Identification and kinetic study of tyrosinase inhibitors found in sake lees.
The present study found that the n-hexane extract of freeze-dried sake lees inhibits tyrosinase activity and showed that the constituents isolated from the n-hexane extract are the mixture of triacylglycerols. The inhibitory effects of triolein and trilinolein found as the triacylglycerols were examined using tyrosinases from mushroom and Streptomyces castaneoglobisporus. The IC50 values of the triacylglycerol mixture for the oxidase activity on mushroom and Streptomyces tyrosinases were 20 and 0.14 microg/mL, respectively. The IC50 values of trilinolein for the oxidase activity on mushroom and Streptomyces tyrosinases were 8.4 and 0.1 microM, respectively. However, the inhibitory effect of triolein (IC50=30 microM) was lower than that of trilinolein, even when the Streptomyces tyrosinase was used for the assay. Kinetic analyses indicate that both trilinolein and triolein inhibit the tyrosinase activity noncompetitively. When transformed with a plasmid carrying the Streptomyces tyrosinase gene, the melanin-synthesizing ability of the transformed Escherichia coli host was dose-dependently interfered with by trilinolein.


Bud composition, branching patterns and leaf phenology in cerrado woody species.
Plants have complex mechanisms of aerial biomass exposition, which depend on bud composition, the period of the year in which shoot extension occurs, branching pattern, foliage persistence, herbivory and environmental conditions. The influence of water availability and temperature on shoot growth, the bud composition, the leaf phenology, and the relationship between partial leaf fall and branching were evaluated over 3 years in Cerrado woody species Bauhinia rufa (BR), Leandra lacunosa (LL) and Miconia albicans (MA). Deciduous BR preformed organs in buds and leaves flush synchronously at the transition from the dry to the wet season. The expansion time of leaves is <1 month. Main shoots (first-order axis, A1 shoots) extended over 30 d and they did not branch. BR budding and foliage unfolds were brought about independently of inter-annual rainfall variations. By contrast, in LL and MA evergreen species, the shoot extension rate and the neoformation of aerial organs depended on rainfall. Leaf emergence was continuous for 2-6 months and lamina expansion took place over 1-4 months. The leaf life span was 5-20 months and the main A1 shoot extension happened over 122-177 d. Both evergreen species allocated biomass to shoots, leaves or flowers continuously during the year, branching in the middle of the wet season to form second-order (A2 shoots) and third-order (A3 shoots) axis in LL and A2 shoots in MA. Partial shed of A1 shoot leaves would facilitate a higher branching intensity A2 shoot production in LL than in MA. MA presented a longer leaf life span, produced a lower percentage of A2 shoots but had a higher meristem persistence on A1 and A2 shoots than LL. It was possible to identify different patterns of aerial growth in Cerrado woody species defined by shoot-linked traits such as branching pattern, bud composition, meristem persistence and leaf phenology. These related traits must be considered over and above leaf deciduousness for searching functional guilds in a Cerrado woody community. For the first time a relationship between bud composition, shoot growth and leaf production pattern is found in savanna woody plants.


A synthetic small-molecule Isoxazole-9 protects against methamphetamine relapse.
Adult neurogenesis in the dentate gyrus (DG) is strongly influenced by drug-taking behavior and may have a role in the etiology of drug-seeking behavior. However, mechanistic studies on the relationship of neurogenesis on drug seeking are limited. Outbred Wistar rats experienced extended access methamphetamine self-administration and individual differences in drug taking defined animals with higher preferred and lower preferred levels of drug intake. Forced abstinence from higher preferred levels of drug taking enhanced neurogenesis and neuronal activation of granule cell neurons (GCNs) in the DG and produced compulsive-like drug reinstatement. Systemic treatment with the drug Isoxazole-9 (a synthetic small molecule known to modulate neurogenesis in the adult rodent brain) during abstinence blocked compulsive-like context-driven methamphetamine reinstatement. Isoxazole-9 modulated neurogenesis, neuronal activation and structural plasticity of GCNs, and expression of synaptic proteins associated with learning and memory in the DG. These findings identify a subset of newly born GCNs within the DG that could directly contribute to drug-seeking behavior. Taken together, these results support a direct role for the importance of adult neurogenesis during abstinence in compulsive-like drug reinstatement.


Role of Teriparatide in Medication-Related Osteonecrosis of the Jaws (MRONJ).
While the optimal treatment concept of medication-related osteonecrosis of the jaws (MRONJ) is still in debate, several adjunct therapies have been introduced. Among these adjunctive measures, recombinant human parathyroid hormone (rhPTH, teriparatide) seems to be the most promising treatment modality. Several studies have presented the beneficial effect of short-term teriparatide; they have shown an improved level of bone markers and radiographic evidence of bone healing. Although clinical validation by a controlled trial with prospective design would be essential, short-term teripratide therapy would be a good treatment option for MRONJ patients with impaired bone remodeling.


Theta oscillations synchronize human medial prefrontal cortex and amygdala during fear learning.
Numerous animal studies have demonstrated that fear acquisition and expression rely on the coordinated activity of medial prefrontal cortex (mPFC) and amygdala and that theta oscillations support interregional communication within the fear network. However, it remains unclear whether these results can be generalized to fear learning in humans. We addressed this question using intracranial electroencephalography recordings in 13 patients with epilepsy during a fear conditioning paradigm. We observed increased power and inter-regional synchronization of amygdala and mPFC in theta (4 to 8 hertz) oscillations for conditioned stimulus (CS+) versus CS-. Analysis of information flow revealed that the dorsal mPFC (dmPFC) led amygdala activity in theta oscillations. Last, a computational model showed that trial-by-trial changes in amygdala theta oscillations predicted the model-based associability (i.e., learning rate). This study provides compelling evidence that theta oscillations within and between amygdala, ventral mPFC, and dmPFC constitute a general mechanism of fear learning across species.


Growth hormone (GH) effects on central fat accumulation in adult Japanese GH deficient patients: 6-month fixed-dose effects persist during second 6-month individualized-dose phase.
Both Japanese and Caucasian adults with GH deficiency (GHD) have pronounced abdominal obesity, which is associated with increased risk of cardiovascular complications. We investigated the effects of GH treatment in 27 adult Japanese GHD patients, 15 with adult onset (AO) and 12 with childhood onset (CO) GHD. Patients initially received GH titrated to 0.012 mg/kg/day for 24 weeks in a double-blind design and the dose was then individualized for each patient according to IGF-I for a further 24 weeks. Dual-energy x-ray absorptiometry (DXA) data were evaluated for percentages of trunk fat, total body fat and lean body mass. Serum IGF-I and lipid concentrations were determined at a central laboratory. There were 25 patients who completed 48 weeks of treatment, with 7, 6 and 12 patients then receiving GH at 0.003, 0.006 and 0.012 mg/kg/day, respectively. With the reductions in dose when individualized between weeks 24 and 48, mean serum IGF-I level was reduced and excessively high values, observed in AO patients on the fixed GH dose, were no longer seen. The decrease from baseline in trunk fat was similar at week 24 (-3.8 +/- 3.3%, p<0.001) and week 48 (-3.1 +/- 3.7%, p<0.001), and the difference between changes was not significant. Total cholesterol was decreased from baseline by -24 +/- 28 mg/dl (p<0.001) at week 24 and -17 +/- 28 mg/dl (p = 0.007) at week 48. Two patients had elevated HbA1c levels: one continued GH treatment after a dose reduction and the other discontinued due to persistent impaired glucose tolerance. Therefore, excessively high IGF-I levels can be avoided by individualized dosing during long-term GH treatment. Individualized dosing maintains the decrease in abdominal fat in adult Japanese GHD patients and should reduce the cardiovascular risk.


How do nurses deal with their own grief when a patient dies on an intensive care unit, and what help can be given to enable them to overcome their grief effectively?
There is an expectation that nurses are good at caring for relatives on the death of a patient. Who, though, cares for the nurses? Using both a quantitative and a qualitative approach, this study looks at how nurses overcome their own grief when a patient dies on an intensive care unit. Information was first collected using a questionnaire. Personal grief, however, is a very emotive area, so a proportion of the nurses from the initial study were then asked to take part in a semi-structured interview, to explore their feelings in more depth. The quantitative data were analysed using the computer software Statistical Package for the Social Sciences and the results were related to the interview responses. This showed how nurses deal with their grief, and that many, but not all, felt that the informal support network already present was sufficient. Some nurses, however, felt that a support group would also be helpful and some felt the availability of a counsellor would be useful. All nurses felt that more training about how to deal with their own grief was needed.


[Inhibitory effect of 5-fluorouracil on HT-1080 human fibrosarcoma cells in vitro].
To evaluate the inhibitory effect of 5-fluorouracil (5-Fu) on HT-1080 human fibrosarcoma cells in vitro. HT-1080 human fibrosarcoma cells were cultured for 3 days in the proliferation period. Then adriamycin or 5-Fu at different concentrations were used to treat these cells for 24 h, 72 h and 144 h. MTT assay was used to evaluate the cytotoxic effects through measuring optical density and calculating the inhibition rate of cell growth. Morphologic changes of the cells were observed under a phase contrast microscope. Flow cytometry (FCM) was performed to detect the changes in cell cycle and DNA ploidy in the fibrosarcoma cells treated with 5-Fu. 10 µg/ml 5-Fu showed an inhibition rate of 45.9% (24 h), 64.7% (72 h) and 90.6% (144 h) of the HT-1080 cell growth. 100 µg/ml 5-Fu showed an inhibition rate of 53.1% (24 h), 86.4% (72 h), 93.0% (144 h) of the HT-1080 cell growth, results similar to those in the adriamycin group. Untreated fibrosarcoma cells accounted for 67.5% in G(1) phase, 21.2% in S phase and 11.3% in G(2) phase. With the increasing drug concentrations, cells in G(1) + S phase increased rapidly and no cells in G(2) phase were observed later. The cells treated with 5-Fu showed a G(1) + S cell cycle arrest. 5-Fu has an antitumor activity in human fibrosarcoma HT-1080 cells in vitro, in a time-dependent and dose-dependent manner. The cytotoxity of 5-Fu at high concentrations and continuous use can induce tumor cell cycle arrested at G(1) + S phase, a similar result induced with adriamycin.


