Aortic neck dilation is not associated with adverse outcomes after fenestrated endovascular aneurysm repair.
Long-term outcomes after endovascular aneurysm repair (EVAR) are threatened by aortic neck dilation (AND), graft migration, and subsequent endoleak development. The aim of this study was to determine the rate of AND and the occurrence of endoleaks after fenestrated EVAR of juxtarenal aneurysms with physician-modified endovascular grafts (PMEGs). The study included 77 patients presenting with asymptomatic and ruptured juxtarenal abdominal aortic aneurysms treated with PMEGs who received radiologic follow-up. Analysis of computed tomography images took place on a three-dimensional workstation (TeraRecon, San Mateo, Calif). Aortic neck diameter was measured before and after EVAR at the lowest patent renal artery outer wall to outer wall. Significant AND was defined as >3-mm increase between baseline and follow-up, and sac regression >5 mm was considered significant. The patient's 1-month initial postoperative computed tomography measurement was considered baseline. The rate of AND was measured by comparing the baseline measurement with measurements at 6 months, 12 months, and annually thereafter up to 4 years. In this cohort of patients, 75% were men with a mean age of 74 ± 7.9 years. Median preoperative aneurysm size was 62 (57-73) mm, and median follow-up was 12 (3.5-30) months. Mean endograft oversizing was 17% ± 12.5%, and mean seal zone length was 41 ± 11 mm. At 1-year follow-up, the median aortic neck increase was 1.7 (0-3) mm. Maximum aneurysm size decreased dramatically during the first postoperative year, with significant sac regression in 65% of the patients. Aortic neck diameter at 1 year did correlate positively with the percentage of device oversizing. No other correlations were found. During the 4-year follow-up, there were no cases of type IA endoleaks. AND does not influence outcome after endovascular repair of juxtarenal aneurysms using PMEGs. These midterm results support the applicability of PMEGs in juxtarenal aneurysm repair.


Senobtusin, a novel alkaloid with amidine moiety from Senecio obtusatus Wall. ex DC.
Phytochemical investigation of Senecio obtusatus Wall. ex DC led to the isolation of a novel alkaloid, senobtusin (1). Compound 1 possesses an atypical amidine moiety, and the structure was determined on the basis of extensive NMR analysis and HR-ESI-MS technique. This is the first report of this class of natural products obtained from family Asteraceae, and the systematic importance was also discussed.


Potential SECIS elements in HIV-1 strain HXB2.
It has been proposed on the basis of sequence analysis that HIV-1 encodes a protein containing the amino acid selenocysteine (Sec). Selenocysteine is known to be incorporated into protein in response to a specific RNA secondary structure motif within the mRNA that is being translated. This RNA motif, the selenocysteine insertion sequence (SECIS) element, has not yet been identified in the HIV genome by either biologic or computation methods. This report uses computer-based sequence analysis to identify those locations in HIV-1 strain HXB2 where the current model of the SECIS element could exist. One particularly good match to the SECIS element occurs in an interesting location, spanning the end of env and the start of nef, in a position theoretically capable of directing the previously proposed Sec incorporation.


A framework for integrating NANDA, NIC, and NOC terminology in electronic patient records.
To describe the methods used in design of a framework that (a) encompasses nursing knowledge, (b) functions as a cognitive map for clinicians, and (c) increases the efficiency of using the North American Nursing Diagnosis Association (NANDA), Nursing Intervention Classification (NIC), and Nursing Outcome Classification (NOC) terminologies together in the electronic patient record. The taxonomies of the NANDA, NIC, and NOC terminologies were integrated to form a preliminary structure of domains and classes. New concepts and collocations of concepts were constructed using Walker and Avant's (1983, 1988) method for concept synthesis. The framework was validated using an expert group and clinical testing. A framework organized as a taxonomy with eight domains (Physiological, Functional, Psychocognitive, Safety, Existential, Lifestyle, Family, and Environment) and 29 classes. The framework has the potential to enhance the quality of nursing documentation, contribute to nursing research and education, and reduce job stress.


A universal model of electrochemical safety limits in vivo for electrophysiological stimulation.
Electrophysiological stimulation has been widely adopted for clinical diagnostic and therapeutic treatments for modulation of neuronal activity. Safety is a primary concern in an interventional design leveraging the effects of electrical charge injection into tissue in the proximity of target neurons. While modalities of tissue damage during stimulation have been extensively investigated for specific electrode geometries and stimulation paradigms, a comprehensive model that can predict the electrochemical safety limits in vivo doesn't yet exist. Here we develop a model that accounts for the electrode geometry, inter-electrode separation, material, and stimulation paradigm in predicting safe current injection limits. We performed a parametric investigation of the stimulation limits in both benchtop and in vivo setups for flexible microelectrode arrays with low impedance, high geometric surface area platinum nanorods and PEDOT:PSS, and higher impedance, planar platinum contacts. We benchmark our findings against standard clinical electrocorticography and depth electrodes. Using four, three and two contact electrochemical impedance measurements and comprehensive circuit models derived from these measurements, we developed a more accurate, clinically relevant and predictive model for the electrochemical interface potential. For each electrode configuration, we experimentally determined the geometric correction factors that dictate geometry-enforced current spreading effects. We also determined the electrolysis window from cyclic-voltammetry measurements which allowed us to calculate stimulation current safety limits from voltage transient measurements. From parametric benchtop electrochemical measurements and analyses for different electrode types, we created a predictive equation for the cathodal excitation measured at the electrode interface as a function of the electrode dimensions, geometric factor, material and stimulation paradigm. We validated the accuracy of our equation in vivo and compared the experimentally determined safety limits to clinically used stimulation protocols. Our new model overcomes the design limitations of Shannon's equation and applies to macro- and micro-electrodes at different density or separation of contacts, captures the breakdown of charge-density based approaches at long stimulation pulse widths, and invokes appropriate power exponents to current, pulse width, and material/electrode-dependent impedance.


Is the chemistry of collagen in intervertebral discs an expression of Wolff's Law? A study of the human lumbar spine.
The collagen content, proportion of Types I and II collagen, and the relative concentrations of the reducible crosslinks of human lumbar intervertebral discs have been found to vary with age and location and to be highly dependent on the topography of the tissue. From adolescence to mature adulthood, the most significant change is an increase in the content of Type I collagen at the expense of genetically distinct Type II collagen in the outer lamella of the posterior quadrant, while just the reverse is true of the anterior quadrant. These changes are accompanied by similar but smaller alterations in the total collagen content and in the crosslink hydroxylysinohydroxynorleucine . The same differences in the distribution of Types I and II collagens occur in the annuli on the concave and convex sides of scoliotic curves. Together, these data establish that active cellular activity and tissue remodelling occur in the annuli fibrosi and suggest that these specific changes are initiated in response to overall increases in compressive loading on the concave side and tensile loading on the convex side of the spine and the subsequent changes they induce in the magnitude and distribution of internal stresses within the annuli. In its most general formulation, the biological behavior of annuli fibrosi to mechanical forces appears to follow Wolff's Law.


Isotopic evidence for breastfeeding and possible adult dietary differences from Late/Sub-Roman Britain.
Historical documents indicate that breastfeeding and weaning practices have fluctuated in England through history. In order to obtain evidence for general breastfeeding patterns in Late/Sub-Roman Britain, stable carbon and nitrogen isotope values were measured in juvenile and adult skeletons (n = 87) from the cemetery of Queenford Farm, Dorchester-on-Thames, Oxfordshire. As the site contained few individuals between 0-1.5 years of age, it was not possible to determine the initial timing for the introduction of weaning foods. Between ages 2-4 years, the mean +/- SD delta(13)C results (-20.2 +/- 0.3 per thousand) are significantly more negative (t = -4.03, P < 0.001) compared to adult females (-19.7 +/- 0.3 per thousand). This is interpreted as evidence of a different diet being fed to children during weaning. After age 2, the delta(15)N values gradually decline, indicating complete cessation of breastfeeding by 3-4 years. Among adults, stature (males = 1.68 +/- 0.06 m; females = 1.58 +/- 0.07 m) and sexual dimorphism (106) were low, suggesting that the population was possibly under environmental stress. The delta(13)C results for adults are similar, but females show a small but statistically significantly (t = -2.86, P < 0.01) lower mean delta(15)N value (9.9 +/- 0.9 per thousand) compared to males (10.6 +/- 0.5 per thousand). These lower female delta(15)N values possibly reflect the different physiology of the sexes (pregnancy and/or lactation) or the reduced consumption of animal/fish protein by women, and this may have been influenced by individual preference, family needs, or societal values of the era.


133Xe clearance estimates the effect of vasopressin on peritoneal blood flow in rats.
When assessing the peritoneal microcirculation with invasive methods, interference with the mechanisms of vaso-regulation may occur. The 133Xe clearance technique renders the possibility, by minimal invasiveness, to estimate the influence of a vasoactive agent on the peritoneal microcirculation. Ten to 15MBq of 133Xe were injected in the abdominal cavity in thirty-eight Wistar-FU (W-FU) rats and 35 Lister-Hooded (LH) rats. A NaI (Tl)-scintillation detector registered activity before and during vasopressin infusion. Gamma camera imaging confirmed the washout from the abdominal cavity. The laser Doppler flowmetry technique was used as a comparison. Vasopressin at 0.07 IU/kg/min IV significantly reduced 133Xe-clearance by 37% (p = 0.029) and 52% (p=0.036) and laser Doppler flowmetry by 69% (p=0.0019) and 44% (p=0.0039) in W-FU and LH rats, respectively. A linear correlation between dose of vasopressin and relative decrease in 133Xe clearance was demonstrated in the W-FU rat model (r2=0.98, p=0.023). The 133Xe clearance from the abdominal cavity in rat using a single-compartment model or the slow compartment in a double-compartment model gave reproducible information. The usefulness of this mini-invasive technique for sequential measurements before and during intervention will render the 133Xe clearance suitable for assessment of blood flow changes in the abdominal cavity.


