A model based rule for selecting spiking thresholds in neuron models.
Determining excitability thresholds in neuronal models is of high interest due to its applicability in separating spiking from non-spiking phases of neuronal membrane potential processes. However, excitability thresholds are known to depend on various auxiliary variables, including any conductance or gating variables. Such dependences pose as a double-edged sword; they are natural consequences of the complexity of the model, but proves difficult to apply in practice, since gating variables are rarely measured. In this paper a technique for finding excitability thresholds, based on the local behaviour of the flow in dynamical systems, is presented. The technique incorporates the dynamics of the auxiliary variables, yet only produces thresholds for the membrane potential. The method is applied to several classical neuron models and the threshold's dependence upon external parameters is studied, along with a general evaluation of the technique.


ImmunoTrack: the novel antibody-based technology for tracing in animal health.
This paper describes a novel antibody-based livestock movement control tool and method of meat allocation, both in livestock husbandry as well as during the meat-processing chain. Immuno Track fulfills diverse prerequisites and meets regulatory demands which are substantial for a successful monitoring technology: (i) the induction of long-lasting antibody responses detectable onsite throughout the whole mast period of pigs, (ii) a single immunization injection with protein derivatives is sufficient to evoke a strong epitope-specific antibody response, and (iii) the complete degradation of the protein markers after the antibody response has been triggered in meatproducing animals such as cattle or pigs. There are diverse fields of application for the Immuno-Track marker technology, such as in quality meat programs, as compliance markers for animal vaccines or as a tool for verification of origin. Combination of this monitoring technology with the husbandry and identification databases for cattle and pigs within the European Community will lead to greater transparency in meat production, thereby regaining consumers' trust in concomitant structures of the meat-producing industry.


Mutant nicastrin protein can induce the cytochrome c release and the Bax expression.
This study investigated whether nicastrin can induce apoptotic cell death in SK-N-MC cells. MTT assays revealed the transfected cells expressing mutant nicastrin, compared with those expressing wild nicastrin or the control vector, showing significantly increased cell death. The mutant nicastrin transfectants were also observed to induce cytosolic cytochrome c release from the mitochondria, and Bax protein expression in response, to increased cell death. These observations suggested that nicastrin, as well as the APP and PS proteins, were also involved in the upregulated Bax mediated neuroblastoma cell death and the release of cytochrome c in the neuroblastoma.


Protein-Encoding RNA-to-RNA Information Transfer in Mammalian Cells: Principles of RNA-Dependent mRNA Amplification.
The transfer of protein-encoding genetic information from DNA to RNA to protein, a process formalized as the "Central Dogma of Molecular Biology", has undergone a significant evolution since its inception. It was amended to account for the information flow from RNA to DNA, the reverse transcription, and for the information transfer from RNA to RNA, the RNA-dependent RNA synthesis. These processes, both potentially leading to protein production, were initially described only in viral systems, and although RNA-dependent RNA polymerase activity was shown to be present, and RNA-dependent RNA synthesis found to occur, in mammalian cells, its function was presumed to be restricted to regulatory. However, recent results, obtained with multiple mRNA species in several mammalian systems, strongly indicate the occurrence of protein-encoding RNA to RNA information transfer in mammalian cells. It can result in the rapid production of the extraordinary quantities of specific proteins as was seen in cases of terminal cellular differentiation and during cellular deposition of extracellular matrix molecules. A malfunction of this process may be involved in pathologies associated either with the deficiency of a protein normally produced by this mechanism or with the abnormal abundance of a protein or of its C-terminal fragment. It seems to be responsible for some types of familial thalassemia and may underlie the overproduction of beta amyloid in sporadic Alzheimer's disease. The aim of the present article is to systematize the current knowledge and understanding of this pathway. The outlined framework introduces unexpected features of the mRNA amplification such as its ability to generate polypeptides non-contiguously encoded in the genome, its second Tier, a physiologically occurring intracellular polymerase chain reaction, iPCR, a "Two-Tier Paradox" and RNA "Dark Matter". RNA-dependent mRNA amplification represents a new mode of genomic protein-encoding information transfer in mammalian cells. Its potential physiological impact is substantial, it appears relevant to multiple pathologies and its understanding opens new venues of therapeutic interference, it suggests powerful novel bioengineering approaches and its further rigorous investigations are highly warranted.


First branchial cleft anomaly, a case for misdiagnosis.
First branchial cleft anomaly is a rare condition that is often misdiagnosed and falsely mistreated before complete and definitive surgical treatment. Its origin is uncertain and the presence of ectodermal and sometimes also mesodermal elements has led some authors to the conclusion that it represents buried nests of cells forming the first branchial cleft and the underlying mesoderm. First branchial cleft anomaly can be presented as a cystic lesion, fistula or sinus extending towards the membranous external ear canal. The sinus tract runs through the parotid gland in close association with the facial nerve. There is no imaging method capable of identifying a first branchial cleft anomaly with certainty. The danger of facial nerve injury during surgery and the failure to identify the sinus tract running to the external ear canal are the main reasons for incomplete excision. The facial nerve must be identified and preserved and the lesion completely excised. Facial nerve injury is more common in attempts to remove recurrent branchial cleft lesions.


Human-Like Obstacle Avoidance Trajectory Planning and Tracking Model for Autonomous Vehicles That Considers the River's Operation Characteristics.
Developing a human-like autonomous driving system has gained increasing amounts of attention from both technology companies and academic institutions, as it can improve the interpretability and acceptance of the autonomous system. Planning a safe and human-like obstacle avoidance trajectory is one of the critical issues for the development of autonomous vehicles (AVs). However, when designing automatic obstacle avoidance systems, few studies have focused on the obstacle avoidance characteristics of human drivers. This paper aims to develop an obstacle avoidance trajectory planning and trajectory tracking model for AVs that is consistent with the characteristics of human drivers' obstacle avoidance trajectory. Therefore, a modified artificial potential field (APF) model was established by adding a road boundary repulsive potential field and ameliorating the obstacle repulsive potential field based on the traditional APF model. The model predictive control (MPC) algorithm was combined with the APF model to make the planning model satisfy the kinematic constraints of the vehicle. In addition, a human driver's obstacle avoidance experiment was implemented based on a six-degree-of-freedom driving simulator equipped with multiple sensors to obtain the drivers' operation characteristics and provide a basis for parameter confirmation of the planning model. Then, a linear time-varying MPC algorithm was employed to construct the trajectory tracking model. Finally, a co-simulation model based on CarSim/Simulink was established for off-line simulation testing, and the results indicated that the proposed trajectory planning controller and the trajectory tracking controller were more human-like under the premise of ensuring the safety and comfort of the obstacle avoidance operation, providing a foundation for the development of AVs.


Four-digit allele genotyping of the HLA-A and HLA-B genes in Japanese patients with Behcet's disease by a PCR-SSOP-Luminex method.
The present study represents the first four-digit allele genotyping of HLA-A and -B in Japanese Behcet's disease (BD) patients and controls using a new genotyping method (named the PCR-SSOP-Luminex method) to determine the association of certain HLA-A or -B alleles with BD. Peripheral blood lymphocytes were collected from 180 Japanese BD patients and 170 healthy controls. The genotype frequency of HLA-B*5101 was significantly increased in the patients (61.7%) as compared with the controls (15.9%) (Pc = 1 x 10(-16), OR = 8.5). When we recalculated the phenotype frequencies after excluding the HLA-B*51-positive patients and controls to account for the effects of the linkage disequilibrium and the abundance of the HLA-B*51 allele, the frequencies of HLA-A*2602 and HLA-B*3901 had a weak association in the patient group without HLA-B*51 as compared with the control group without HLA-B*51 (A*2602; Pc = 0.130, OR = 4.3, B*3901; Pc = 0.099, OR = 3.5). This study confirmed on the basis of using a new and more accurate genotyping method that Japanese BD patients have a strong primary association with HLA-B*5101. The significant increase of HLA-A*2602 and B*3901 in the patient group without HLA-B*51 suggests that these two alleles might also have some secondary influence on the onset of BD.


Safety and efficacy of ProEquo® (Lactobacillus plantarum DSM 11520) as a feed additive for horses.
Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of ProEquo® as a feed additive for horses. This additive is a preparation single strain of Lactobacillus plantarum intended for use as a zootechnical additive in feed for horses. The identity of the bacterial strain was not established. Consequently, the qualified presumption of safety approach to safety assessment cannot be applied, and separate studies on target animals, consumer and environmental safety are required. The tolerance trial provided could not be considered due to non-compliance with the minimum requirements. No additional studies or data were provided for the other safety aspects. Therefore, in the absence of data, the FEEDAP Panel was not in the position to conclude on the safety of ProEquo® for the target animals, consumers of products derived from animals fed the additive and the environment. ProEquo® should be considered a respiratory sensitiser. In the absence of data, the FEEDAP Panel cannot conclude on the irritancy potential of the additive to skin and eyes or on its dermal sensitisation potential. The FEEDAP Panel is not in the position to conclude on the efficacy of ProEquo® for horses.


Efficacy of prophylactic placement of inferior vena cava filter in patients undergoing spinal surgery.
Retrospective case series. To evaluate the safety and efficacy of prophylactic inferior vena cava filter (IVCF) to prevent pulmonary embolism (PE) in high risk patients undergoing major complex spinal surgery. PE has been reported to be the major cause of death after spinal reconstructive surgery. Mechanical prophylaxis alone is often not sufficient whereas anticoagulation therapy carries a significant risk of bleeding complications. Prophylactic IVCF placement is advocated in high-risk patients. A total of 129 high-risk patients undergoing complex spine surgery, having prophylactic IVCF were compared to a matched cohort of age, diagnosis, and risk factors of 193 patients for whom only mechanical prophylaxis was used. Patients were observed for potential complications related to the IVCF and also for clinical signs and symptoms of PE. Eight cases (4.2%) of symptomatic PE were detected in the matched cohort control group (5 cases having combined anterior + posterior surgery and 3 patients having only posterior surgery). One of them died due to massive PE (0.5%). Symptomatic PE was detected in only 2 patients (1.5%), having combined anterior + posterior surgery due to lumbar spinal stenosis in IVCF group who responded well to medical treatment (P < 0.05). No complications were associated with filter insertion. Prophylactic IVCF is effective and safe in prevention of pulmonary embolism in patients with risk factors for PE.