Pharmacokinetics of monoester-diterpenoid alkaloids in myocardial infarction and normal rats after oral administration of Sini decoction by microdialysis combined with liquid chromatography-tandem mass spectrometry.
Monoester-diterpenoid alkaloids are the main bioactive components of Sini decoction, which is a well-known traditional Chinese medicine formula for the treatment of myocardial infarction (MI) and heart failure in China. In this work, an ultra-high-performance liquid chromatography-mass spectrometry combined with microdialysis method was successfully established and applied for investigating for the first time comparative plasma pharmacokinetics of three monoester-diterpenoid alkaloids (benzoylmesaconitine, benzoylaconitine and benzoylhypacoitine) in normal and MI rats after oral administration of Sini decoction. The statistical results of pharmacokinetic parameters demonstrated that benzoylmesaconitine, benzoylaconitine and benzoylhypacoitine showed lower peak concentration, longer half-life, smaller area under the concentration-time curve, slower clearance, time to peak concentration and mean residence time in MI rats than in normal rats (p < 0.05), which indicated that monoester-diterpenoid alkaloids exhibited lower systemic exposure and slower elimination in the MI rats. The results provided the experimental basis for understanding the metabolic fate and therapeutic effects of Sini decoction.


Sorption kinetics of toluene in humin under two different levels of relative humidity.
To identify any resistant fraction for desorption of toluene from humin and to quantify the sorption-desorption rates, the time courses of toluene sorption to compressed humin disks and to a thin humin film were investigated. The apparent diffusivity of toluene with humin disks ranges from 10(-8) to 10(-9) cm2/s and increases with temperature, based on the weight change of humin disks mounted on a microbalance and on the results simulated by use of a diffusion model. No detectable level of residual toluene was found after desorption, as revealed either by the gravimetric analysis or by the Fourier transform infrared (FTIR) spectrum obtained at either low or high humidity. The time scale for intrinsic vapor sorption without mass transfer hindrance is less than a few minutes with the thin film. All the results indicate that the sorption of toluene to humin is reversible and mainly diffusion controlled. This finding helps to better understand the sorption kinetics associated with humin and soil organic matter.


Evaluations of coronary microvascular dysfunction in a patient with thrombotic microangiopathy and cardiac troponin elevation: a case report.
Thrombotic microangiopathy (TMA) syndromes include thrombotic thrombocytopenic purpura (TTP) and haemolytic uremic syndrome, and contribute to myocardial infarction and multiple organ failure. Although coronary microvascular dysfunction (CMD) is the key for understanding the pathophysiology of cardiac involvement in TMA, there is limited knowledge on the recovery from CMD in patients with TMA. An 80-year-old woman was brought to the emergency department due to worsening back pain, dyspnoea on exertion, jaundice, and fever. Although she had typical TTP symptoms and elevated cardiac troponin level, ADAMTS13 activity was preserved (34%), leading to the diagnosis of TMA with myocardial infarction. She underwent plasma exchange and was administered aspirin and prednisolone. Magnetic resonance imaging revealed iliopsoas abscess, which is a possible aetiologic factor of sepsis-related TTP. She had impaired coronary flow reserve (CFR) with angiographically non-obstructive epicardial coronary arteries. Improved CFR was observed on follow-up, suggesting existence of transient CMD caused by TMA. After treatment of the iliopsoas abscess with antibiotics for 3 months, she was discharged without any adverse complications. Coronary microvascular dysfunction is an underlying mechanism of myocardial infarction, with or without epicardial obstructive coronary artery stenosis. TMA is characterized by pathological lesions caused by endothelial cell damage in small terminal arteries and capillaries, with complete or partial occlusion caused by platelet and hyaline thrombi. CMD and its recovery are keys for understanding the natural history of cardiac involvement in TMA. In vivo evaluations of CMD can provide mechanistic insights into the cardiac involvement in TMA.


Nonallergic bronchial hyperexcitability in chronic bronchitis.
The aim of this study was to assess responsiveness to inhaled histamine and methacholine using PC20, the concentration causing a 20% fall in forced expiratory volume in one second (FEV1) in 28 subjects with chronic bronchitis excluding asthma. Eighteen subjects had airway hyperexcitability, as demonstrated by a PC20 less than 16 mg/ml. The response to histamine and methacholine was not significantly different and the correlation coefficient was 0.75. Baseline airway caliber was related to the level of hyperexcitability, as 14 of 14 subjects with a FEV1 to forced vital capacity ratio less than 95% pred and/or a forced expiratory flow during the middle half of the FVC less than 80% pred, and only 4 of 10 subjects with normal spirometry, had a PC20 less than 16 mg/ml (x2 = 15.6, p less than 0.001). There was no correlation between blood or sputum eosinophilia, total IgE levels, or atopy and the level of airway hyperexcitability. Spontaneous daily variations of peak expiratory flow rates were significantly (t = 2.43, p less than 0.05) more pronounced in subjects with PC20 less than 16 mg/ml. We conclude that airway hyperexcitability assessed with PC20 is often present in chronic bronchitis and more often so in the presence of airway obstruction.


Reducing the risk of burns during electroconvulsive therapy.
Poor contact between electroconvulsive therapy (ECT) electrodes and the skin can result in patient burns during ECT treatment. Proper site preparation and electrode application are essential to ensure adequate contact and to reduce the risk of burns.


Bioinspired Protein-Based Assembling: Toward Advanced Life-Like Behaviors.
The ability of living organisms to perform structure, energy, and information-related processes for molecular self-assembly through compartmentalization and chemical transformation can possibly be mimicked via artificial cell models. Recent progress in the development of various types of functional microcompartmentalized ensembles that can imitate rudimentary aspects of living cells has refocused attention on the important question of how inanimate systems can transition into living matter. Hence, herein, the most recent advances in the construction of protein-bounded microcompartments (proteinosomes), which have been exploited as a versatile synthetic chassis for integrating a wide range of functional components and biochemical machineries, are critically summarized. The techniques developed for fabricating various types of proteinosomes are discussed, focusing on the significance of how chemical information, substance transportation, enzymatic-reaction-based metabolism, and self-organization can be integrated and recursively exploited in constructed ensembles. Therefore, proteinosomes capable of exhibiting gene-directed protein synthesis, modulated membrane permeability, spatially confined membrane-gated catalytic reaction, internalized cytoskeletal-like matrix assembly, on-demand compartmentalization, and predatory-like chemical communication in artificial cell communities are specially highlighted. These developments are expected to bridge the gap between materials science and life science, and offer a theoretical foundation for developing life-inspired assembled materials toward various applications.


Vascular access survival in children and young adults receiving long-term hemodialysis.
The delivery of long-term hemodialysis therapy in children is complicated by smaller vascular caliber and the potential lifelong requirement for hemodialysis access. Various factors have resulted in the increased use of cuffed central venous catheters (CVLs) in preference to autologous arteriovenous fistulae (AVFs) and arteriovenous synthetic grafts (AVGs). The aim of this study is to compare CVL, AVF, and AVG survival and determine factors affecting their survival. A 20-year retrospective study was undertaken of pediatric patients receiving long-term hemodialysis therapy. Age, height, weight, body mass index, and sex were noted at each procedure, in addition to the presence of hypoalbuminemia, underlying diagnosis, type and site of vascular access, and effect of previous access surgery. The grade of operator also was noted. Three hundred four vascular access procedures were performed on 114 patients, with a median age at initial access formation of 12.0 years (range, 4 weeks to 21.9 years). The most common procedure was CVL insertion (182 procedures) and then AVF formation (107 procedures), with only 15 AVGs created. Median censored survival was 3.14 years (95% confidence interval, 1.22 to 5.06) for AVFs and 0.6 years (95% confidence interval, 0.20 to 1.00) for CVLs. Factors adversely affecting vascular access survival were younger age, trainee operator, presence of hypoalbuminemia, and type of access undertaken, with AVF better than CVL. This study shows increased survival of AVFs over CVLs and AVGs. Vascular access in children and adolescents may impact on future dialysis accessibility and should be undertaken by those most experienced in each technique.


Improving the efficiency of selection to Core Medical Training: a study of the use of multiple assessment stations.
To compare three separate assessment stations used for selection to Core Medical Training (CMT) and to determine the effect of reducing the number from three to two. Quantitative analysis of candidates' assessment station scores, financial analysis of costs of the selection process and quantitative and qualitative surveys of candidates and assessors. The assessment stations used for selection to CMT were reliable and valid for assessing suitability for employment as a CMT trainee. There was no significant difference in candidate ranking if only two assessment stations were used rather than three, i.e. there was no change in the likelihood of receiving a job offer. All of the assessment stations were perceived to have face validity by candidates and assessors. The efficiency of the selection process could be improved without loss of quality if two stations were used rather than three. Using two assessment stations rather than three would appear to improve the efficiency and maintain the quality of the CMT selection process while reducing costs.


Transfer effects of training-induced visual field recovery in patients with chronic stroke.
Visual training of light detection in the transition zone between blind and healthy hemianopic visual fields leads to improvement of color and simple pattern recognition. Recently, we demonstrated that visual field enlargement (VFE) also occurs when an area just beyond the transition zone is stimulated. In the current study, we attempted to determine whether this peripheral training also causes improvement in color and shape perception and reading speed. Further, we evaluated which measure of VFE relates best to improvements in performance: the average border shift (ABS) in degrees or the estimated amount of cortical surface gain (ECSG) in millimeters, using the cortical magnification factor (CMF). Twelve patients received 40 sessions of 1-hour restorative function training (RFT). Before and after training, we measured visual fields and reading speed. Additionally, color and shape perception in the trained visual field area was measured in 7 patients. VFE was found for 9 of 12 patients. Significant improvements were observed in reading speed for 8 of 12 patients and in color and shape perception for 3 of 7 patients. ECSG correlates significantly with performance; ABS does not. Our data indicate that the threshold ECSG, needed for significant changes in color and shape perception and reading speed, is about 6 mm. White stimulus training-induced VFE can lead to improved color and shape perception and to increased reading speed in and beyond the pretraining transition zone if ECSG is sufficiently large. The latter depends on the eccentricity of the VFE.


Chemokines: inflammatory mediators of atherosclerosis.
Atherosclerosis as the underlying mechanisms of myocardial infarction, stroke and peripheral artery disease remains the major cause of morbidity and mortality in developed countries. Recent developments in vascular biology have indicated that atherosclerosis can be best characterized as a chronic inflammatory disease of the vessel wall that promotes lesion development and progression. Chemokines regulate and control these processes by orchestrating adhesive interactions of circulating blood cells with the arterial wall and their subsequent extravasation. Exhibiting a high degree of specialization and cooperation, different chemokines mediate distinct steps during the atherogenic recruitment of monocytes and T cells. This diversity of chemokine expression and function might lead to the identification of selective therapeutic targets for the prevention and treatment of atherosclerosis.