Experimental infection of high health pigs with porcine circovirus type 2 (PCV2) and Lawsonia intracellularis.
Porcine circovirus type 2 (PCV2) and Lawsonia intracellularis infections can cause enteritis in pigs. A Danish study showed a significantly higher probability of detecting PCV2 without concurrent L. intracellularis infection, indicating that one of these pathogens has an impact on the dynamics of the other. Therefore, a delayed co-infection model was set up, initially aiming at investigating the interaction between PCV2 and L. intracellularis in pigs challenged with PCV2 and 2 weeks later with L. intracellularis. But due to PCV2 contamination of the L. intracellularis inoculum the aim was revisited to describing the infection dynamics and pathogenesis of pigs infected with PCV2 followed by delayed simultaneous exposure to PCV2 and L. intracellularis. Twenty-four high-health piglets were divided into three groups of eight pigs (A, B, C) and inoculated at experimental day (EXD) 0 with mock (groups A and B) or PCV2 (group C), and at EXD 14 with mock (group A) or L. intracellularis/PCV2 (groups B and C). The pigs underwent daily clinical examination, and were necropsied at EXD 51-52. Furthermore, histology, immunohistochemistry, serology and PCR for PCV2 and L. intracellularis, and measurement of C-reactive protein were carried out. Group A remained negative for PCV2 and L. intracellularis. Following inoculation with L. intracellularis/PCV2, no significant differences were observed between group B and C, however pigs already infected with PCV2 (group C) showed milder clinical signs and exhibited milder intestinal lesions, less shedding of L. intracellularis and developed higher L. intracellularis antibody titers than the pigs in group B that only received the combined infection. Though the differences between group B and C were non-significant, all results pointed in the same direction, indicating that the pigs in group B were more affected by the L. intracellularis infection compared to the pigs in group C. Previous exposure to PCV2 had limited impact on the subsequent exposure to a combined L. intracellularis/PCV2 inoculation. However, there was a tendency that the infection dynamics of PCV2 and development of antibodies to PCV2 and L. intracellularis were altered in pigs previously exposed to PCV2. These differences should be confirmed in further experimental trials.


Immunoglobulin g4-related hypertrophic pachymeningitis with skull involvement.
Immunoglobulin G4 (IgG4)-related hypertrophic pachymeningitis, defined as focally or diffusely thickened dura mater and lymphoplasmacytic infiltration with increased IgG4 bearing plasma cells, is a rare disease. Moreover, cases involving bone are even rarer. In this report, the authors describe a case of IgG4-related hypertrophic pachymeningitis involving the skull in a 65-year-old man presenting with generalized tonic seizures. There is a 2.4 cm diameter extra-axial mass at the vertex of the left frontal convexity and thickened dura mater with contrast enhancement on magnetic resonance (MR) imaging. In addition, the skull adjacent to the mass was focally enhanced. He underwent surgical resection of the enhanced mass and skull. Histopathological findings revealed chronic inflammation with fibrosis, and idiopathic hypertrophic intracranial pachymeningitis was considered. However, eight months after surgery, partial seizures developed and brain MR imaging revealed a recurrence adjacent to the previous mass. We decided to perform additional immunohistochemical staining of the previous specimen, instead of a re-excision. Immunohistochemical staining showed markedly increased IgG4 (+) plasma cells. Consequently, IgG4-related hypertrophic meningitis was confirmed. Since then, steroids and immunosuppressant medications were started. Follow-up MR imaging at 3 months after medication initiation demonstrated complete remission. In conclusion, IgG4-related hypertrophic pachymeningitis should be considered in the differential diagnosis of hypertrophic cranial pachymeningitis.


Charnley wear model for validation of hip simulators--ball diameter versus polytetrafluoroethylene and polyethylene wear.
Wear rates of polytetrafluoroethylene (PTFE) and polyethylene cups were compared in 9-channel and 12-channel simulators, using serum lubrication and gravimetric techniques for wear assessment. Cobalt-chromium (CoCr) and alumina ceramic femoral heads in 22-42 mm diameter range were used to validate simulator wear rates against clinical data. This was also the first study of three femoral head sizes evaluated concurrently in a simulator (with three replicate specimens) and also the first report in which any wear experiments were repeated. Fluid absorption artefacts were within +/-1 per cent of wear magnitude for PTFE and +/-8 per cent for polyethylene and were corrected for. Wear rates were linear as a function of test duration. Precision within each set of three cups was within +/-6 per cent. The wear rates from experiments repeated over 15 months were reproducible to within +/-24 per cent. However, the magnitudes of the simulator wear rates were not clinically accurate, the PTFE wear rates (2843 mm3/10(6) cycles; 22 mm diameter) were over three times higher than in vivo, the polyethylene 30 to 50 per cent on the low side (23 mm3/10(6) cycles; 22 mm diameter). Volumetric wear rate increased with respect to size of femoral head and a linearly increasing relationship of 7 8 per cent/mm was evident with respect to femoral head diameter for both PTFE and polyethylene. These data compared well with the clinical data.


The Effectiveness of Combined Exercise Interventions for Preventing Postmenopausal Bone Loss: A Systematic Review and Meta-analysis.
Study Design Systematic review and meta-analysis. Background It remains unclear whether exercise combining different types of physical activities (combined exercise interventions) would effectively preserve postmenopausal women's bone mineral density (BMD) at different sites. Objective To examine the impact of combined exercise interventions on lumbar spine, femoral neck, total hip, and total body BMD in postmenopausal women. Methods An electronic database search was conducted in PubMed, EMBASE, SPORTDiscus, and Web of Science up to January 1, 2016. Randomized controlled trials that conducted combined exercise interventions and reported BMD values in postmenopausal women were included. Two authors independently extracted the data from individual studies. The primary end point was the change in BMD values from baseline to follow-up. The effect sizes were estimated by the standardized mean difference (SMD) methods using fixed-effects models. Results Eleven randomized controlled trials including 1061 postmenopausal women met the inclusion criteria. The levels of between-study heterogeneity were relatively low (I2<50%). Exercise integrating different physical activities significantly increased lumbar spine (SMD, 0.170; 95% confidence interval [CI]: 0.027, 0.313; P = .019), femoral neck (SMD, 0.177; 95% CI: 0.030, 0.324; P = .018), total hip (SMD, 0.198; 95% CI: 0.037, 0.359; P = .016), and total body (SMD, 0.257; 95% CI: 0.053, 0.461; P = .014) BMD. Combined exercise interventions generated a beneficial effect on femoral neck BMD (SMD, 0.219; 95% CI: 0.034, 0.404; P = .020) in groups with women aged younger than 60 years, and significantly improved lumbar spine BMD (SMD, 0.349; 95% CI: 0.064, 0.634; P = .016) in groups with women aged 60 years or older. Conclusion Our findings suggest that combined exercise interventions appear to be effective in preserving postmenopausal women's BMD at the lumbar spine, femoral neck, total hip, and total body. Level of Evidence Therapy, level 1a. J Orthop Sports Phys Ther 2017;47(4):241-251. Epub 3 Mar 2017. doi:10.2519/jospt.2017.6969.


A phantom for targeted endomyocardial biopsy training.
Endomyocardial biopsy (EMB) of the right ventricular (RV) septal surface during cardiac catheterization is the standard method to assess cardiac allograft rejection, heart failure, or inflammatory cardiomyopathies. We developed methodology using a three-dimensional (3D) printed phantom to provide proof of concept for using biplane overlay technology for targeted EMB. A standard bioptome and steerable sheath were used to discern feasibility of biopsy for seven regions of the RV septum guided by 3D overlay. This novel biopsy phantom can help train operators in biopsy techniques, and biplane overlay technology has the potential to advance targeted EMB in transplant and cardiomyopathy populations.


Use of short fiber-reinforced composite with semi-interpenetrating polymer network matrix in fixed partial dentures.
The aim of this study was to determine the static load-bearing capacity of fixed partial dentures (FPDs) made of experimental composite resin (FC) with short fiber fillers and interpenetrating polymer network (IPN) polymer matrix. Experimental composite FC resin was prepared by mixing short E-glass fibers (3mm in length) of 22.5wt% and IPN-resin 22.5wt% with silane treated silica fillers 55wt%. Four groups of FPDs (3-unit) were fabricated (n=6); Group A: made from commercial composite resin (Sinfony dentin, 3M-ESPE, control), Group B: Sinfony and fiber-reinforced composite (FRC) substructure, Group C: made from FC, Group D: made from FC with 1mm surface layer of Sinfony. The bridges were polymerized with a hand-light curing unit for 40s then post-cured in vacuum curing device (Visio Beta) for 15min before they were statically loaded with speed of 1mm/min until fracture. Failure modes were visually examined. Data were analyzed using ANOVA (p=0.05). ANOVA revealed that bridges made from experimental fiber composite had statistically significantly higher load-bearing capacity (2171N) (p<0.05) than the control restorations (1482N). Restorations made from short glass fiber containing composite resin with IPN-polymer matrix showed better load bearing capacity than in those made with conventional composites resin and similar with those reinforced with FRC-substructure.


Observation of peptide differences between cancer and control in gastric juice.
Biomarkers for various diseases have been extensively searched for the past 5 years. Nevertheless, most efforts were focused on the search for protein biomarkers from serum samples. In this work, we tried to look for peptide biomarkers from gastric juice samples with MALDI-TOF-MS. More than 200 gastric juice samples from healthy people, gastric ulcer patients, duodenal ulcer patients, and cancer patients were examined. There were clear pattern differences of mass spectra among samples from healthy people and patients with different gastric diseases. We found five peptides for gastric cancer diagnosis with high sensitivity and specificity. Sequences of these five peptides, including two pepsinogen fragments, leucine zipper protein fragment, albumin fragment, and α-1-antitrypsin fragment, have been identified by mass spectrometric analysis and immuno-deplete assay with antibodies.


Prospects for treatment of paraquat-induced lung fibrosis with immunosuppressive drugs and the need for better prediction of outcome: a systematic review.
Acute paraquat self-poisoning is a significant problem in parts of Asia, the Pacific and the Caribbean. Ingestion of large amounts of paraquat results in rapid death, but smaller doses often cause a delayed lung fibrosis that is usually fatal. Anti-neutrophil ('immunosuppressive') treatment has been recommended to prevent lung fibrosis, but there is no consensus on efficacy. To review the evidence for the use of immunosuppression in paraquat poisoning, and to identify validated prognostic systems that would allow the use of data from historical control studies and the future identification of patients who might benefit from immunosuppression. Systematic review. We searched PubMed, Embase and Cochrane databases for 'paraquat' together with 'poisoning' or 'overdose'. We cross-checked references and contacted experts, and searched on [www.google.com] and [www.yahoo.com] using 'paraquat', 'cyclophosphamide', 'methylprednisolone' and 'prognosis'. We found ten clinical studies of immunosuppression in paraquat poisoning. One was a randomized controlled trial (RCT). Seven used historical controls only; the other two were small (n = 1 and n = 4). Mortality in controls and patients varied markedly between studies. Three of the seven non-RCT controlled studies measured plasma paraquat; analysis using Proudfoot's or Hart's nomograms did not suggest that immunosuppression increased survival in these studies. Of 16 prognostic systems for paraquat poisoning, none has been independently validated in a large cohort. The authors of the RCT have performed valuable and difficult research, but their results are hypothesis-forming rather than conclusive; elsewhere, the use of historical controls is problematic. In the absence of a validated prognostic marker, a large RCT of immunosuppression using death as the primary outcome is required. This RCT should also prospectively test and validate the available prognostic methods, so that future patients can be selected for this and other therapies on admission.