Comparative biological effects of spherical noble metal nanoparticles (Rh, Pd, Ag, Pt, Au) with 4-8 nm diameter.
For a comparative cytotoxicity study, nanoparticles of the noble metals Rh, Pd, Ag, Pt, and Au (spherical, average diameter 4 to 8 nm) were prepared by reduction in water and colloidally stabilized with poly(N-vinyl pyrrolidone) (PVP). Thus, their shape, size, and surface functionalization were all the same. Size and morphology of the nanoparticles were determined by dynamic light scattering (DLS), analytical disc centrifugation (differential centrifugal sedimentation, DCS), and high-resolution transmission electron microscopy (HRTEM). Cell-biological experiments were performed to determine the effect of particle exposure on the viability of human mesenchymal stem cells (hMSCs). Except for silver, no adverse effect of any of the metal nanoparticles was observed for concentrations up to 50 ppm (50 mg L-1) incubated for 24 h, indicating that noble metal nanoparticles (rhodium, palladium, platinum, gold) that do not release ions are not cytotoxic under these conditions.


[The role and significance of microRNA in human cardiovascular disease and forensic science].
microRNA (miRNA or miR) is a small single stranded non-coding RNA (21-25nt) that regulates gene expression in almost creatures. Currently, plenty of researches on how miRNA affects human cardiovascular disease have been reported. This review highlights recent findings about the role of miRNA in heart tissue and circulation correlated with human cardiovascular disease and explores the application of miRNA in sudden cardiac death in forensic science.


Evaluation of the efficacy and safety of isepamicin in the treatment of various bacterial infections.
A multicentre, non-comparative study evaluated the efficacy and safety of the new aminoglycoside isepamicin in hospitalised patients with various infections. Isepamicin was administered once daily with the daily dosage stratified according to the severity of infection: 15 mg/kg isepamicin for severe potentially systemic infections (53 patients) or 8 mg/kg isepamicin for less severe and localised infections (56 patients). The largest groups of patients had urinary tract infection (n = 54) or lower respiratory tract infection (n = 31); smaller numbers of patients were enrolled with skin and soft tissue infections (n = 9), intra-abdominal infections (n = 8) or obstetric and gynaecological infections (n = 7). In the patients receiving 15 mg/kg isepamicin, clinical cure or improvement occurred in 19/21 patients with lower respiratory tract infections, 8/13 patients with urinary tract infections, 6/6 patients with skin infections, 5/6 patients with intra-abdominal infections and 6/7 patients with obstetric gynaecological infections. In the patients receiving 8 mg/kg isepamicin, 40 out of 41 patients with urinary tract infections were considered cured or improved as were 8/10 patients with lower respiratory tract infections, 1/3 patients with skin infections and 1/2 patients with intra-abdominal infections. Nine per cent of patients reported at least on adverse event during the study. Two patients (one from each dosage group) discontinued treatment because of adverse events, respiratory disorder and erythematous rash, but neither event was considered to be severe of life threatening No patients had evidence of ototoxicity by pure-tone audiometry and no patients had potentially significant increases in serum creatinine which were considered to be treatment related. The results of this study indicate that treatment with isepamicin once daily is effective and well tolerated in hospitalised adults with various infections.


Development of an innovative delivery system for bacillus Calmette-Guérin bladder administration.
To describe the development of an innovative process to deliver bacillus Calmette-Guérin (BCG) to an offsite urology clinic for bladder instillation. The use of BCG, a live virus vaccine for treatment of patients with localized cancer of the urinary bladder, has created many logistical problems for hospitals and infusion center pharmacies. Due to its short stability, the drug cannot be made ahead of time and coordination with a patient's arrival at an infusion site is challenging. This becomes exceptionally challenging when a urology clinic has limited compounding capacity and/or is distant from the site of BCG medication preparation. This article describes an innovative process involving use of closed-system transfer devices (CSTDs) to allow for the administration of BCG in a urology clinic offsite from a medical center's infusion center facilities. The use of the CSTD allowed the patients to continue to receive bladder instillations at an offsite urology clinic without significantly disrupting compounding workflow at the small infusion center pharmacy that was the nearest to the clinic.


Increase in p21 expression independent of the p53 pathway in bleomycin-induced lung fibrosis.
Although a number of animal models have been used to study the pathogenesis of lung disease, to date few studies have looked at changed in the expression of cell cycle regulatory genes. We have studied the variation in the expression of p21, p53, p27 and PCNA in bleomycin-induced lung fibrosis using animal mouse models using immuno-histochemistry and gene-expression analysis. No difference in the p53, PCNA and p27 expressions were observed from the bleomycin-induced fibrosis when compared to saline-induced non-fibrotic lungs. Although no difference in nuclear p21 expression was observed, the level of cytoplasmic p21 expression was found to be higher in fibrotic lungs at day 14 after bleomycin injection. p21 expression was found to increase independent of p53 in fibrotic lungs at 14 days after bleomycin induction.


A multi-state fragment charge difference approach for diabatic states in electron transfer: extension and automation.
The electron transfer (ET) rate prediction requires the electronic coupling values. The Generalized Mulliken-Hush (GMH) and Fragment Charge Difference (FCD) schemes have been useful approaches to calculate ET coupling from an excited state calculation. In their typical form, both methods use two eigenstates in forming the target charge-localized diabatic states. For problems involve three or four states, a direct generalization is possible, but it is necessary to pick and assign the locally excited or charge-transfer states involved. In this work, we generalize the 3-state scheme for a multi-state FCD without the need of manual pick or assignment for the states. In this scheme, the diabatic states are obtained separately in the charge-transfer or neutral excited subspaces, defined by their eigenvalues in the fragment charge-difference matrix. In each subspace, the Hamiltonians are diagonalized, and there exist off-diagonal Hamiltonian matrix elements between different subspaces, particularly the charge-transfer and neutral excited diabatic states. The ET coupling values are obtained as the corresponding off-diagonal Hamiltonian matrix elements. A similar multi-state GMH scheme can also be developed. We test the new multi-state schemes for the performance in systems that have been studied using more than two states with FCD or GMH. We found that the multi-state approach yields much better charge-localized states in these systems. We further test for the dependence on the number of state included in the calculation of ET couplings. The final coupling values are converged when the number of state included is increased. In one system where experimental value is available, the multi-state FCD coupling value agrees better with the previous experimental result. We found that the multi-state GMH and FCD are useful when the original two-state approach fails.


Activation of the IGF1 receptor stimulates glycogen synthesis by mink uterine epithelial cells.
Glycogen synthesis by mink uterine epithelial cells is stimulated by estradiol (E2 ) during estrus, although the mechanism/s through which the steroid promotes glycogen accumulation are unknown. Our aim was to determine if insulin is required for E2 induced glycogen synthesis by an immortalized mink uterine epithelial cell line (GMMe). We show that the cells expressed the genes for glycogen metabolizing enzymes (hexokinase 1, glucose-6-phosphatase 3, glycogen synthase 1, and glycogen phosphorylase-muscle), receptors for insulin, insulin-like growth factor 1 and E2 (Esr1). Interestingly, treatment of cells with E2 alone failed to stimulate glycogen production, whereas supraphysiological concentrations of insulin (50 μg/ml) only, significantly increased glycogen content. Moreover, insulin + E2 increased glycogen content when compared to insulin alone (p < 0.05), an affect that was blocked when cells were treated with the pure E2 receptor antagonist ICI 182,780. Glycogen synthesis in response to insulin was significantly inhibited when cells were pre-treated with picropodophyllotoxin, an IGF1R antagonist. Treatment of cells with LY294002, a phosphatidylinositol 3-kinase (PI3K) antagonist, blocked insulin's effects on glycogen production whereas treatment with U0126, an inhibitor of mitogen activated kinase-kinase (MEK1/2) was without effect. These findings suggest to us that the affects of E2 on glycogen synthesis by GMMe cells is mediated through Esr1 and increased responsiveness of the cells to insulin. Because picropodophylotoxin blocked the effects of insulin on glycogen production, and both insulin and IGF1 act through PI3K, it is possible that IGF1 plays a role in glycogen production by these cells.


[Airwaymanagement: video-assisted airway management].
Endotracheal intubation remains the "goldstandard" in airway management. If with use of conventional techniques intubation of the patient fails, or if an anticipated difficult airway is present, video-assisted techniques may help to increase intubation success. Video-assisted techniques give the possibility to indirectly visualise the laryngeal structures with fibreoptical or camerachip-technique, and to display the videopicture on an external or integrated monitor. For the anticipated difficult airway, awake flexible fibreoptical intubation still is the first choice. However, if Oxygenation and Ventilation can be established with bag-mask ventilation or supraglottic airways, the use of an endoscopic optical stylet or a videolaryngoscope may be alternatives. If the algorithm for the unanticipated difficult airway can be safely administered, the latter techniques may also be used as emergency intubation devices.


SET-related cell division autoantigen-1 (CDA1) arrests cell growth.
We used an autoimmune serum from a patient with discoid lupus erythematosus to clone a cDNA of 2808 base pairs. Its open reading frame of 2079 base pairs encodes a predicted polypeptide of 693 amino acids named CDA1 (cell division autoantigen-1). CDA1 has a predicted molecular mass of 79,430 Daltons and a pI of 4.26. The size of the cDNA is consistent with its estimated mRNA size. CDA1 comprises an N-terminal proline-rich domain, a central basic domain, and a C-terminal bipartite acidic domain. It has four putative nuclear localization signals and potential sites for phosphorylation by cAMP and cGMP-dependent kinases, protein kinase C, thymidine kinase, casein kinase II, and cyclin-dependent kinases (CDKs). CDA1 is phosphorylated in HeLa cells and by cyclin D1/CDK4, cyclin A/CDK2, and cyclin B/CDK1 in vitro. Its basic and acidic domains contain regions homologous to almost the entire human leukemia-associated SET protein. The same basic region is also homologous to nucleosome assembly proteins, testis TSPY protein, and an uncharacterized brain protein. CDA1 is present in the nuclear fraction of HeLa cells and localizes to the nucleus and nucleolus in HeLa cells transfected with CDA1 or its N terminus containing all four nuclear localization signals. Its acidic C terminus localizes mainly to the cytoplasm. CDA1 levels are low in serum-starved cells, increasing dramatically with serum stimulation. Expression of the CDA1 transgene, but not its N terminus, arrests HeLa cell growth, colony numbers, cell density, and bromodeoxyuridine uptake in a dose-dependent manner. The ability of CDA1 to arrest cell growth is abolished by mutation of the two CDK consensus phosphorylation sites. We propose that CDA1 is a negative regulator of cell growth and that its activity is regulated by its expression level and phosphorylation.