Psychoanalytic psychotherapy improves quality of life, depression, anxiety and coping in patients with systemic lupus erythematosus: a controlled randomized clinical trial.
Systemic Lupus Erythematosus (SLE) is an autoimmune disease which impairs the quality of life. The objective of study was to evaluate the effectiveness of Brief Group Psychoanalytic Psychotherapy to improve quality of life, depression, anxiety and coping strategies in SLE patients. In a randomized clinical trial, 80 female SLE patients were allocated into two groups: therapy group (n = 37) and control group (n = 43). Therapy group (TG) attended weekly psychotherapy sessions for 20 weeks; control group (CG) remained on a waiting list. Both groups received standard medical care. Questionnaires and scales were applied by blinded evaluators at baseline (T1) and after 20 weeks (T2): Socioeconomic Status, SLE International Collaborating Clinic/American College of Rheumatology-Damage Index, SLE International Disease Activity, SLE Specific Symptom Checklist, SLE Quality of life, Hospital Anxiety Depression Scale, Coping Strategies Inventory. Intent to treat intra- and inter-group analysis was performed for all variables in T1 and T2 using Qui-square, t-Student, Mann-Whitney and Wilcoxon tests. Analysis of Variance was used to compare categorical variables over time. P < 0.05 was considered significant. The mean age of patients was 42 years; 54% were white, with mean disease duration of years 12. At baseline, both groups were homogeneous in all variables, including medications. After 20 weeks of psychotherapy TG was significantly different from CG, with lower frequency of symptoms (p = 0.001), lower level of anxiety (p = 0.019) and depression (p = 0.022), better index in five of six domains of quality of life scale (p ≤ 0.005), including total SLEQOL (p < 0.001) and with higher positive planful problem solving strategy (p = 0.017). No change in disease activity score was observed in both groups. Psychoanalytic psychotherapy was effective to improve many domains of quality of life and one positive coping skill and to reduce SLE symptoms, anxiety and depression levels. Brief group psychotherapy can be a useful tool to complement medical care in SLE patients. Number NCT01840709 .


[Streptococcus suis meningitis in an immunocompetent patient].
A case of Streptococcus suis meningitis is described in an immunocompetent patient presenting asthenia, general weakness, fever, vomiting, sensory deterioration and temporospatial disorder. The cerebrospinal fluid and two blood cultures (2/2 bottles) were positive. The isolate was preliminary identified by conventional biochemical tests, and the identification was completed at the Special Bacteriology Service of INEI-ANLIS "Dr. Carlos G. Malbrán". Ampicillin and ceftriaxone treatment was initiated. The isolate was susceptible to ampicillin, cefotaxime and vancomycin. The patient experienced a good outcome but suffered hearing loss. However, after four months he returned with walking ataxia, deafness in his left ear, and hearing loss in the right ear. The patient's retrospective exposure to pigs had been verified. It is important to evaluate predisposing and epidemiologic factors in order to alert about the possible presence of this etiological agent in cases of meningitis or bacteremia.


Development of a soil extraction procedure for ecotoxicity characterization of energetic compounds.
The acetonitrile-sonication extraction method (US EPA Method 8330) associated with aquatic-based toxicity tests was examined to study the ecotoxicity of energetic substances in soil. Three studies were carried out: (1) toxicological characterization of different energetic substances to select a representative toxicant and to validate the choice of bioassays; (2) choice of an appropriate solvent to transfer acetonitrile extracts to the bioassay incubation media; and (3) optimization of Method 8330 using soil samples spiked with the toxicant. Initial studies indicated that pure 2,4,6-trinitrotoluene (TNT) was toxic to Vibrio fischeri [Microtox; IC50 (15 min) of 4.2 microM], whereas RDX was less toxic (IC20 = 181 microM) and HMX was not toxic up to its limit of water solubility (< 22 microM). Selected pure TNT metabolites were less toxic than TNT. Similar results were found using the 96-h Selenastrum capricornutum growth inhibition test. The toxicity of pure TNT in different solvents (acetonitrile, acetone, and DMSO) and that from Method 8330-extracted TNT-spiked soil samples were compared to TNT dissolved in water. Data indicated that DMSO was the most appropriate solvent to transfer the acetonitrile extracts. A modified Method 8330 may be used in conjunction with bioassays and chemical analyses to examine the ecotoxicity of soils contaminated with energetic substances.


Teaching an insulin-dependent blind patient about self-care.
Today's home care nurse faces many challenges in providing patient-centered care while working within the guidelines set forth by the payor. A patient with Type 1 diabetes who was blind and lived alone was referred to our agency. A multidisciplinary approach for diabetes education along with tools for the visually impaired led our patient to independent diabetes management while keeping within the managed care guidelines.


Biochemical characterization of cysteine-rich peptides from Oxyopes sp. venom that block calcium ion channels.
Oxytoxins (OxyTx1 and OxyTx2) are disulfide-rich peptides isolated from the venom of the spider Oxyopes lineatus that block voltage-sensitive calcium ion channels (VSCCs). OxyTx1 was identified previously and isolated from the related spider Oxyopes kitabensis; however, its pharmacology was unknown. OxyTx1 and OxyTx2 contain 69 and 55 amino acid residues with molecular masses of 8058.2 and 6175.2Da, respectively. Oxytoxins contain five disulfide bridges, are amidated at their C-terminus, antagonize P/Q-, N- or L-type VSCCs, and have low amino acid identity to known VSCC blockers from arthropod venoms. OxyTx1 is not specific for VSCCs subtypes when compared to the classical P/Q-type blocker omega-AgaIVA, but OxyTx1 has higher paralytic activity towards Spodoptera litura larvae. Because of their structural and biochemical characteristics OxyTx1 and OxyTx2 may represent a new family of insecticidal peptides.


Effect of pindolol on intraocular pressure.
Pindolol, a strong beta-adrenergic blocking agent, instilled into the conjunctival sac of normal and glaucomatous eyes, produced a significant drop in intraocular pressure. This was not, at first, accompanied by any variation in outflow facility; only after prolonged treatment did an increase in facility appear, which accounted only for one-third of the tension-lowering effect. The drug was well tolerated, and did not affect either pupil motility or corneal sensitivity. It seems suitable for a trial use in the treatment of glaucoma.


Beyond upgrading typologies - In search of a better deal for honey value chains in Brazil.
Selection of value chain strategies by development practitioners and value chain participants themselves has been restricted to preset types of upgrading. This paper argues for an extension of the range of strategy solutions to value chains. An empirical application identifies successful strategies for honey value chains in Brazil for 2015-2020. Strategy and performance indicators were selected using the value chain Structure-Conduct-Performance (SCP) framework. Experts' opinion was elicited in a Delphi for business scenarios, and adaptive conjoint analysis was used to identify strategies for increasing production growth and local value-added. This study identifies important strategies beyond upgrading typologies, and finds that important strategies differ by performance goal and scenario. The value chain SCP allows searching for promising strategies towards performance-the "better deal"-in an integrated way.


Secondary causes of osteoporosis.
Secondary causes of bone loss are not often considered in patients who are diagnosed as having osteoporosis. In some studies, 20% to 30% of postmenopausal women and more than 50% of men with osteoporosis have a secondary cause. There are numerous causes of secondary bone loss, including adverse effects of drug therapy, endocrine disorders, eating disorders, immobilization, marrow-related disorders, disorders of the gastrointestinal or biliary tract, renal disease, and cancer. Patients who have undergone organ transplantation are also at increased risk for osteoporosis. In many cases, the adverse effects of osteoporosis are reversible with appropriate intervention. Because of the many treatment options that are now available for patients with osteoporosis and the tremendous advances that have been made in understanding the pathogenesis and diagnosis of the condition, it is important that medical disorders are recognized and appropriate interventions are undertaken. This article provides the framework for understanding causes of bone loss and approaches to their management.


A family of lambda phage cDNA cloning vectors, lambda SWAJ, allowing the amplification of RNA sequences.
This paper describes the construction and characterization of a family of lambda phage cDNA cloning vectors that allows high-efficiency directional cDNA cloning and selective amplification of either sense or antisense cRNA sequences. These vectors contain several unique restriction sites (EcoRI, XbaI, and SacI) positioned between two specific phage promoters, SP6 and T7. This system facilitates the in vitro preparation of single-stranded (ss) RNA molecules that should be useful in subtractive hybridization and in situ hybridization procedures. Using subtractive hybridization and this vector system, it should be possible to identify sequences present in one cDNA library and not another. In addition, it should be possible to construct subtracted cDNA libraries in these vectors and to generate high specific activity, ss, antisense cRNA probes directly from DNA prepared from the whole subtracted library or from individual clones.


Nucleophosmin: a versatile molecule associated with hematological malignancies.
Nucleophosmin (NPM) is a nucleolar phosphoprotein that plays multiple roles in ribosome assembly and transport, cytoplasmic-nuclear trafficking, centrosome duplication and regulation of p53. In hematological malignancies, the NPM1 gene is frequently involved in chromosomal translocation, mutation and deletion. The NPM1 gene on 5q35 is translocated with the anaplastic lymphoma kinase (ALK) gene in anaplastic large cell lymphoma with t(2;5). The MLF1 and RARA genes are fused with NPM1 in myelodysplastic syndrome and acute myeloid leukemia (AML) with t(3;5) and acute promyelocytic leukemia with t(5;17), respectively. In each fused protein, the N-terminal NPM portion is associated with oligomerization of a partner protein leading to altered signal transduction or transcription. Recently, mutations of exon 12 have been found in a significant proportion of de novo AML, especially in those with a normal karyotype. Mutant NPM is localized aberrantly in the cytoplasm, but the molecular mechanisms for leukemia remain to be studied. Studies of knock-out mice have revealed new aspects regarding NPM1 as a tumor-suppressor gene. This review focuses on the clinical significance of the NPM1 gene in hematological malignancies and newly discovered roles of NPM associated with oncogenesis.


Lanthanide derivatives of Ta/W mixed-addendum POMs as proton-conducting materials.
Four lanthanide derivatives of Ta-containing POMs [Ln3(H2O)22][P2W15Ta3O62]·nH2O (Ln = La, 1; Ce, 2; Pr, 3; and Nd, 4) were isolated by the self-assembly of Wells-Dawson type Ta/W mixed-addendum POM and lanthanide ions. Compound 1 showed excellent proton conduction performance at high relative humidities (RHs), with conductivity reaching 1.26 × 10-2 S cm-1 at 95 °C under 98% RH.