Bridging the gap between translational medicine and unmet clinical needs.
To date, the actual rate of successful translation has been extremely low although those few successes have been notable and provide for continued and expanding enthusiasm and support. This paper examines whether the fundamental premise may be flawed. Could the success rate be improved to further enhance quality of life and cost optimization for patients by changing the paradigm to "bedside to bench to bedside", and focusing the research on addressing unmet clinical needs? It examines all aspects of the healthcare ecosystem to understand issues that arise with real world patients and in real world clinical practice and how addressing these should be the focus of translational research.


A Sakurai-Prins-Ritter sequence for the three-component diastereoselective synthesis of 4-amino tetrahydropyrans.
A simple one-pot procedure for the Sakurai-Prins-Ritter sequence allows rapid assembly of 4-acylamino-2,6-substituted tetrahydropyrans in high yields and with excellent diastereoselectivity from readily available 4-acetoxy-1,3-dioxanes, allylsilanes, and nitriles. A variety of nitriles have been shown to participate. Diastereoselectivities are uniformly high and observed stereochemistry of cation trapping proceeds according to Alder's model of the 4-tetrahydropyranyl cation.


Comparison of plasma viscosity as a marker of endothelial dysfunction with nitric oxide and asymmetric dimethylarginine in subjects with dyslipidemia.
In this study, we aimed to investigate the alterations in plasma viscosity and whether there was a relationship between plasma viscosity and endothelial dysfunction markers such as nitric oxide (NOx), asymmetric dimethylarginine (ADMA) and oxidized Low Density Lipoprotein (oxLDL) in dyslipidemic subjects. 35 subjects with normolipidemia and 30 subjects with hyperlipidemia were involved in this study. Dyslipidemia was defined as total cholesterol levels ≥200 mg/dL and/or triglyceride level ≥150 mg/dL. Plasma total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglycerides, total protein, albumin levels and NOx were determined by enzymatic methods using commercial kits. Plasma ADMA concentrations and serum levels of total oxLDL were determined by ELISA. Plasma viscosity was measured by Harkness capillary viscometer. Plasma viscosity, ADMA and oxLDL values were significantly higher in subjects with dyslipidemia than in subjects with normolipidemia. Plasma NOx concentration was decreased in dyslipidemic subjects compared to the normo-lipidemic subjects. We found that fibrinogen had no effect upon plasma viscosity in selected patients with dyslipidemia. Our results demonstrated that the rheological impairment of dyslipidemic patients was related with endothelial dysfunction and this was a possible cause of both micro and macrovascular complications. Therefore, as plasma viscosity is also a sensitive parameter, it can add useful information about the diagnosis and treatment of various disorders, and it should be utilized more frequently in clinical medicine.


The Shikani Seeing Stylet for difficult intubation in children: initial experience.
The Shikani Seeing Stylet is a recently introduced reusable intubating stylet, produced in adult and paediatric versions. It combines features of a fibreoptic bronchoscope and a lightwand. Inside a malleable stainless steel sheath, the Shikani Seeing Stylet has a fibreoptic cable leading to a distal light source and high-resolution lens. In use, the stylet is placed in the lumen of the selected endotracheal tube and the light source enables the stylet to be used as a lightwand, while the fibreoptic capability enables visualization of the laryngeal inlet. It is portable, relatively inexpensive and easy to maintain. This report describes the use of the stylet on eight occasions in seven children, all of whom were assessed preoperatively as being potentially difficult to intubate. Three had been difficult to intubate previously. All were anaesthetized using inhalational anaesthesia. Once an adequate depth of anaesthesia had been achieved, conventional direct laryngoscopy was performed and identified as Grade 3 in six of the patients and Grade 1 in one. Tracheal intubation was then attempted using the Shikani Seeing Stylet. On six of the eight occasions the attempt was made by different anaesthetists, none of whom had any prior clinical experience with the stylet. There were seven successful intubations and one failure in a patient who could not be intubated by any method. The Shikani Seeing Stylet seems a useful device for use in children with difficult airway problems, suspected cervical spine instability or limited mouth-opening.


Synergistic inactivation of anaerobic wastewater biofilm by free nitrous acid and hydrogen peroxide.
Free nitrous acid (FNA) was recently revealed to be a strong biocide for microbes in anaerobic biofilm, achieving approximately 1-log (90%) inactivation at a concentration of 0.2-0.3 mgHNO2-N/L with an exposure time longer than 6h. The combined biocidal effects of FNA and hydrogen peroxide (H2O2) on anaerobic wastewater biofilm are investigated in this study. H2O2 greatly enhances the inactivation of microorganisms by FNA. About 2-log (99%) of microbial inactivation was achieved when biofilms were exposed to FNA at 0.2 mgN/L or above and H2O2 at 30 mg/L or above for 6h or longer. It was found, through response surface methodology and ridge analysis, that FNA is the primary inactivation agent and H2O2 enhances its efficiency. The loss and the subsequent slow recovery of biological activity in biofilm reactors subjected to FNA and H2O2 dosing confirmed that the chemical combination could achieve higher microbial inactivation than with FNA alone. Reaction simulation shows that intermediates of reactions between FNA and H2O2, like peroxynitrite and nitrogen dioxide, would be produced at elevated levels and are likely responsible for the synergism between FNA and H2O2. The combination of FNA and H2O2 could potentially provide an effective solution to sewer biofilm control.


Changes in task parameters during walking prism adaptation influence the subsequent generalization pattern.
An understanding of the transfer (or generalization) of motor adaptations between legs and across tasks during walking has remained elusive due to limited research and mixed results. Here, we asked whether stepping sequences or task constraints introduced during walking prism-adaptation tasks influence generalization patterns. Forty subjects adapted to prism glasses in precision-walking or obstacle-avoidance tasks that required a specific stepping sequence to the center of two/three targets or laterally over an obstacle. We then tested for generalization, reflected by aftereffects in the nonadapted task. Our previous study using these tasks found that only one leg generalized. Here, we reversed the stepping sequence and found that only the opposite leg generalized in the subject group that adapted in a precision-walking task. The combination of stepping sequence and direction of prism shift caused subjects in two groups to collide with the obstacle early during adaptation, thus making the step prior to going over the obstacle more important. Both legs subsequently generalized. A fourth subject group experienced a three-target, precision-walking task, resulting in a balanced, right-left, left-right stepping sequence, meant to induce bilateral generalization. While only one leg generalized, foot placement aftereffects before stepping over the obstacle would have caused subjects to collide with it. Together with our previous study, the results suggest a contribution of stepping sequence during the adapted task on generalization patterns, likely driven by proprioceptive feedback. The results also support the idea that negative consequences during adaptation and/or perceived threat can influence generalization.


Antiepileptic drugs as prophylaxis for postcraniotomy seizures.
This is the protocol for a review and there is no abstract. The objectives are as follows: The objective of this review is to determine the efficacy and safety of AEDs when used prophylactically for people undergoing craniotomy.


Discovery and Development of ATP-Competitive mTOR Inhibitors Using Computational Approaches.
The mammalian target of rapamycin (mTOR) is a central controller of cell growth, proliferation, metabolism, and angiogenesis. This protein is an attractive target for new anticancer drug development. Significant progress has been made in hit discovery, lead optimization, drug candidate development and determination of the three-dimensional (3D) structure of mTOR. Computational methods have been applied to accelerate the discovery and development of mTOR inhibitors helping to model the structure of mTOR, screen compound databases, uncover structure-activity relationship (SAR) and optimize the hits, mine the privileged fragments and design focused libraries. Besides, computational approaches were also applied to study protein-ligand interactions mechanisms and in natural product-driven drug discovery. Herein, we survey the most recent progress on the application of computational approaches to advance the discovery and development of compounds targeting mTOR. Future directions in the discovery of new mTOR inhibitors using computational methods are also discussed.


Food consumption trends and nutrition transition in Korea.
This review article aims to provide an overview of food consumption trends in relation to the nutritional status of Koreans. Food consumption patterns and nutritional status of Koreans have changed substantially due to economic improvements and the adoption of a western lifestyle. The traditional habit of consuming vegetable foods like cereals, soybeans and potatoes has seen a decline, while consumption of meat, poultry, egg and fruits has increased. Although the proportion of animal foods has increased from 3.0% in 1969 to 19.2% in 1998, the Korean diet is still not sufficient in milk and eggs. The total energy intake has gradually decreased with reduced consumption of cereals, and concomitantly carbohydrates intake has decreased. Fat intake has increased with elevated consumption of animal foods and added fats and oils, but the level of fat intake remains low with a high consumption of vegetables and increased fruit consumption. This food consumption pattern might have contributed to the ideal proportion of energy from carbohydrates, protein and fat at 66%, 15% and 19% respectively in 1998, which is almost close to the composition of 65%, 15%, and 20% that most nutritionists would term as an ideal ratio. It would appear that the Korean food consumption trend is ideal except for the consumption of salty foods which is high.


Effect of Peanut Protein Treated with Alkaline Protease and Flavorzyme on BALB/c Mice.
This article aims to analyze the effects of enzyme treatment concentration, temperature, and time on peanut protein so as to obtain an optimal enzymatic hydrolysis condition for flavorzyme (Fla) and alkaline protease (Alk). The results were as follows: enzymatic hydrolysis temperature 60 °C and 55 °C, enzyme concentration 10% and 4%, enzymatic hydrolysis time 80 min and 60 min, and double enzyme hydrolysis ratio 2% Fla + 5% Alk, respectively. The BALB/c mice were sensitized with gavage of peanut protein before and after enzyme treatment to evaluate the effects of different enzyme treatments on peanut allergenicity. Compared with the mice sensitized with raw peanuts, the weight growth rate of the mice sensitized with enzyme treatment peanut increased but not as much as the control, the degranulation degree of mast cell and basophils decreased, the inflammatory infiltration and congestion in jejunum and lung tissue decreased, the expression of proinflammatory factors and thymic stromal lymphopoietin (TSLP) gene decreased, and the secretion of specific antibodies (IgE, and IgG) decreased, and the binding ability of peanut protein with peanut-specific IgE antibodies decreased as well. The results above indicate that the allergenicity of peanut protein decreases after enzyme treatment and the dual enzyme (Fla + Alk) treatment can be much more efficient.