State-specific liquor excise taxes and retail prices in 8 US states, 2012.
The authors investigated the relationship between state excise taxes and liquor prices in 8 states, using 2012 data for 45 brands. The authors made 6042 price observations among 177 liquor stores with online prices. Using a hierarchical model, the authors examined the relationship between excise taxes and product prices. State excise taxes were significantly related to liquor prices, with an estimated pass-through rate of 0.93. The proportion of price accounted for by excise taxes averaged 7.0%. The authors find that excise taxes do increase the price of alcohol, but states are not taking advantage of this opportunity to reduce alcohol-related morbidity and mortality.


Loose abrasive grinding of optical surfaces.
The aim of the effort reported in this paper was to identify working parameters responsible for the development of a surface shape during lapping with a loose abrasive. A study of the parameters responsible for radius changes during lapping indicates that the complexity of this process can be significantly reduced if proper working parameters are chosen. Deviation from spherical shape for surfaces generated in loose abrasive lapping was investigated interferometrically. Generally, a nonspherical surface is produced in this process, but under some conditions the departure from sphericity can be minimized below 1/10 of a wavelength.


A Study on the Bioavailability of a Proprietary, Sustained-release Formulation of Astaxanthin.
Astaxanthin has been shown to provide important health benefits, such as functioning as an anti-inflammatory, antioxidant, anticancer, and cardioprotective agent. Astaxanthin is a lipid-soluble molecule with low oral bioavailability, which limits its therapeutic potential. The low oral bioavailability is due to dissolution limitations in the gastrointestinal fluids. The objective of this study was to compare the relative bioavailability of a proprietary sustained-release formulation of astaxanthin (astaxanthin-SR)-a micronized dispersion of astaxanthin oil that is 2.5% astaxanthin in a sustained-release matrix-with that of an unformulated astaxanthin oil containing 10% astaxanthin. A dissolution study compared the solubility of formulated and unformulated astaxanthin oils. The research team also performed a single-dose, 24-h crossover, uptake study. The dissolution study took place at BioActives (Worcester, MA, USA). The single-dose study was done at the MAZE Laboratories (Purchase, NY, USA). Six healthy male and female volunteers aged 21 to 66 y took part in the single-dose study. The participants were people from the community. That proprietary formulation is a free-flowing paste that is able to form a stable dispersion in water and achieve sustained-release when presented in a capsule form. For the samples used in the dissolution study, hard gelatin capsules were filled either with the unformulated astaxanthin oil or with the proprietary astaxanthin-SR formulation, both with the equivalent of 10 mg of astaxanthin. For the single-dose study, participants received a 60-mg dose of astaxanthin in each form, as capsules, with a 15-d washout period between the 2 doses. The astaxanthin-SR capsules were administered after breakfast, and blood samples were drawn at 3, 8, 10, and 24 h postintervention. After a 15-d washout period, the protocol was repeated with astaxanthin oil capsules. For the dissolution study, the astaxanthin was quantified using spectrophotometry. For the single-dose study, plasma astaxanthin was quantified using reverse-phase high-performance liquid chromatography equipped with an ultraviolet-visible detector and a Phenomenex Synergy Hydro-RP column 150 × 4.6 mm, 4 μm (Phenomenex, Torrance, CA, USA) at room temperature. The dissolution study indicated that the astaxanthin-SR formulation formed a stable dispersion in the simulated gastric and intestinal fluids. The formulation also showed greater dissolution for 12 h at all points tested, compared with the astaxanthin oil, which showed no dissolution during the same period of 12 h. The results of the single-dose uptake study indicated that the astaxanthin-SR formulation was 3.6 times more bioavailable than astaxanthin oil, with P < .0005 in a paired t test. In addition, all participants showed uptake from the sustained-release formulation. The formulation of astaxanthin oil in a sustained-release matrix significantly improved the absorption of astaxanthin. The formulation also reduced interindividual variations in absorption. Participants who were poor absorbers from the unformulated astaxanthin oil, showed higher absorption with the astaxanthin-SR formulation.


Infectious cDNA clones of Langat tick-borne flavivirus that differ from their parent in peripheral neurovirulence.
Tick-borne flavivirus strain Langat TP21 (LGT TP21) recovered from ticks, is naturally attenuated for humans but retains demonstrable neurovirulence and peripheral virulence ("neuroinvasiveness") for mice. Previously a mutant, strain E5, less virulent for mice was derived from LGT TP21. Multiple attempts to prepare a full-length infectious TP21 cDNA from cDNA fragments cloned in E. coli were uniformly unsuccessful. A more informative sequence than that obtained from these cloned cDNA fragments and similar E5 cDNA fragments was derived from RT-PCR fragments that had not been cloned in E. coli. Comparison of the RT-PCR consensus sequence of TP21 and E5 identified only seven amino acid differences that might be responsible for the observed difference in virulence of these strains for mice. Eleven independent infectious cDNA clones of TP21 were recovered using two overlapping long RT-PCR fragments. Importantly, low-titered virus used to prepare cDNA as template for PCR was harvested early in the growth cycle to minimize the frequency of deletion mutants that accumulated late in infection. The four analyzed rescued clones exhibited clone-specific minimal divergence from the consensus sequence but this limited variation was associated with diminished peripheral virulence for immunocompetent mice. Manipulation of these clones should facilitate elucidation of LGT virulence.


Kikuchi-Fujimoto disease: case report.
We present the case of a 27-year-old woman with local cervical lymphadenopathy without other symptoms. Due to a gradual progression of lesions, a biopsy was performed, and a specimen excised from an enlarged lymph node was subjected to histological examination. Kikuchi-Fujimoto disease (KFD), that is histiocytic necrotizing lymhadenitis, was diagnosed. Lymphadenopathy resolved without medical treatment over 6 months. KFD should be considered in the differential diagnosis of lymphadenopathy, even though this disease rarely occurs in Poland.


Periorbital swelling in emergency room: Get your eyes in.
Facial swelling and eye pain are very common patient complaints in Emergency Departments. Clinical evidence and investigations play a crucial role in making the correct diagnosis which impacts the final disposition and management of the patient. We present a case of a patient who presented with facial swelling and headache.


Electrophysiological effects of endothelin-1 on canine myocardial cells.
Endothelin-1 (ET-1) has been shown to induce severe ventricular arrhythmias associated with myocardial ischemia. However, ET-1 may have a direct arrhythmogenic action that is not related to myocardial ischemia. To examine this possibility, we studied the electrophysiological effects of ET-1 on cardiac tissues. The right bundle branch, false tendon, ventricular muscle, and atrial muscle were isolated from the dog, and transmembrane potentials were recorded by the conventional microelectrode technique. ET-1 prolonged the action potential duration (APD) in all of the tissues tested except in the atrial muscle, where the APD was shortened. Bay K 8644, a calcium channel agonist, prolonged the APD in all cardiac tissues. Spontaneous firing of the right bundle branch was suppressed by ET-1 but not Bay K 8644. The prolongation of the APD by ET-1 was far more marked in the right bundle branch than in other tissues, and it was followed by the development of early after depolarizations (EADs) only in the right bundle branch. The EADs induced by ET-1 or Bay K 8644 were abolished by nicardipine. These data suggest that L-type calcium current is involved in the genesis of EADs by ET-1, although other ionic mechanisms can not be ruled out. Since EADs underlie some types of arrhythmias, arrhythmias caused by ET-1 are at least partly attributable to the direct actions of the agent on myocardial cells.


Direct interaction between a quinoline derivative, MS-209, and multidrug resistance protein (MRP) in human gastric cancer cells.
MS-209 is a novel quinoline derivative reversing P-glycoprotein-mediated multidrug resistance (MDR). We investigated the interaction between MS-209 and multidrug resistance protein (MRP) in MRP-overexpressing human gastric cancer cells. We measured [3H]leukotriene C4 uptake into the membrane vesicles of the cells and intracellular calcein and [3H]vincristine accumulation with or without MS-209. In multi-drug-resistant MKN45R0.8 cells selected by doxorubicin, MS-209 dose dependently reduced MRP-mediated [3H]leukotriene C4 uptake and increased calcein accumulation. In both resistant and unselected cell lines expressing the MRP gene, MS-209 increased [3H]vincristine accumulation in proportion with the level of MRP mRNA expression and enhanced the cytotoxicity of etoposide, doxorubicin, and vincristine. The reversal effects correlated with the level of MRP mRNA expression in these cells. Our results indicate that MS-209 effectively reverses intrinsic and acquired MRP-mediated MDR of gastric cancer cells by interacting directly with MRP.


Treatment of vascular dementia.
We report positron emission tomography (PET) findings of our patients with vascular dementia, asymptomatic cerebral infarction, and chronic cerebral circulatory insufficiency. According to the PET studies, it was suggested that frontal lobe hypoperfusion and hypometabolism play important roles in dementia caused by cerebral infarctions. It was also suggested that patients with subjective complaints associated with asymptomatic strokes and patients with chronic cerebral circulatory insufficiency already exhibited decreased cerebral circulation. Since therapeutic approaches to vascular dementia after its development are limited, active control of risk factors and prevention of recurrent stroke during the developmental process of vascular dementia are important. We review recent situations in prevention and treatment of vascular dementia.


Sudden appearance of new upper extremity motor function while performing neurophysiologic intraoperative monitoring during tethered cord release: a case report.
: Tethered cord syndrome occurs when the distal spinal cord or filum adheres to adjacent structures resulting in progressive sensorimotor deficits in the lower extremities, fecal and/or urinary incontinence, and musculoskeletal deformities. Tethering of the distal cord may be idiopathic, may be associated with an intraspinal abnormality such as a lipoma, but most commonly the distal spinal cord remnant is adherent to the area of the original dysraphism repair in patients with myelodysplasia. Surgery to untether the cord is indicated in patients with worsening pain symptoms, progressive limb deformity or spasticity, or before any acute correction of an associated spinal deformity. Neurophysiologic intraoperative monitoring is used to minimize the risk of inadvertent nerve root or spinal cord injury during the untethering procedure and to assess any changes in cord function at the time of an associated spinal deformity correction. We present a patient with a lumbar level myelodysplasia, Chiari II malformation, severe scoliosis, and tethered cord that underwent concurrent scoliosis correction and tethered cord syndrome surgery, who demonstrated immediate intraoperative improvement in neurophysiologic responses in a previously flaccid upper extremity after untethering. These monitoring changes correlated with clinical improvements noted by physicians and family postoperatively. Level IV.


