital admissions on or after January 1, 2001, and concluded by March 31, 2005, were included if they met any of the following conditions as defined in the ACCP Consensus Conference on Antithrombotic Therapy guidelines: patients at risk of VTE medical conditions, major orthopedic surgery, general surgery, gynecological surgery, urologic surgery, trauma, neurosurgery, and acute spinal cord injury. Hospitalizations were identified using the International Classification of Diseases, 9th Revision, Clinical Modification codes. The primary objective was to examine whether patients received one of the indicated anticoagulants at the proper dosage and during the relevant hospital days as determined in the ACCP guidelines. Rates of compliance were assessed, and the reasons for guideline noncompliance were also determined. The overall compliance rate with ACCP guidelines was 13.3% (ranging from 2.8% for neurosurgery to 52.4% for orthopedic surgery) in the 123,304 hospital admissions that were reviewed. Only 15.3% of patients with at-risk medical conditions received prophylaxis in accordance with ACCP guidelines. Potential reasons for guideline noncompliance among selected conditions included the omission of prophylaxis, inadequate prophylaxis duration, and the wrong type of anticoagulant. A retrospective study found low rates of compliance with guidelines for thromboprophylaxis.


Identification of C3a and N-truncated C3a as vascular permeability-enhancing factors from the exudate of chronic phase of carrageenan-induced inflammation in rats.
Two basic proteins enhancing vascular permeability have been purified from the exudate of the chronic phase of carrageenan-induced inflammation in rats. One major and one minor peak on reversed-phase HPLC showed molecular masses of 9.3 kDa and 7.6 kDa, respectively, on sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions. NH2-terminal amino acid sequencing analysis of the purified proteins revealed that the major peak is identical to C3a, while the main sequence of the minor peak is identical to NH2-terminal 11 amino acids truncated C3a. In addition, plasmin was able to cleave C3a into the N-truncated C3a. Intradermal injection of both purified C3a and N-truncated C3a into rat skin enhanced vascular permeability, and the increased permeability was suppressed by the pretreatment with cyproheptadine. Our results suggest that the purified C3a and N-truncated C3a have the characteristics of anaphylatoxins and may contribute to exudation in the chronic phase of carrageenan-induced inflammation in rats.


Characteristics of histamine release from rat mast cells induced by a bracken toxin, braxin A1.
The effect of braxin A1, a new bracken glucoside, on histamine release from isolated rat peritoneal mast cells was studied. Braxin A1 caused the release of histamine in a dose-dependent manner; the release was slow and increased gradually with time, finally reaching a maximum release of 100%. The action of braxin A1 depended on the incubation temperature in the range from 4 degrees C to 49 degrees C, while it was almost abolished at 0 degree C. The action of braxin A1 was unaffected by removing calcium or any inorganic ions from the incubation medium and by the addition of 2,4-dinitrophenol or theophylline. The mast cells exposed to braxin A1 were vitally stained with trypan blue and swelled greatly. The cell swelling was characterized by the protrusion of swollen cytoplasmic granules. The present results for braxin A1 were similar to those for the ionophore X537A except for the extracellular inorganic ion dependency, but they were different from those observed with compound 48/80. These results suggest that braxin A1 releases histamine from mast cells without both exocytosis and membrane lysis, but with a cytotoxic action on cytoplasmic membranes by a different mode of action from that of X537A.


[Neurobehavioural testing in lead smelter workers].
Several recent meta-analyses, although some inconsistencies between studies, provide evidence for subtle deficits in neurobehavioural tests being associated with average blood levels (PbB) between 350 and 600 microg/l and for significant correlations between impairments in some test results and increasing indices present andlor cumulative exposure to inorganic lead. In this study we assessed the relationship between blood lead level (PbB) and results of some neurobehavioural tests derived from the SPES battery and from the WAIS-R among a sample of 94 lead smelter workers (median PbB: 302 microg/l; range: 60-690 microg/l). The stepwise multiple regression analysis shows that, even after adjusting for age, education level, score in the vocabulary test and for alcohol and cigarette consumption, the rise of PbB above 300 microg/l was significantly associated with the rise in the number of errors and in the response time of the Symbol Digit test. No significant relationship between PbB and results of the other tests was observed after adjusting for the main confounding factors. Despite the small size of this study and the few number of neurobehavioural tests applied, our results are suggestive for suble potential neurotoxic effects of inorganic lead even at the present exposure levels found in the studied sample of smelter workers and support the ACGIH BEI and the SCOEL recommendation for a biological limit of 300 microg/l of PbB.


Correlation between conductivity or diffusivity and activation energy in amorphous solids.
There exist many investigations of ionic transport in a variety of glasses. These studies exhibit strong correlation between ionic conductivity and activation energy: Typically, it is found that higher conductivity is associated with lower activation energies and vice versa. Although there are explanations for this at a phenomenological level, there is no consistent physical picture to explain the correlation between conductivity and activation energy. We have carried out molecular dynamics simulation as a function of the size of the impurity atom or diffusant (both neutral and charged) in a host amorphous matrix. We find that there is a maximum in self-diffusivity as a function of the size of the impurity atom suggesting that there is an appropriate size for which the diffusivity is maximum. The activation energy is found to be the lowest for this size of the impurity. A similar maximum has been previously found in other condensed phases, such as confined fluids and dense liquids, and has its origin in the levitation effect. The implications of this result for understanding ionic conductivity in glasses are discussed. Our results suggest that there is a relation between microscopic structure of the amorphous solid, diffusivity or conductivity, and activation energy. The nature of this relationship is discussed in terms of the levitation parameter showing that diffusivity is maximum when the size of the neck or doorway radius is comparable with the size of the diffusant. Our computational results here are in excellent agreement with independent experimental results of Nascimento et al. [Braz. J. Phys. 35, 626 (2005)] that structural features of the glass are important in determining the ionic conductivity.


Experience after 12 cases with the adjustable transobturator male sling for postprostatectomy stress urinary incontinence.
The aim of the study was the prospective evaluation of the efficacy of the adjustable transobturator male system (ArgusT®) for the treatment of postprostatectomy stress urinary incontinence (PPI). Twelve consecutive patients were treated with ArgusT system for PPI. All patients were comprehensively evaluated preoperatively and after 3 and 6 months regarding daily pad use, residual urine, Incontinence Quality of Life Scale (I-QoL) score and International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) score. Cure rate was defined as no pad use or one pad (used for security reasons). At 3 and 6 months, we achieved a cure rate of 91%. The mean number of pads per day decreased from 4 ± 1.3 to 0.7 ± 0.9 and 0.5 ± 0.9 after 3 and 6 months, respectively (p<0.001). Only one patient showed no significant improvement. Compared with baseline, the mean ICIQ-SF score dropped from 17.3 ± 2.8 to 2.7 ± 3.8 and 2.4 ± 3.8, at 3 and 6 months, respectively (p<0.001). The mean I-QoL score also improved significantly from 53.1 ± 20.3 to 99.5 ± 11 and 96.8 ± 12.5 after 3 and 6 months, respectively (p<0.001). Postoperative acute urinary retention was seen in one patient. In our early experience, the ArgusT system offers effective, safe and minimally invasive treatment option for PPI.


[Effect of temperature on the phototransformation of purple sulfur bacteria bacteriochlorophylls and isolated chromatophores].
Photobleaching of P890 was shown to be independent of temperature within the range of +20 to -160 degrees C in purple sulphur bacteria and isolated chromatophores under oxidative conditions; therefore changes in the absorption at 890 nm are due to the primary photoact. No changes were detected in the absorption at 850 nm upon a slight decrease of temperature, which suggested the absorption at 850 nm upon a slight decrease of temperature, which suggested the conformation nature of these changes. The effect of temperature, which suggested the conformation nature of these changes. The effect of temperature on the photoinduced changes of absorption under reductive conditions seems to be due to the electron transport and the accompanying processes being blocked. The effect of temperature on the kinetics of P890+ reduction in the darkness under conditions when the cytochromes are preliminarily oxidized is determined by the participation of the secondary electron acceptors in this process. A decrease in temperature leads to blocking the transport of electrons from the primary acceptor to the secondary acceptors, which is expressed by a gradual disappearance of a slow component in the kinetics of p890+ reduction in the disappearance of a slow component in the kinetics of P890+ reduction in the darkness and by the intensification of a fast component resulting from the darkness and by the intensification of a fast component resulting from the interaction between the primary acceptor and P890+. Methodical aspects of absorption differential spectrophotometry of photosynthesizing organisms at low temperatures are discussed.