Systemic lupus erythematosus and complement.
SLE is characterized by a host of immune abnormalities. It is not clear to date which of these are primary and which are secondary. The observation of a number of genetic defects suggests that they are primary. Multiple genetic defects may then lead to abnormal immune responses to common pathogens, antigens, or even autoantigens. As a result of this abnormal immune response, immune complexes form with resultant complement fixation and activation. These immune complexes interacting with cells and complement initiate an inflammatory response. One can also speculate that this inflammatory response represents a normal response to an abnormal event, or is also abnormal in the SLE patient. The ultimate result is tissue inflammation and often damage. While at present our therapy is aimed at controlling these secondary inflammatory phenomena mediated by immune complexes and complement, ultimately therapy may be more successful after the primary defects are corrected.


Detection of a novel 20 kDa shrimp allergen showing cross-reactivity to house dust mites.
Allergy to crustacean shellfish is one of the most common IgE-mediated food allergies, and tropomyosin has been identified as the major allergen. However, not all subjects affected by this allergy are IgE-positive to tropomyosin. To evaluate whether sera of patients with shrimp allergy but negative for tropomyosin react to other allergen(s); and to evaluate the role such allergen(s) may play in cross-reactivity between crustaceans and house dust mites (HDMs). Three different pools of sera-one from subjects with shellfish allergy and HDMs positivity, but negative for recombinant and native tropomyosin (rPen a 1 and nPen m 1) (Pool 2); a second from subjects with tropomyosin and HDMs positivity (Pool 1); and the last from subjects allergic only to HDMs (Pool 3) were submitted to immunoblotting. Subsequently, a 20 kDa protein- enriched fraction of shrimp extract was used at two different concentrations (10 and 100 microg/mL) to pre-absorb the Pool 2 serum and to evaluate, by ELISA assay, the level of inhibition on shrimp and HDMs-coated wells, respectively. The Pool 2 serum showed IgE reactivity against a 20 kDa component. Its pre-absorption with an enriched fraction of 20 kDa protein caused an inhibition of 56% in IgE binding to shrimp extract at a concentration of 100 microg/mL, and of 14% and 35% to HDMs extract at concentrations of 10 and 100 microg/mL, respectively, as measured by ELISA assay. The 20 kDa component seems to be a new crustacean allergen and it could play a role in cross-reactivity with HDMs.


Transcriptomic patterns in early-secretory and mid-secretory endometrium in a natural menstrual cycle immediately before in vitro fertilization and embryo transfer.
This study aimed to evaluate the endometrial transcriptomic patterns in the early secretory phase (ESP) and mid-secretory phase (MSP) of the natural menstrual cycle before in vitro fertilization and embryo transfer (IVF-ET). Thirty patients whose endometrial tissues were obtained from the ESP or MSP of a natural menstrual cycle immediately before IVF-ET were included. Endometrial dating was histologically confirmed as ESP (cycle days 16-18) or MSP (cycle days 19-21), according to the noyes criteria. The patients were divided into two groups depending on the IVF-ET outcome: pregnant (n=14; 7 in ESP and 7 in MSP) or non-pregnant (n=16; 8 in ESP and 8 in MSP). Differentially expressed genes (DEGs) in the MSP, compared to the ESP, were identified using NanoString nCounter (NanoString Technologies, Seattle, WA, USA) data for both the pregnant and non-pregnant groups. Thirteen DEGs in the pregnant group and 11 DEGs in the non-pregnant group were identified in the MSP compared to those in the ESP. In both groups, adrenoceptor alpha 2A, interleukin 1 receptor-associated kinase 2, a disintegrin and metalloproteinase with thrombospondin repeats 15 (ADAMTS15), serpin family E member 1, integrin subunit beta 3, transmembrane protein 252 (TMEM252), huntingtin associated protein 1, C2 calcium-dependent domain containing 4A, and integrin subunit alpha 2 were upregulated in the MSP, compared to the ESP. TMEM37, galactosidase beta 1 like 2, Rho family GTPase 3, and cytochrome P450 family 24 subfamily A member 1 were upregulated in the MSP only in the pregnant group. ADAMTS8 was downregulated and monoamine oxidase A was upregulated in the MSP only in the non-pregnant group. Transcriptomic patterns in the endometrium immediately before IVF-ET appear to differ according to the IVF-ET outcome. These novel DEGs, which have not been previously studied, may have functional significance during the window of implantation and serve as potential biomarkers of endometrial receptivity.


Radiologic findings in seven patients with fibrodysplasia ossificans progressiva.
Fibrodysplasia ossificans progressiva is a rare and disabling syndrome, which is characterized by heterotopic ossifications and skeletal deformities. So far, around 200 patients with fibrodysplasia ossificans progressiva have been reported in the world literature. Herein, we analyze the clinical records of 7 known cases of fibrodysplasia ossificans progressiva from Iran who were admitted to the pediatrics wards of our centers between 1983 and 2002, and present the radiologic findings.


Factors influencing drop-out of households from community based health insurance membership in rural districts of Gurage Zone, Southern Ethiopia: Community based case-control study.
Financial risk-sharing through community-based health insurance is a critical component of universal health coverage. However, its development is a great challenge, not only due to low enrollment but also due to the high dropout rate of members from the program, which threatens its sustainability. So far, the few existing studies in this area have focused on household enrollment into community-based health insurance, rather than on the number of members dropping out. This study aims to identify factors influencing households to drop out of community-based health insurance membership in rural districts of the Gurage Zone, Southern Ethiopia. A community-based case-control study was carried out from May to July 2021. Supplemented by qualitative focus group discussions. Multi-stage sampling was employed. An interviewer-administered prearranged tool was used for collecting data. Epi-data version 3.1 and SPSS version 21 were used for data entry and analysis. The association between factor and outcome variable was determined using binary logistic regression analysis at p < 0.05 and 95% CI. Qualitative data were analyzed thematically and triangulated. From 525 (175 cases and 350 controls) rural household heads 171 cases and 342 controls responded, yielding a response rate of 97.7%. Of those, 73.1 and 69.0% were males in cases and controls, respectively. The statistically significant influencing factors associated with dropout from community-based health insurance were: highest wealth status (adjusted odds ratio [AOR] = 2.36, 95% confidence interval [CI]:1.14-4.87), unfavorable attitude toward CBHI (AOR: 1.81, 95% CI: 1.87-3.37), no illness experienced in the last 3 months (AOR: 5.21, 95% CI: 2.90-9.33). no frequent health facility visits (AOR:5.03, 95% CI:1.17-23.43), no exposure to indigenous community insurance (AOR:0.10, 95% CI: 0.03-0.37), not graduated in the model household (AOR: 3.20, 95% CI:1.75-5.83), being a member in the program for more than 3 years (AOR:0.55, 95% CI: 0.29-0.94), not trusting governing bodies (AOR:10.52, 95% CI:4.70-23.53), the ordered drug was not available in the contractual facility (AOR:14.62, 95% CI:5.37-39.83), waiting time was >3 h (AOR:4.26, 95% CI:1.70-10.66), and poor perception of service quality (AOR:12.38, 95%CI:2.46-62.24). The findings of this study illustrated various factors which positively and negatively influenced households to drop out from CBHI: wealth status, attitude toward CBHI, perceived poor provider attitude toward CBHI members, illness experience in the household, the experience of frequent health facility visits, model household graduation status, trust on CBHI committee (governing bodies), availability of a prescribed drug in the contractual health facility, waiting time and perceived quality of health service from the contractual facility, exposure to any of the indigenous insurance (IDIR and/or IQUB) and length of membership in program. We strongly recommend all responsible stakeholders give strong attention to promoting the community, and for providers to project a favorable attitude toward community-based health insurance, to achieve model household graduation, and improve quality of service by addressing the basic quality-related areas like waiting time, and drug availability).


Large-scale, high-density freezing of hybridomas and its application to high-density culture.
Large-scale, high-density freezing of hybridomas was studied to apply frozen cells to start high-density culture. We showed here that hybridomas can be frozen at 1.5 x 10(8) cells/mL, without decrement in viability and proliferating activity. Blood transporting bags were used for large-scale freezing to store 25 mL of cell suspension with a cell density, 1.5 x 10(8)/mL. The number of cells stored in a bag (3.0 x 10(9) cells) was enough to start a high-density culture at a 10 times higher cell density (6.0 x 10(6) cells/mL) than normal inoculation, and the cells proliferated to 10(7) cells/mL within 2 days. These results indicate that the large-scale freezing method is useful for large-scale culture of mammalian cells.


Ultrastructure and localization of a visual Gq protein in hypertrophied epitoke ocelli of Perinereis brevicirris (Polychaeta, Annelida).
Functional ultrastructural changes in the rhabdomeric photoreceptors of the cerebral ocelli are described for normal and sexually mature (epitoke) Perinereis brevicirris (Polychaeta, Annelida). With sexual maturation, the cerebral ocelli hypertrophied, increasing in volume to 5.5 times that of ocelli in the normal state, and the thickness of the retinal layer increased up to 10 times. Perinereis ocelli have a pigmented retinal layer consisting of at least two cell types: photoreceptor cell (PR) and pigmented supporting cells (PS). In epitoke ocelli, PR bear well-developed rhabdomeric microvilli, multilamellar bodies, and numerous cytoplasmic membranous structures, including vesicles, smooth endoplasmic reticulum, and secondary lysosomes. Localization of a visual Gq protein in the ocelli was studied with anti-GqC antibody. The antibody strongly labeled not only microvilli and multilamellar bodies throughout the retinal layer, but also secondary lysosomes and vesicles in the cytoplasm of the PR in the epitoke ocelli, although labeling was observed only in the microvilli and multilamellar bodies in normal ocelli. Reverse transcription/polymerase chain reaction analysis revealed that the amount of G protein alpha subunit mRNA in the epitoke head increased by roughly twice that of the normal head. Since Gq protein is essential for phototransduction in Perinereis ocelli, these results suggest that the sites are involved in photoreceptive membrane turnover, which occurs much more extensively in epitoke ocelli. Thus, epitoke ocelli may represent a model system for studying rhabdomeric photoreceptive membrane turnover.