Association of VDR gene polymorphisms with risk of relapsing-remitting multiple sclerosis in an Iranian Kurdish population.
The purpose of this study was to evaluate the association of VDR Apa-I, Bsm-I, Fok-I, Taq-I single nucleotide polymorphisms (SNPs) with multiple sclerosis (MS) risk in an Iranian Kurdish population. A population including of 118 patients and 124 healthy matched controls were recruited to the study. Genotyping of the SNPs was accomplished using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The frequency of allele T of Fok-I (P = 0.003) and allele C of Taq-I (P = 0.0003) was significantly different between case and control subjects and showed significant association with risk of MS (OR = 1.84, 95% CI = 1.23-2.76; OR = 1.98, 95% CI = 1.36-2.87, respectively). CT genotype (OR = 1.7, 95% CI = 1.05-2.99) of Fok-I and CC genotype (OR = 2.18, 95% CI = 1.05-4.52) of Taq-I showed a predisposing effect. Combined TT+TC vs. CC for Fok-I (OR = 2.15, 95% = CI 1.29-3.60) and combined CC+TC vs. TT for Taq-I (OR = 2.58, 95% CI 1.51-4.40) were susceptibility genotypes for MS. Apa-I and Bsm-I were not significantly associated with risk of MS (OR < 1, P > 0.05) and any genotypes in any genetic models were not significantly different between cases and controls (P > 0.05). As a result, Fok-I and Taq-I showed significant association with risk of MS, while Apa-I and Bsm-I were not observed to be related to the risk of the disease in this population.


Insights Regarding Resistance of 'Nemaguard' Rootstock to the Bacterium Xylella fastidiosa.
'Nemaguard' is a commonly used rootstock for almond and stone fruits due to resistance to nematodes and enhanced scion vigor. Nemaguard also happens to be resistant to strains of Xylella fastidiosa that cause almond leaf scorch disease. Previous research showed that prior to June-budding, this rootstock can prevent infection of almond nursery stock by X. fastidiosa. Further, the rootstock also promotes recovery from infection in susceptible almond scions. Objectives of this study were to 1) compare movement and bacterial populations of X. fastidiosa in almond and Nemaguard, 2) determine whether the metabolic profile of infected versus noninfected plants of each species correspond with differences in pathogen distribution, and 3) evaluate the impact of feeding on Nemaguard on transmission efficiency and pathogen populations in insects. Results showed limited or no movement of X. fastidiosa beyond the point of mechanical inoculation in Nemaguard, whereas X. fastidiosa was detected in susceptible almond and isolated from plant samples distal to the point of inoculation. Large differences in the concentration of phenolic compounds between Nemaguard and almond were also found, although this was not impacted by infection status. After acquiring X. fastidiosa from infected plants, vector access periods of up to 14 days on Nemaguard neither reduced pathogen populations in vectors nor reduced transmission efficiency of X. fastidiosa to susceptible plants when compared with similar vector-access periods on susceptible grapevines. Results suggest Nemaguard, in spite of having high phenolic concentrations in its xylem, does not directly impact X. fastidiosa survival and that future research should focus on identification of potential physical traits that prevent bacterial attachment, multiplication, or movement within the plant.


Potent sub-MIC effect of GSK1322322 and other peptide deformylase inhibitors on in vitro growth of Staphylococcus aureus.
Peptide deformylase (PDF), a clinically unexploited antibacterial target, plays an essential role in protein maturation. PDF inhibitors, therefore, represent a new antibiotic class with a unique mode of action that provides an alternative therapy for the treatment of infections caused by drug-resistant pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). GSK1322322 is a novel PDF inhibitor that is in phase II clinical development for the treatment of lower respiratory tract and skin infections. We have discovered that PDF inhibitors can prevent S. aureus in vitro growth for up to 6 h at concentrations 8- to 32-fold below their MICs. This phenomenon seems specific to PDF inhibitors, as none of the antimicrobial agents with alternative mechanisms of action tested show such a potent and widespread effect. It also appears limited to S. aureus, as PDF inhibitors do not show such an inhibition of growth at sub-MIC levels in Streptococcus pneumoniae or Haemophilus influenzae. Analysis of the effect of GSK1322322 on the early growth of 100 randomly selected S. aureus strains showed that concentrations equal to or below 1/8× MIC inhibited growth of 91% of the strains tested for 6 h, while the corresponding amount of moxifloxacin or linezolid only affected the growth of 1% and 6% of strains, respectively. Furthermore, the sub-MIC effect demonstrated by GSK1322322 appears more substantial on those strains at the higher end of the MIC spectrum. These effects may impact the clinical efficacy of GSK1322322 in serious infections caused by multidrug-resistant S. aureus.


Basic principles of fluorescence and energy transfer.
Fluorescence is highly sensitive to environment, and the distance separating fluorophores and quencher molecules can provide the basis for effective homogeneous nucleic acid hybridization assays. Molecular interactions leading to fluorescence quenching include collisions, ground state and excited state complex formation, and long-range dipole-coupled energy transfer. These processes are well understood and equations are provided for estimating the effects of each process on fluorescence intensity. Estimates for the fluorescein-tetramethylrhodamine donor-acceptor pair reveal the relative contributions of dipole-coupled energy transfer, collisional quenching, and static quenching in several common assay formats, and illustrate that the degree of quenching is dependent upon the hybridization complex formed and the manner of label attachment.


Narrow mass extraction of time-of-flight data for quantitative analysis of proteins: determination of insulin-like growth factor-1.
Methods for quantitative analysis of proteins by mass spectrometry have progressed dramatically. While isotope-dilution approaches using selected reaction monitoring of tryptic peptides (also known as bottom up) have become common, the potential to use narrow mass extraction of high-resolution mass spectra provides a compelling alternative. We investigated the relationships between instrument performance and data processing with the aim of determining whether this approach can lead to robust bioanalytical assays for proteins. Our approach utilized off-line sample preparation combined with online sample extraction coupled to HPLC with the effluent from the analytical column directed to a high-resolution, high-mass accuracy quadrupole time-of-flight (qTOF) mass spectrometer operated in full scan mode. Narrow mass extraction of a single isotope from IGF-1 in the 7+ charge state (m/z 1093.5209) was used to generate extracted ion chromatograms. We found that with appropriate attention to instrument performance and data processing, quantitative protein assays with good sensitivity, high selectivity, and excellent analytical performance can be developed.


Posterior nasal cautery with silver nitrate.
A method of cauterizing the posterior parts of the nose without damage to the anterior mucosa is presented. A silver nitrate stick was sheathed within a cut segment of a nasogastric (NG) tube and endoscopically advanced within the nose until the vessel was reached. The stick was then pushed until the silver nitrate protruded and the vessel was cauterized.


Impaired cortisol binding to glucocorticoid receptors in hypertensive patients.
We compared glucocorticoid receptor binding characteristics and glucocorticoid responsiveness of human mononuclear leukocytes (HML) from hypertensive patients and matched normotensive volunteers. We also considered associations of these variables with plasma renin activity, aldosterone, cortisol, corticotropin, and electrolyte concentrations. We calculated binding affinity (Kd; nmol/L) and capacity (Bmax; sites/cell) for dexamethasone and cortisol from homologous and heterologous competition curves for specific [3H]dexamethasone binding sites on HML isolated from the blood of normotensive volunteers and subjects with essential hypertension. Glucocorticoid responsiveness of HML was evaluated as IC50 values (nmol/L) for dexamethasone and cortisol for the inhibition of lysozyme release. We measured plasma hormones by radioimmunoassay. Kd values (mean+/-SE) for cortisol in HML of hypertensive patients were higher than in control subjects (24.6+/-2.4 versus 17.5+/-1.7 nmol/L, P<.04). Binding capacity (4978+/-391 versus 4131+/-321 sites/cell), Kd values for dexamethasone (6.7+/-0.5 versus 5.7+/-0.3 nmol/L), and IC50 values for dexamethasone (3.4+/-0.3 versus 3.1+/-0.2 nmol/L) and cortisol (12.2+/-1.6 versus 9.5+/-0.3 nmol/L) were not significantly different. Patients with renin values less than 0.13 ng angiotensin I/L per second were markedly less sensitive to cortisol than those with higher values. Both Kd (30.3+/-2.5 versus 19.2+/-2.4 nmol/L) and IC50 values (15.5+/-1.8 versus 8.9+/-1.2 nmol/L) for cortisol were significantly higher in patients with lower renin values (P<.03). Other variables, including plasma hormone and electrolyte values and binding characteristics for dexamethasone, were not different. These data suggest that cortisol binding to glucocorticoid receptor is slightly impaired in patients with essential hypertension. In vivo, this could lead to inappropriate binding of cortisol to mineralocorticoid receptors. Hence, decreased sensitivity to cortisol is associated with renin suppression. This hypothesis is supported by evidence of hypertension and low renin activity, which others have described in patients with primary glucocorticoid resistance due to mutations of the glucocorticoid receptor.


Kinetic disposition of (+)-S- and (-)-R-sotalol enantiomers in cardiac patients with tachyarrhythmias using an improved HPLC-fluorescence stereoselective method.
Since the enantioselective pharmacokinetic profiles of R,S-sotalol in cardiac patients are controversial, the present investigation aimed to study the kinetic disposition of sotalol enantiomers in patients with tachycardia. Thirteen cardiac patients, who gave their written consent, were included (6F/7M; 53 +/- 12 yrs, 66 +/- 13 kg, 163 +/- 8 cm height). They had tachycardia, normal renal function and had been chronically treated with tablets of sotalol 160 mg b.i.d. The patients were submitted to blood samples collection at zero, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 h after drug administration. The quantitation of sotalol enantiomers were performed by a stereoselective HPLC method with fluorescence detection previously published. A one open compartment model was applied and the main pharmacokinetic parameters obtained for R-/S-sotalol were, respectively (Mean +/- SD): CSSMAX = 1007 +/- 307/1040 +/- 340 ng/mL; TMAX = 1.82 +/- 0.6/1.83 +/- 0.6 h; AUCSST = 6959 +/- 2153/7388 +/- 2563 ng.h/mL; CISSr/F = 2.7 +/- 1.2/2.5 +/- 1.2 mL/min/kg and VdSS/F = 1.9 +/- 0.9/2.0 +/- 1.0 L/kg. The pharmacokinetic parameters of R,S-sotalol were within the published range and the kinetic parameters for the isomers were grouped as two independent samples and statistically compared. In conclusion, stereoselective pharmacokinetic for sotalol was not observed in cardiac arrhythmic patients, i.e., both R- and S-sotalol enantiomers have the same pharmacokinetic profile.