Effectiveness of a digital device providing real-time visualized tooth brushing instructions: A randomized controlled trial.
The aim of this trial was to investigate whether a digital device that provides real-time visualized brushing instructions would contribute to the removal of dental plaque over usual brushing instructions. We conducted a single-center, parallel-group, stratified permuted block randomized control trial with 1:1 allocation ratio. Eligibility criteria included people aged ≥ 18 years, and exclude people who met the following criteria: severely crowded teeth; using interdental cleaning implement; having external injury in the oral cavity, or stomatitis; having less than 20 teeth; using orthodontic apparatus; visited to a dental clinic; having the possibility of consulting a dental clinic; having a dental license; not owning a smartphone or tablet device; smoker; taken antibiotics; pregnant; an allergy to the staining fluid; and employee of Sunstar Inc. All participants received tooth brushing instructions using video materials and were randomly assigned to one of two groups for four weeks: (1) an intervention group who used the digital device, providing real-time visualized instructions by connection with a mobile application; and (2) a control group that used a digital device which only collected their brushing logs. The primary outcome was the change in 6-point method plaque control record (PCR) score of all teeth between baseline and week 4. The t-test was used to compare the two groups in accordance with intention-to-treat principles. Among 118 enrolled individuals, 112 participants were eligible for our analyses. The mean of PCR score at week 4 was 45.05% in the intervention group and 49.65% in the control group, and the change of PCR score from baseline was -20.46% in the intervention group and -15.77% in the control group (p = 0.088, 95% confidence interval -0.70-10.07). A digital device providing real-time visualized brushing instructions may be effective for the removal of dental plaque.


Extracellular matrix and gene expression in mammary epithelium.
Correct cellular environment is required for the differentiation of many cell types. In mammary epithelium the extracellular matrix as well as lactogenic hormones cooperate to direct accurate tissue-specific gene expression. Current evidence indicates that the promoters of milk protein genes contain elements that are regulated by both extracellular matrix and hormones. Some mechanisms by which the extracellular matrix might control transcription are considered.


XY-spin fluids in an external magnetic field: an integral equation approach.
We develop an integral equation approach to study anisotropic fluids with planar spins in the presence of an external field. As a result, the integral equation calculations for these systems appear to be no more difficult than those for ordinary isotropic liquids. The method presented is applied to the investigation of phase coexistence properties of ferromagnetic XY-spin fluids in a magnetic field. The soft mean spherical approximation is used for the closure relation connecting the orientationally dependent two-particle direct and total correlation functions. The Lovett-Mou-Buff-Wertheim and Born-Green-Yvon equations are employed to describe the one-particle orientational distribution. The phase diagrams are obtained in the whole range of varying the external field for a wide class of XY-spin fluid models with various ratios of the strengths of magnetic to nonmagnetic Yukawa-like interactions. The influence of changing the screening radii of the interaction potentials is also considered. Different types of the phase diagram topology are identified. They are characterized by the existence of critical, tricritical, critical end, and triple points related to transitions between gas, liquid, and para- and ferromagnetic states, accompanied by different external field dependencies of critical temperatures and densities corresponding to the gas-liquid and liquid-liquid transitions. As is demonstrated, the integral equation approach leads to accurate predictions of the complicated phase diagram behavior which coincide well with those evaluated by the cumbersome Gibbs ensemble simulation and multiple-histogram reweighting techniques.


An assessment of rural women's knowledge, constraints and perceptions on cervical cancer screening: the case of two districts in Zimbabwe.
This paper gives a sociological and anthropological insight into the rural women's perceptions and understanding of cervical symptomatology, screening and cancer. Qualitative data was collected through in-depth interviews and focus group discussions with women and health personnel. Quantitative data was obtained through questionnaires administered to 356 women from Mutoko and Shurugwi districts. The study revealed that cervical cancer is a disease that is of concern among health practitioners and women. 95.78% of the interviewed women had never gone for screening and had little knowledge about the various aspects of the disease in terms of causes, prevention and treatment. The study made four recommendations: the need for national screening policy and programme to be put in place, health education to women about cervical cancer, use of VIA in low resource settings and sensitisation of women about the availability of screening facilities in the districts where programmes are in place.


Clinical significance of the phosphorylation of MAPK and protein expression of cyclin D1 in human osteosarcoma tissues.
The aim of the present study was to investigate the significance of the phosphorylation of mitogen-activated protein kinase (MAPK) and the protein expression of cyclin D1 in human osteosarcoma tissues. Human osteosarcoma tissue samples were collected from 30 patients, benign bone tumor samples were collected from 30 patients, and normal bone tissues were collected from 10 individuals as controls. Immunohistochemistry was performed to measure the levels of phosphorylated (p)-MAPK and cyclin D1 protein in cases of human osteosarcoma. The results showed that the positive rates of MAPK and cyclin D1 in osteosarcoma were 86.67% (26/30) and 73.00% (22/30), respectively. The positive staining rates of MAPK and cyclin D1 in benign bone tumor tissues were 10.00% (3/30) and 3.30% (1/30), respectively. The positive rate in the normal bone tissues was 0% (0/30), which was significantly lower, compared with that of the cancerous bone tissue. The positive rates of MAPK and cyclin D1 in osteosarcoma were increased (P<0.05), and the expression of cyclin D1 and p‑MAPK were positively correlated. The phosphorylation of MAPK may be important in the development of osteosarcoma, and the overactivation of MAPK may induce high expression of cyclin D1 and induce tumor cells to proliferate continuously.


Pronounced polarization-induced energy level shifts at boundaries of organic semiconductor nanostructures.
Organic semiconductor devices rely on the movement of charge at and near interfaces, making an understanding of energy level alignment at these boundaries an essential element of optimizing materials for electronic and optoelectronic applications. Here we employ low temperature scanning tunneling microscopy and spectroscopy to investigate a model system: two-dimensional nanostructures of the prototypical organic semiconductor, PTCDA (3,4,9,10-perylenetetracarboxylic dianhydride) adsorbed on NaCl (2 ML)/Ag(111). Pixel-by-pixel scanning tunneling spectroscopy allows mapping of occupied and unoccupied electronic states across these nanoislands with sub-molecular spatial resolution, revealing strong electronic differences between molecules at the edges and those in the centre, with energy level shifts of up to 400 meV. We attribute this to the change in electrostatic environment at the boundaries of clusters, namely via polarization of neighbouring molecules. The observation of these strong shifts illustrates a crucial issue: interfacial energy level alignment can differ substantially from the bulk electronic structure in organic materials.


Role of autoantibodies in the pathogenesis and association of endocrine autoimmune disorders.
This review has focused on the nature and significance of aAB detected in the serum of patients with EAD. Although many antibodies are characteristically detected in the serum of patients with such disorders, only a few are of known pathogenic significance. Antibodies that react with soluble cytoplasmic antigens are not expected to be harmful. On the other hand, membrane or cell surface-directed antibodies are likely to be damaging, either by lysis of the cell membrane, or by reaction with hormone or other surface receptors. Clinically, measurement of aAB has important diagnostic and management value. Moreover, detection of certain antibodies before the onset of disease raises hope that the corresponding disorders may be preventable, e.g. by specific immunosuppression of those subjects, or patients, with positive tests. The possible role of aAB in the association of organ-specific AID by cross-reacting with shared epitopes in various tissues has been highlighted by the recent finding, from the authors' laboratory, of antibodies reactive with a 64-kDa membrane protein found in several tissues, including thyroid, eye muscle, and pancreas, which are frequent sites for autoimmune inflammation. Study of such antibodies and the molecular characterization of the corresponding antigens in the various involved tissues should provide information concerning the role of cross-reactivity in autoimmunity as well as leading to the development of specific immunotherapeutic agents.


LncRNA TUG1 sponges miR-145 to promote cancer progression and regulate glutamine metabolism via Sirt3/GDH axis.
Long noncoding RNAs (lncRNAs) are important regulators in cancer progression. Deregulation of the lncRNA taurine upregulated gene 1 (TUG1) predicts poor prognosis and is implicated in the development of several cancers. In this study, we investigated the role of TUG1 in the pathogenesis of intrahepatic cholangiocarcinoma (ICC). We found that TUG1 is upregulated in ICC samples, which correlates with poor prognosis and adverse clinical pathological characteristics. Knockdown of TUG1 inhibited the proliferation, motility, and invasiveness of cultured ICC cells, and decreased tumor burden in a xenograft mouse model. When we explored the mechanisms underlying these effects, we found that TUG1 acts as an endogenous competing RNA (ceRNA) that 'sponges' miR-145, thereby preventing the degradation of Sirt3 mRNA and increasing expression of Sirt3 and GDH proteins. Accordingly, glutamine consumption, α-KG production, and ATP levels were dramatically decreased by TUG1 knockdown in ICC cells, and this effect was reversed by miR-145 inhibition. These findings indicate that the TUG1/miR-145/Sirt3/GDH regulatory network may provide a novel therapeutic strategy for treatment of ICC.


Clinical association: Lyme disease and Guillain-Barre syndrome.
Guillain-Barre Syndrome (GBS) is a life-threatening condition in which patients may present to the Emergency Department in respiratory distress leading to death. The early identification and treatment of such a condition is paramount in preventing mortality. While there are many infections associated with GBS, the association with Lyme disease is uncommon. Through our case we aim to highlight Borrelia burgdorferi as an important antecedent infection associated with the development of GBS. In this case we report a 31-year-old male who was diagnosed with Lyme disease and GBS with relevant clinical presentation including progressive numbness and weakness in bilateral hands and feet for the past 1week along with areflexia. Initiation of medical therapy with intravenous immunoglobulin and parenteral ceftriaxone resulted in resolution of his symptoms. The treatment of both diseases early can help prevent further central nervous complications leading to high morbidity and mortality.


Peptides derived from viral glycoprotein Gc Inhibit infection of severe fever with thrombocytopenia syndrome virus.
Severe fever with thrombocytopenia syndrome (SFTS) is an acute infectious disease caused by a novel phlebovirus (SFTSV), characterized by fever, thrombocytopenia and leukocytopenia which lead to multiple organ failure with high mortality in severe cases. The SFTSV has spread rapidly in recent years and posed a serious threat to public health in endemic areas. However, specific antiviral therapeutics for SFTSV infection are rare. In this study, we demonstrated that two peptides, SGc1 and SGc8, derived from a hydrophobic region of the SFTSV glycoprotein Gc, could potently inhibit SFTSV replication in a dose-dependent manner without apparent cytotoxicity in various cell lines and with low immunogenicity and good stability. The IC50 (50% inhibition concentration) values for both peptides to inhibit 2 MOI of SFTSV infection were below 10 μM in L02, Vero and BHK21 cells. Mechanistically, SGc1 and SGc8 mainly inhibited viral entry at the early stage of the viral infection. Inhibition of SFTSV replication was specific by both peptides because no inhibitory effect was shown against other viruses including Zika virus and Enterovirus A71. Taken together, our results suggested that viral glycoprotein-derived SGc1 and SGc8 peptides have antiviral potential and warrant further assessment as an SFTSV-specific therapeutic.