AFLP marker analysis revealing genetic structure of the tree Parapiptadenia rigida (Benth.) Brenan (Leguminosae-Mimosoideae) in the southern Brazilian Tropical Rainforest.
Parapiptadenia rigida is a tropical early secondary succession tree characteristic of the Tropical Atlantic Rainforest. This species is of great ecological importance in the recovery of degraded areas. In this study we investigated the variability and population genetic structure of eight populations of P. rigida. Five AFLP primer combinations were used in a sample of 159 individuals representing these eight populations, rendering a total of 126 polymorphic fragments. The averages of percentage of polymorphic loci, gene diversity, and Shannon index were 60.45%, 0.217, and 0.322, respectively. A significant correlation between the population genetic variability and the population sizes was observed. The genetic variability within populations (72.20%) was higher than between these (22.80%). No perfect correlation was observed between geographic and genetic distances, which might be explained by differences in deforestation intensities that occurred in these areas. A dendrogram constructed by the UPGMA method revealed the formation of two clusters, these also confirmed by Bayesian analysis for the number of K cluster. These results show that it is necessary to develop urgent management strategies for the conservation of certain populations of P. rigida, while other populations still preserve reasonably high levels of genetic variability.


Provoked Vestibulodynia: Diagnosis, Self-Reported Pain, and Presentation During Gynaecological Examinations.
To explore factors associated with the diagnosis of provoked vestibulodynia (PVD) through (1) self-reported pain characteristics and (2) Friedrich's criteria (vestibular pain during sexual activity/gynaecological examination). We also identified cases in which incorrect diagnoses were assigned and explored group differences in gynaecological examination presentation and associations with self-reported pain. Data were extracted from nine studies conducted in our research laboratory. Information obtained during a telephone interview and a standardized gynaecological examination was compiled for 106 participants with vulvar pain and 106 pain-free control participants, matched for age, hormonal contraceptive use, and parity. Cohen's kappa (0.78) indicated substantial agreement (87.3%) between the telephone interview group categorization and diagnosis after the gynaecological examination. A discriminant function analysis yielded one significant function: Friedrich's first two criteria correctly classified 84.2% of cases, accounting for 76.0% of group membership variance. Of note, those in the other genital pain group were most likely to have received an incorrect diagnosis following the telephone interview (P < 0.001). Paired-samples t tests showed that those with pain reported lower pain intensity during the gynaecological examination than during intercourse (P < 0.001) and that intercourse pain was not necessarily related to pain during the examination. However, many participants (72.8%) indicated that the pain elicited during the cotton swab test was similar to the pain they felt with intercourse. These results support the use of a targeted clinical interview and the evaluation of vestibular pain during sexual activity and the gynaecological examination for diagnosing PVD. Caution should be exercised when a patient presents with genital pain symptoms other than those typically observed in PVD. Furthermore, the cotton swab test may underestimate the degree of pain regularly experienced.


COVID-19 and Fatty Liver Disorders.
In late 2019, the world was shaken by the COVID-19 pandemic. Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection became one of the main causes of illness and hospitalization worldwide, especially in subjects with metabolic comorbidities such as obesity, diabetes, or liver disease. This scenario crosses with the metabolic liver disorders' "pandemic", caused by the exponential spreading of non-alcoholic fatty liver disease, which is now the most prevalent cause of chronic liver disease (CLD). The aim of this review is to analyze the key factors of the relationship between COVID-19 and the spectrum of fatty liver disorders (FLD), in terms of molecular mechanisms and clinical presentation which can predict a more severe course of the infection. In addition, this review will face the change in management of FLD during pandemics, with a central role of telemedicine, and the role of other interventions in preventing and treating severe infection in these subjects.


[Cocaine abuse in Vienna and European cities--a multi-center study].
As cocaine consumption seems to have increased over the last decades, the EU has funded this multi-center, cross-sectional survey to investigate cocaine consumption in three different target groups. The study was conducted by the Addiction Clinic, Department of Psychiatry, Medical University Vienna and other nine European cities. Data were collected by structured face-to-face interviews. The sample was composed of 211 cocaine abusers out of three target groups: (1) treatment group undergoing opioid maintenance therapy, (2) marginalized scene group and (3) integrated party group. Sociodemographic data such as age, education, employment, monthly expenses on cocaine/crack, data on consumption patterns, physical and mental health and personal needs regarding cocaine consumption were evaluated. Urine toxicology results for cocaine in the treatment group completed the analysis. The marginalized scene group was the oldest with a mean age of 29.35 years, with the highest unemployment rate (mean 25.11 days) and the longest duration of cocaine consumption (mean 5.80 years). They had the highest cocaine consumption pattern with a mean of 22.32 days within the last month. On average 1969 Euros/months was spent for their addiction. The treatment group had the lowest school education with a mean of 10.36 years, but showed a sufficient insight in their cocaine problem. However, the party group (with the lowest mean age, 25.64 years) highly underestimated their drug problem, the mean amount of money they spent for their addiction was 588.99 Euro/months. Structured urine toxicology between 1996 and 2002 in patients undergoing opioid maintenance therapy ("treatment group") revealed a significant increase of concomitant cocaine consumption (1996: 33.1%; 2002: 40.2%; p = 0.044). The European trend of increased cocaine use could also be observed in Vienna. One of the greatest barriers for establishing adequate treatment settings for this target group is the difficulty to reach this population. In addition, multiple substance abuse seems to be one of the predominating patterns of cocaine consumption and this aspect should be integrated within treatment (in the treatment and scene groups additional heroin and benzodiapzepines abuse is observed, in the party group intensive alcohol consumption). The Viennese results are in line with those of the other European cities; however, it could not be confirmed that consumption of crack cocaine and binge play a similarly significant role as in cities such as Hamburg or London.


Regenerative medicine: learning from past examples.
Regenerative medicine products have characteristically shown great therapeutic potential, but limited market success. Learning from the past attempts at capturing value is critical for new and emerging regenerative medicine therapies to define and evolve their business models as new therapies emerge and others mature. We propose a framework that analyzes technological developments along with alternative business models and illustrates how to use both strategically to map value capture by companies in regenerative medicine. We analyze how to balance flexibility of the supply chain and clarity in the regulatory pathway for each business model and propose the possible pathways of evolution between business models. We also drive analogies between cell-based therapies and other healthcare products such as biologicals and medical devices and suggest how to strategically evolve from these areas into the cell therapy space.


Obstacles to the uptake of breast, cervical, and colorectal cancer screenings: what remains to be achieved by French national programmes?
In France, equality in access to screening has been one of the main thrusts of public policies implemented between 2009 and 2013 (the national cancer plan). Our aim in this study was to analyse the obstacles to and levers for breast, cervical, and colorectal cancer screening uptake and their trends over time. Based on representative data from the French Health Care and Health Insurance Survey (three independent, cross-sectional surveys: 2006, 2008, and 2010), multivariate logistic regressions were used to model the association between the nonuse of screening for the three cancers and various independent variables. Then, interactions with survey year dummies allowed the changes in the determinants of these cancer screenings over time to be estimated. Whereas the incentives for screening were strengthened during the period considered, cervical and breast cancer screenings decreased, and colorectal cancer screenings increased sharply (from 18.2% (95% CI = [17.0-19.4]) in 2006 to 38.9% (95% CI = [37.4-40.5] in 2010. Under-users of the three cancer screenings were primarily unskilled workers (ORcervix = 1.64 [1.38-1.95]), individuals without complementary health insurance (ORbreast = 2.05 [1.68-2.51]), or individuals with free complementary health insurance who more rarely use outpatient care. Moreover, individuals reporting either risky behaviours, namely heavy smokers (ORcolorectal = 1.70) and high-risk drinkers (ORcervix = 1.42) or very safe behaviours, namely neither smoking nor drinking, underused screenings. Despite the implementation of national programmes for breast and colorectal cancer screenings, the disparities and inequalities in screening uptake did not decrease over the study period. These results demonstrate the need for additional primary prevention efforts targeting the identified under-users by focusing on, for instance, individuals with a very healthy lifestyle. Health authorities could also intensify their efforts to promote increased access to screening for the most disadvantaged individuals.


[Comparison of once-daily nonpreserved timolol and timolol maleate gel-forming solution associated with latanoprost].
To compare the efficacy and safety of a single daily instillation of nonpreserved timolol to a timolol maleate gel-forming solution in patients with chronic glaucoma or ocular hypertension already treated with latanoprost. A randomized, prospective, multicenter, open, parallel-group clinical trial was undertaken with 73 patients with chronic glaucoma treated with latanoprost and a timolol maleate gel-forming solution. In 36 patients, the previous regimen was substituted by nonpreserved timolol given instead of timolol maleate gel for 3 months. The changes in intraocular pressure (IOP) were recorded as well as local and systemic tolerance and patient compliance. At 3 months, both regimens were found equivalent in maintaining IOP control between D0 and D84. The difference with baseline was -0.08 +/- 2.22 mmHg and -0.38 +/- 2.41 mmHg in the nonpreserved timolol group and in the timolol maleate gel-forming solution group, respectively (CI 95% [-0.79; 1.38]). After 84 days of treatment, blurred vision (5.9%) and eyelid deposits (5.9%) were reduced in the preservative-free timolol group compared to the other group (respectively, 33.3% and 24.2%). These differences were statistically significant for both signs (blurred vision: p < 0.0001 and for eyelid deposits: p = 0.03). This short-term study has demonstrated the equivalence of nonpreserved timolol to timolol maleate gel-forming solution in terms of IOP control. Moreover, the local tolerance of nonpreserved timolol was better.