Different Effect of Media Opacity on Vessel Density Measured by Different Optical Coherence Tomography Angiography Algorithms.
Several studies show that media opacity reduces vessel density (VD) measured by image processing algorithms of optical coherence tomography angiography (OCTA). However, different models of OCTA designed their own algorithms and computational methods, which may have different effects of opacity on VD. This study is aimed to investigate the impact of a simulated model of media opacity on quantitative measurement of two OCTA devices. A spectral-domain based OCTA (Cirrus 5000; Carl Zeiss Meditec) and a swept-source based OCTA (Triton DRI-OCT, Topcon Inc.) were used to image retinal microvasculature at the macula using 3 × 3 mm scanning protocol from 22 eyes of 22 healthy subjects. Media opacity was simulated with neutral-density filters (optical density (OD)λ=840nm ranges 0.10-0.48 in Cirrus; ODλ=1050nm ranges 0.15-0.51 in Triton). The filters were placed in front of each study eye, and signal strength (SS) or signal strength intensity (SSI) was recorded during imaging. The parafoveal VD of superficial capillary plexus was then measured using the built-in software from the two devices. The correlations among OD, SS/SSI, and VD were analyzed. Increased OD was significantly correlated with decreased SS and SSI (rs = -0.576 and -0.922, respectively, both P < 0.001) in Cirrus and Triton, respectively. Although increased OD was significantly correlated with decreased VD in Cirrus (rs = -0.539, P < 0.001), there was no significant correlation between OD with VD in Triton (rs = -0.143, P = 0.137). The effect of media opacity on quantitative measurement of VD is different between different Cirrus and Triton OCTA devices. This study demonstrates that the effect of media opacity on VD measurement is different among different OCTA devices, suggesting that caution must be taken when interpreting VD measurement on OCTA, particularly among individuals with media opacity.


Outcomes of an In Vitro Fertilization Pregnancy With COVID-19 and the Perinatal Outcome in Riyadh, Saudi Arabia.
Coronavirus disease 2019 (COVID-19) caused by the novel severe respiratory syndrome coronavirus 2 (SARS-CoV-2) is a pandemic and potentially fatal disease. COVID-19 cases are on the rise globally; this also includes risk groups such as pregnant women and neonates. Herein, we report the first COVID-19 cesarean delivery case of an in vitro fertilization (IVF) pregnancy in a Saudi woman. A postdate pregnant healthy woman tested positive with COVID-19 on her 38 weeks + five days. On her 40 weeks + five days, the woman had dilation without contractions; thereby, cesarean delivery was decided. The delivery was successful, with no complications in the mother and neonate. The preferable outcomes of this case could be attributable to some factors: multidisciplinary medical management, the mother's young age, and COVID-19 infection during the late trimester.


Psychological effects of idiopathic adolescent scoliosis.
This article reviews the literature concerning psychological characteristics of adolescents with idiopathic scoliosis. Although much has been written on the topic, it is largely based on clinical judgment rather than empirical data. In spite of methodological flaws, the few empirical studies available raise questions regarding the following issues: maladjustment occurs in a significant number of adolescents with scoliosis; there are sex and age differences in response to scoliosis diagnosis and treatment; and noncompliance is a major factor in treatment. Implications for further research are discussed.


The Effect of Anticoagulation on the Treatment of Dupuytren Contracture with Collagenase.
There have been no formal studies of the use of collagenase clostridium histolyticum (Xiaflex; Endo Pharmaceuticals, Malvern, Pa.) in the anticoagulated patient. Previous study on its use excluded patients receiving anticoagulation therapy. This study reviewed the effects of anticoagulation use in patients undergoing collagenase clostridium histolyticum injection and cord rupture to determine safety and efficacy. The authors retrospectively reviewed patients receiving collagenase clostridium histolyticum injections for Dupuytren contracture between 2010 and 2017. Outcomes included type of anticoagulation, skin tear, tendon rupture, lymphadenopathy, sensory abnormality, hematoma, and bleeding. A total of 388 injections were performed in 197 patients. The average clinical follow-up was 311 days. Fifty-two percent of patients (n = 201) were anticoagulated. The vast majority were taking aspirin (acetylsalicylic acid) (n = 182), followed by warfarin (n = 27), clopidogrel (n = 9), apixaban (n = 8), rivaroxaban (n = 4), and dabigatran (n = 2). There were 42 skin tears, 21 in the anticoagulated group. One tendon rupture occurred in the anticoagulated group (acetylsalicylic acid) and none occurred in the nonanticoagulated group (p = 0.34). No patients experienced sensory abnormalities, a hematoma requiring intervention, or uncontrollable bleeding. Anticoagulation is commonly encountered by hand surgeons treating Dupuytren contracture. There is no significant difference in complications in the anticoagulated patient versus the nonanticoagulated patient. It is safe to perform collagenase clostridium histolyticum injections for Dupuytren contracture in the anticoagulated patient, regardless of the type of anticoagulation. Therapeutic, III.


In vivo synergistic antitumor effect and safety of siRNA and lonidamine dual-loaded hierarchical targeted nanoparticles.
Based on development of nano-delivery system, co-delivery of chemotherapeutic drug and small interfering RNA (siRNA) has exerted a promising advantage in cancer therapy. In this work, the superiority of synergistic therapy and safety of the hierarchical targeted co-delivery system loaded with siRNA and lonidamine (LND) were evaluated. The in vivo tumor accumulation ability and cancer growth inhibition effect of the polymer-blend nanocarriers were evaluated by a H22 subcutaneous sarcoma model. Moreover, hematoxylin and eosin (H&E) staining and transferase-mediated dUTP nick end-labeling (TUNEL) staining of tumor sections from each group were compared to assess the therapeutic efficacy. The dual-loaded nanocarriers had better tumor accumulation ability, remarkably inhibited growth of solid tumor in a synergistic manner, even significantly decreased hepatotoxicity of LND, and had good in vivo biocompatibility whereas LND alone showed serious hepatotoxicity. We believed that the dual-loaded hierarchical targeted delivery system with high effectiveness and biocompatibility would provide a promising approach for cancer combination therapy.


Low-dose furosemide administered with adequate hydration reduces contrast-induced nephropathy in patients undergoing coronary angiography.
We investigated the effects of low-dose furosemide, administered with adequate hydration on contrast-induced nephropathy (CIN). A total of 859 patients scheduled to undergo coronary angiography or angioplasty were enrolled and randomly assigned to a furosemide treatment or control group. All patients received supplemental hydration. Immediately after surgery, patients in the furosemide group received intravenous furosemide injection (20 mg); those in the control group received no treatment. Total fluid intake and urine output were recorded. Pre- and postsurgical changes in serum creatinine levels (SCr), glomerular filtration rate (GFR) and creatinine clearance rate (CCr) were assessed, and the incidence of CIN was also evaluated between the two groups. Logistic regression analysis was used to study risk factors for CIN. General baseline conditions were similar between the two groups. Patients who received furosemide had significantly less increase in SCr and a more marked increase in GFR and CCr than those who did not. The incidence of CIN was significantly higher in the control group. Logistic regression analysis revealed that female gender and angiotensin-converting enzyme inhibitor were risk factors for CIN, whereas furosemide acted as a protective agent. With full hydration, small doses of furosemide can reduce CIN better than hydration alone.


Cetuximab functionalization strategy for combining active targeting and antimigration capacities of a hybrid composite nanoplatform applied to deliver 5-fluorouracil: toward colorectal cancer treatment.
Antibody-functionalized targeted nanocarriers to deliver chemotherapeutics have been widely explored. However, it remains highly desirable to understand and apply the antitumor potential of antibodies integrated in hybrid composite nanoplatforms. Herein, mesoporous silica nanoparticles, a supported lipid bilayer and cetuximab were integrated to fabricate a hybrid nanoplatform for effectively encapsulating and selectively delivering 5-fluorouracil (5-FU) against colorectal cancer (CRC) cells. The specially designed nanoplatform exhibited superior properties, such as satisfying size distribution, dispersity and stability, drug encapsulation, controlled release, and cellular uptake. Interestingly, the modification of cetuximab onto nanoplatforms without drug loading can significantly inhibit the migration and invasion of CRC cells through suppressing the epidermal growth factor receptor (EGFR)-associated signaling pathway. Furthermore, delivery of 5-FU by using this nanoplatform can remarkably induce cytotoxicity, cell cycle arrest, and cell apoptosis for CRC cells with high EGFR expression. Overall, this nanostructured platform can dramatically improve the tumor killing effects of encapsulated chemotherapeutics and present antimigration effects derived from the antibody modified on it. Moreover, in vivo biodistribution experiments demonstrated the superior tumor targeting ability of the targeted nanoparticles. Thus, this targeted nanoplatform has substantial potential in combinational therapy of antibodies and chemotherapy agents against colorectal cancer.


[The use of antioxidants in the complex therapy of patients with infiltrating pulmonary tuberculosis].
Clinical and laboratory investigations examined the possibility of a lower load of antibacterial drugs (ABD) in combination with the two antioxidants, alpha-tocopherol and sodium thiosulfate, in combined therapy of patients with infiltrative pulmonary tuberculosis. Higher efficacy of two ABDs supplemented by two antioxidants than three or more ABDs was evidenced by a shorter period of sputum negativity (1.6 +/- 0.26 and 2.7 +/- 0.27 months; p less than 0.01) and higher rates of cavity closure (95.6 +/- 4.3 and 63.2 +/- 6.7%; p less than 0.05).


[Efficacy of Hushen Gujing (HSGJ) in preventing chronic allograft nephropathy in rats].
To evaluate the effect of HSGJ on chronic allograft nephropathy (CAN) using standard rat model of CAN. Renal transplantation was performed with Fisher rats as donors and Lewis rats as recipients. All the recipients were randomly divided into control group and medication groups (high and low dosage of HSGJ, fed every other day). After 16 weeks of treatment, renal function and the histological alteration of CAN were measured. The expression of the TGFbeta1 mRNA in the allograft was evaluated by real-time PCR. The content of 24 h urine protein and the level of serum creatinine in the medication groups were significantly decreased (P < 0.01) as compared with control group, whereas the creatinine clearance was increased (P < 0.01). The degree of glomerular sclerosis and the Banff score of medication groups were lower than the control group respectively (P < 0.01), in consistent with decreased expression of the TGF 1mRNA. HSGJ can prevent the chronic allograft nephropathy and the mechanism may be related with its influence on the expression of the TGFbeta1.