Endovascular treatment of iliac artery aneurysms.
Endovascular treatment is now an alternative to surgery for the treatment of iliac artery aneurysms (IAAs). A variety of minimally invasive therapeutic options are available (eg, coil embolization, stent-graft placement), and choosing an appropriate option is essential for achieving excellent long-term results and reducing potential complications. Preprocedural imaging with multi-detector row computed tomography or magnetic resonance imaging is necessary for evaluating patient eligibility and planning the interventional procedure. An imaging classification system for IAAs that is based on anatomic features and endovascular treatment options has been developed and may help determine therapeutic strategies for affected patients. Early experience indicates that endovascular treatment is safe and effective in treating IAAs, and it is expected that various devices that will make endovascular treatment easier to perform will soon become commercially available. However, large, long-term follow-up studies will be needed to determine whether this approach is a practical alternative to open surgery.


Sintering Metal-Organic Framework Gels for Application as Structural Adhesives.
Metal-organic frameworks (MOFs)/coordination polymers are promising materials for gas separation, fuel storage, catalysis, and biopharmaceuticals. However, most applied research on MOFs is limited to these functional materials thus far. This study focuses on the potential of MOFs as structural adhesives. A sintering technique is applied to a zeolitic imidazolate framework-67 (ZIF-67) gel that enables the joining of Cu substrates, resulting in a shear strength of over 30 MPa, which is comparable to that of conventional structural adhesives. Additionally, systematic experiments are performed to evaluate the effects of temperature and pressure on adhesion, indicating that the removal of excess 2-methylimidazole and the by-product (acetic acid) from the sintered material by vaporization results in a microstructure composed of large spherical ZIF-67 crystals that are densely aggregated, which is essential for achieving a high shear strength.


Epigenetic causes of overgrowth syndromes.
Human overgrowth disorders are characterized by excessive prenatal and/or postnatal growth of various tissues. These disorders often present with tall stature, macrocephaly, and/or abdominal organomegaly and are sometimes associated with additional phenotypic abnormalities such as intellectual disability and increased cancer risk. As the genetic etiology of these disorders have been elucidated, a surprising pattern has emerged; multiple monogenic overgrowth syndromes result from variants in epigenetic regulators: variants in histone methyltransferases NSD1 and EZH2 cause Sotos syndrome and Weaver syndrome respectively; variants in DNA methyltransferase DNMT3A cause Tatton-Brown-Rahman syndrome; variants in chromatin remodeler CHD8 cause an autism spectrum disorder with overgrowth; while very recently, a variant in histone reader protein SPIN4 was identified in a new X-linked overgrowth disorder. In this review, we discuss the genetics of these overgrowth disorders and explore possible common underlying mechanisms by which epigenetic pathways regulate human body size.


Regulation of branched-chain alpha-ketoacid dehydrogenase complex by covalent modification.
The branched-chain alpha-ketoacid dehydrogenase complex, like the pyruvate dehydrogenase complex, is an intramitochondrial enzyme subject to regulation by covalent modification. Phosphorylation causes inactivation and dephosphorylation causes activation of both complexes. The branched-chain alpha-ketoacid dehydrogenase kinase, believed distinct from pyruvate dehydrogenase kinase, is an integral component of the branched-chain alpha-ketoacid dehydrogenase complex and is sensitive to inhibition by branched-chain alpha-ketoacids, alpha-chloroisocaproate, phenylpyruvate, clofibric acid, octanoate and dichloroacetate. Phosphorylation of branched-chain alpha-ketoacid dehydrogenase occurs at two closely-linked serine residues (sites 1 and 2) of the alpha-subunit of the decarboxylase. HPLC and sequence data suggest homology of the amino acid sequence adjacent to phosphorylation sites 1 and 2 of complexes isolated from several different tissues. Stoichiometry for phosphorylation of all of the complexes studies was about 1 mol P/mol alpha-subunit for 95% inactivation and 1.5 mol P/mol alpha-subunit for maximally phosphorylated complex. Site 1 and site 2 were phosphorylated at similar rates until total phosphorylation exceeded 1 mol P/mol alpha-subunit. The complexes from rabbit kidney, rabbit heart, and rat heart showed 30-40% additional phosphorylation of the alpha-subunit beyond 95% inactivation. Site specificity studies carried out with the kinase partially inhibited with alpha-chloroisocaproate suggest that phosphorylation of site 1 is primarily responsible for regulation of the complex. The capacity of the branched-chain alpha-ketoacid dehydrogenase to oxidize pyruvate (Km = 0.8 mM, Vmax = 20% of that of alpha-ketoisovalerate) interferes with the estimation of activity state of the hepatic pyruvate dehydrogenase complex. The disparity between the activity states of the two complexes in most physiologic states contributes to this interference. An inhibitory antibody for branched-chain alpha-ketoacid dehydrogenase can be used to prevent interference with the pyruvate dehydrogenase assay. Almost all of the hepatic branched-chain alpha-ketoacid dehydrogenase in chow-fed rats is active (greater than 90% dephosphorylated). In contrast, almost all of the hepatic enzyme of rats fed a low-protein (8%) diet is inactive (greater than 85% phosphorylated). Fasting of chow-fed rats has no effect on the activity state of hepatic branched-chain alpha-ketoacid dehydrogenase, i.e. greater than 90% of the enzyme remains in the active state. However, fasting of rats maintained on low-protein diets greatly activates the hepatic enzyme.(ABSTRACT TRUNCATED AT 400 WORDS)


An Update Review on the Paneth Cell as Key to Ileal Crohn's Disease.
The Paneth cells reside in the small intestine at the bottom of the crypts of Lieberkühn, intermingled with stem cells, and provide a niche for their neighbors by secreting growth and Wnt-factors as well as different antimicrobial peptides including defensins, lysozyme and others. The most abundant are the human Paneth cell α-defensin 5 and 6 that keep the crypt sterile and control the local microbiome. In ileal Crohn's disease various mechanisms including established genetic risk factors contribute to defects in the production and ordered secretion of these peptides. In addition, life-style risk factors for Crohn's disease like tobacco smoking also impact on Paneth cell function. Taken together, current evidence suggest that defective Paneth cells may play the key role in initiating inflammation in ileal, and maybe ileocecal, Crohn's disease by allowing bacterial attachment and invasion.


Denoising infrared maritime imagery using tailored dictionaries via modified K-SVD algorithm.
Recent work has shown that tailored overcomplete dictionaries can provide a better image model than standard basis functions for a variety of image processing tasks. Here we propose a modified K-SVD dictionary learning algorithm designed to maintain the advantages of the original approach but with a focus on improved convergence. We then use the learned model to denoise infrared maritime imagery and compare the performance to the original K-SVD algorithm, several overcomplete "fixed" dictionaries, and a standard wavelet denoising algorithm. Results indicate the superiority of overcomplete representations and show that our tailored approach provides similar peak signal-to-noise ratios as the traditional K-SVD at roughly half the computational cost.


Suspected malignant hyperthermia reactions in New Zealand.
Early clinical signs, triggering agents, time to onset of reaction, mortality and methods of treatment were identified in 123 suspected malignant hyperthermia reactions. In vitro contracture test results were compared with clinical signs and the Malignant Hyperthermia Clinical Grading Scale. Increased end-tidal carbon dioxide is the earliest sign when not preceded by masseter spasm. Earlier diagnosis reduces the incidence of rigidity and severe metabolic acidosis. The combination of suxamethonium and a potent volatile anaesthetic agent triggers an earlier reaction compared with a volatile agent alone. There has been zero mortality since 1981, essentially due to a combination of advanced monitoring capability, increased anaesthetist awareness of malignant hyperthermia, and dantrolene availability. DNA analysis has identified nine New Zealand families with ryanodine receptor gene mutations. A positive DNA test indicates malignant hyperthermia susceptibility with "causative" mutations but discordance requires that negative DNA tests are confirmed with in vitro contracture test. This test also demonstrated the shortcomings of the Malignant Hyperthermia Clinical Grading Scale.


Effect of MPTP on Serotonergic Neuronal Systems and Mitochondrial Complex I Activity in the Living Brain: A PET Study on Conscious Rhesus Monkeys.
The objective of the present PET study was to compare the effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on serotonergic neuronal systems and mitochondrial complex I (MC-I) activity with that of dopamine in conscious rhesus monkeys (Macaca mulatta). Methods: A Parkinson disease monkey model was prepared by repeated administration of MPTP. For the PET measurements, normal and MPTP-treated conscious monkeys received an intravenous injection of 11C-DASB for serotonin transporter, 18F-MPPF for serotonin 1A receptor, 11C-PE2I for dopamine transporter, 11C-6MemTyr for dopamine synthesis, 11C-raclopride for dopamine D2 receptor, or 18F-BCPP-EF for MC-I. Serotonin and dopamine parameters were calculated using time-activity curves in the cerebellum as the input function. The total distribution volume of 18F-BCPP-EF was assessed using Logan plot graphical analysis with metabolite-corrected plasma as the input function. Results: MPTP-induced diffuse reductions in MC-I activity were observed throughout the brain, except the cerebellum. Significant reductions in the presynaptic dopamine parameters-dopamine transporter and dopamine synthesis-were detected in the striatum and substantia nigra pars compacta of MPTP-treated monkeys, whereas no significant differences in postsynaptic dopamine D2 receptor binding were observed. Serotonin transporter binding was reduced by MPTP not only in striatal regions but also in extrastriatal regions. In contrast, serotonin 1A receptor binding was unaffected by MPTP anywhere in the brain. In the cortex, the reduction of serotonin transporter binding correlated with that of MC-I. Conclusion: The results obtained by multiparametric PET measurements in a Parkinson disease monkey model demonstrated that chronic MPTP treatment induced reductions not only in the dopaminergic system in the nigrostriatal pathway but also in serotonin transporter in the cortical and subcortical regions. These results suggest that the neurotoxicity of MPTP is not exclusive to the nigrostriatal pathway, as predicted from MC-I damage in the extrastriatal regions of the brain.