Mechanochemical synthesis of mesoporous tin oxide: a new generation nanosorbent for (68)Ge/(68)Ga generator technology.
The present article reports the synthesis and characterization of mesoporous tin oxide (MTO) nanoparticles by a solid-state mechanochemical route. The synthesized material was used as an advanced sorbent material for (68)Ge/(68)Ga radionuclide generator technology. Gallium-68 (t½ = 68 min) obtained from the (68)Ge/(68)Ga generator is an important diagnostic radioisotope which holds tremendous potential in the non-invasive monitoring of various diseases, including cancer, using positron emission tomography (PET). The crystallite size of the MTO nanoparticles was in the range of 6-12 nm with a large surface area of 265 ± 16 m(2) g(-1), while the mean pore radius was found to be 2.1 ± 0.6 nm. Determination of the zeta-potential of the MTO nanoparticles dispersed in solutions at different pH values aided in understanding the sorption and separation mechanisms, which were based on the surface charge developed on the nanosorbent. The sorption capacity observed under column-flow conditions was 85 ± 5 mg Ge per g of nanosorbent. A clinical-scale (68)Ge/(68)Ga generator (740 MBq) was developed using this nanosorbent. Gallium-68 could be regularly eluted from this generator over a prolonged period of 1 year with >70% elution yield and met all the requirements for clinical use. The suitability of (68)Ga obtained from it was evaluated in preclinical settings by the preparation of a (68)Ga-labeled peptide containing the arginine-glycine-aspartic acid (RGD) motif. To the best of our knowledge, this is the first report on the synthesis of MTO nanoparticles by a mechanochemical route which could be effectively utilized for the routine preparation of clinical-scale (68)Ge/(68)Ga generators. The promising results obtained in this study would facilitate greater implementation of mechanochemistry for the synthesis of nanosorbents for radionuclide generator technology since this method is simple, economical and convenient.


A Multimodal Analysis to Explore Upper Limb Motor Recovery at 4 Weeks After Stroke: Insights From EEG and Kinematics Measures.
Background. Stroke is a leading cause of death and disability worldwide and there is a very short period of increased synaptic plasticity, fundamental in motor recovery. Thus, it is crucial to acquire data to guide the rehabilitation treatment. Promising results have been achieved with kinematics and neurophysiological data, but currently, few studies integrate these different modalities. Objectives. We explored the correlations between standardized clinical scales, kinematic data, and EEG measures 4 weeks after stroke. Methods. 26 patients were considered. Among them, 20 patients also performed the EEG study, beyond the kinematic analysis, at 4 weeks. Results. We found correlations between the Fugl-Meyer Assessment-Upper Extremity, movement duration, smoothness measures, and velocity peaks. Moreover, EEG measures showed a tendency for the healthy hemisphere to vicariate the affected one in patients characterized by better clinical conditions. Conclusions. These results suggest the relevance of kinematic (in particular movement duration and smoothness) and EEG biomarkers to evaluate post-stroke recovery. We emphasize the importance of integrating clinical data with kinematic and EEG analyses from the early stroke stages, in order to guide rehabilitation strategies to best leverage the short period of increased synaptic plasticity.


Second allogeneic hematopoietic cell transplantation for relapse after first allografts.
We analyzed outcomes of 126 patients with hematologic malignancies, who relapsed after first allogeneic hematopoietic cell transplantation (HCT) and received subsequent allografts. In 17 cases, the original donors were utilized, while in 109 cases different donors were identified. The 2-year overall survival (OS), relapse, and non-relapse mortality (NRM) rates were 33%, 42%, and 33%, respectively. Patients with early relapse after first allogeneic HCT (within 100 days vs. 100 days to 12 months vs. >12 months) had higher relapse rates (50% vs. 47% vs. 34%, respectively; p = .01) and worse OS (15% vs. 25% vs. 45%, respectively, p = .005) at 2 years after second allogeneic HCT. In conclusion, second allogeneic HCT should be considered in patients who relapse after first allografts, especially in those who relapse after more than a year. Utilizing a different donor for the second allotransplant including umbilical cord blood or HLA-haploidentical, related donors did not adversely impact outcomes.


Effects of substance P and other peptides on the release of somatostatin, insulin, and glucagon in vitro.
We studied the actions of substance P, bombesin, vasoactive intestinal peptide (VIP), and the octapeptide of cholecystokinin (CCK-8-S) on the release of somatostatin, insulin, and glucagon from the isolated perfused pancreatico-duodenal canine preparation. Substance P at concentrations ranging from 0.2-5.0 nM stimulated the secretion of somatostatin, insulin, and glucagon in a dose-dependent manner. However, the responses evoked by substance P were modified by the prevailing glucose level; higher somatostatin and insulin and lower glucagon responses were obtained at the high glucose concentration of 8.3 mM rather than at the low glucose concentration of 2.8 mM. At a glucose concentration of 5.5 mM, somatostatin release was above the prestimulation level in response to 1 nM substance P (89 +/- 15%; P less than 0.01), VIP (49 +/- 7%; P less than 0.01), or CCK-8-S (99 +/- 21%; P less than 0.01); bombesin was without effect (16 +/- 14; P = NS). Insulin release was enhanced by substance P (150 +/- 45%; P less than 0.05), bombesin (162 +/- 56%; P less than 0.05), VIP (44 +/- 5%; P less than 0.01), and CCK-8-S (190 +/- 17%; P less than 0.001). Furthermore, a significant release of glucagon was evoked by 1 nM substance P (501 +/- 158%; P less than 0.05), bombesin (30 +/- 10%; P less than 0.05), VIP (43 +/- 8%; P less than 0.01), or CCK-8-S (140 +/- 19%; P less than 0.001).


Trace mineral deficiencies in rats caused by feeding rapeseed flours during growth, gestation and lactation.
The present study determined the effect of duration of feeding and dietary levels of rapeseed flours on growth, outcome of gestation and lactation and blood trace element content of rats. In the first two experiments, female rats were fed either casein or rapeseed flour diets during gestation and lactation, or prior to and during gestation. In the last two experiments, weanling male rats were fed for 4 weeks either casein or rapeseed flour diets with or without added zinc. Feeding rapeseed flours prior to and/or during gestation caused a reduction in weight gains and food consumption but did not affect the number or weight of the pups born. Plasma zinc levels were low in the mother rats at parturition and plasma zinc and iron levels were low in weanling rats after 4 weeks of feeding the rapeseed diets. Adding 300 ppm zinc to the diet prevented the decrease in food consumption, weight gains and plasma zinc levels in the weanling rats. It is concluded that the recommended levels of trace elements in the rat diet are inadequate for the purpose of bioassay and toxicological evaluation or rapeseed preparations. In order that the nutritional potenital of new protein sources be correctly evaluated, guidelines for adequacy of mineral in such diets should be determined.


IgE and IgG4 Epitope Mapping of Food Allergens with a Peptide Microarray Immunoassay.
Peptide microarrays are a powerful tool to identify linear epitopes of food allergens in a high-throughput manner. The main advantages of the microarray-based immunoassay are the possibility to assay thousands of targets simultaneously, the requirement of a low volume of serum, the more robust statistical analysis, and the possibility to test simultaneously several immunoglobulin subclasses. Among them, the last one has a special interest in the field of food allergy, because the development of tolerance to food allergens has been associated with a decrease in IgE and an increase in IgG4 levels against linear epitopes. However, the main limitation to the clinical use of microarray is the automated analysis of the data. Recent studies mapping the linear epitopes of food allergens with peptide microarray immunoassays have identified peptide biomarkers that can be used for early diagnosis of food allergies and to predict their severity or the self-development of tolerance. Using this approach, we have worked on epitope mapping of the two most important food allergens in the Spanish population, cow's milk and chicken eggs. The final aim of these studies is to define subsets of peptides that could be used as biomarkers to improve the diagnosis and prognosis of food allergies. This chapter describes the protocol to produce microarrays using a library of overlapping peptides corresponding to the primary sequences of food allergens and data acquisition and analysis of IgE- and IgG4-binding epitopes.


On-off switching of gene expression regulated with carbohydrate-lectin interaction.
A novel strategy for artificial regulation system of gene expression applying the specific molecular recognition between carbohydrate and lectin is proposed. Plasmid-lactose conjugates (pActin-lactose and pGFP-lactose) prepared via diazocoupling maintained the transcription activity with T7 RNA polymerase. Gel-shift assay showed that the pActin-lactose conjugates were specifically complexed with galactose-specific lectin RCA(120) with a strong binding affinity (K(a) = 7.6 x 10(5) M(-1) per Lac-unit). The complexes were observed to form aggregates of sub-several micrometer size by means of transmission electron microscopy (TEM) and atomic force microscopy (AFM). The activities of transcription and expression of the conjugates were evaluated, respectively, on the basis of the amount of transcript of pActin and the fluorescent intensity of the expressed GFP. These activities were repressed in the presence of an increasing concentration of RCA120, and then recovered by adding lactose, lactosylceramide-containing liposomes, and lactose-carrying polymers to the conjugate-RCA120 complex. Gel-shift assay and TEM observation revealed that the aggregation form of the complex was relaxed partially in the presence of the lactose derivatives, which increased the accessibility of T7 RNA polymerase to result in the recovery of transcription activity.


Iatrogenic Ventricular Fibrillation after Direct-Current Cardioversion of Preexcited Atrial Fibrillation Caused by Inadvertent T-Wave Synchronization.
Direct-current cardioversion is an important means of managing arrhythmias. During treatment, carefully synchronizing energy delivery to the QRS complex is necessary to avoid ventricular fibrillation caused by a shock during the vulnerable period of ventricular repolarization, that is, a shock on the T wave. The presence of an accessory pathway and ventricular preexcitation can lead to difficulty in distinguishing the QRS complex from the T wave because of bizarre, wide, irregular QRS complexes and prominent repolarization. We present the cases of 2 patients who had iatrogenic ventricular fibrillation from inappropriate T-wave synchronization during direct-current cardioversion of preexcited atrial fibrillation. Our experience shows that rapidly recognizing the iatrogenic cause of VF and immediate treatment with unsynchronized defibrillation can prevent adverse clinical outcomes.


Correlation properties and regularity of heart period time series: influence of posture and heart disease.
Nonlinear measures of heart period variability (HPV) were determined in supine rest and standing posture in children and young adults with heart disease and compared to the control. The aim was to study influence of posture and heart disease on heart period dynamics. It was found that standing increases short-term scaling exponent in all subjects and decreases sample entropy in healthy and less severely ill patients. Severely ill patients compared to control have higher short-term scaling exponent in supine. Changes in nonlinear measures of HPV upon standing are more pronounced in healthy than diseased subjects due to different vagal activity.


Memory and Specificity in the Insect Immune System: Current Perspectives and Future Challenges.
The immune response of a host to a pathogen is typically described as either innate or adaptive. The innate form of the immune response is conserved across all organisms, including insects. Previous and recent research has focused on the nature of the insect immune system and the results imply that the innate immune response of insects is more robust and specific than previously thought. Priming of the insect innate immune system involves the exposure of insects to dead or a sublethal dose of microbes in order to elicit an initial response. Comparing subsequent infections in primed insects to non-primed individuals indicates that the insect innate immune response may possess some of the qualities of an adaptive immune system. Although some studies demonstrate that the protective effects of priming are due to a "loitering" innate immune response, others have presented more convincing elements of adaptivity. While an immune mechanism capable of producing the same degree of recognition specificity as seen in vertebrates has yet to be discovered in insects, a few interesting cases have been identified and discussed.