Stem Cells in Skeletal Tissue Engineering: Technologies and Models.
This review surveys the use of pluripotent and multipotent stem cells in skeletal tissue engineering. Specific emphasis is focused on evaluating the function and activities of these cells in the context of development in vivo, and how technologies and methods of stem cell-based tissue engineering for stem cells must draw inspiration from developmental biology. Information on the embryonic origin and in vivo differentiation of skeletal tissues is first reviewed, to shed light on the persistence and activities of adult stem cells that remain in skeletal tissues after embryogenesis. Next, the development and differentiation of pluripotent stem cells is discussed, and some of their advantages and disadvantages in the context of tissue engineering are presented. The final section highlights current use of multipotent adult mesenchymal stem cells, reviewing their origin, differentiation capacity, and potential applications to tissue engineering.


Structural and functional identification of the uncharacterized metallo-β-lactamase superfamily protein TW9814 as a phosphodiesterase with unique metal coordination.
Metallo-β-lactamase (MBL) superfamily proteins have a common αβ/βα sandwich fold and perform a variety of functions through metal-mediated catalysis. However, because of the enormous scale of this superfamily, only a small percentage of the proteins belonging to the superfamily have been annotated structurally or functionally to date. Therefore, much remains unknown about the MBL superfamily proteins. Here, TW9814, a hypothetical MBL superfamily protein, was structurally and functionally investigated. Guided by the crystal structure of dimeric TW9814, it was demonstrated that TW9814 functions as a phosphodiesterase (PDE) in the presence of divalent metal ions such as manganese(II) or nickel(II). A docking model between TW9814 and the substrate bis(p-nitrophenyl)phosphate (bpNPP) showed the importance of the dimerization of TW9814 for its bpNPP-hydrolyzing activity and for the interaction between the enzyme and the substrate. TW9814 showed outstanding catalytic efficiency (kcat/Km) under alkaline conditions compared with other PDEs. The activity of TW9814 appears to be regulated through a disulfide bond, which is a feature that is not present in other MBL superfamily members. This study provides a platform for the functional characterization of other hypothetical proteins of the MBL or other superfamilies.


Fluctuation in electrolyte solutions: the self energy.
We address the issue of the self energy of the mobile ions in electrolyte solutions within a general Gaussian renormalized fluctuation theory using a field-theoretic approach. We introduce the Born radii of the ions in the form of a charge distribution allowing for different Born radii between the cations and anions. The model thus automatically yields a theory free of divergences and accounts for the solvation of the ions at the level of continuous dielectric media. In an inhomogeneous dielectric medium, the self energy is in general position dependent and differences in the self energy between cations and anions can give rise to local charge separation in a macroscopically neutral system. Treating the Born radius a as a smallness parameter, we show that the self energy can be split into an O(a(-1)) nonuniversal contribution and an O(a0) universal contribution that depends only on the ion concentration, valency, and the spatially varying dielectric constant. For a weakly inhomogeneous dielectric medium, the nonuniversal part of the self energy is shown to have the form of the Born energy with the local dielectric constant. This self energy is incorporated into the Poisson-Boltzmann equation as a simple means of including this local fluctuation effect in a mean-field theory. We illustrate the phenomenon of charge separation by considering cations and anions of difference sizes and valencies in a periodic dielectric medium.


Biodegradation of petroleum hydrocarbons in estuarine sediments: metal influence.
In this work, the potential effect of metals, such as Cd, Cu and Pb, on the biodegradation of petroleum hydrocarbons in estuarine sediments was investigated under laboratory conditions. Sandy and muddy non-vegetated sediments were collected in the Lima River estuary (NW Portugal) and spiked with crude oil and each of the metals. Spiked sediments were left in the dark under constant shaking for 15 days, after which crude oil biodegradation was evaluated. To estimate microbial abundance, total cell counts were obtained by DAPI staining and microbial community structure was characterized by ARISA. Culturable hydrocarbon degraders were determined using a modified most probable number protocol. Total petroleum hydrocarbons concentrations were analysed by Fourier Transform Infrared Spectroscopy after their extraction by sonication, and metal contents were determined by atomic absorption spectrometry. The results obtained showed that microbial communities had the potential to degrade petroleum hydrocarbons, with a maximum of 32 % degradation obtained for sandy sediments. Both crude oil and metals changed the microbial community structure, being the higher effect observed for Cu. Also, among the studied metals, only Cu displayed measurable deleterious effect on the hydrocarbons degradation process, as shown by a decrease in the hydrocarbon degrading microorganisms abundance and in the hydrocarbon degradation rates. Both degradation potential and metal influence varied with sediment characteristics probably due to differences in contaminant bioavailability, a feature that should be taken into account in developing bioremediation strategies for co-contaminated estuarine sites.


Depsidones from the endophytic fungus BCC 8616.
Three new depsidones (1-3) have been isolated from the endophytic fungus BCC 8616 and their structures analyzed on the basis of spectroscopic data interpretation. Compound 1 exhibited weak cytotoxic activity against breast and epidermoid carcinoma cell lines.


Lymphedema tarda.
The clinical recognition and evaluation of congenital lymphedema of the lower extremities with abrupt onset in a 51-year-old man are reviewed. A rational, systematic approach is outlined and exemplifies the use of an interdisciplinary effort to achieve accurate diagnosis through readily available diagnostic procedures.


Ginsenoside Rd from Panax notoginseng is cytotoxic towards HeLa cancer cells and induces apoptosis.
The saponin ginsenoside Rd (1), isolated from Panax notoginseng, is used for the treatment of cardiovascular diseases, inflammation, different body pains, trauma, and internal and external bleeding due to injury. In this study, we report that 1 inhibits the cell growth of human cervical cancer (HeLa) cells in a concentration- and time-dependent manner, with an IC(50) value of 150.5+/-0.8 mcirog/ml after 48 h of incubation. The drug-treated cells displayed features of apoptosis, including typical morphological characteristics and formation of DNA ladders, as evident from agarose-gel electrophoresis. Flow-cytometric analysis showed that the cell-cycle distribution of HeLa cells exposed to 1 is characterized by a decrease of the G(0)/G(1)-phase and an increase of the S-phase cells, respectively, in a dose-dependent manner. The apoptotic rate of HeLa cells treated for 48 h with 210 microg/ml of 1 was 35.8%. Further, 1 was found to increase the expression of Bax and to decrease the expression of Bcl-2 proteins, respectively, and to lower the mitochondrial transmembrane potential of HeLa cells. The caspase-3 inhibitor DEVD-CHO (at 2 microM) increased the viability of HeLa cells treated with 1. Taken together, our study suggests that ginsenoside Rd (1) significantly inhibits HeLa cell proliferation, and induces cell apoptosis through down-regulating Bcl-2 expression, up-regulating Bax expression, lowering the mitochondrial transmembrane potential, and activating the caspase-3 pathway. Thus, 1 could serve as a lead to develop novel chemotherapeutic or chemopreventive agents against human cervical cancer.


Periodic change of viscosity and density in an oscillating chemical reaction.
It was found that the periodic change of the solution viscosity and density was generated in the Belousov-Zhabotinsky (BZ) reaction. This rhythmic phenomenon was observed in both the iron catalyst [[Fe(Phen)(3)](2+)-[Fe(Phen)(3)](3+)] and the cerium catalyst [Ce(III)-Ce(IV)] system, where the solution viscosity and density were synchronized with the redox potential in the in-phase mode. However, the time delay existed between the redox potential and the solution viscosity and density. The behavior of the BZ reaction was also monitored in the presence of the nonionic surfactant. This experiment revealed that, beyond the critical micelle concentration, the phase between the redox potential and the solution viscosity and density was synchronized into the antiphase mode. We suggested that the variation of the catalyst drove the oscillation of the solution viscosity and density in the BZ reaction.