Intron bypass: a rapid procedure for eliminating introns from cloned genomic DNA and its application to a cellulase gene.
We have devised a DNA cloning procedure in which the introns present in a genomic DNA fragment can be eliminated easily and rapidly. The technique combines the methods of cDNA and genomic cloning in a way which assures full-length representation of the intron-free transcript. Moreover, plasmids made by this technique can be designed to contain flanking untranscribed regions which may play a role in the regulation of expression. One strand of a linearized plasmid containing the 3'-end of a gene is used to prime cDNA synthesis from an annealed mRNA template. A second plasmid containing the 5'-end of the gene is linearized, denatured, and annealed to the extended 3'-end molecules and the resulting circular, partial duplexes are used to transform bacterial cells. Two different recombinant plasmids which contain DNA encoding the cellulase, exocellobiohydrolase I, from Trichoderma reesei have been constructed using this method. They both contain the entire translated region of the gene uninterrupted by introns. One plasmid contains additional DNA at the 5'-end, including approximately 150 bp 5' to the start of transcription. The inserts of both plasmids can be excised in one piece.


Sleep enhances memory consolidation in the hippocampus-dependent object-place recognition task in rats.
The positive impact of sleep on memory consolidation has been shown for human subjects in numerous studies, but there is still sparse knowledge on this topic in rats, one of the most prominent model species in neuroscience research. Here, we examined the role of sleep in the object-place recognition task, a task closely comparable to tasks typically applied for testing human declarative memory: It is a one-trial task, hippocampus-dependent, not stressful and can be repeated within the same animal. A test session consisted of the Sample trial, followed by a 2-h retention interval and a Test trial, the latter examining the memory the rat had for the places of two objects presented at the Sample trial. In Experiment 1, each rat was tested twice, with the retention interval taking place either in the morning or evening, i.e., in the inactive or active phase, respectively. Rats showed significantly (p<0.01) better memory for object place after the Morning session. To control for confounding circadian factors, in Experiment 2 rats were tested four times, i.e., in the morning or in the evening while sleep was or was not deprived. Sleep during the retention interval was recorded polysomnographically. Rats only showed significant memory for the target object place in the Test trial after the Morning retention interval in the absence of sleep deprivation, and recognition performance in this condition was significantly superior to that in the three other conditions (p<0.05). EEG recordings during spontaneous morning sleep revealed increased slow oscillation (0.85-2.0 Hz) and upper delta (2.0-4.0 Hz), but reduced spindle band (10.5-13.5 Hz) activity, as compared to evening sleep. However, spindle band power was increased in the Morning retention interval in comparison to a Morning Baseline period (p<0.05). We conclude that consolidation of object-place memory depends on sleep, and presumably requires NonREM sleep rich in both slow wave and spindle activity.


Textbook coverage of holistic spiritual care.
Nursing guidelines recommend that attention should be given to the spiritual and religious needs of patients. This suggests that meeting the spiritual needs of patients is an important aspect of holistic care, and that it should be considered and supported wherever relevant.


Cyclomodulins and Hemolysis in E. coli as Potential Low-Cost Non-Invasive Biomarkers for Colorectal Cancer Screening.
The frequent occurrence of E. coli positive for cyclomodulins such as colibactin (CLB), the cytotoxic necrotizing factor (CNF), and the cytolethal distending factor (CDT) in colorectal cancer (CRC) patients published so far provides the opportunity to use them as CRC screening markers. We examined the practicability and performance of a low-cost detection approach that relied on culture followed by simplified DNA extraction and PCR in E. coli isolates recovered from 130 CRC patients and 111 controls. Our results showed a statistically significant association between CRC and the presence of colibactin genes clbB and clbN, the cnf gene, and newly, the hemolytic phenotype of E. coli isolates. We also observed a significant increase in the mean number of morphologically distinct E. coli isolates per patient in the CRC cohort compared to controls, indicating that the cyclomodulin-producing E. coli strains may represent potentially preventable harmful newcomers in CRC patients. A colibactin gene assay showed the highest detection rate (45.4%), and males would benefit from the screening more than females. However, because of the high number of false positives, practical use of this marker must be explored. In our opinion, it may serve as an auxiliary marker to increase the specificity and/or sensitivity of the well-established fecal immunochemical test (FIT) in CRC screening.


Transcriptome analysis of salinity stress responses in common wheat using a 22k oligo-DNA microarray.
In this study, we constructed a 22k wheat oligo-DNA microarray. A total of 148,676 expressed sequence tags of common wheat were collected from the database of the Wheat Genomics Consortium of Japan. These were grouped into 34,064 contigs, which were then used to design an oligonucleotide DNA microarray. Following a multistep selection of the sense strand, 21,939 60-mer oligo-DNA probes were selected for attachment on the microarray slide. This 22k oligo-DNA microarray was used to examine the transcriptional response of wheat to salt stress. More than 95% of the probes gave reproducible hybridization signals when targeted with RNAs extracted from salt-treated wheat shoots and roots. With the microarray, we identified 1,811 genes whose expressions changed more than 2-fold in response to salt. These included genes known to mediate response to salt, as well as unknown genes, and they were classified into 12 major groups by hierarchical clustering. These gene expression patterns were also confirmed by real-time reverse transcription-PCR. Many of the genes with unknown function were clustered together with genes known to be involved in response to salt stress. Thus, analysis of gene expression patterns combined with gene ontology should help identify the function of the unknown genes. Also, functional analysis of these wheat genes should provide new insight into the response to salt stress. Finally, these results indicate that the 22k oligo-DNA microarray is a reliable method for monitoring global gene expression patterns in wheat.


Spectral method for fast measurement of twisted nematic liquid crystal cell parameters.
We present an experimental approach for the fast measurement of twisted nematic (TN) liquid crystal (LC) cells' parameters. It is based on the spectral measurements of the light transmitted by the system polarizer-reference wave plate-LC cell-analyzer. The cell parameters are obtained by fitting the theoretical model to the experimental data. This method allows determining the rubbing angle, the twist angle and its sense, and the spectral dispersion of the LC cell retardation, simultaneously, with few measurements and without the need of applying voltage or any specific analytical conditions. The method is validated by characterizing two different TN cells with retardations of about 0.91 and 1.85 μm. The birefringence relative error is less than 1.3%.


Endovascular selective hypothermia facilitates giant aneurysm clipping: illustrative case.
The authors present a case of selective hypothermia used for neuroprotection during clipping of a giant partially thrombosed middle cerebral artery (MCA) aneurysm. Although these cases have traditionally required deep hypothermic cardiac arrest, this case illustrates a novel and entirely endovascular solution that avoids cardiac standstill and whole-body cooling. This is, to the authors' knowledge, the first case in human surgery of a catheter-based selective hypothermic circuit used to facilitate MCA trapping for almost 30 minutes. Core temperatures never dropped below 34°C, and the patient recovered uneventfully and has been well for over 5 years. The technical nuances and physiological changes unique to selective hypothermia are discussed.


Strong cationic oxidizers: thermal decomposition, electronic structure and magnetism of their compounds.
Strong oxidizers could be provisionally defined as compounds for which the standard redox potential exceeds 2.0 V in the NHE scale. Compounds which contain transition or post-transition metals at their unusually high positive oxidation states constitute one important family of strong oxidizers. Majority of such systems typically exhibit either diamagnetic or 'simple' paramagnetic properties down to very low temperatures. This is connected with the fact that highest oxidation states of metals are stabilized in fluoride environment and that binary high-valence metal fluorides form either molecular(OD) or low-dimensional (usually !D) crystals. The ternary and higher fluorides are usually OD in electronic sense leading again to low ordering temperatures. The situation becomes more interesting in selected compounds of Ag(II),the strongest oxidizer among all divalent cations, where one finds 2D or even 3D magnetic ordering at elevated temperatures.Thermal stability, electronic structure and magnetic properties of strong oxidizers are discussed jointly in this contribution with emphasis on the compounds of unique divalent silver.


[Work disability in public press professions].
In this study more than 1,000 cases of long-term disability among members of the press and media were evaluated. Mental disorders were the main cause of disability in almost every fourth case. In women psychiatric illnesses were even more important. The most common diagnosis was that of a depressive disorder which accounted for more than half of all psychiatric cases. The causes of disability of other insurance systems such as the German social security scheme and the pension and disability plan for the medical profession were compared. Mental illnesses are the leading cause of disability in white collar workers and orthopaedic illnesses, especially disorders of the vertebral column, are the leading cause in blue collar workers, as one might have expected. In females mental disorders are even more common than in men whereas men tend to have more cardiovascular problems than women. In this study also some interesting features regarding disability caused by various illnesses after long-term follow-up were found. This opens unknown perspectives allowing new assessment of diseases and eventually will enable the actuary to price medical diagnoses for disability insurance.


Negligible Risk of Acute Renal Failure Among Hospitalized Patients After Contrast-Enhanced Imaging With Iodinated Versus Gadolinium-Based Agents.
The potential adverse renal outcome among patients undergoing iodine-based contrast-enhanced computerized tomography (CT) has been questioned recently, given the caution undertaken in patients' selection, hydration protocols, and the low radiocontrast volume, used with advanced imaging equipment. This study is a retrospective assessment of renal outcome in 12,580 hospitalized patients undergoing contrast-enhanced CT, compared with 754 patients subjected to gadolinium-based magnetic resonance imaging, with subsequent propensity matching for clinical characteristics and potential risk factors. The risk of postcontrast acute kidney injury (PC-AKI) was found to be negligible as compared with patients undergoing enhanced magnetic resonance imaging studies, before and after propensity matching (8% vs 7.3% rate of AKI in the nonmatched iodine-based contrast agents [IBCAs] and gadolinium-based contrast agents [GBCAs], respectively, P = 0.3, and 7% in the matched IBCA group, P = 0.9), including comparisons among subgroups with well-defined risk factors such as chronic renal failure, diabetes, older age, and hypertension. However, lower systolic blood pressure before imaging was associated with higher risk to develop PC-AKI after IBCA administration but not with GBCA (for systolic blood pressure lower than 110 mm Hg, odds ratio for AKI after IBCA was 1.49; 95% confidence interval, 1.16-1.88, and after GBCA; odds ratio, 0.12; 95% confidence interval, 0.003-0.73). With the current precautions undertaken, the real-life risk of PC-AKI among inpatients undergoing CT is insignificant. Possible reasons for the diverse impact of blood pressure on the propensity to develop acute kidney failure after iodine-based but not gadolinium-based enhancement imaging are discussed.