The role of rodents and shrews in the transmission of Toxoplasma gondii to pigs.
Inadequate rodent control is considered to play a role in Toxoplasma gondii infection of pigs. This issue was addressed in the current study by combining a 4-month rodent control campaign and a 7-month longitudinal analysis of T. gondii seroprevalence in slaughter pigs. Three organic pig farms with known rodent infestation were included in the study. On these farms, presence of T. gondii in trapped rodents was evaluated by real-time PCR. All rodent species and shrews investigated had T. gondii DNA in brain or heart tissue. Prevalence was 10.3% in Rattus norvegicus, 6.5% in Mus musculus, 14.3% in Apodemus sylvaticus and 13.6% in Crocidura russula. Initial T. gondii seroprevalence in the slaughter pigs ranged between 8% and 17% and dropped on the three farms during the rodent control campaign to 0-10%, respectively. After 4 months of rodent control, T. gondii infection was absent from pigs from two of the three farms investigated and appeared again in one of those two farms after the rodent control campaign had stopped. This study emphasizes the role of rodents and shrews in the transmission of T. gondii to pigs and the importance of rodent control towards production of T. gondii-free pig meat.


The extracellular nucleotide UTP is a potent inducer of hematopoietic stem cell migration.
Homing and engraftment of hematopoietic stem cells (HSCs) to the bone marrow (BM) involve a complex interplay between chemokines, cytokines, and nonpeptide molecules. Extracellular nucleotides and their cognate P2 receptors are emerging as key factors of inflammation and related chemotactic responses. In this study, we investigated the activity of extracellular adenosine triphosphate (ATP) and uridine triphosphate (UTP) on CXCL12-stimulated CD34+ HSC chemotaxis. In vitro, UTP significantly improved HSC migration, inhibited cell membrane CXCR4 down-regulation by migrating CD34+ cells, and increased cell adhesion to fibronectin. In vivo, preincubation with UTP significantly enhanced the BM homing efficiency of human CD34+ cells in immunodeficient mice. Pertussis toxin blocked CXCL12- and UTP-dependent chemotactic responses, suggesting that G-protein alpha-subunits (Galphai) may provide a converging signal for CXCR4- and P2Y-activated transduction pathways. In addition, gene expression profiling of UTP- and CXCL12-treated CD34+ cells and in vitro inhibition assays demonstrated that Rho guanosine 5'-triphosphatase (GTPase) Rac2 and downstream effectors Rho GTPase-activated kinases 1 and 2 (ROCK1/2) are involved in UTP-promoted/CXCL12-dependent HSC migration. Our data suggest that UTP may physiologically modulate the homing of HSCs to the BM, in concert with CXCL12, via the activation of converging signaling pathways between CXCR4 and P2Y receptors, involving Galphai proteins and RhoGTPases.


Short wavelength far infrared laser polarimeter with silicon photoelastic modulators.
A short wavelength far infrared laser whose wavelength lambda is about 50 microm is preferable for a polarimeter and an interferometer for high density operations in the Large Helical Device (LHD) and on future large fusion devices such as ITER. This is because the beam bending effect (proportional to lambda(2)) in a plasma, which causes fringe jump errors, is small and the Faraday and the Cotton-Mouton effects are moderate. We have developed a polarimeter with highly resistive silicon photoelastic modulators (PEMs) for the CH(3)OD laser (lambda=57.2 and 47.7 microm). We performed bench tests of the polarimeter with a dual PEM and demonstrated the feasibility for the polarimeter. Good linearity between actual and evaluated polarization angles is achieved with an angular resolution of 0.05 degrees and a temporal resolution of 1 ms. The baseline drift of the polarization angle is about 0.1 degrees for 1000 s.


Pectolinarigenin from the leaves of Clerodendrum volubile shows potent immunomodulatory activity by inhibiting T - cell proliferation and modulating respiratory oxidative burst in phagocytes.
There have been increasing interest in the use of plant-derived substance as immunomodulators for the treatment and management of inflammatory ailments. Clerodendrum volubile, a leafy vegetable is known for its folkloric applications in the treatments of several inflammatory related ailments, but with little scientific evidence. This study reports the isolation, structure elucidation and in vitro immunomodulatory potentials of pectolinarigenin from C. volubile leaves. The immunomodulatory potentials of the crude methanolic extract and fractions [n-hexane (Hex), dichloromethane (DCM), ethyl acetate (EtOAc) and n - butanol (BuOH)] were investigated on whole blood, neutrophil and macrophage phagocytic respiratory burst using luminol-amplified chemiluminescence technique. DCM fraction showed higher inhibitory activity on respiratory burst, indicating high suppressive immunomodulatory potency. The DCM fraction was further fractionated using a gravity column chromatography loaded with silica gel. The column was eluted with mixtures of Hex and DCM (92.5:7.5) in increasing order of polarity up to Hex: DCM (88:12) to afford 5,7-Dihydroxy-6,4'-dimethoxyflavone (pectolinarigenin). The structure of the compound was established using data obtained from 1H- and 13C NMR spectroscopies and mass spectrometry. The isolated flavone was investigated for its inhibitory activity of neutrophil phagocytes respiratory burst as well as T - Cell proliferation. The compound exhibited significant activities (at p <0.05) indicating high suppressive immunomodulatory potency. The potent suppressive effect of pectolinarigenin on polymorphonuclear neutrophils (PMNs) respiratory oxidative burst and T - cell proliferation suggests an immunomodulatory potential and pathway of the flavonoid.


Optimizing Hydrogen Storage in MOFs through Engineering of Crystal Morphology and Control of Crystal Size.
Metal-organic frameworks (MOFs) are promising materials for hydrogen storage that fail to achieve expected theoretical values of volumetric storage density due to poor powder packing. A strategy that improves packing efficiency and volumetric hydrogen gas storage density dramatically through engineered morphologies and controlled-crystal size distributions is presented that holds promise for maximizing storage capacity for a given MOF. The packing density improvement, demonstrated for the benchmark sorbent MOF-5, leads to a significant enhancement of volumetric hydrogen storage performance relative to commercial MOF-5. System model projections demonstrate that engineering of crystal morphology/size or use of a bimodal distribution of cubic crystal sizes in tandem with system optimization can surpass the 25 g/L volumetric capacity of a typical 700 bar compressed storage system and exceed the DOE targets 2020 volumetric capacity (30 g/L). Finally, a critical link between improved powder packing density and reduced damage upon compaction is revealed leading to sorbents with both high surface area and high density.


Delayed recall deficits in aphasic stroke patients: evidence of Alzheimer's dementia?
In a comparative study of the performance of patients with Alzheimer's disease (AD), aphasia resulting from stroke, and normal elders on a variety of neuropsychological tasks, 3 aphasic patients performed similarly to AD patients in the delayed recall of verbal material. The memory deficit of these aphasic patients raised the question of incipient dementia because memory impairment is the hallmark characteristic of AD. However, when the performance profiles of the aphasic patients on all four memory measures administered in the study were compared to those of AD patients, differences made the presence of dementia unlikely. Nonetheless, the possibility remained that a deficit in delayed free recall might be the primordial symptom of dementia. Therefore, the four memory tasks were readministered to the 3 aphasic patients 2 years later, and intergroup performance comparisons again were made. The performance profiles of the aphasic patients obtained 2 years later were superior to and distinct from the AD patients, confirming the absence of dementia at Test Time 1.


Interaction of light and hormone signals in germinating seeds.
Seed germination is regulated by several environmental factors, such as moisture, oxygen, temperature, light, and nutrients. Light is a critical regulator of seed germination in small-seeded plants, including Arabidopsis and lettuce. Phytochromes, a class of photoreceptors, play a major role in perceiving light to induce seed germination. Classical physiological studies have long suggested the involvement of gibberellin (GA) and abscisic acid (ABA) in the phytochrome-mediated germination response. Recent studies have demonstrated that phytochromes modulate endogenous levels of GA and ABA, as well as GA responsiveness. Several key components that link the perception of light and the modulation of hormone levels and responsiveness have been identified. Complex regulatory loops between light, GA and ABA signaling pathways have been uncovered.


Primary access surgery for long-term haemodialysis.
This paper assessed the efficacy of arterio-venous fistulae, vein grafts, and synthetic grafts for long-term haemodialysis. Over a selected 10 year period, 486 primary access sites were established and 182 revisions were necessary. Access procedures were assessed for primary survival, the success or otherwise of revision surgery, and long-term efficacy for haemodialysis. Significant differences were shown for long-term survival of fistulae over vein grafts and synthetic grafts. Successful revision surgery favoured fistulae over synthetic grafts. Arterio-venous fistulae offered the best prospect for effective long-term dialysis. Revision surgery with continued dialysis using the primary-access site was largely unsuccessful, secondary access reconstruction being required in 78.2% of all failures.


Evaluating group psychological interventions for mental health in women with infertility undertaking fertility treatment: A systematic review and meta-Analysis.
ABSTRACTWe conducted a systematic review and meta-analysis of the published literature concerning the effectiveness of group psychological interventions in improving anxiety, depression, marital dissatisfaction, fertility quality of life and stress, and pregnancy outcomes of women with infertility, participating in fertility treatment. A search of five databases yielded 1603 studies; 30 articles met inclusion criteria, and computations of effect sizes ensued (Hedges' g and Odds Ratios (OR)). The total sample comprised 2752 participants, with 1279 participants receiving group intervention and 1473 participants in the comparison group. Group psychological interventions reduced depression (Hgw = -1.277; 95% CI = [-1.739- -0.815]; p = 0.000), anxiety (Hgw = -1.136, 95% CI [-1.527- -0.744]; p = 0.000), fertility stress (Hgw = -0.250, 95% CI [-0.388- -0.122]; p = 0.000), and marital dissatisfaction (Hgw = -0.938; 95% [CI -1.455- -0.421]; p = 0.000), and pregnancy rates improved (OR = 2.422 95% CI [2.037-2.879]; p = 0.000). No improvement was observed regarding fertility quality of life (Hgw = 0. 144; 95% CI [-0.176- 0.463]; p = 0.379). Our findings highlight that participation in group psychological intervention improved the mental health, fertility stress and pregnancy rates of women with infertility.