Pentoxifylline as adjunctive therapy in cognitive deficits and symptoms of schizophrenia: A randomized double-blind placebo-controlled clinical trial.
Due to the inflammatory factors in the pathophysiology of schizophrenia, Pentoxifylline, as anti-inflammatory medication, seems to improve the symptoms of schizophrenia. This study aims to evaluate the efficacy of Pentoxifylline as an adjunctive therapy on cognitive deficits and symptoms of schizophrenia. This randomized double-blind placebo-controlled clinical trial was conducted on 52 patients diagnosed with chronic schizophrenia. All patients were divided into two, treatment and control groups. They received a 400 mg dose of Pentoxifylline and the placebo in the treatment and control groups, respectively, twice a day for 8 weeks. Then, they were tested with the Positive and Negative Syndrome Scale (PANSS), Wisconsin Card Sorting Test (WCST), digit span, Stroop test, and Rey Auditory and Verbal Learning Test at baseline and the end of the weeks 4 and 8. Data analysis was done by Kolmogorov-Smirnov test, t-test, Mann-Whitney test, chi-square test, and generalized estimating equation model. After analyzing the data, it was revealed that the positive symptoms of PANSS, the number of errors in the incongruent Stroop test, and reaction time in the congruent Stroop test were significantly lower in the treatment group (p < 0.05). Moreover, the number of categories of WCST was significantly higher in the treatment group (p < 0.05). There was no statistically significant difference in other parameters between the control and treatment groups (p > 0.05). As evidenced by the results of this study, Pentoxifylline can help alleviate schizophrenia cognitive deficits and can reduce psychotic symptoms. Therefore, it can potentially be useful for schizophrenia treatment.


An acid phosphatase from Aspergillus ficuum has homology to Penicillium chrysogenum PhoA.
Three secreted acid phosphatases had previously been characterized from Aspergillus ficuum grown under conditions of limited phosphate. One of these could not be readily separated from AFPhyB, a pH 2.5 optimum acid phosphatase with phytase activity. From extensive protein sequence analysis and subsequent cloning of the gene, we have shown that the AFPhyB protein fraction contains a fourth secreted acid phosphatase (AFPhoA) that has 64% homology to a phosphate-repressible acid phosphatase from Penicillium chrysogenum. Garnier plot analysis revealed that the putative phosphate catalytic domain of AFPhoA at His215Asp216 is similar to those of other acid phosphatases, but that AFPhoA lacks the phosphate-binding motif RHGXRXP of known histidine phosphatases.


Cerebral phaeohyphomycosis caused by Cladosporium spp. in two domestic shorthair cats.
Two domestic shorthair cats presented for clinical signs related to multifocal central nervous system dysfunction. Both cats had signs of vestibular system involvement and anisocoria, and one had generalized seizure activity. Cerebrospinal fluid analysis revealed a neutrophilic pleocytosis with protein elevation in one cat and pyogranulomatous inflammation in the second. Electroencephalography and brain-stem auditory-evoked potentials in the first cat confirmed cerebral cortical and brain-stem involvement. Euthanasia was performed in both cats, and postmortem diagnoses of phaeohyphomycosis secondary to Cladosporium spp. were made based on histopathology and fungal culture in both cats.


[The effect of water with modified isotope (D/H) composition on the reproductive function and postnatal development in rats].
Reproductive parameters and postnatal progeny development were evaluated in 4 generations of Wistar rats treated with deuterium depleted water (DDW): parental (F0), first (F1), second (F2) and third (F3). The experiment was carried out on 2 groups of animals: experimental group consumed DDW (50 ppm) and control group consumed purified tap water (150 ppm). Experiment was consist of a preparatory stage, the stage of studying the F0, F1, F2 reproductive parameters and F1, F2, F3 postnatal progeny development Reproductive parameters was assessed by F0, F1, F2 fertility index and F1, F2, F3 offspring viability and development. Fertility index was assessed as the male's ability to fertilize females in the percentage of pregnant females/fertilized males to the total number females and males placed together for mating. Offspring maturing were evaluated by pups viability, development of physical and sexual parameters, emotional and locomotors reflexes within the 1st month of life. Group 1 fertility index in F0 females was 100%, in F1 and F2 females - 99%, in males all generations - 89-100%. Group 1 F1, F2 and F3 offspring viability was high. Number of pups in group 1 F2 offspring was higher by 20% than in group 2. Pups of the 1st group F1, F2 and F3 were less intensively gained weight from the 1st to the 21st day of life compared with group 2, the final weight of the animals in group 1 was higher than in group 2 by 4-6% from 25th to 30th days of life. Assessment of physical parameters development as well as emotional and locomotors reflexes formation did not reveal any difference between group 1 and group 2 F1, F2 and F3 offspring. Obtained results confirmed that DDW did not effect on rat fertility, viability and development of offspring.


Intracavitary right heart cooling during coronary bypass surgery. A prospective randomized trial.
Augmented right heart cooling (RHC) with bicaval cannulation, pulmonary artery venting, and intracavitary cooling has been advocated for prevention of right ventricular failure and supraventricular tachyarrhythmias after open heart surgery. To evaluate RHC, 78 patients undergoing coronary bypass surgery were prospectively randomized to receive added RHC (n = 38) or standard protection with single atrial cannulation (SC) (n = 40). RHC and SC patients were similar regarding right coronary artery occlusion (n = 10 and 12, respectively), number of grafts performed (3.7 +/- 1.0 and 3.4 +/- 0.9), and cross-clamp time per graft (10.2 +/- 1.8 and 9.8 +/- 2.3 minutes). RHC led to significantly lower right atrial (11.6 degrees +/- 1.0 degree vs. 19.5 degrees +/- 3.3 degrees C) and right ventricular (7.2 degrees +/- 1.9 degrees vs. 12.2 degrees +/- 1.9 degrees C) temperatures. There was no detectable deterioration in right heart function or left heart function in either group after cardiopulmonary bypass. Bypass time was longer in RHC patients (86.7 +/- 17.9 vs. 76.0 +/- 18.2 minutes, p less than 0.05). Technical problems related to multiple cannulation occurred in four RHC patients. After cross-clamp removal, creatine kinase-MB levels were significantly higher with RHC at 2 hours (14.2 +/- 7.6 vs. 6.4 +/- 4.6 IU/l, p less than 0.001), 12 hours (19.1 +/- 19.5 vs. 8.6 +/- 10.3 IU/l, p less than 0.005), and 24 hours (14.1 +/- 19.6 vs. 7.1 +/- 9.2 IU/l, p less than 0.05). Mortality and morbidity were similar in the two groups. In particular, supraventricular tachyarrythmias occurred in 11 (28.9%) RHC and 10 (25%) SC patients.(ABSTRACT TRUNCATED AT 250 WORDS)


Research on Toxocara canis antibodies obtained from patients with eosinophilia.
Eosinophils may suggest the presence of a great variety of anomalies whereupon allergies, malignancies, certain tissue disorders, idiopathic hypereosynophilic syndrome and parasitic infections (with the exception of protozoons) can be cited as a few. Although the clinical manifestations may differ, the eosinophils level is quite an important data in cases related to the helminth infections. Similarly, in parasitic infections related to larva migrans (visceral, cutaneous, ocular), the eosinophils level is again a primary indicator and its evident cause is the roundworm Toxocara spp. The aim of this study was to evaluate the significance characteristics of Toxocara spp. in patients with eosonophilia. In our study, serums were collected from 93 patients of various age groups with eosonophilia (10% and above) while visiting Istanbul University Medical Faculty due to various complaints. Serum samples were treated with Toxocara IgG ready ELISA kit and Toxocara western blot IgG ready kit. Based on the ELISA method; out of 93 patients, 30 patients (32.3%) were positive. Western blot technique; 45 (48.4%) were positive with anti-toxocara IgG antibodies. Results point out to western blot technique being more sensitive and superior on a scale of (P < 0.0001) when compared with the ELISA method.