The efficacy and safety of bevacizumab in addition to platinum-based chemotherapy for the first-line treatment of patients with advanced nonsquamous non-small-cell lung cancer: Final results of AVALANCHE, an observational cohort study.
The previous results of former clinical studies confirmed that first-line bevacizumab (BEV) in combination with chemotherapy improves clinical outcomes in patients with advanced non-squamous non-small cell lung cancer. The AVALANCHE study (ClinicalTrials.gov Identifier NCT03170284) was undertaken to assess the clinical outcomes of first-line BEV combined with standard platinum-based regimens in the Hungarian clinical practice. This observational study was conducted in 28 Hungarian sites, with patients enrolled between July 2008 and April 2011. Patients with untreated locally advanced, metastatic or recurrent lung adenocarcinoma received BEV (7.5 mg/kg, q3w) with any platinum-doublet for up to 6 cycles, and then non-progressors proceeded to receive BEV until disease progression or unacceptable toxicity. The primary endpoint was time-to-progression, and secondary endpoints included overall survival (OS), tumour control rate and safety. Patients were also analysed as two cohorts (non-progressors vs. progressors) based on whether or not they received BEV maintenance therapy following completion of first-line chemotherapy plus BEV. The study enrolled 283 patients (median age: 58.2 (18-78) years; males: 50.5%; stage: III/B: 18.4%, IV: 79.9%; adenocarcinoma/other: 95.8/4.2%; ECOG PS 0/1/2/≥3: 30.8/59.7/2.6/1.4%). Centrally located tumours were reported in 21.6%. Cisplatin/carboplatin-based regimens: 53.8/46.2%. A total of 43% of patients received BEV maintenance therapy. The median number of BEV cycles was 6. Median progression-free survival (PFS) was 7.2 months and OS was 15.2 months for the entire cohort. Longer PFS and OS were observed in patients who received BEV maintenance therapy [median OS, 26.2 vs. 10.2 months (P<0.001); median PFS, 9.2 vs. 5.8 months (P<0.001)]. Contrary to the results of previous OCS no significant difference was recorded in the different age groups or gender. Best tumour response: Complete remission/partial remission/stable disease/progressive disease/not reported were: 1.5/29.9/26.9/9.1/32.6% of all patients. In conclusion, clinical outcomes obtained in this real-life population were consistent with pivotal studies. BEV maintenance treatment was associated with a significantly longer PFS and OS.


Modelling accretion disc and stellar wind interactions: the case of Sgr A.
Sgr A* is an ideal target to study low-luminosity accreting systems. It has been recently proposed that properties of the accretion flow around Sgr A* can be probed through its interactions with the stellar wind of nearby massive stars belonging to the S-cluster. When a star intercepts the accretion disc, the ram and thermal pressures of the disc terminate the stellar wind leading to the formation of a bow shock structure. Here, a semi-analytical model is constructed which describes the geometry of the termination shock formed in the wind. With the employment of numerical hydrodynamic simulations, this model is both verified and extended to a region prone to Kelvin-Helmholtz instabilities. Because the characteristic wind and stellar velocities are in ∼108 cm s-1 range, the shocked wind may produce detectable X-rays via thermal bremsstrahlung emission. The application of this model to the pericentre passage of S2, the brightest member of the S-cluster, shows that the shocked wind produces roughly a month long X-ray flare with a peak luminosity of L ≈ 4 × 1033 erg s-1 for a stellar mass-loss rate, disc number density, and thermal pressure strength of [Formula: see text], nd = 105 cm-3, and α = 0.1, respectively. This peak luminosity is comparable to the quiescent X-ray emission detected from Sgr A* and is within the detection capabilities of current X-ray observatories. Its detection could constrain the density and thickness of the disc at a distance of ∼3000 gravitational radii from the supermassive black hole.


Toxicity of furazolidone to Nubian goats.
Male Nubian goats were given furazlidone orally at daily doses of 40, 80, 160 and 320 mg/kg for up to 10 days. Animals given 160 and 320 mg/kg became anemic, and showed anorexia, hyperexcitability, uneasiness , backward walking, locomotory disturbances and circling. These animals died within 5 to 7 days of treatment. Postmortem examination showed mild congestion in brain, and fatty change in liver and kidneys. There was histopathological evidence of hepatic and renal damage, and some necrosis in brain and adrenals. Biochemical examination of serum confirmed the presence of hepatic and renal damage. Goats given furazolidone at daily doses of 40 and 80 mg/kg showed similar signs as above, but to a lesser degree. They were killed at the end of the experiment (10 days). The signs of furazolidone intoxication resembled those of cerebrocortical necrosis (thiamine deficiency in ruminants). Therefore, thiamine (100 mg/animal) was injected iv daily to goats receiving 320 mg furazolidone/kg. The vitamin ameliorated the severity of the drug toxicity.


Detection of pulmonary ground-glass opacity based on deep learning computer artificial intelligence.
A deep learning computer artificial intelligence system is helpful for early identification of ground glass opacities (GGOs). Images from the Lung Image Database Consortium and Image Database Resource Initiative (LIDC-IDRI) database were used in AlexNet and GoogLeNet to detect pulmonary nodules, and 221 GGO images provided by Xinhua Hospital were used in ResNet50 for detecting GGOs. We used computed tomography image radial reorganization to create the input image of the three-dimensional features, and used the extracted features for deep learning, network training, testing, and analysis. In the final evaluation results, we found that the accuracy of identification of lung nodule could reach 88.0%, with an F-score of 0.891. In terms of performance and accuracy, our method was better than the existing solutions. The GGO nodule classification achieved the best F-score of 0.87805. We propose a preprocessing method of red, green, and blue (RGB) superposition in the region of interest to effectively increase the differentiation between nodules and normal tissues, and that is the innovation of our research. The method of deep learning proposed in this study is more sensitive than other systems in recent years, and the average false positive is lower than that of others.


Ostertagia ostertagi in first-season grazing cattle in Belgium, Germany and Sweden: general levels of infection and related management practices.
The objective of this study was to determine the prevailing levels of infection with Ostertagia ostertagi in first-season grazing calves and related management factors in three European countries (Belgium, Germany and Sweden). A cross-sectional survey was performed in first-season grazing dairy cattle during 2 consecutive years. Levels of infection with O. ostertagi were assessed by a standardized serum pepsinogen assay at the end of the grazing periods 2006 and 2007 and information on control measures against gastrointestinal nematodes were collected at the same time through a questionnaire. Information was collected from a total of 358 herds in 2006 and 726 herds in 2007. The general infection patterns were similar in the different countries and the 2 years with the majority of the herds having a low (<1 UTyr) or intermediate pepsinogen result (1-3 UTyr) and only 2-6% of the herds having levels of infection that are considered to induce significant production losses (>3 UTyr). The level of nematode control was high in each country, which is illustrated by the widespread use of anthelmintics (69-83% of herds) and the frequent combination of anthelmintic use and control through pasture management (>50% of herds combined two or more protective measures). However, the used control methods showed clear differences between the countries. After taking into account the effect of anthelmintic treatment, herd mean pepsinogen levels were significantly lower in large herds, in calves grazing on a small paddock (vs. pasture) and on mown (vs. non-mown) pastures and if turn out on pasture was postponed. The collected data may serve as a baseline from which we can monitor the methods and success of gastrointestinal nematode control in dairy cattle.


Distribution of brain HIV load in AIDS.
Approximately one quarter of patients with AIDS develop severe cognitive deficits called HIV-associated dementia complex (ADC). There is some controversy regarding the importance of viral load in mediating neurologic disease. With the advent of sensitive, quantitative and reproducible RNA assays for HIV load in plasma and CSF, we quantified viral load in brains from 10 autopsied HIV-infected subjects and 2 non-infected controls. The new quantitative HIV RNA assays showed general agreement with previously used semi-quantitative immunocytochemical assessments of HIV envelope protein, and were performed without professional subjective interpretation. All cases with very high levels of HIV in the CSF, had high overall levels in the brain, suggesting that CSF viral loads exceeding 10(6) copies per mL may be a surrogate marker of high viral load in the brain. Levels of virus in the spleen showed no clear association with those found in the brain. HIV RNA was not uniformly distributed throughout the brain. Selective regions, including basal ganglia and hippocampus, showed higher levels of virus than the cerebellar cortex and mid-frontal cortical gray matter. Assessment of overall brain viral load requires careful attention to regional quantitation.


[Feasibility of diagnostic contrast-enhanced CT for attenuation correction of whole body PET images].
Image fusion has been recognized as a useful technique in diagnostic imaging. We have been evaluating the manual image fusion of PET and contrast-enhanced (CE) CT obtained separately. The CT images can be used for attenuation correction as well as for image fusion; however, the quantitative accuracy of CT-corrected PET images has yet to be assessed. The purpose of this study was to compare the radioactivity concentration between conventional (68)Ge-corrected and CECT-corrected PET images. Twenty patients underwent a whole-body PET scan, followed by a CT scan with intravenous contrast material, after careful positioning using an individually molded vacuum cushion. Two different attenuation-corrected emission data sets were produced, i.e., (68)Ge-corrected images and CECT-corrected images. Image registration was performed by maximizing mutual information-based cost function, between the CT and the combination of emission and transmission PET volumes. The CT pixel values in Hounsfield units were transformed into linear attenuation coefficients in cm(-1), using a conversion formula for a lookup-table from phantom experiments. Measured activity concentrations from identical regions of interest in representative normal organs and in 25 pathologic foci of uptake were compared. In addition, the quality of the reconstructed images was assessed using the normal mean square error (NMSE). Measured average radioactivity concentrations were 1.38-9.56% higher for CECT-corrected images than for (68)Ge-corrected images. Overall, the NMSE value of CECT-corrected images compared with (68)Ge-corrected images was 0.02+/-0.01. The difference in quantitative values between (68)Ge-corrected and CECT-corrected PET images was comparable to that of an integrated PET/CT system. Diagnostic CT images with intravenous contrast performed separately before or after a PET scan could be used clinically not only for fusion but also for attenuation correction.


The effect of Bacillus coagulans-fermented and nonfermented Ginkgo biloba on the immunity status of broiler chickens.
To evaluate and compare the effects of Bacillus coagulans-fermented Ginkgo biloba (FG) and nonfermented Ginkgo biloba (NFG) on the immunity status of broiler chickens, 180 1-d-old female Arbor Acres chicks were divided into 3 groups and fed either a basal diet, a basal diet supplemented with 0.3% NFG, or a basal diet supplemented with 0.3% FG. Blood samples were taken on the seventh (before vaccination), 14th, 21st, 28th and 35th day for the assessment of serum IL-18 and interferon γ (IFN-γ) levels by ELISA. In addition, Newcastle disease antibody titer analysis was made via hemagglutination and hemagglutination inhibition test methods. On d 35, 6 chickens from each group were sacrificed and the thymus, liver, spleen, small intestine (jejunum segment), cecum, and bursa of Fabricius from each chicken were removed for analysis. RNA was isolated for defensin expression detection by real-time PCR (q-PCR). The results showed that serum IL-18 and IFN-γ levels decreased after treatment with NFG and FG compared with untreated control chickens. The ND antibody titers did not differ significantly between the 3 groups on the seventh, 14th, 21st and 28th day; however, on the 35th day, the ND antibody titers of the NFG and FG chickens were both significantly higher than those of control group chickens. Defensin RNA expression levels were inhibited by NFG; however, they were induced by FG. In conclusion, fermentation of Ginkgo biloba with Bacillus coagulans can promote the beneficial effect of Gingko biloba on the immunity status of broiler chickens.