National trends in the use of psychotropic medications by children.
Little information exists on national trends in the use of psychotropic medication by children and adolescents. The objective of this report is to compare patterns and predictors of psychotropic medication use by children and adolescents in the United States in 1987 and 1996. An analysis of medication use data is presented from two nationally representative surveys of the general population focusing on children 18 years of age and younger who used one or more prescribed psychotropic medication during the survey years. Rates of stimulant, antidepressant, and other psychotropic medication use are reported. The overall annual rate of psychotropic medication use by children increased from 1.4 per 100 persons in 1987 to 3.9 in 1996 (p < .0001). Significant increases were found in the rate of stimulant use (0.6 per 100 persons to 2.4 per 100 persons), antidepressant use (0.3 per 100 persons to 1.0 per 100 persons), other psychotropic medications (0.6 per 100 persons to 1.2 per 100 persons), and coprescription of different classes of psychotropic medications (0.03 per 100 persons to 0.23 per 100 persons), especially antidepressants and stimulants. Rates of antipsychotic and benzodiazepine use remained stable. In 1996, stimulant use was especially common in children aged 6 to 14 years (4.1 per 100), and antidepressant use was common in children aged 15 to 18 years (2.1 per 100 persons). Between 1987 and 1996, there was a marked expansion in use of psychotropic medications by children, especially stimulants and antidepressants.


What cognitive changes can be expected with normal ageing?
This paper briefly summarizes recent evidence on the nature of cognitive decline, the variability in individual responses to ageing, and risk factors known to affect the rate of cognitive decline. Data from the Canberra Longitudinal Study were used to examine the course and diversity of cognitive decline. The sample consisted of 887 participants aged 70-93 years, who were examined in 1991 and followed up in 1994 and 1998. Data summarizing significant risk factors for cognitive decline were based on a review of 34 studies that examined the following predictors: education, the APOE epsilon4 allele, health, activity and blood pressure. Using data from participants living in the community, there is evidence that cognitive speed and memory performance decline with age, but that crystallized abilities remain largely intact in those who survive for long-term follow-up. Variability in test scores for memory and speed increases with age. There is evidence that poor health, fewer years of education, lower activity, the presence of the APOE epsilon4 allele, and blood pressure predict faster cognitive decline. The diversity in cognitive ageing suggests that more than one process may be operating to produce the observed cognitive outcomes. Education, good health, absence of the APOE epsilon4 allele, and activity may be protective of cognitive decline. Preventative strategies for sustaining high intellectual performance in later life may therefore be possible. These findings also speak to the need to extend analysis beyond examining mean changes in cognitive performance to an analysis based on individual differences in change.


The critical roles of TBC proteins in human diseases.
The Tre-2/Bub2/Cdc16 (TBC) domain is a conserved protein motif consisting of approximately 200 amino acids, and is present in many eukaryotic proteins. TBC domain-containing proteins (TBC proteins) function as GTPase activating proteins (GAPs) for the small GTPase Rab, which can promote the hydrolysis of Rab-GTP to Rab-GDP in regulation of specific intracellular trafficking pathways. Several TBC proteins play important roles in cellular functions in mammals, and defects of which are closely associated with numerous disease processes. In this review, we summarize the structures and functions of the mammalian TBC proteins and recent advances in understanding their critical roles in the development of human diseases. This review serves as a reference for further investigations on the functions of TBC proteins in disease pathogeneses.


Improved nuclear localization of DNA-binding polyamides.
Regulation of endogenous genes by DNA-binding polyamides requires effective nuclear localization. Previous work employing confocal microscopy to study uptake of fluorophore-labeled polyamides has demonstrated the difficulty of predicting a priori the nuclear uptake of a given polyamide. The data suggest that dye identity influences uptake sufficiently such that a dye-conjugate cannot be used as a proxy for unlabeled analogs. Polyamides capable of nuclear localization unaided by fluorescent dyes are desirable due to size and other limitations of fluorophores. Recently, a polyamide-fluorescein conjugate targeted to the hypoxia response element (HRE) was found to inhibit vascular endothelial growth factor (VEGF) expression in cultured HeLa cells. The current study uses inhibition of VEGF expression as a biological read-out for effective nuclear localization of HRE-targeted polyamides. We synthesized a focused library of non-fluorescent, HRE-targeted polyamides in which the C-terminus 'tail' has been systematically varied. Members of this library bind the HRE with affinities comparable or superior to that of the fluorescein-labeled analog. Although most library members demonstrate modest or no biological activity, two non-fluorescent polyamides are reported with activity rivaling that of the previously reported fluorescein-labeled polyamide. We also show evidence that promoter occupancy by HIF-1, the transcription factor that binds the HRE, is inhibited by HRE-targeted polyamides.


18F-FDG uptake in reactive neck lymph nodes of oral cancer: relationship to lymphoid follicles.
PET using (18)F-FDG is acceptable as a preoperative diagnostic tool for head and neck cancer. PET combined with CT provides precise localization of neck lymph nodes. Reactive lymphadenopathy is well known as a principal cause of false-positive findings on PET/CT for nodal staging. We investigated the reactive lymph nodes of oral cancer to elucidate the (18)F-FDG-avid area in these nodes. Surgically dissected neck lymph nodes of oral cancer were retrospectively reviewed. Of the patients without pathologic nodal metastasis who underwent preoperative PET/CT, 11 patients with 31 enlarged lymph nodes at 20 levels were enrolled. The maximum standardized uptake value (SUVmax) of each lymph node was recorded. The diameters of the long and short axes were measured by pathologic sectioning, and the sectional surface area was calculated in square millimeters. Besides being stained with hematoxylin and eosin, the sections were immunohistochemically stained by CD79a for B cells, CD3 for T cells, CD68 for macrophages, CD21 for follicular dendritic cells (FDCs), and ubiquitous glucose transporter type 1 (GLUT1). The expression of GLUT1 was compared with staining of lymphoid cells. The numbers of total lymphoid follicles and hyperplastic secondary follicles were counted on CD21 and hematoxylin and eosin sections, respectively. The follicular reactivity index was determined as the ratio of secondary follicles relative to total follicles on the corresponding section. These parameters of reactive lymph nodes were analyzed on a level basis. GLUT1 was expressed exclusively in lymphoid follicles, whose staining pattern was identical to that of FDCs. The calculated sectional area correlated significantly with the number of total follicles (r = 0.560; P = 0.0101). SUVmax did not correlate with the number of total follicles (P = 0.8947) but correlated significantly with the number of secondary follicles (r = 0.535; P = 0.0152). In addition, a strong positive correlation between SUVmax and the follicular reactivity index was demonstrated (r = 0.829; P < 0.0001). GLUT1 was expressed on cytoplasmic protrusions of FDCs in lymphoid follicles. The (18)F-FDG accumulation in reactive lymphadenopathy depended on secondary follicles. FDCs in germinal centers of secondary follicles are suggested to be avid for (18)F-FDG and the principal cause of false-positive findings for nodal staging.


[Ecology of Sporothrix schenckii and of Ceratocystis stenoceras in Corsica and Alsace, French provinces free of sporotrichosis].
The study was conducted in 2 French Provinces free of sporotrichosis. Of 40 samples (soil, plant fragments, . . .) taken from Corsica, 59 isolations were obtained. All of these contained S. schenckii type of growth. Of 30 retained for further study, 14 were later identified as Ceratocystis stenoceras. All 14 needed pyrimidine as a growth factor. They developed well at 37 degrees and gave a yeast-like growth in shaken medium at 35 degrees and 25 degrees. One of the strains was pathogenic to mice. From 422 small mammals trapped in Alsace 37 isolations were made which morphologically were identified as S. schenckii. From these 31 were identified as C. stenoceras. Six isolations were considered as S. schenckii. The presence of nature of C. stenoceras and S. scheckii is discussed. Both fungi were isolated from various materials collected in tropical areas where sporotrichosis is endemic but also in such temperate areas as Corsica and Alsace where the mycosis is non-existent.


HIV reservoir dynamics in the face of highly active antiretroviral therapy.
Upon discontinuation of highly active antiretroviral therapy (HAART), human immunodeficiency virus (HIV)-infected individuals experience a brisk rebound in blood plasma viremia due to the exodus of HIV from various body reservoirs. Assessment of HIV dynamics during HAART and following treatment discontinuation is essential to better understand HIV persistence. Here we will first provide a brief overview of the molecular mechanisms involved in HIV reservoir formation and persistence. After a summary of HAART-mediated HIV decay within peripheral blood, we discuss findings from clinical studies examining the effects of HAART initiation and interruption on HIV reservoir dynamics in major anatomical compartments, including lymph nodes and spleen, gut associated lymphoid tissue, reproductive organs, the central nervous system, and the lungs. Features contributing to these reservoirs as distinct compartments, including anatomical features, the presence of drug transporters, and the effect of co-infection, are also discussed.


Live cell imaging of mitochondrial movement along actin cables in budding yeast.
Mitochondrial inheritance is essential for cell division. In budding yeast, mitochondrial movement from mother to daughter requires (1) actin cables, F-actin bundles that undergo retrograde movement during elongation from buds into mother cells; (2) the mitochore, a mitochondrial protein complex implicated in linking mitochondria to actin cables; and (3) Arp2/3 complex-mediated force generation on mitochondria. We observed three new classes of mitochondrial motility: anterograde movement at velocities of 0.2-0.33 microm/s, retrograde movement at velocities of 0.26-0.51 microm/s, and no net anterograde or retrograde movement. In all cases, motile mitochondria were associated with actin cables undergoing retrograde flow at velocities of 0.18-0.62 microm/s. Destabilization of actin cables or mutations of the mitochore blocked all mitochondrial movements. In contrast, mutations in the Arp2/3 complex affected anterograde but not retrograde mitochondrial movements. Actin cables are required for movement of mitochondria, secretory vesicles, mRNA, and spindle alignment elements in yeast. We provide the first direct evidence that one of the proposed cargos use actin cables as tracks. In the case of mitochondrial inheritance, anterograde movement drives transfer of the organelle from mothers to buds, while retrograde movement contributes to retention of the organelle in mother cells. Interaction of mitochondria with actin cables is required for anterograde and retrograde movement. In contrast, force generation on mitochondria is required only for anterograde movement. Finally, we propose a novel mechanism in which actin cables serve as "conveyor belts" that drive retrograde organelle movement.