Pancreatic neuroendocrine neoplasms - management guidelines (recommended by the Polish Network of Neuroendocrine Tumours).
This article presents updated diagnostic and therapeutic guidelines for the management of pancreatic neuroendocrine tumours (PNEN), proposed by the Polish Network of Neuroendocrine Tumours. The guidelines contain new data received in the years 2013-2016, which confirm previous recommendations, and have led to modification of previous guidelines or have resulted in the formulation of new guidelines. Biochemical and imaging (anatomical and functional) tests are of great importance in diagnostics, as well as histopathological diagnosis to determine the management of PNEN patients, but they must be confirmed by an immunohistochemical examination. PNEN therapy requires collaboration among the members a multidisciplinary team of specialists experienced in the management of these neoplasms. Surgery is the basic form of treatment in many cases. Further therapy requires a multidirectional procedure; therefore, the rules of biotherapy, peptide receptor radionuclide therapy, molecular targeted therapy, and chemotherapy are discussed.


Pharmacokinetics of intramuscularly administered aminosidine in healthy subjects.
Aminosidine is an older, broad-spectrum aminoglycoside antibiotic that has been shown to be effective in in vitro and animal models against multiple-drug-resistant tuberculosis and the Mycobacterium avium complex. The objective of this randomized, parallel trial was to characterize the single-dose pharmacokinetics of aminosidine sulfate in healthy subjects (eight males, eight females). Sixteen adults (mean [+/- standard deviation] age, 27.6 +/- 5.6 years) were randomly allocated to receive a single, intramuscular aminosidine sulfate injection at a dose of 12 or 15 mg/kg of body weight. Serial plasma and urine samples were collected over a 24-h period and used to determine aminosidine concentrations by high-performance liquid chromatographic assay. A one-compartment model with first-order input, first-order output, and a lag time (Tlag) and with a weighting factor of 1/y2 best described the data. Compartmental and noncompartmental pharmacokinetic parameters were estimated with the microcomputer program WinNonlin. One subject was not included (15-mg/kg group) because of the lack of sampling time data. On average, subjects attained peak concentrations of 22.4 +/- 3.2 microg/ml at 1.34 +/- 0.45 h. All subjects had plasma aminosidine concentrations below 2 microg/ml at 12 h, and all but two subjects (one in each dosing group) had undetectable plasma aminosidine concentrations at 24 h. The dose-adjusted area under the concentration-time curve from 0 h to infinity of aminosidine was identical for the 12- and 15-mg/kg groups (9.29 +/- 1.5 versus 9.29 +/- 2.2 microg x h/ml per mg/kg; P = 0.998). Similarly, no significant differences (P > 0.05) were observed between dosing groups for peak aminosidine concentration in plasma, time to peak aminosidine concentration in plasma, Tlag, apparent clearance, renal clearance, elimination rate constant, and elimination half-life. A significant difference was observed for the volume of distribution (0.35 versus 0.41 liters/kg; P = 0.037) between the 12 and 15 mg/kg dosing groups. Now that comparable pharmacokinetic profiles between dosing groups have been demonstrated, therapeutic equivalency testing via in vitro pharmacokinetic and pharmacodynamic modelling and randomized clinical trials in humans should be conducted.


Measurement of the spin relaxation time of single electrons in a silicon metal-oxide-semiconductor-based quantum dot.
We demonstrate direct detection of individual electron spin states, together with measurement of spin relaxation time (T1), in silicon metal-oxide-semiconductor-based quantum dots (QD). Excited state spectroscopy of the QD has been performed using a charge-sensing technique. T1 of single spin excited states has been done in the time domain by a pump-and-probe method. For an odd and an even number of electrons, we found a magnetic field dependent and invariant T1, respectively.


Marmoset Viral Hepatic Inflammation Induced by Hepatitis C Virus Core Protein via IL-32.
Common marmosets infected with GB virus-B (GBV-B) chimeras containing hepatitis C virus (HCV) core and envelope proteins (CE1E2p7) developed more severe hepatitis than those infected with HCV envelope proteins (E1E2p7), suggesting that HCV core protein might be involved in the pathogenesis of viral hepatitis. The potential role of HCV core in hepatic inflammation was investigated. Six individual cDNA libraries of liver tissues from HCV CE1E2p7 or E1E2p7 chimera-infected marmosets (three animals per group) were constructed and sequenced. By differential expression gene analysis, 30 of 632 mRNA transcripts were correlated with the immune system process, which might be associated with hepatitis. A protein-protein interaction network was constituted by STRING database based on these 30 differentially expressed genes (DEGs), showing that IL-32 might play a central regulatory role in HCV core-related hepatitis. To investigate the effect of HCV core protein on IL-32 production, HCV core expressing and mock constructs were transfected into Huh7 cells. IL-32 mRNA and secretion protein were detected at significantly higher levels in cells expressing HCV core protein than in those without HCV core expression (P < 0.01 and P < 0.001, respectively). By KEGG enrichment analysis and using the specific signaling pathway inhibitor LY294002 for inhibition of PI3K, IL-32 expression was significantly reduced (P < 0.001). In conclusion, HCV core protein induces an increase of IL-32 expression via the PI3K pathway in hepatic cells, which played a major role in development of HCV-related severe hepatitis.


Parabrachial area and nucleus raphe magnus-induced modulation of nociceptive and nonnociceptive trigeminal subnucleus caudalis neurons activated by cutaneous or deep inputs.
1. The aim of this study was to test whether parabrachial area (PBA) stimulation exerts inhibitory influences on the spontaneous activity and responses evoked by skin and deep afferent inputs in trigeminal subnucleus caudalis (Vc) neurons, and to compare these effects with those of nucleus raphe magnus (NRM) stimulation. A total of 92 nonnociceptive and nociceptive Vc neurons was recorded in urethan/alpha-chloralose-anesthetized rats. Each neuron was functionally classified as low-threshold mechanoceptive (LTM), wide dynamic range (WDR), nociceptive-specific (NS), nociceptive convergent with both skin and deep inputs (S+D), or deep nociceptive (D); the LTM neurons could be subdivided as rapidly adapting (RA) or slowly adapting (SA). Conditioning stimulation was applied to histologically verified sites in PBA and NRM. 2. The spontaneous or evoked activity of all classes of neurons could be inhibited by PBA as well as by NRM stimulation, but generally the incidence and magnitude of inhibition were lower for the LTM neurons. Occasionally, facilitation of neuronal activity was also produced by PBA and NRM stimulation. 3. The spontaneous activity of 11 LTM neurons (6 RA, 5 SA), 13 nociceptive neurons (6 WDR, 7 NS), and 5 D neurons was tested with stimulation of PBA or NRM or both. LTM spontaneous activity was more significantly inhibited by NRM stimulation than by PBA stimulation, whereas both NRM and PBA stimulation had similar and significant inhibitory effects on NS, WDR, and D neurons. 4. The evoked nonnociceptive responses of 28 LTM neurons (16 RA, 12 SA) and of 6 WDR neurons were also tested with stimulation of PBA or NRM or both. The magnitudes of inhibition of the responses produced by PBA conditioning stimulation were statistically significantly less than those induced by NRM conditioning stimulation. 5. The cutaneous and deep nociceptive responses of cutaneous nociceptive neurons (9 NS, 19 WDR) and seven D neurons, respectively, were also tested with PBA and NRM stimulation. There was a significant difference in potency between PBA- and NRM-induced inhibition, but no difference in the magnitude of inhibitory effects among NS, WDR, and D neurons. For both PBA and NRM conditioning stimulation, graded increases in intensities of stimulation produced linear increases in inhibitory effects on nociceptive responses; an increase in stimulation frequency from 5 to 400 Hz also produced increases in inhibition of the nociceptive responses. 6. In five S+D nociceptive convergent neurons, the responses elicited by deep inputs were more powerfully inhibited by PBA stimulation than those elicited by cutaneous inputs.(ABSTRACT TRUNCATED AT 400 WORDS)


Insulin-like growth factor binding protein-3. Organization of the human chromosomal gene and demonstration of promoter activity.
Insulin-like growth factor binding protein-3 (IGFBP-3) can modulate the mitogenic and metabolic effects of the insulin-like growth factors (IGFs). IGFBP-3 protein levels are developmentally regulated and influenced by a number of hormonal stimuli both in vitro and in vivo. As a first step toward understanding how hormonal and developmental factors regulate IGFBP-3 production, we are characterizing the human IGFBP-3 chromosomal gene and promoter. Southern analysis demonstrates a single copy of the IGFBP-3 gene in the human genome. This gene spans 8.9 kilobases; the protein-coding region is divided into four exons while a fifth exon contains the 3'-untranslated region. Primer extension studies locate the IGFBP-3 mRNA cap site 132 base pairs 5' to the ATG translation initiation codon. On the chromosomal gene, this cap site is located 30 base pairs 3' to the start of a TATA box and 97 base pairs 3' to a consensus GC upstream promoter element, an organization common to many eukaryotic promoters. When this potential IGFBP-3 promoter region is placed upstream to the chloramphenicol acetyltransferase reporter gene, it directs high-level production of chloramphenicol acetyltransferase in transfected COS-1 cells. These observations suggest an uncomplicated organization for the IGFBP-3 chromosomal gene and promoter in the human genome.