An ensemble method for predicting subnuclear localizations from primary protein structures.
Predicting protein subnuclear localization is a challenging problem. Some previous works based on non-sequence information including Gene Ontology annotations and kernel fusion have respective limitations. The aim of this work is twofold: one is to propose a novel individual feature extraction method; another is to develop an ensemble method to improve prediction performance using comprehensive information represented in the form of high dimensional feature vector obtained by 11 feature extraction methods. A novel two-stage multiclass support vector machine is proposed to predict protein subnuclear localizations. It only considers those feature extraction methods based on amino acid classifications and physicochemical properties. In order to speed up our system, an automatic search method for the kernel parameter is used. The prediction performance of our method is evaluated on four datasets: Lei dataset, multi-localization dataset, SNL9 dataset and a new independent dataset. The overall accuracy of prediction for 6 localizations on Lei dataset is 75.2% and that for 9 localizations on SNL9 dataset is 72.1% in the leave-one-out cross validation, 71.7% for the multi-localization dataset and 69.8% for the new independent dataset, respectively. Comparisons with those existing methods show that our method performs better for both single-localization and multi-localization proteins and achieves more balanced sensitivities and specificities on large-size and small-size subcellular localizations. The overall accuracy improvements are 4.0% and 4.7% for single-localization proteins and 6.5% for multi-localization proteins. The reliability and stability of our classification model are further confirmed by permutation analysis. It can be concluded that our method is effective and valuable for predicting protein subnuclear localizations. A web server has been designed to implement the proposed method. It is freely available at http://bioinformatics.awowshop.com/snlpred_page.php.


Acute Presentation of Urachal Cyst: A Case Report.
Urachus is an embryonic organ related to the bladder that degenerates after birth. Defective obliteration of the urachus leads to urachal malformations, the most common of which is a urachal cyst. A urachal cyst is often misdiagnosed due to its myriad presentations. Delay in diagnosis can lead to complications such as sepsis, fistula formation, and rupture of the cyst mimicking peritonitis. Hence, a high index of suspicion is required for the timely diagnosis and management of urachal cysts presenting in the emergency room. We report the case of a 32-year-old woman who presented with clinical features suggestive of an acute abdomen. The judicious use of imaging confirmed the diagnosis of an infected urachal cyst, which was surgically managed.


Changes in granulocyte chemiluminescence and plasma fibronectin concentrations following major blunt trauma.
Chemiluminescence activity of granulocytes in phagocytosis of zymosan and Escherichia coli and their responses to chemoattractant N-formylmethionyl-leucyl-phenylalanine (FMLP) were evaluated in 13 major blunt trauma patients (Injury Severity Score 31 +/- 6) and their plasma fibronectin concentrations were measured. Chemiluminescence responses to zymosan and E. coli were at control levels immediately after injury and a week thereafter, but responses to FMLP were increased compared to the controls (p less than 0.05). Plasma fibronectin concentrations were depressed on the day after trauma (p less than 0.001) but increased to control values over 1 week. The changes had no correlation with the patients' recovery.


Predictive Immunological, Virological, and Routine Laboratory Markers for Critical COVID-19 on Admission.
Early identification of COVID-19 patients at risk of critical illness is a challenging endeavor for clinicians. We aimed to establish immunological, virological, and routine laboratory markers, which, in combination with clinical information, may allow identifying such patients. Blood tests to measure neutrophil/lymphocyte ratio (NLR) and levels of ferritin, CRP, D-dimer, complement components (C3 and C4), cytokines, and lymphocyte subsets, as well as SARS-Cov-2 RT-PCR tests, were performed in COVID-19-confirmed cases within 48 hours of admission. RT-PCR cycle threshold (Ct) values from oropharyngeal or nasopharyngeal swabs were determined on the day of admission. Symptom severity was categorized as mild (grade 1), severe (grade 2), or critical (grade 3). Of 120 patients who were included, 49 had mild, 32 severe, and 39 critical COVID-19. Levels of ferritin >370 ng/mL (OR 16.4, 95% CI 5.3-50.8), D-dimer >440 ng/mL (OR 5.45, 95% CI 2.36-12.61), CRP >7.65 mg/dL (OR 11.54, 95% CI 4.3-30.8), NLR >3.77 (OR 13.4, 95% CI 4.3-41.1), IL-6 >142.5 pg/mL (OR 8.76, 95% CI 3.56-21.54), IL-10 >10.8 pg/mL (OR 16.45, 95% CI 5.32-50.81), sIL-2rα (sCD25) >804.5 pg/mL (OR 14.06, 95% CI 4.56-43.28), IL-1Ra >88.4 pg/mL (OR 4.54, 95% CI 2.03-10.17), and IL-18 >144 pg/mL (OR 17.85, 95% CI 6.54-48.78) were associated with critical COVID-19 in the univariate age-adjusted analysis. This association was confirmed in the multivariate age-adjusted analysis only for ferritin, CRP, NLR, IL-10, sIL-2rα, and IL-18. T, B, and NK cells were significantly decreased in critical patients. SARS-CoV-2 was not detected in blood except in 3 patients who had indeterminate results. RT-PCR Ct values from oropharyngeal or nasopharyngeal swabs on admission were not related to symptom severity. Ferritin, D-dimer, CRP, NLR, cytokine (IL-18 and IL-10), and cytokine receptor (IL-6, IL1-Ra, and sCD25) test results combined with clinical data can contribute to the early identification of critical COVID-19 patients.


Interventions for squamous cell carcinoma of the conjunctiva in HIV-infected individuals.
Squamous cell carcinoma of the conjunctiva is described in the ophthalmic literature as a rare, slow-growing tumour of the eye, normally affecting elderly men around 70 years of age. In Africa, however, the disease is different. The incidence is rising rapidly, affecting young persons (around 35 years of age), and usually affecting women. It is more aggressive, with a mean history of three months at presentation. This pattern is related to the co-existence of the HIV/AIDS pandemic, high HPV exposure, and solar radiation in the region. Various interventions exist, but despite therapy, there is a high recurrence rate (up to 43%) and poor cosmetic results in late disease. This review was conducted to evaluate the interventions for treatment of conjunctival squamous cell carcinoma in HIV-infected individuals. To evaluate the effect of interventions for treating squamous cell carcinoma of the conjunctiva in HIV-infected individuals on local control, recurrence, death, time to recurrence, and adverse events. Using a sensitive search strategy, we attempted to identify all relevant trials, regardless of language or publication status, from the following electronic databases; PubMedPubMed, EMBASE and The Cochrane Library. We also searched clinical trial registries; WHO International Clinical Trials Registry Platform (ICTRP) and the US National Institutes of Health Clinicaltrials.gov. We searched the international conference proceedings of HIV/AIDS and AIDS-related cancers from the AIDS Education Global Education System (AEGIS). Searches were conducted between January and February 2012. Randomised controlled trials (RCTs) involving HIV-infected individuals with ocular surface squamous neoplasia. We independently screened the results of the search to select potentially relevant studies and to retrieve the full articles. We independently applied the inclusion criteria to the potentially relevant studies. No studies were identified that fulfilled the selection criteria. No RCTs of interventions currently used against conjunctival squamous cell carcinoma in HIV-infected individuals were identified.There is one ongoing RCT in Kenya that was registered in July 2012. Current clinical practice in treatment of squamous cell carcinoma of the conjunctiva rests on a weak evidence base of case series and case reports. Randomised controlled trials for treatment of this disease are needed in settings where it occurs most frequently. Preventive interventions also need to be identified. HIV/AIDS research has not focused on treatment of this tumour.


Accuracy of cytological examination of Tao brush endometrial sampling in diagnosing endometrial premalignancy and malignancy.
Although Tao brush has become one of the most studied and used endometrial cytological samplers, concerns remain about the adequacy of the cytological sample compared with definitive histology. We aimed to assess accuracy of cytological examination from Tao brush sampling in diagnosing endometrial premalignancy and malignancy through a systematic review and meta-analysis. Seven electronic databases were searched from January 2000 to July 2021 for all studies which allowed assessment of accuracy of Tao brush in diagnosing endometrial premalignancy and malignancy. We calculated sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-), diagnostic odds ratio (DOR) and area under the curve (AUC) on summary receiver operating characteristic (SROC) curve. Five studies with 774 patients were included. In diagnosing endometrial premalignancy and malignancy, cytological examination from Tao brush endometrial sampling showed pooled sensitivity of 0.95 (95% CI, 0.90-0.98), specificity of 0.92 (95% CI, 0.90-0.94), LR+ of 12.73 (95% CI, 3.94-41.18), LR- of 0.09 (95% CI, 0.05-0.18), DOR of 184.84 (95% CI, 24.37-1401.79), AUC of 0.9757 (standard error: 0.013). In conclusion, cytological examination from Tao brush seems to have a high diagnostic accuracy and might be proposed as both screening and diagnostic tool. However, further studies are necessary to confirm these findings.


Urologic complications of spinal cord injury.
Spinal cord injuries in the past were associated with a very high mortality, predominantly from urologic complications and sepsis. Improvements in the urologic and medical management of these patients have significantly decreased the morbidity and mortality. Many complications may still develop during the urologic management, however. Periodic follow-up is thus essential to recognize and treat urologic complications in order to preserve renal function.


Moxifloxacin-warfarin interaction.
Two case reports presented here show elevated prothrombin time/international normalized ratios (PT/INR) following coadministration of warfarin and moxifloxacin. Although the underlying mechanism of this interaction still remains unclear, health care providers should be careful when prescribing moxifloxacin to patients on warfarin therapy, especially to patients with low albumin levels. More frequent monitoring of INR in these patients may be warranted.