Critical assessment of high-circulation print newspaper coverage of the Institute of Medicine report Dietary Reference Intakes for Calcium and Vitamin D.
To evaluate high-circulation US and Canadian newspaper coverage of the Institute of Medicine (IOM) report Dietary Reference Intakes for Calcium and Vitamin D and assess pre-report and post-report reporter-specific vitamin D-related coverage. Two independent reviewers analysed the newspaper articles. The key report findings cited, proportion of sentences describing the IOM report and proportion of sentences describing critical viewpoints on the report were calculated. The content of articles written by reporters with a history of pre-report vitamin D-related articles was compared with that of articles written by reporters without such a history. Factiva and LexisNexis searches of the top thirty US and three English-language Canadian print newspapers, by circulation. Articles on the IOM report published from 30 November to 21 December 2010 and previous vitamin D-related articles written by the same reporters. Only ten articles met inclusion/exclusion criteria. Articles inconsistently cited the key findings in the IOM report. Reporters with a history of pre-report articles highlighting the benefits of vitamin D dedicated a greater proportion of sentences to viewpoints critical of the IOM report (P < 0·01). There was no significant difference between pre-report publication history and proportion of sentences focused on the IOM report. A borderline-significant difference (P = 0·058) was observed between pre-report articles highlighting the benefits of vitamin D and the absence of reference to potential risks of vitamin D overconsumption. Our findings suggest that newspaper articles did not consistently or comprehensively report the IOM recommendations and that pre-report publication history of reporters was related to post-report article content.


Changes in Frost Hardiness of Stem Cortical Tissues of Cornus stolonifera Michx. after Recovery from Water Stress.
Moderate water stress increases frost hardiness in many woody plants but little attention has been given to changes in hardiness after recovery from water stress. Tests were carried out to examine how much water stress-induced frost hardiness remained when plants were rewatered under different day length regimes. Red osier dogwood plants (Cornus stolonifera Michx.) were water-stressed at normal growing temperatures in long day (LD) or short day (SD) conditions, exposed to 6 nights of freezing temperatures, and then returned to normal growing conditions with full water supply. Water-stressed plants gained an additional 8 to 10 C of hardiness. The amount of freeze-induced hardiness in both stressed and control plants was not significant (approximately 2 C) and was not affected by photoperiod. When plants were kept in or transferred to LD, they lost nearly all of their water stress-induced hardiness within 7 days after rewatering. Water-stressed plants in SD lost the least amount of hardiness (5 C) when rewatered. In dogwood, water stress is an effective way to increase hardiness temporarily, but the photoperiod has a large effect on the retention of the acquired hardiness.


An ex-vivo angiogenesis assay as a screening method for natural compounds and herbal drug preparations.
Angiogenesis is a fundamental component of complex biological processes, including oncogenesis. The aim of this work was to optimise and validate an ex-vivo angiogenesis assay as a quantitative (PC image) biological method for testing promising natural compounds and herbal drug preparations for their pro-/anti-angiogenic activity. The bioassay is based on the principle of wound healing and quantifies the effect of angiogenic agents on neovessel outgrowth of human placental vessels embedded in a three-dimensional fibrin matrix. The assay was validated by using known, well characterised pro- and anti-angiogenic effectors (basic fibroblast growth factor and carboxyamidotriazole, respectively), and an angiogenesis inhibitor of plant origin (green tea leaves extract) was used as a reference product to demonstrate the applicability of the assay for plant extracts. Other standardised plant extracts prepared from olive tree leaves and horse chestnut seeds were tested for their angiogenic potential, but showed only slight inhibitory or no activity, respectively. The results presented here indicate that this human ex-vivo angiogenic assay is "ready to use" for screening of herbal drug preparations and pure compounds.


Structure-Cytotoxicity Relationships of Analogues of N14-Desacetoxytubulysin H.
Herein we report structure-cytotoxicity relationships for analogues of N14-desacetoxytubulyisn H 1. A novel synthetic approach toward 1 enabled the discovery of compounds with a range of activity. Calculated basicity of the N-terminus of tubulysins was shown to be a good predictor of cytotoxicity. The impact of structural modifications at the C-terminus of 1 upon cytotoxicity is also described. These findings will facilitate the development of new tubulysin analogues for the treatment of cancer.


Surface Reconstruction on Electro-Spun PVA/PVP Nanofibers by Water Evaporation.
Tailoring the secondary surface morphology of electro-spun nanofibers has been highly desired, as such delicate structures equip nanofibers with distinct functions. Here, we report a simple strategy to directly reconstruct the surface of polyvinyl alcohol/polyvinylpyrrolidone (PVA/PVP) nanofibers by water evaporation. The roughness and diameter of the nanofibers depend on the temperature during vacuum drying. Surface changes of the nanofibers from smooth to rough were observed at 55 °C, with a significant drop in nanofiber diameter. We attribute the formation of the secondary surface morphology to the intermolecular forces in the water vapor, including capillary and the compression forces, on the basis of the results from the Fourier-transform infrared (FTIR) and X-ray photoelectron (XPS) spectroscopy. The strategy is universally effective for various electro-spun polymer nanofibers, thus opening up avenues toward more detailed and sophisticated structure design and implementation for nanofibers.


Comparison of genomic DNA extraction techniques from whole blood samples: a time, cost and quality evaluation study.
Genomic DNA obtained from patient whole blood samples is a key element for genomic research. Advantages and disadvantages, in terms of time-efficiency, cost-effectiveness and laboratory requirements, of procedures available to isolate nucleic acids need to be considered before choosing any particular method. These characteristics have not been fully evaluated for some laboratory techniques, such as the salting out method for DNA extraction, which has been excluded from comparison in different studies published to date. We compared three different protocols (a traditional salting out method, a modified salting out method and a commercially available kit method) to determine the most cost-effective and time-efficient method to extract DNA. We extracted genomic DNA from whole blood samples obtained from breast cancer patient volunteers and compared the results of the product obtained in terms of quantity (concentration of DNA extracted and DNA obtained per ml of blood used) and quality (260/280 ratio and polymerase chain reaction product amplification) of the obtained yield. On average, all three methods showed no statistically significant differences between the final result, but when we accounted for time and cost derived for each method, they showed very significant differences. The modified salting out method resulted in a seven- and twofold reduction in cost compared to the commercial kit and traditional salting out method, respectively and reduced time from 3 days to 1 hour compared to the traditional salting out method. This highlights a modified salting out method as a suitable choice to be used in laboratories and research centres, particularly when dealing with a large number of samples.


Stress proteins expression in rat kidney and liver chronically exposed to aluminium sulphate.
Aluminium (Al) is the third most widespread metal in the environment. It is toxic for the brain, bone and haematological system but unfortunately very little data exist for other organs. Stress proteins are induced or enhanced against metal toxicity with an essential role in the recovery of organules and other cellular proteins. This immunohistochemical study was performed to analyze the distribution of three stress proteins (HSP25, HSP72, GRP75) in rat kidney and liver orally exposed to Al sulphate daily for 3 and 6 months. Al-induced alterations were further studied by histopathology (H-E, PAS, Perl's, Masson) and ultrastructural morphometry. In the kidney: HSP25 was enhanced in proximal tubules after 6 months Al-exposure when abnormal brush borders were observed; HSP72 was induced in proximal tubules only after long Al-treatment; GRP75 was raised in midcortical area sometimes within nuclei. Furthermore, lysosomal and lipofuscins densities increased in the juxtamedullary tubules after 3 months Al exposure with respect to controls. In the liver: Perl's-positive deposits and fibrosis became evident after Al treatment. HSP25 was very weak; HSP72 focal in pericentral hepatocytes at 3 months and induced also in Kupffer cells at 6 months; GRP75 diffuse in periportal hepatocytes and non parenchymal cells at 6 months. Prolonged Al exposure stimulated stress proteins strictly organ-dependently in the rat. Their distribution in kidney and liver seems related to cumulative sublethal effects induced by metal and could be a sensitive index of Al susceptibility of these organs.


Microfluidics meet cell biology: bridging the gap by validation and application of microscale techniques for cell biological assays.
Microscale techniques have been applied to biological assays for nearly two decades, but haven't been widely integrated as common tools in biological laboratories. The significant differences between several physical phenomena at the microscale versus the macroscale have been exploited to provide a variety of new types of assays (such as gradient production or spatial cell patterning). However, the use of these devices by biologists seems to be limited by issues regarding biological validation, ease of use, and the limited available readouts for assays done using microtechnology. Critical validation work has been done recently that highlights the current challenges for microfluidic methods and suggest ways in which future devices might be improved to better integrate with biological assays. With more validation and improved designs, microscale techniques hold immense promise as a platform to study aspects of cell biology that are not possible using current macroscale techniques.


Reconstructing Denisovan Anatomy Using DNA Methylation Maps.
Denisovans are an extinct group of humans whose morphology remains unknown. Here, we present a method for reconstructing skeletal morphology using DNA methylation patterns. Our method is based on linking unidirectional methylation changes to loss-of-function phenotypes. We tested performance by reconstructing Neanderthal and chimpanzee skeletal morphologies and obtained >85% precision in identifying divergent traits. We then applied this method to the Denisovan and offer a putative morphological profile. We suggest that Denisovans likely shared with Neanderthals traits such as an elongated face and a wide pelvis. We also identify Denisovan-derived changes, such as an increased dental arch and lateral cranial expansion. Our predictions match the only morphologically informative Denisovan bone to date, as well as the Xuchang skull, which was suggested by some to be a Denisovan. We conclude that DNA methylation can be used to reconstruct anatomical features, including some that do not survive in the fossil record.


Distal regeneration and symmetry.
A revision of the "polar coordinate model" shows how pattern formation in diverse regenerating systems can be understood in terms of strictly local cell interactions.