Community-based participatory research: understanding a promising approach to addressing knowledge gaps in palliative care.
Concern over the need for effective and accessible healthcare for individuals with advanced chronic illness has drawn attention to the significant gaps in our knowledge of palliative medicine. To advance our understanding of this field, community-based participatory research (CBPR) is proposed as a tool for future research initiatives. This paper offers a rationale for how CBPR may be employed to address specific gaps in palliative care research. Several examples where this approach has been used previously are described, and potential obstacles to implementing this research method are delineated. Despite challenges to incorporating CBPR to palliative care research, this approach holds substantial potential to advance our current understanding of the field and promote sensitivity for future programs, practices and policies.


Relationship Between Anifrolumab Pharmacokinetics, Pharmacodynamics, and Efficacy in Patients With Moderate to Severe Systemic Lupus Erythematosus.
This study aimed to elucidate the pharmacokinetic/pharmacodynamic and pharmacodynamic/efficacy relationships of anifrolumab, a type I interferon receptor antibody, in patients with moderate to severe systemic lupus erythematosus. Data were pooled from the randomized, 52-week, placebo-controlled TULIP-1 and TULIP-2 trials of intravenous anifrolumab (150 mg/300 mg, every 4 weeks for 48 weeks). Pharmacodynamic neutralization was measured with a 21-gene type I interferon gene signature (21-IFNGS) in patients with high IFNGS. The pharmacokinetic/pharmacodynamic relationship was analyzed graphically and modeled with a nonlinear mixed-effects model. British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) response rates were compared across 21-IFNGS neutralization quartiles. Overall, 819 patients received ≥1 dose of anifrolumab or placebo, of whom 676 were IFNGS high. Over 52 weeks, higher average anifrolumab serum concentrations were associated with increased median 21-IFNGS neutralization, which was rapid and sustained with anifrolumab 300 mg (>80%, weeks 12-52), lower and delayed with anifrolumab 150 mg (>50%, week 52), and minimal with placebo. The proportion of patients with week 24 anifrolumab trough concentration exceeding the IC80 (3.88 μg/mL) was greater with anifrolumab 300 mg vs anifrolumab 150 mg (≈83% vs ≈27%), owing to the higher estimated median trough concentration (15.6 vs 0.2 μg/mL). BICLA response rates increased with 21-IFNGS neutralization; more patients had a BICLA response in the highest vs lowest neutralization quartiles at week 52 (58.1% vs 37.6%). In conclusion, anifrolumab 300 mg every 4 weeks rapidly, substantially, and sustainably neutralized the 21-IFNGS and was associated with clinical efficacy, supporting this dosing regimen in patients with systemic lupus erythematosus.


Determination of diclofenac sodium in commercial pharmaceutical formulations and human control serum using a kinetic-spectrophotometric method.
A kinetic method for the determination of micro quantities of diclofenac sodium (DS) is described in this paper. The method is based on a ligand-exchange reaction. The reaction was followed spectrophotometrically by monitoring the rate of appearance of the cobalt diclofenac complex at 376 nm. The optimum operating conditions regarding reagent concentrations and temperature were established. The optimized conditions yielded a theoretical detection limit of 1.29 microg ml(-1) based on the 3S(b) criterion. The interference effects of certain drugs, foreign ions and amino acids upon the reaction rate were studied in order to assess the selectivity of the method. The developed procedure was successfully applied to the rapid determination of diclofenac sodium in commercial pharmaceutical preparations and human control serum. The unique features of this procedure are that determination can be carried out at room temperature and the analysis time is short. The newly developed method is simple, inexpensive, and efficient for use in the analysis of a large number of samples.


Sonochemical Synthesis of a Zinc Oxide Core-Shell Nanorod Radial p-n Homojunction Ultraviolet Photodetector.
We report for the first time on the growth of a homogeneous radial p-n junction in the ZnO core-shell configuration with a p-doped ZnO nanoshell structure grown around a high-quality unintentionally n-doped ZnO nanorod using sonochemistry. The simultaneous decomposition of phosphorous (P), zinc (Zn), and oxygen (O) from their respective precursors during sonication allows for the successful incorporation of P atoms into the ZnO lattice. The as-formed p-n junction shows a rectifying current-voltage characteristic that is consistent with a p-n junction with a threshold voltage of 1.3 V and an ideality factor of 33. The concentration of doping was estimated to be NA = 6.7 × 1017 cm-3 on the p side from the capacitance-voltage measurements. The fabricated radial p-n junction demonstrated a record optical responsivity of 9.64 A/W and a noise equivalent power of 0.573 pW/√Hz under ultraviolet illumination, which is the highest for ZnO p-n junction devices.


Detection of focal inflammation with Tc-99m HMPAO labeled leukocytes in children.
To evaluate the applicability of Tc-99m HMPAO leukocyte scintigraphy in the assessment of focal infections in children, we retrospectively analyzed 26 studies performed between 1988 and 1992. All patients (n = 25, age range 1 month-15 years) were severely ill and suspected to have invasive bacterial infection. In each case, whole body scintigraphy was performed 2-4 hours after injection of autologous labeled leukocytes. There were 8 true positive and 14 true negative cases; specificity was 88% and sensitivity 80%. The two false negative findings were observed in patients on immunosuppressive therapy; both had fungal infections. In one case, atypical non-specific bowel accumulation of the tracer was falsely interpreted as an abscess. The other false positive finding was hip accumulation in a patient who later turned out to have Mucha-Haberman disease; transient synovitis may explain the finding. Of the eight true positive cases, six had an invasive infection focus and two had an aseptic inflammatory process. Tc-99m HMPAO leukocyte scintigraphy is a valuable method in the assessment of focal inflammation in children, including infants.


Gastrointestinal stromal tumors with BRAF gene fusions. A report of two cases showing low or absent KIT expression resulting in diagnostic pitfalls.
Although most gastrointestinal stromal tumors (GISTs) exhibit activating mutations in either KIT or PDGFRA, rare cases have shown to be driven by gene fusions involving kinases, mainly involving NTRK3, and rarely BRAF or FGFR1. BRAF gene rearrangements have been described in only two patients to date, as separate case reports. In addition, BRAF V600E mutation is an uncommon but established oncogenic pathway in GIST. In this report, we describe two new GIST cases harboring novel BRAF fusion genes, arising in two young-adult women (37 and 40 years of age) in the small bowel and distal esophagus, both with a spindle cell phenotype. The small bowel GIST measured 2.8 cm and showed a high cellularity and a mitotic rate of 20/50 HPFs, while the esophageal lesion measured 7 cm and 1/50 HPFs. Immunohistochemically, both tumors showed diffuse reactivity for DOG1, while KIT/CD117 was weakly positive in the small bowel GIST and completely negative in the esophageal tumor. Based on these findings, the latter case was misinterpreted as a low-grade myxoid leiomyosarcoma, as it showed a myxoid stroma, reactivity for SMA and focal positivity for desmin. Archer FusionPlex revealed a fusion between BRAF with either AGAP3 or MKRN1 gene partners. Moreover, MSK-IMPACT DNA targeted sequencing confirmed both fusions but did not identify additional mutations. In one case with available material, the BRAF gene rearrangement was also validated by FISH. The recognition of BRAF fusion-positive GISTs is critical as it may be associated with a low level of KIT expression and may result in diagnostic challenges with significant impact on therapeutic management. The clinical benefit with KIT inhibitors, such as imatinib, remains to be determined.