In Silico Prediction of Stratum Corneum Partition Coefficients via COSMOmic and Molecular Dynamics Simulations.
Stratum corneum (SC) is the main barrier of human skin where the inter-corneocytes lipids provide the main pathway for transdermal permeation of functional actives of skin care and health. Molecular dynamics (MD) has been increasingly used to simulate the SC lipid bilayer structure so that the barrier property and its affecting factors can be elucidated. Among reported MD simulation studies, solute partition in the SC lipids, an important parameter affecting SC permeability, has received limited attention. In this work, we combine MD simulation with COSMOmic to predict the partition coefficients of dermatologically relevant solutes in SC lipid bilayer. Firstly, we run MD simulations to obtain equilibrated SC lipid bilayers with different lipid types, compositions, and structures. Then, the simulated SC lipid bilayer structures are fed to COSMOmic to calculate the partition coefficients of the solutes. The results show that lipid types and bilayer geometries play a minor role in the predicted partition coefficients. For the more lipophilic solutes, the predicted results of solute partition in SC lipid bilayers agree well with reported experimental values of solute partition in extracted SC lipids. For the more hydrophilic molecules, there is a systematical underprediction. Nevertheless, the MD/COSMOmic approach correctly reproduces the phenomenological correlation between the SC lipid/water partition coefficients and the octanol/water partition coefficients. Overall, the results show that the MD/COSMOmic approach is a fast and valid method for predicting solute partitioning into SC lipids and hence supporting the assessment of percutaneous absorption of skin care ingredients, dermatological drugs as well as environmental pollutants.


Prospective memory in multiple sclerosis: clinical utility of the Miami Prospective Memory Test.
Objective: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system that frequently affects cognition. Persons with MS (PwMS) complain of difficulties with prospective memory (PM), the capacity to remember to perform an intended action at the appropriate moment in the future. The objective of this study was to assess the clinical utility of the Miami Prospective Memory Test (MPMT) in detecting PM deficits in MS. The test is brief, easy to administer and accessible, and allows direct comparison between scores on event- and time-based conditions. A secondary objective was to examine the relationship between PM performance and cognitive functioning. Method: Eighty-four PwMS between 27 and 78 years old were compared to 50 age-, sex- and education-matched healthy adults on the MPMT. Results: Time-based (TB) scores, but not event-based (EB) scores, were significantly lower in PwMS than in healthy adults. The MPMT showed good internal consistency, and correlations were found with disability assessed by the Expanded Disability Status Scale (EDSS). PM was also correlated with memory and executive/attention functioning. Conclusions: This study supports the clinical utility of the MPMT in assessing the presence of PM deficits in PwMS especially under TB constraints.


Beyond the diffusing-wave spectroscopy model for the temporal fluctuations of scattered light.
We extend the theory of diffusing-wave spectroscopy using a random-walk approach and a numerical solution of the radiative transfer equation. The theory is not restricted to the diffusive regime and allows one to describe the crossover between the single-scattering and the diffusive regimes, which has been observed experimentally. It also predicts a lower bound of the scattered-field correlation time at long paths. This extended theory should have broad experimental applications in the field of imaging through biological tissues.


Murine gammaherpesvirus infection is skewed toward Igλ+ B cells expressing a specific heavy chain V-segment.
One of the defining characteristics of the B cell receptor (BCR) is the extensive diversity in the repertoire of immunoglobulin genes that make up the BCR, resulting in broad range of specificity. Gammaherpesviruses are B lymphotropic viruses that establish life-long infection in B cells, and although the B cell receptor plays a central role in B cell biology, very little is known about the immunoglobulin repertoire of gammaherpesvirus infected cells. To begin to characterize the Ig genes expressed by murine gammaherpesvirus 68 (MHV68) infected cells, we utilized single cell sorting to sequence and clone the Ig variable regions of infected germinal center (GC) B cells and plasma cells. We show that MHV68 infection is biased towards cells that express the Igλ light chain along with a single heavy chain variable gene, IGHV10-1*01. This population arises through clonal expansion but is not viral antigen specific. Furthermore, we show that class-switching in MHV68 infected cells differs from that of uninfected cells. Fewer infected GC B cells are class-switched compared to uninfected GC B cells, while more infected plasma cells are class-switched compared to uninfected plasma cells. Additionally, although they are germinal center derived, the majority of class switched plasma cells display no somatic hypermutation regardless of infection status. Taken together, these data indicate that selection of infected B cells with a specific BCR, as well as virus mediated manipulation of class switching and somatic hypermutation, are critical aspects in establishing life-long gammaherpesvirus infection.


Effects of budesonide on toll-like receptor expression in alveolar macrophages from smokers with and without COPD.
Alveolar macrophages (AMs) are equipped with innate immune receptors such as toll-like receptor 2 (TLR2) and toll-like receptor 4 (TLR4). In primary bronchial epithelial cells, exposure of toll-like receptor (TLR) ligands or tumor necrosis factor-alpha (TNF-α) increased TLR2 mRNA expression and reduced interleukin-8 (IL-8) release when coincubated with glucocorticosteroids. The aim of this study was to compare TLR2 and TLR4 expression levels and the effect of a glucocorticosteroid after stimulation with TLR ligands on AMs from smokers with and without COPD compared with the healthy controls. Bronchoalveolar lavage was performed, and AMs were isolated from smokers with (n=10) and without COPD (n=11) and healthy controls (n=10) and stimulated ex vivo with peptidoglycan (PGN), lipopolysaccharide (LPS), or TNF-α ± budesonide (Bud). Blocking antibodies to TLR2 or TLR4 were added before stimulation with LPS or PGN ± Bud, respectively. The release of proinflammatory cytokine (TNF-α), chemoattractant (CXCL8), and TLR expression was analyzed by enzyme-linked immunosorbent assay and reverse transcription polymerase chain reaction. LPS, PGN, and TNF-α induced an increased release of IL-8 and TNF-α in the AMs in all the groups independent of smoking or disease. These responses were inhibited by a glucocorticosteroid (Bud) in all the three groups, except PGN-induced IL-8 secretion in smokers without COPD. Bud increased TLR2 expression in the healthy controls and smokers without COPD. Costimulation of TLR ligands and Bud significantly enhanced TLR2 mRNA expression in both groups of smokers compared with TLR ligands alone. In smokers, costimulation with PGN and Bud significantly increased TLR2 expression when compared with Bud alone. On stimulation with the TLR4 agonist, LPS downregulated TLR4 mRNA expression in all the three groups. The combination of glucocorticosteroids with TLR ligands can increase TLR2 expression, thereby improving host defense in smokers. Also this combination can decrease the secretion of proinflammatory cytokines and chemokines as an anti-inflammatory response. Our findings indicate that glucocorticosteroid therapy strengthens immune defense pathways, which may have implication during exacerbation caused by microorganisms.


Platelet glycine, glutamate and aspartate in primary headache.
Platelet levels of glutamic and aspartic acid and glycine were measured in patients with migraine with aura, migraine without aura, tension headache and cluster headache. High levels of these amino acids were found in patients with migraine with aura compared to normal subjects and other headache groups. During headache, glutamate levels further increased in migraine with aura patients. These findings may have relevance to the neurological symptoms of migraine with aura.


mPPAR gamma 2: tissue-specific regulator of an adipocyte enhancer.
Previously, we have isolated and characterized an enhancer from the 5'-flanking region of the adipocyte P2 (aP2) gene that directs high-level adipocyte-specific gene expression in both cultured cells and transgenic mice. The key regulator of this enhancer is a cell type-restricted nuclear factor termed ARF6. Target sequences for ARF6 in the aP2 enhancer exhibit homology to a direct repeat of hormone response elements (HREs) spaced by one nucleotide; this motif (DR-1) has been demonstrated previously to be the preferred binding site for heterodimers of the retinoid X receptor (RXR) and the peroxisome proliferator-activated receptor (PPAR). We have cloned a novel member of the peroxisome proliferator-activated receptor family designated mPPAR gamma 2, and we demonstrate that a heterodimeric complex of mPPAR gamma 2 and RXR alpha constitute a functional ARF6 complex. Expression of mPPAR gamma 2 is induced very early during the differentiation of several cultured adipocyte cell lines and is strikingly adipose-specific in vivo. mPPAR gamma 2 and RXR alpha form heterodimers on ARF6-binding sites in vitro, and antiserum to RXR alpha specifically inhibits ARF6 activity in adipocyte nuclear extracts. Moreover, forced expression of mPPAR gamma 2 and RXR alpha activates the adipocyte-specific aP2 enhancer in cultured fibroblasts, and this activation is potentiated by peroxisome proliferators, fatty acids, and 9-cis retinoic acid. These results identify mPPAR gamma 2 as the first adipocyte-specific transcription factor and suggest mechanisms whereby fatty acids, peroxisome proliferators, 9-cis retinoic acid, and other lipids may regulate adipocyte gene expression and differentiation.


Evaluation of the neuro-protective effect of Artemisia judaica extract in a murine diabetic model.
Chronic hyperglycemia is associated with several negative outcomes including neuronal injury. Medicinal plants supplementation has been widely applied to treat or decrease diabetic complications. Here, the possible neuroprotective effect of Artemisia judaica extract (AjE. 300 mg kg-1 day-1 ) against neuronal deficits in diabetes model induced by high-fat diet (HFD) administration and streptozotocin (STZ, 30 mg/Kg) injection in rats was investigated. Diabetic rats showed a disturbance in the neuronal redox homeostasis as confirmed by the elevated lipoperoxidation and nitric oxide formation along with the decreased antioxidant molecules. In addition, a state of neuroinflammation and apoptosis were recorded in the brain tissue in diabetic rats. Furthermore, HFD/STZ provoked neurochemical alterations. However, AjE administration was found to abrogate significantly the neuronal impairments associated with diabetes. This neuroprotective effect comes from its strong antioxidant, anti-inflammatory, antiapoptotic, and neuromodulatory activity; suggesting that AjE may be applied to alleviate neurological impairments in diabetic patients. PRACTICAL APPLICATIONS: Diabetes mellitus (DM) is a metabolic disorder characterized by high blood glucose level comes from the dysregulation of insulin production and/or its action. The persisted hyperglycemia is correlated with the progression of several physical complications including renal, hepatic, vascular, retinal, and neuronal dysfunction. Artemisia is used in the nutritional and medicinal proposes due to the enriched bioactive molecules such as essential oil, flavonoids, phenolics, sesquiterpenoids, triterpenoids, and artemisinin. And we found that Artemisia judaica extract (AjE) administration was able to abrogate significantly the neuronal impairments associated with diabetes. This neuroprotective effect comes from its strong antioxidant, anti-inflammatory, anti-apoptotic and neuromodulatory activity; suggesting that AjE may be applied to alleviate neurological impairments in diabetic patients.