Effect of lignocaine in myocardial contusion: an experiment on rabbit isolated heart.
1. The reported incidence of myocardial contusion after blunt chest trauma varies from 16 to 76%. Of these patients, about 6% present a severe, life threatening contusion. We used an isolated heart preparation to examine the effect of lignocaine on myocardial performance after contusion. 2. Thirty hearts obtained from male New Zealand rabbits were perfused at constant flow according to the Langendorff technique and were divided into four groups. The following parameters were measured at frequent intervals for 60 min: mean coronary perfusion pressure (CPP), left ventricular diastolic pressure (LVDP), developed pressure (DP), dP/dtmax, dP/dtmin. 3. Group 1 (n = 6) served as control, group 2 (n = 7) received lignocaine for 20 min (15 microM for the first 10 min and 30 microM for the following 10 min), group 3 (n = 9) had a contusion leading to a 30-50% decrease in dP/dtmax and group 4 (n = 8) had the contusion and the lignocaine infusion was started 10 min after the contusion and stopped after 30 min. Lignocaine concentration was measured in the effluent. 4. Lignocaine alone moderately decreased contractility in group 2. In group 3, after contusion, DP, dP/ dtmax, and dP/dtmin were markedly decreased during the 60 min recording period. In group 4, lignocaine infusion rapidly restored contractility. DP, dP/dtmax and dP/dtmin returned towards their basal values. This improvement of contractility remained stable, even after lignocaine infusion was discontinued. 5. In our rabbit isolated heart preparation, lignocaine at a low therapeutic concentration was able to restore contractility after contusion. These results need to be confirmed by other studies but this may lead to promising therapeutic intervention.


Curcumin in Hepatobiliary Disease: Pharmacotherapeutic Properties and Emerging Potential Clinical Applications.
Curcumin, an aromatic phytoextract from the turmeric (Curcuma longa) rhizome, has been used for centuries for a variety of purposes, not the least of which is medicinal. A growing body of evidence suggests that curcumin has a broad range of potentially therapeutic pharmacological properties, including anti-inflammatory, anti-fibrotic, and anti-neoplastic effects, among others. Clinical applications of curcumin have been hampered by quality control concerns and limited oral bioavailability, although novel formulations appear to have largely overcome these issues. Recent in vitro and in vivo studies have found that curcumin's cytoprotective and other biological activities may play a role in an array of benign and malignant hepatobiliary conditions, including but not limited to non-alcoholic fatty liver disease, cholestatic liver disease (e.g. primary sclerosing cholangitis), and cholangiocarcinoma. Here we provide an overview of fundamental principles, recent discoveries, and potential clinical hepatobiliary applications of this pleiotropic phytocompound.


Tuberculosis and diabetes: current state and future perspectives.
This review outlines the association between tuberculosis and diabetes, focusing on epidemiology, physiopathology, clinical aspects, diagnosis and treatment, and evaluates future perspectives, with particular attention to developing countries.


The acquired immune deficiency syndrome (AIDS): current status and implications for respiratory care practitioners.
The acquired immune deficiency syndrome (AIDS) has affected more than 2,600 persons since 1981, with the number of reported cases rising exponentially. The disease is characterized by a deficiency in the cell-mediated immune system, which allows entrance to a host of opportunistic infections as well as tumors. The most common infection associated with AIDS is Pneumocystis carinii pneumonia, a previously uncommon infection of immunocompromised hosts. The most common neoplasm associated with AIDS is an otherwise rare skin tumor, Kaposi's sarcoma. AIDS is most often seen in homosexuals and intravenous-drug abusers, but the spectrum of the disease is widening and now includes other high-risk groups. The pulmonary manifestations of AIDS range from a nonproductive cough to acute respiratory failure. Once hospitalized, the AIDS patient may require several diagnostic and therapeutic services from respiratory care personnel. We review the epidemiology of this new syndrome, provide the basic framework for an understanding of the immunologic dysfunction in AIDS victims, review the clinical manifestations, and discuss the implications of the communicability of AIDS for the respiratory care practitioner.


Evaluation of the ultrastructure of the small intestine of hiv infected children by transmission and scanning electronic microscopy.
To describe HIV children's small intestinal ultrastructural findings. Descriptive, observational study of small intestine biopsies performed between August 1994 and May 1995 at São Paulo, SP, Brazil. This material pertained to 11 HIV infected children and was stored in a laboratory in paraffin blocks. Scanning and transmission electronic microscopy were used to view those intestine samples and ultrastructural findings were described by analyzing digitalized photos of this material. Ethical Committee approval was obtained. In most samples scanning microscopy showed various degrees of shortening and decreasing number of microvilli and also completes effacements in some areas. Derangement of the enterocytes was seen frequently and sometimes cells well defined borders limits seemed to be loosened. In some areas a mucous-fibrin like membrane with variable thickness and extension appeared to partially or totally coat the epithelial surface. Fat drops were present in the intestinal lumen in various samples and a bacterium morphologically resembling bacilli was seen in two occasions. Scanning microscopy confirmed transmission microscopy microvilli findings and also showed little "tufts" of those structures. In addition, it showed an increased number of vacuoles and multivesicular bodies inside various enterocytes, an increased presence of intraepithelial lymphocytes, mitochondrial vacuolization and basement membrane enlargement in the majority of samples analyzed. However, some samples exhibited normal aspect. Our study showed the common occurrence of various important intestinal ultrastructural alterations with variable degrees among HIV infected children, some of them in our knowledge not described before.


[Essentials for transition of palliative care patients to palliative home care and for management of their cancer pain].
Multi-disciplinary team work among visiting doctors, nurses, care managers and pharmacists located close to the patient's home is essential for smooth transition of a palliative care patient from hospital care to palliative home care and should be set up prior to the patient's discharge from the hospital. Palliative home care physicians should have knowledge of the fundamental support by the government to spare excessive cost to the patients. As for cancer pain management, opioid-centered analgesic therapies have lead to better quality home care for patients. In Japan, although oxycodone SRs and fentanyl patches are available besides morphine, there is no rescue opioid other than morphine. On the other hand, some cancer pain refractory to opioids such as neuropathic cancer pain should be carefully treated by adjuvant analgesics in conjunction with non-pharmacological treatments.


Homocitrate synthase connects amino acid metabolism to chromatin functions through Esa1 and DNA damage.
The enzyme homocitrate synthase (HCS) catalyzes the first step in lysine biosynthesis, and early biochemical data placed it in the cytoplasm or mitochondria, where most amino acid synthesis occurs. It was therefore surprising when refined fractionation techniques and specific immunoreagents clearly demonstrated its localization to the nucleus. These observations raised the question of whether HCS had a function within the nucleus independent of lysine synthesis. We demonstrate that HCS encoded by LYS20 in yeast is linked to the key process of DNA damage repair through the essential MYST family histone acetyltransferase Esa1 and the H2A.Z histone variant. This discovery indicates that HCS has a role in addition to amino acid synthesis, and that it functions in nuclear activities involving chromatin regulation that are distinct from its previously established role in lysine biosynthesis. The chromatin-linked roles are dependent on nuclear localization of Lys20, but are independent of HCS catalytic activity. Thus, Lys20 appears to have evolved as a bifunctional protein that connects cellular metabolism with chromatin functions.


Patch Testing Ingredients of Dermabond and Other Cyanoacrylate-Containing Adhesives.
Cyanoacrylates are strong adhesives used for a variety of medical, industrial, and cosmetic applications and have been implicated as a cause of allergic contact dermatitis. The aim of the study was to review our experience in patch testing with cyanoacrylates. We reviewed patch test results of 38 patients with a clinical history of contact dermatitis due to a cyanoacrylate-containing adhesive (mostly Dermabond). Testing used cyanoacrylates of >99% purity diluted to 10% to 30% in petrolatum (pet.), undiluted octyl cyanoacrylate, and/or Dermabond Mini or Advanced "as is." Patch tests were also performed with methacrylates, formaldehyde (a cyanoacrylate impurity), benzalkonium chloride, and cyanoacrylate polymerization inhibitors. Three patients were also tested with Dermabond Mini on abraded skin. Commercial cyanoacrylate patch testing material (ethyl cyanoacrylate 10% pet.) detected 29% of Dermabond-allergic patients, whereas patch testing with octyl cyanoacrylate 10% pet. increased detection to 50%. Testing with higher concentrations and/or on abraded skin further increased yield. Thirteen (37%) of our 35 cyanoacrylate-allergic patients were also allergic to methacrylates or acrylates. Octyl cyanoacrylate is the usual allergenic ingredient in Dermabond. Patch testing with high concentrations is often required. Testing Dermabond on abraded skin further improves diagnostic sensitivity by more closely simulating clinical use.


Monoseeding Increases Peanut (Arachis hypogaea L.) Yield by Regulating Shade-Avoidance Responses and Population Density.
We aimed to elucidate the possible yield-increasing mechanisms through regulation of shade-avoidance responses at both physiological and molecular levels under monoseeding. Our results revealed that monoseeding decreased the main stem height but increased the main stem diameter and the number of branches and nodes compared to the traditional double- and triple-seeding patterns. The chlorophyll contents were higher under monoseeding than that under double- and triple-seeding. Further analysis showed that this, in turn, increased the net photosynthetic rate and reallocated higher levels of assimilates to organs. Monoseeding induced the expression patterns of Phytochrome B (Phy B) gene but decreased the expression levels of Phytochrome A (Phy A) gene. Furthermore, the bHLH transcription factors (PIF 1 and PIF 4) that interact with the phytochromes were also decreased under monoseeding. The changes in the expression levels of these genes may regulate the shade-avoidance responses under monoseeding. In addition, monoseeding increased pod yield at the same population density through increasing the number of pods per plant and 100-pod weight than double- and triple-seeding patterns. Thus, we inferred that monoseeding is involved in the regulation of shade-avoidance responsive genes and reallocating assimilates at the same population density, which in turn increased the pod yield.


Conclusions and treatment recommendations for the acute episode in schizophrenia.
Interventions which reduce symptoms, vulnerability and stress on the one hand and improve psychosocial competence and quality of life on the other are essential components of a comprehensive treatment program in schizophrenia. Drug treatment of acute exacerbations which is adequate with respect to drug type, dose and treatment duration and takes risk/benefit measures into account is at the heart of these interventions and should be applied as early as possible. Subsequent neuroleptic treatment to prevent a relapse should be administered in accordance with established treatment guidelines. Drug treatment must be combined with psychosocial interventions, which should be properly adapted to the particular phase and stage of the illness. Implementation and coordination of various interventions require cooperation between therapists, institutions, the patient and the patient's family.