Developmental differences in the understanding of and reaction to others' inhibition of emotional expression.
In Study 1,160 individuals from kindergarten (kd), 3rd, 6th, 9th, and college grades were presented story protagonists who facially expressed or did not express sadness/fear when encountering events that likely caused (relevant-inhibitory cause) or did not cause (irrelevant cause) the inhibition of the expression of emotion. In Study 2, 108 kd, 3rd-, and 6th-grade children viewed peers engaging in real interactions similar to the stories. In both studies, kindergartners judged that relevant-inhibitory causes decreased a peer's emotions. Older individuals displayed an understanding of the inhibition of emotional expression by ascribing greater emotion to the peer under relevant-inhibitory than irrelevant causal conditions. In Study 2, age differences in children's search for social information and prosocial behavior paralleled judgments of emotion.


The role of the primary care physician in the management of bladder dysfunction.
Urinary incontinence is a major health challenge for primary care physicians. Unfortunately, the majority of incontinent patients remain untreated. Primary care physicians are ideally positioned to screen for and manage urinary incontinence. A knowledge of basic micturition physiology is important for the physician to accurately identify the cause of incontinence and arrive at the correct treatment course. To this end, this article reviews the physiology of the lower urinary tract, describes the clinical types of urinary incontinence, and outlines a stepwise approach for the primary care physician to the basic evaluation and management of patients with this condition.


Immunotherapy of tumors with vaccines based on xenogeneic homologous molecules.
This review summarizes and discusses a new vaccine strategy based on xenogeneic homologous molecules by the breaking of immune tolerance against the growth factors or their receptors associated with tumor growth in a cross-reaction between the xenogeneic homologs and self-molecules. The xenogeneic vaccine may circumvent the fact that few tumor-specific antigens have been identified in human solid tumors and that the host usually shows immune tolerance to self-molecules as antigens. It may be of importance for the further exploration of the applications of xenogeneic homologous genes identified in human and other animal genome sequence projects in cancer therapy.


Rupture of the spleen in a newborn infant: report of a new roentgen sign.
The authors report a case of splenic rupture diagnosed preoperatively in a newborn infant. High-dose excretory urography is recommended in newborn infants who exhibit signs of severe anemia or hemoperitoneum.


Metadiffusers: Deep-subwavelength sound diffusers.
We present deep-subwavelength diffusing surfaces based on acoustic metamaterials, namely metadiffusers. These sound diffusers are rigidly backed slotted panels, with each slit being loaded by an array of Helmholtz resonators. Strong dispersion is produced in the slits and slow sound conditions are induced. Thus, the effective thickness of the panel is lengthened introducing its quarter wavelength resonance in the deep-subwavelength regime. By tuning the geometry of the metamaterial, the reflection coefficient of the panel can be tailored to obtain either a custom reflection phase, moderate or even perfect absorption. Using these concepts, we present ultra-thin diffusers where the geometry of the metadiffuser has been tuned to obtain surfaces with spatially dependent reflection coefficients having uniform magnitude Fourier transforms. Various designs are presented where, quadratic residue, primitive root and ternary sequence diffusers are mimicked by metadiffusers whose thickness are 1/46 to 1/20 times the design wavelength, i.e., between about a twentieth and a tenth of the thickness of traditional designs. Finally, a broadband metadiffuser panel of 3 cm thick was designed using optimization methods for frequencies ranging from 250 Hz to 2 kHz.


Vessel Wall Imaging of the Intracranial and Cervical Carotid Arteries.
Vessel wall imaging can depict the morphologies of atherosclerotic plaques, arterial walls, and surrounding structures in the intracranial and cervical carotid arteries beyond the simple luminal changes that can be observed with traditional luminal evaluation. Differentiating vulnerable from stable plaques and characterizing atherosclerotic plaques are vital parts of the early diagnosis, prevention, and treatment of stroke and the neurological adverse effects of atherosclerosis. Various techniques for vessel wall imaging have been developed and introduced to differentiate and analyze atherosclerotic plaques in the cervical carotid artery. High-resolution magnetic resonance imaging (HR-MRI) is the most important and popular vessel wall imaging technique for directly evaluating the vascular wall and intracranial artery disease. Intracranial artery atherosclerosis, dissection, moyamoya disease, vasculitis, and reversible cerebral vasoconstriction syndrome can also be diagnosed and differentiated by using HR-MRI. Here, we review the radiologic features of intracranial artery disease and cervical carotid artery atherosclerosis on HR-MRI and various other vessel wall imaging techniques (e.g., ultrasound, computed tomography, magnetic resonance, and positron emission tomography-computed tomography).


Association between abdominal muscle stiffness, diaphragm thickness and peak expiratory flow in younger versus older adults.
The present study aimed to evaluate forced expiration based on transverse abdominis (TrA) stiffness by identifying the relationship between TrA stiffness and peak expiratory flow (PEF) in both younger and older adults. We also assessed the relationship between diaphragm thickness and PEF. A total of 31 younger (21.24 ± 2.73 years) and 34 older (71.35 ± 5.26 years) adults were included in the present study. TrA muscle stiffness was measured at rest and during abdominal bracing using shear wave elastography. Diaphragm thickness was measured during deep inspiration and expiration using B-mode ultrasound, and respiratory function was assessed by measuring PEF using a spirometer. We found that TrA stiffness during bracing was significantly lower in older than younger adults (p < 0.05). Similarly, the difference in absolute stiffness of the TrA when bracing versus at rest was significantly lower in older than younger adults (p < 0.05). Additionally, TrA stiffness during bracing was positively associated with PEF in the younger group (r = 0.483), while a very weak correlation was found in the older group (r = 0.172). Similarly, PEF was moderately correlated with diaphragm thickness during expiration as well as during changes between inspiration and expiration in the younger group (r = 0.405 and r = 0.403); however, no significant correlation was found in the older group. These findings of the present study indicate that the variations in PEF between younger and older adults may be due to age-associated changes in the musculoskeletal structure and muscle fibre type.


Neuroleptanalgesia for intra-ocular surgery: experience in a developing country.
A technique of neuroleptanalgesia is described for effective and reliable sedation during intra-ocular surgery under local analgesia. The absence of side effects using modified neuroleptanalgesia was of particular value in a situation in a developing country in which large numbers of patients had to be handled in a comparatively short period of time.


Acoustic analysis of speech tasks performed by three individuals with spinocerebellar ataxia.
A number of speech tasks produced by three female subjects with different types of genetically diagnosed spinocerebellar ataxia and with mild dysarthria were investigated using acoustic instrumentation. All subjects showed a number of signs of decreased speech rate, increased pause duration, increased and more variable durations of alternating motion rate, sequential motion rate syllables and inter-stress intervals in addition to vocal instability. These signs were consistent with the perceptual judgment of ataxic dysarthria. Furthermore, the severity of impairment found using these speech analysis methods seemed to correspond to the general severity of the disease and the duration of the illness in these few subjects. The tasks studied appeared to be relevant and suitable for acoustic analyses as they did reveal deviations in the speech of the subjects compared with controls.


Focal fibrocartilaginous dysplasia ("fibrous periosteal inclusion"): an additional series of eleven cases and literature review.
Focal fibrocartilaginous dysplasia (FFCD) is a benign condition first described in 1985 as a cause of tibia vara. We are reporting on 11 cases. The lesions involved proximal tibia (9 cases), distal femur (1 case), and distal ulna (1 case). We believe that this entity represents a bony anchor preventing natural sliding of the periosteum during growth (an "epiphysiodesis-like" effect). For the tibia, we believe this is the pes anserinus. We are suggesting that this entity be called a "fibrous periostal inclusion." Treatment indications result from this concept: (1) for tibial lesions with a metaphyseal-diaphyseal angle less than 20 degrees observation for 6 to 12 months; (2) if the deformity improves, the tether likely broke spontaneously, and no treatment is required; and (3) curettage early if the deformity worsens. This will be followed by rapid correction into physiological valgus (tibia) and prevent the need for osteotomy. Early curettage for other less common locations is recommended.


Sulfones as Synthetic Linchpins: Transition-Metal-Free sp3 -sp2 and sp2 -sp2 Cross-Couplings Between Geminal Bis(sulfones) and Organolithium Compounds.
A valuable umpolung strategy that highlights the ambiphilic nature of the bis(phenylsulfonyl)methyl synthon and demonstrates its utility as a synthetic linchpin is reported. Although the bis(phenylsulfonyl)methyl group is typically introduced as an sp3 -carbon nucleophile, it is demonstrated that it can also function as an effective sp2 -carbon electrophile in the presence of organolithium nucleophiles. Alkyl- and aryllithiums couple with the central carbon of the bis(phenylsulfonyl)methyl unit to ultimately generate trisubstituted alkenes, comprising formal sp3 -sp2 and sp2 -sp2 cross-couplings between organolithium reagents and bis(sulfones). This process occurs almost instantaneously at -78 °C in the absence of any transition metals. By developing this curious transformation, it has been demonstrated that bis(phenylsulfonyl)methane is a valuable synthetic linchpin, which can undergo two C-C bond-forming processes as an sp3 -nucleophile, followed by a third C-C bond-forming reaction as an effective sp2 -electrophile. This discovery significantly enhances the utility of this ubiquitous, but underutilized, linker group.


Do social insects support Haig's kin theory for the evolution of genomic imprinting?
Although numerous imprinted genes have been described in several lineages, the phenomenon of genomic imprinting presents a peculiar evolutionary problem. Several hypotheses have been proposed to explain gene imprinting, the most supported being Haig's kinship theory. This theory explains the observed pattern of imprinting and the resulting phenotypes as a competition for resources between related individuals, but despite its relevance it has not been independently tested. Haig's theory predicts that gene imprinting should be present in eusocial insects in many social scenarios. These lineages are therefore ideal for testing both the theory's predictions and the mechanism of gene imprinting. Here we review the behavioral evidence of genomic imprinting in eusocial insects, the evidence of a mechanism for genomic imprinting and finally we evaluate recent results showing parent of origin allele specific expression in honeybees in the light of Haig's theory.


Aortic Root Dilatation Is Associated With Incident Cardiovascular Events in a Population of Treated Hypertensive Patients: The Campania Salute Network.
Aortic root (AR) dimension (ARD) at the Valsalva sinuses has been associated with incident cardiovascular (CV) events in population-based studies, but this effect could be due to the association with increased left ventricular (LV) mass. There is also uncertainty on how to define clear-cut AR dilatation. Thus, we analyzed the Campania Salute Network (CSN) registry to (i) establish criteria for evaluation of ARD, (ii) propose cut-points for AR dilatation, and (iii) determine whether AR dilatation has prognostic value independent of LV hypertrophy (LVH). We analyzed hypertensive patients with available follow-up, in sinus rhythm and free of prevalent valvular and CV disease (n = 8,573). AR exceeding the 75th percentile of the AR z-score (Ao-Z) obtained by comparison with the value predicted by age, sex, and height (i.e., Ao-Z > 0.80) was considered dilated. Patients with baseline-dilated ARD by Ao-Z were more likely to be younger, men, and obese and had higher baseline blood pressure (BP; all <0.02) but similar kidney function as those without ARD dilatation. In multivariable Cox regression model, dilated ARD predicted 36% increased rate of CV events, independently of older age, male sex, systolic BP, LVH, and class of antihypertensive medications used during follow-up (95% confidence interval: 1.07-1.71, P = 0.011). In the context of a population of treated hypertensive patients, ARD defined by z-score of predicted values is an independent predictor of CV events regardless of LVH and other common confounders. Trial Number NCT02211365.


Triose phosphate isomerase deficiency is caused by altered dimerization--not catalytic inactivity--of the mutant enzymes.
Triosephosphate isomerase (TPI) deficiency is an autosomal recessive disorder caused by various mutations in the gene encoding the key glycolytic enzyme TPI. A drastic decrease in TPI activity and an increased level of its substrate, dihydroxyacetone phosphate, have been measured in unpurified cell extracts of affected individuals. These observations allowed concluding that the different mutations in the TPI alleles result in catalytically inactive enzymes. However, despite a high occurrence of TPI null alleles within several human populations, the frequency of this disorder is exceptionally rare. In order to address this apparent discrepancy, we generated a yeast model allowing us to perform comparative in vivo analyses of the enzymatic and functional properties of the different enzyme variants. We discovered that the majority of these variants exhibit no reduced catalytic activity per se. Instead, we observed, the dimerization behavior of TPI is influenced by the particular mutations investigated, and by the use of a potential alternative translation initiation site in the TPI gene. Additionally, we demonstrated that the overexpression of the most frequent TPI variant, Glu104Asp, which displays altered dimerization features, results in diminished endogenous TPI levels in mammalian cells. Thus, our results reveal that enzyme deregulation attributable to aberrant dimerization of TPI, rather than direct catalytic inactivation of the enzyme, underlies the pathogenesis of TPI deficiency. Finally, we discovered that yeast cells expressing a TPI variant exhibiting reduced catalytic activity are more resistant against oxidative stress caused by the thiol-oxidizing reagent diamide. This observed advantage might serve to explain the high allelic frequency of TPI null alleles detected among human populations.


Traditional Chinese Medicine Combined With Chemotherapy and Cetuximab or Bevacizumab for Metastatic Colorectal Cancer: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.
Huangci Granule is a traditional Chinese medicine for treating metastatic colorectal cancer (mCRC). To evaluate the efficacy and safety of Huangci Granule combination with chemotherapy and cetuximab (CET) or bevacizumab (BV) for treating mCRC. We performed a randomized, controlled, and double-blind trial and recruited patients with mCRC who were planned to undergo chemotherapy combined with CET or BV. The treatment group was treated with Huangci Granule, while the control group was treated with placebo. Continuous treatment until disease progression, death, intolerable toxicity or up to 6 months. The primary endpoint was progression-free survival (PFS), and the secondary endpoint was quality of life and safety. 320 patients were randomly assigned to receive treatment, including 200 first-line patients and 120 second-line patients. In the first-line treatment, the median PFS was 9.59 months (95% CI, 6.94-13.25) vs 6.89 months (95% CI, 4.99-9.52) in treatment group and control group (HR, 0.69; 95% CI, 0.50-0.97; P = 0.027). Chinese medicine was an independent factor affecting the PFS. In the second-line treatment, the median PFS was 6.51 months (95% CI, 4.49-9.44) vs 4.53 months (95% CI, 3.12-6.57) in the treatment group and control group (HR, 0.65; 95% CI, 0.45-0.95; P = 0.020). Compared with the control group, "role function," "social function," "fatigue," and "appetite loss" were significantly improved in the treatment (P < 0.05) and drug related grades 3 to 4 adverse events were less. Huangci Granule combined with chemotherapy and CET or BV can prolong the PFS of mCRC, improve the quality of life, reduce adverse reactions, and have good safety.


Effect of Different Laser Treatments on the Bond Strength of Intracanal Fiber Posts Cemented with a Self-Adhesive Resin Cement.
To evaluate the influence of laser-activated irrigation by Er:YAG and Er:YSGG (LAI) protocols and Nd:YAG laser irradiation on the bond strength of self-adhesively cemented fiber posts to root canal dentine. The study sample consisted of 84 human single-rooted permanent teeth instrumented with ProTaper Next technique. After obturation, post space preparations were created for fiber-reinforced composite posts. The prepared specimens were divided according to the laser treatment of the post space preparations: group 1: LAI (Er:YAG) + saline solution (pulse energy: 20 mJ, repetition rate: 15 Hz); group 2: LAI (Er:YAG) + QMiX solution (pulse energy: 20 mJ, repetition rate: 15 Hz); group 3: LAI (Er,Cr:YSGG) + saline solution (pulse energy: 62.5 mJ, 20 Hz); group 4: LAI (Er,Cr:YSGG) + QMiX (pulse energy: 62.5 mJ, 20 Hz); Nd:YAG laser (pulse energy: 100 mJ, 10 Hz). Fiber-reinforced posts were cemented with a self-adhesive cement. The bond strength was evaluated by the push-out bond strength test, and the mode of failure was determined under a stereomicroscope. Kruskal-Wallis test was used for the intergroup comparative analysis with 5% level of significance. The highest bond strength was recorded in the Er:YAG + QMiX group (mean 3.401 MPa) (p < 0.05), followed by the Er,Cr:YSGG and the Er:YAG + saline solution (mean 1.111 MPa and 1.094 MPa, respectively), which did not differ significantly (p = 0.232). The irradiation with the Nd:YAG laser caused similar bond strength as the Er,Cr:YSGG + QMiX (p = 0.942). All laser protocols enhanced the bond strength of the self-adhesive cement in root canals compared to only saline irrigation. The bond strength of the self-adhesive cement depended on the laser parameters and irrigant used for the LAI.


Current trends in admissions and outcomes of cardiac diseases in Ghana.
Cardiovascular diseases (CVDs) pose a major burden in Africa, but data on temporal trends in disease burden are lacking. We assessed trends in CVD admissions and outcomes in central Ghana using a retrospective analysis of data from January 2004 to December 2015 among patients admitted to the medical wards of a tertiary medical center in Kumasi, Ghana. Rates of admissions and mortality were expressed as CVD admissions and deaths divided by the total number of medical admissions and deaths, respectively. Case fatality rates per specific cardiac disease diagnosis were also computed. Over the period, there were 4226 CVD admissions, with a male-to-female ratio of 1.1 to 1. There was a progressive increase in percentage of CVD admissions from 4.6% to 8.2%, representing an 78% increase, between 2004 and 2014. Of the 2170 CVD cases whose data were available, the top 3 causes of CVD admissions were heart failure (HF; 88.3%), ischemic heart disease (IHD; 7.2%), and dysrhythmias (1.9%). Of all HF admissions, 52% were associated with hypertension. IHD prevalence rose by 250% between 2005 and 2015. There were 976 deaths (23%), with an increase in percentage of hospital deaths that were cardiovascular in nature from 3.6% to 7.3% between 2004 and 2014, representing a 102% increase. Cardiac disease admissions and mortality have increased progressively over the past decade, with HF as the most common cause of admission. Once rare, IHD is emerging as a significant contributor to the CVD burden in sub-Saharan Africa.


[Comparison of subjective and objective quality of life in a group of schizophrenic patients].
The aim of this study is a comparison of subjective and objective quality of life in schizophrenic patients. The research was carried out on 120 in- and out-patients (from 19 to 65 years) who fulfilled ICD-10 and DSM-IV criteria for schizophrenia. The quality of life was assessed by means of two instruments: Quality of Life Scale (QLS, Heinrichs et al. 1984), Self-Report Quality of Life Measure for People with Schizophrenia (SQLS, Wilkinson et al. 2000). The basic statistical methods used were: correlation analysis between measurable variables with Pearson's index (P), t-Student test, analysis of variance, factor analysis. In the investigated group there is no correlation between subjective and objective quality of life. Sex does not influence a correlation between these variables. Subjective and objective quality of life correlate with each other only in out-patients' group (P = -0.386). The factor analysis of SQLS distinguished 7 factors: mood; everyday activities, side effects connected with movement; side effects- others; support; interpersonal contacts; others; this division differs completely from a division on subscales. The factor analysis of QLS distinguished 3 factors: intrapsychic functioning; social functioning; functioning in roles; this division is similar to a division on subscales. It seems that in the schizophrenic patients' group using subjective and objective ways to assess the quality of life determines a difference of the obtained results. Only the subjective measurement fulfills the assumption of quality of life definition, that is why the usefulness of QLS in assessing quality of life is rather restricted.


[The neuronal organization of the plexus myentericus (Auerbach) in the small intestine of the pig. II. Typ II-neurone (author's transl)].
The population of type II-neurons in the Auerbach's plexus of the pig's small intestine consisting of bipolar, pseudo-unipolar, and multipolar elements could be characterized a.o. as follows: 1. The type II-cells are on principle concentrated in aggregates in the periphery and outside the ganglia. 2. The processes of type II-cells all leaving the ganglia or aggregates of origin, are of the same axonal structure. Considering further characteristics type II-cells are defined therefore as adendritic, multiaxonal neurons. 3. Contrary to the axons of the other multidendritic, uniaxonal types of neurons (type I, III, IV, V) those of type II-cells forming circular routes (besides the vertical ones) in the secondary branches of Auerbach's plexus can be followed up to the intramuscular plexus. That's why the type II-cells finally can be considered as adendritic, multiaxonal, and efferent neurons.


How Magnetic is the Dirac Neutrino?
We derive model-independent, "naturalness" upper bounds on the magnetic moments munu of Dirac neutrinos generated by physics above the scale of electroweak symmetry breaking. In the absence of fine-tuning of effective operator coefficients, we find that current information on neutrino mass implies that[EQUATION: SEE TEXT] bohr magnetons. This bound is several orders of magnitude stronger than those obtained from analyses of solar and reactor neutrino data and astrophysical observations.


[Comparison of efficacy between nateglinide and repaglinide in treating type 2 diabetes: a randomized controlled double-blind clinical trial].
To compare the efficacy of nateglinide with repaglinide in the treatment of type 2 diabetes mellitus. Forty-six type 2 diabetic patients were randomly treated with repaglinide (group A, 1.0 mg tid, n=23) or nateglinide (group B, 90.0 mg tid, n=23). The trial consisted of a 4-week equilibrated period followed by 12 weeks of treatment course. In group A, the fasting blood glucose (FBG) and 30-, 60-, 120- min postprandial blood glucose (PBG), as well as hemoglobin A1c were decreased significantly (P<0.05). In group B, the 60-min and 120-min PBG decreased remarkably (P<0.05), but FBG, 30-min PBG and A1c decreased with no statistical significance (P>0.05). After 12 weeks treatment, the 30-, 60-, 120-min postprandial insulin level, area under the curve of insulin and C peptide (0 to 120 min) increased in both groups (P<0.05). No significant difference was found between the effects of repaglinide and nateglinide on early phase insulin secretion. The glucose lowering effect of repaglinide at a dosing level of 1.0 mg tid was better than that of nateglinide 90 mg tid on fasting blood glucose and A1c during 12 weeks treatment period, yet the insulinotropic effects of the two drugs were similar.


Distinct structural motifs are necessary for targeting and import of Tim17 in Trypanosoma brucei mitochondrion.
Nuclear-encoded mitochondrial proteins are correctly translocated to their proper sub-mitochondrial destination using location specific mitochondrial targeting signals (MTSs) and via multi-protein import machineries (translocases) in the outer and inner mitochondrial membranes (TOM and TIMs, respectively). However, MTSs of multi-pass Tims are less defined. Here we report the characterization of the MTSs of Trypanosoma brucei Tim17 (TbTim17), an essential component of the most divergent TIM complex. TbTim17 possesses a characteristic secondary structure including four predicted transmembrane (TM) domains in the center with hydrophilic N- and C-termini. After examining mitochondrial localization of various deletion and site-directed mutants of TbTim17 in T. brucei using subcellular fractionation and confocal microscopy we located at least two internal signals, 1) within TM1 (31-50 AAs) and 2) TM4 + Loop 3 (120-136 AAs). Both signals are required for proper targeting and integration of TbTim17 in the membrane. Furthermore, a positively charged residue (K 122 ) is critical for mitochondrial localization of TbTim17. This is the first report of characterizing the internal mitochondrial targeting signals (ITS) for a multipass inner membrane protein in a divergent eukaryote, like T. brucei . Internal targeting signals within the TM1, TM4 with Loop 3, and residue K122 are required collectively for import and integration of TbTim17 in the T. brucei mitochondrion. This information could be utilized to block parasite growth.


Cardiovascular stress, energy expenditure and subjective perceived ratings of fire fighters during typical fire suppression and rescue tasks.
The study determined physiological and psychophysical responses to fire fighters' typical activities. Self-reported assessment of the most demanding fire fighting/rescue tasks were collected with a questionnaire. Then 19 voluntary fire fighters performed 3 simulated fire fighting/rescue tasks in protective clothing. Heart rate (HR), blood pressure and energy expenditure were measured; the rating of perceived exertion (RPE) was assessed with the Borg scale. The questionnaires showed that carrying out victims, fire suppression and resuscitation were classified as heavy load; climbing stairs with a hose as moderate load. According to RPE the subjects considered their effort during ladder climbing fairly light and only somewhat harder during stair climbing and carrying out injured people. The study demonstrated that typical fire fighting/rescue tasks were associated with high energy expenditure and imposed considerable cardiovascular stress. The Borg scale appeared not suitable for assessing perceived exertion in fire fighters during simulated tasks.